The case has been made for more and better theory-informed process evaluations within trials in an effort to facilitate insightful understandings of how interventions work. In this paper, we provide an explanation of implementation processes from one of the first national implementation research randomized controlled trials with embedded process evaluation conducted within acute care, and a proposed extension to the Promoting Action on Research Implementation in Health Services (PARIHS) framework.The PARIHS framework was prospectively applied to guide decisions about intervention design, data collection, and analysis processes in a trial focussed on reducing peri-operative fasting times. In order to capture a holistic picture of implementation processes, the same data were collected across 19 participating hospitals irrespective of allocation to intervention. This paper reports on findings from data collected from a purposive sample of 151 staff and patients pre- and post-intervention. Data were analysed using content analysis within, and then across data sets.A robust and uncontested evidence base was a necessary, but not sufficient condition for practice change, in that individual staff and patient responses such as caution influenced decision making. The implementation context was challenging, in which individuals and teams were bounded by professional issues, communication challenges, power and a lack of clarity for the authority and responsibility for practice change. Progress was made in sites where processes were aligned with existing initiatives. Additionally, facilitators reported engaging in many intervention implementation activities, some of which result in practice changes, but not significant improvements to outcomes.This study provided an opportunity for reflection on the comprehensiveness of the PARIHS framework. Consistent with the underlying tenant of PARIHS, a multi-faceted and dynamic story of implementation was evident. However, the prominent role that individuals played as part of the interaction between evidence and context is not currently explicit within the framework. We propose that successful implementation of evidence into practice is a planned facilitated process involving an interplay between individuals, evidence, and context to promote evidence-informed practice. This proposal will enhance the potential of the PARIHS framework for explanation, and ensure theoretical development both informs and responds to the evidence base for implementation.ISRCTN18046709 - Peri-operative Implementation Study Evaluation (PoISE). Implementation research is ‘the scientific study of methods to promote the systematic uptake of clinical research findings and other evidence-based practice into routine practice, and hence improve the quality…of healthcare’. HistoriPARIHS was embedded within our evaluation framework because it provided a potentially useful heuristic to guide the development of the study and evaluate the process of implementation. PARIHS represents the complexity of implementation by considering the three core elements and their sub-elements to be dynamic and interrelated. Successful implementation of research evidence is conceived as a function of evidence, context, and facilitation. Specifically, the working proposition is that the most successful implementation will occur when evidence is robust and practitioners ‘agree’ with it, the context is receptive, and where implementation processes are appropriately facilitated by internal and/or external facilitators,14.PARIHS is an example of the development of a middle range explanation or theory about implementation. As suchPARIHS appears to have good face validity in that it has been often used in implementation activity and is widely cited in the international literature. However, in their review of the use of PARIHS, Helfrich et al. found thThere are a number of reviews about the effectiveness of interventions to promote the uptake of evidence in practice-24. GeneIn order to fully understand implementation processes and impacts within the context of a large pragmatic trial evaluating interventions to improve peri-operative fasting times, we designed a process evaluation in which PARIHS was embedded. The maiThe framework developed for this study reflects the multiple components at play in implementation work Figure . PARIHS Strategies for the implementation of two of the evidence-based guideline recommendations were designed. The recommendations include that patients could have water up to two hours and food up to six hours before induction of anaesthesia, with resumption of fluids when fully awake. DrawingIn relation to the study’s evaluation framework, these interventions had the potential to work at multiple levels within an organization’s context and with varying degrees of interactivity from none (standard dissemination) to local particularisation based on an assessment of readiness (PDSA). All included attention to a robust evidence base in the form of a guideline that had been developed using National Institute for Health and Clinical Excellence’s (NICE) approach. There were facilitation components in the web-based resource and opinion leader intervention, as well as in the PDSA intervention, which included a local facilitator. Successful implementation in this study meant the use of the recommendations in practice and impact on practice and patient outcomes. The intervention period was six months.Data were collected pre- and post-intervention between November 2006 and February 2009 across the 19 participating hospitals. The samSemi- structured audio-recorded interviews were conducted with patients from each hospital during pre- and post-intervention data collection periods about their experiences of fasting. An interview schedule was developed with the help of the project’s patient advisor. Ward staff identified potential patients for interview and the majority of patients were interviewed within three days post-operatively.Semi-structured audio-recorded telephone interviews took place with PDSA facilitators and opinion leaders about their experiences of implementation including activities, barriers and facilitators, and perceived impact were collected in pre- and post-intervention periods.Semi-structured audio recorded telephone interviews took place with hospital key contacts who had facilitated access and the running of the project locally about their experiences of intervention implementation, including the identification of any changes in practice and use of resources were conducted pre- and post-intervention, including whether these had been sustained three months post-intervention.The interview topics for patient and staff interviews were developed based on the evaluation framework and therefore included questions about perceptions of the evidence about fasting, the receptiveness of the contexts of implementation, the role and activities of the opinion leaders and PDSA facilitators, and any other facilitators and barriers perceived and experienced by participants.Multi-professional audio-recorded focus groups were conducted by two moderators to gather information about the experience of staff in clinical areas where the study had been taking place post-intervention. A sample of hospitals was identified within each intervention arm as having made the largest change to fluid fast time (n = 3) and those that had made the smallest/no/marginal change (n = 2). The schedule was based on emerging findings from the staff interview data and included awareness and impact of the study/interventions, changes to fasting practice, inter-professional issues, and processes of practice change, including barriers and facilitators.Qualitative audio-recorded data was transcribed in full, and managed in N*DIST 5 (pre-intervention) and NVIVO 7 (post-intervention). A process of inductive and deductive analysis was undertaken informed by Ritchie and Spencer’s approachThis study was approved by a multi-site ethics committee (06/MRE01/20).Overall findings from the trial are published separately. ParticiThe results from the trial showed no significant effect of the interventions on the primary outcome of fluid fasting time. The process evaluation data provides a rich picture of implementation processes that offers an explanation for the trial findings, and about how the implementation of interventions played out within the practice context. Particular themes about implementation facilitators and barriers were not specific to interventions; rather we observed patterns across sites. There are some findings that are specific to the components of particular interventions. The main tenets of PARIHS: evidence, context, and facilitation are used to present the findings. The links to particular interventions and impact(s) are embedded within these descriptions. Consistent with implementation in the reality of the clinical setting, there is a complexity and dynamism that underlies these findings. Linkages and interactions will be highlighted in the following sections, and considered in more detail in the discussion.The research base for any potential change to practice was strong in that the recommendations were underpinned by robust randomized controlled trials. The message for practice was also ‘simple’ and framed within the guideline as the ‘2 and 6 rule’—patients can drink clear fluids up to two hours, and eat up to six hours, before anaesthesia. Apart from one site who used their existing processes to disseminate the guideline package across relevant parts of the organization, it was unclear what happened to it once it was received by hospital directors in other sites. Therefore, we could surmise that the evidence may not have reached the potential users in most sites. Two main findings emerged relating to evidence and its impact on the potential to change practice.Data from interviews with change agents and key contacts who were either senior nursing or anaesthetic staff showed that most respondents believed the evidence base for shortening fasting times to be robust:‘I think there is good evidence and this is just being reinforced over the last few years…there is a rationality behind it.’ Participants’ perceptions of their colleagues’ views of the evidence base were also, on the whole, positive. Apart from some wanting clarity about how to interpret recommendations, for example, how much water patients could drink pre-operatively; the evidence base was relatively uncontested by those involved in the study. These perceptions did not change pre- and post-intervention.This positive attitude to the research base was mediated by practitioner and patient judgements about the need for caution, and perceived attitudes to risk taking. The need for managing operating lists meant that individual staff reportedly took a cautionary approach to fasting practice:‘I think people are fearful that something will go wrong…so they always take what they see as the safest option, which is to fast people from midnight…I think it’s lack of confidence.’ .Participants at one focus group raised a question about whether clinicians were perhaps overestimating the risk of aspiration compared with the risks of prolonged fasting. In another focus group, it was reported that the inexact nature of estimating time for each operation meant many anaesthetists erred on the site of caution. In contrast, another anaesthetist stated that she would ‘modify the rules’ rather than postpone or cancel cases.Some patients also expressed a cautious attitude towards the advice they had been given because they did not want to jeopardize their treatment:‘…I always think that instructions like that, there’s a good reason…I abide by them religiously…I just thought I’d sooner err on the side of safety.’ The guideline recommendations were mainly localized through local policies rather than, for example, consensus processes. At some sites existing policy was in line with the guideline evidence, and in others it was similar . For some, the fasting policy needed updating and two sites did not have a policy. Change agents and key contacts reported that a number of activities had taken place to embed recommendations into local practice including changing patient information letters and leaflets, and information for staff. While this showed the evidence was used locally, it did not impact on practice.In summary, while the research evidence base underpinning the recommendations being implemented in this study was empirically robust and broadly accepted by practitioners (judged as strong within the PARIHS framework), individuals’ responses to it, including patients’ reactions, varied and/or were mediated by other factors. There was a difference between agreeing with evidence, and using it to make decisions and/or change services. In this study, the interventions implemented did not significantly affect fasting times.Across the 19 trusts in the study, some cross-cutting themes emerged from the data about the influence that contextual factors at micro , meso (team within the elective surgery department) and macro  levels had on implementation processes. These themes interact with each other such that, for example, emotional reactions may be a function of inter-professional issues, and a product of individual, team and organizational communication.In addition to cautionary practice, there was also evidence that practitioners were anxious about changing traditional practice; these people were described by one anaesthetist participant as ‘dinosaurs.’ In focus groups several comments were made about clinicians being afraid of moving on with a new practice, and that the amount of work required to change would be too daunting.Such anxiety and caution seemed to lead to an emotional response, with some staff becoming ‘confrontational’ with those that were trying to instigate changes. For example, one respondent spoke of senior consultant anaesthetists challenging junior anaesthetists attempting to implement the recommendations:‘…when they have a consultant say “don’t be so ridiculous” and “if you run into trouble don’t ask me to help you” it doesn’t help…’ This finding was a significant issue across all data and includes different professional approaches, leadership, power and hierarchical structures, and professional cultures. Fasting practice was influenced by how the disciplines functioned together, sometimes bringing them into conflict because they had different objectives, ways of working and power bases. One anaesthetist PDSA facilitator commented that the guidelines ‘are embedded in so many different cultures…so many different aspects of the organization’ (site R) that it makes change difficult to use and embed.One of the challenges encountered concerned the ‘ownership’ of fasting practice. A need was expressed for establishing clarity about roles and responsibilities and for all team members to take ownership:‘…I’d like to see all of us taking more ownership and being more proactive in actually thinking about how long the patient’s been fasted for. At the moment I think everybody else thinks it’s everybody else’s job to do it and it doesn’t get done.’ .This was tempered by a concern expressed by some nurses about getting into trouble if patients were not fasted long enough, with which some anaesthetists sympathized:‘I fully understand where nurses are coming from…if they get it wrong then they get into a lot of difficulty and quite a lot of abuse from irate doctors, because they’ve messed up the theatre list basically…we need a robust mechanism.’ (anaesthetist opinion leader site J)Bringing fasting practice more in line with the guideline recommendations requires a multi-disciplinary team approach and communication within and across teams and departments. Data shows examples of some challenges with communication, which meant that individualising patients’ fasting times in line with recommendations would be difficult, if not impossible to achieve:‘We’ve had a phone call from theatre to say this patient’s been cancelled and you can feed and water them. Half an hour later we’ve had a phone call saying has she or he been fed and watered, she can go down…so there’s been miscommunication or been told completely wrong.’ There were also reports of ward-based team communication problems, which had led to prolonged delays or fasting times for patients.This study was conducted at a time of major NHS changes, including reconfigurations, changes to junior medical staff training grades, and a re-focus on financial deficits impacting on staff turnover, workforce reviews, and reorganizations. Staff reported feeling overwhelmed by competing priorities, and that this project came ‘at a bad time.’ While hospitals had signed up to being involved in the project, the managerial support for it was variable, and consequently so were the commitment and resources dedicated to it. A number of resource issues hindered implementation effort such as time , turnover of staff, and lack of permanent staff. The success of the project locally was vested in individual’s enthusiasm and commitment:‘…it came from me, I would say…the clinical director knows about it and he’s happy to let me do that…the wards do, but they don’t care about the nuts and bolts of it.’ (anaesthetist key contact – site C)Apart from at one site in which the nursing director was supportive and prioritized the issue  generally at hospital level, the buy-in to evidence-based peri-operative fasting was not evident. This finding is likely to be fairly typical of many clinical issues underpinned by national guidelines and a function of how organizations set their priorities.One of the critical issues that limited the potential to make significant changes to fasting times within the intervention period was that hospitals were at different starting points with respect to fasting practice and preparedness. Some hospitals did not have a written fasting policy and had to develop one during the intervention phase, which left limited time to implement it. In other sites there were issues that limited preparedness, for example one site that had been randomized to the PDSA intervention were unable to participate in the allocated intervention because they were unable to identify a replacement facilitator after the proposed facilitator went on sick leave. Additionally sites started from a different base with their actual fasting times, ranging from one extreme of an average fluid fasting time of 12.9 hours to 5.8 hours at the other extreme (where recommendations state it is safe for patients to have clear fluids up to two hours before induction of anaesthesia). Some sites had been championing evidence-based fasting practice for some years which could explain lower baseline times. Different starting points present challenges to implementation researchers, particularly within the relative confines of a trial design and the implementation of complex interventions.There was some evidence that aligning implementation with existing relevant activities enhanced the chances of more successful implementation. For example, in the hospital (standard dissemination) that had the largest decrease in fluid fast times (from 12.5 to 7.7 hours), they added this project to an existing initiative that had been implemented in a different department. In another site (web resource and opinion leader), they used learning and awareness from a patient safety initiative to implement individual review of fasting practice. This hospital started with the lowest pre-intervention fluid fast time (5.8 hours), which continued to get lower (4.2), but not statistically significantly lower.In summary, the implementation context was challenging, proving resistant to the implementation interventions evaluated in this study. The behavior and choices of teams and individuals, including patients, bounded by professional issues, power and a lack of clarity for the authority and responsibility of fasting practice operated within a wider organizational system that mediated the implementation of new practices. In theory, the PDSA intervention had the potential to work with these complexities, however, the delivery of this strategy was itself compromised by the challenging environment, including lack of time and opportunity to bring people together to problem solve. However, in sites where processes were aligned with existing initiatives some progress was made.Facilitation is concerned with enabling and making things easier. In PoISIn interviews, opinion leaders and PDSA facilitators reported engaging in many activities including: amendment of information; dissemination of information; awareness raising; individual review of patient fast; educational meetings; policy development; promotion of guidance; teaching/training ; and using role models of good practice.Opinion leaders and PDSA facilitators reported operationalising these activities in the following ways:1. Using a structure already in place to review fasting times or implement practice change, for example, adding a discussion of fasting times to pre-list theatre meetings introduced as part of The Health Foundation Safer Patient Initiative or adding some information giving process  to pre-assessment clinic appointments.2. Using a real time practice opportunity to initiate practice change, for example using anaesthetic rounds to discuss fasting and educated staff in current practice.3. Using evidence of patient discomfort to prompt practice change.4. Using a key role, for example, theatre manager acted as liaison for reviewing fasting times for patients.5. Putting fasting practice on the ward team’s or clinical department’s agenda to raise awareness and encourage practice change, for example, conducting an audit of ward nurses’ knowledge about fasting and current policy during shift hand over as part of a PDSA cycle to assess need for education or using a slot in educational ward or departmental meetings.6. Starting small in targeted wards and gradually rolling out practice change.7. Putting up posters to raise awareness of practice changes.Given the lack of effect on duration of fasting as a primary outcome, it is difficult to judge the relative impact of the activities of opinion leaders and PDSA facilitators. However, we did record changes to policy and practice, which did not translate into changes to patient outcomes. When questioned about the relative usefulness of these activities in prompting changes, the activities that were rated higher included revised patient and staff information, feedback of audit data, working through pivotal individuals, informal teaching, and using pre-surgery safety briefings. Apart from revision of information, these activities are more active than passive.In summary, many activities were recorded for those in facilitator roles, but their relative and direct impact on policy and practice changes were difficult to judge. There appeared to be no distinguishing features between the activities, skills, and attributes of an opinion leader and those of a PDSA facilitator in this study, despite the interventions being conceptually different, and packaged distinctively.Findings show that while the evidence underpinning the fasting recommendations was strong and relatively uncontested, the delivery of interventions and the practice change was mediated by many factors, including individuals’ behaviors, attitudes, emotional responses, communication by and across individuals and teams, and by challenging implementation contexts, including inter-professional functioning and an organization’s existing surgical systems and processes. Within two of the interventions there was the potential to work with individuals and teams to attempt to overcome some of the challenges, but this was not translated to reductions in fasting times in most sites. Potentially successful strategies included using existing structures or initiatives already in place to review fasting times and practice, aligning with organizational strategies, working with those in pivotal roles, and the initiation of awareness raising activities.The main aim of this paper is to reflect on how findings from the process evaluation have implications for the PARIHS framework and its development as framework that represents the implementation of evidence into practice. In discussing these issues, we draw on Helfich et al.’s critiqueConsistent with the underlying tenant of PARIHS, the findings present a multi-faceted and dynamic story of implementation. Reflecting on the proposition that successful implementation is a function of evidence, context, and facilitation, the element of evidence requires further scrutiny. Previous research indicates that where there is strong research with clinical consensus it is more likely to be used in practice. In thisNilson et al. discuss Helrich et al. suggest Findings from this study show that some factors were more important than others in providing the conditions for, and influencing the effect of implementation interventions, which included inter-professional team working (including communication), decision-making authority , and organizational buy-in, issues evident in others’ work e.g.,,35. The . The 35.Successful Implementation (SI) has not been explicitly defined in previous PARIHS publications. Helfrich et al. suggest Helfrich et al. encourage better elaboration of PARIHS’ core elements. To date, the role, behavior and attributes of individuals have been implicit within the PARIHS framework. Findings from this study and evidence from others’ research and conceptualisations of evidence-based change and theory show the crucial role that individuals plays in the relative success of evidence-based change,27,37-39This is a timely opportunity to consider the inclusion of individuals as an explicit additional element to PARIHS. Individuals are currently implicitly embedded within PARIHS in that facilitators work with individuals, contexts include individuals, and individuals interact with evidence, however, the significance of individuals within implementation is perhaps currently under-represented. In other theories  and frameworks  and senior operational managers (who were not included in our sampling strategy).Although the study design and interventions were prospectively designed based on the core elements of PARIHS, our evaluation of the framework has been retrospective. The addition of the concept of the individual needs further consideration, elaboration and clarification.The process evaluation reported here was embedded in one of the first and largest implementation randomized controlled trials within acute care. The findings from this evaluation lead us to proposing an extension to the PARIHS framework to enhance its usefulness as a conceptual framework that can be applied in practice. To date, this framework has received much attention from the international implementation community as a helpful representation of the ingredients for successful implementation. The framework has been developed and refined over time, therefore the addition of ‘individuals’ to the conceptualisation of successful implementation is timely, particularly in the context of a growing emphasis in the empirical and theoretical literature on behavior and social processes. The findings from this study re-emphasize the multiple and complex deliberative processes involved in implementation work. In this paper, we propose that the PARIHS framework should be enhanced to ensure theoretical development keeps a pace with the current evidence base for implementation.The authors declare they have no competing interests.JRM conceived the study, and led the design in collaboration with KS, IB, and NC. JRM, KS, and IB secured funding. JRM supervised all aspects of the study, with input from KS. JC and CH coordinated and took the lead role in data collection and analysis. CA provided a patient perspective throughout the conduct of the study including the development of patient related materials and data collection processes. LS provided a clinical perspective as an aneasthetist. JRM drafted the paper KS provided feedback on early drafts, NC, CH, JC, CA, IB reviewed later drafts for intellectual comment and all approved the final manuscript.


We have also previously proposed that thermodynamic theory, which allowed for the first time derivation of an absolute measurement scale for temperature (T), could be used to derive an absolute scale for evidence (E). Here we present a novel thermodynamically based framework in which measurement of E on an absolute scale, for which “one degree” always means the same thing, becomes possible for the first time. The new framework invites us to think about statistical analyses in terms of the flow of  information, placing this work in the context of a growing literature on connections among physics, information theory, and statistics.Statistical analysis is used throughout biomedical research and elsewhere to assess strength of evidence. We have previously argued that typical outcome statistics (including  In previous work we have argued for the importance of rigorous methods for measuring statistical evidence in biomedical research and other arenas, and we have proposed using the mathematical foundations of thermodynamics as a template for achieving this end Vieland . Here wemeans the same thing across the range of the measurement scale , and across disparate applications (just as one foot means the same thing whether measuring lengths of rope or lumber). It is worth pointing out from the outset that this understanding of “absolute” goes beyond requiring an absolute 0 point for the measurement scale, which is sometimes misunderstood as the basis on which the Kelvin thermometric scale is said to be absolute. . The Kelvin scale is clearly and by design absolute in the same sense in which we are using the term  as a measure of evidence, but the same conundrum arises. Not only is it unclear whether a change in the log LR from 1 to 2 means the same thing as a change from 10 to 11, or perhaps from 10 to 20; it is, moreover, not even clear how we would go about investigating the matter. We lack a methodological framework in which asking for the meaning of means the same thing is a well-posed question. But surely measurement of any quantity, including evidence, requires at a minimum that the unit of measurement always does in fact mean the same thing.Perhaps the most intellectually challenging aspect of our measurement problem is simply articulating what is meant by It is noteworthy that the abstract and obscure nature of this measurement quandary is directly parallel to that faced and overcome by Kelvin himself in the mid-nineteenth century, a stroke of historical luck that we gladly exploit for our own purposes. We develop a methodological framework in the context of which it becomes possible to articulate a definition of means the same thing in measuring statistical evidence, based on what is meant by this phrase in reference to degrees of temperature in thermodynamics. In essence our approach is extremely simple: we reinterpret fundamental thermodynamic quantities in terms of evidential rather than physical processes and then port the mathematical underpinnings of thermodynamics over to the evidential side en bloc. The quantity denoted by T in thermodynamics—temperature measured on the absolute scale—is in this framework translated as the evidence E, which is then intrinsically measured on the absolute scale, in exactly the same sense in which T is.Various connections have of course been previously made between thermodynamics and certain aspects of statistical inference; see, e.g., Shannon , primarin times and observing the number of times x that the coin lands heads (where both n and x can vary across experiments). For a given experiment, the data  carry information about the coin, which we capture by graphing the likelihood ratio (LR) as a function of P(heads) = θ, fixing θ = 1/2 in the denominator of the LR. Data from subsequent experiments change the LR graph, for instance, causing the height of the graph at its maximum to increase. We consider the evidence itself as a property of the graph and seek to define this property in a way that is amenable to absolute measurement, while preserving our underlying feel for what we mean by evidence.We focus in this paper on one very simple statistical model. Suppose we are interested in the evidence that a certain coin is either fair or biased towards landing tails. We perform one or more experiments, each time tossing the coin Our starting point is what may at first appear as a relatively obscure analogy with the elementary heat engine of thermodynamics; more specifically, with the abstract model of the workings of a heat engine embodied in the Carnot cycle. The purpose of a heat engine is to convert heat into work, say, using the heat to raise a piston, and similarly we might describe the purpose of the coin-tossing experiment to be the conversion of the information conveyed by new data into movement of the LR graph. But more importantly for our purposes, the Carnot cycle constituted the basis for rigorous understanding of the fundamental dynamics of thermal systems. We, therefore, consider what is to be gained by considering the statistical experiment as the analogue of the heat engine, to rigorously characterize the relationships among evidential analogues of heat, work, and temperature. Thus, rather than begin by assuming any particular definition of E, instead, we adopt as our sole methodological constraint that our evidential model must adhere to the equations required to construct and analyze Carnot cycles. The resulting evidential dynamical framework will be justified insofar as it proves fruitful, even if it should remain difficult to relate the idealized workings of an engine to how we ordinarily think about statistical data analyses. Indeed, if this approach does prove to be useful, we may question whether it is based on mere analogy, or possibly, the far deeper connection between thermodynamics and inference championed by Jaynes and many others.We develop the central argument of this paper in three steps, as follows. We begin by postulating that a statistical model can be described by an equation , expressed in the form of the EqS for an ideal gas, and that this EqS defines a system that is governed by analogues of the 1st and 2nd Laws of Thermodynamics. In “x heads out of n tosses, and probability θ that the coin lands heads. We consider the hypothesis contrast “coin is biased” versus “coin is not biased” (θ = 0.5).n, x), we can equally well consider the permissible transformations of the graph per se, where what is permissible is any state of the system that conforms to the underlying binomial LR equation as the data change. In “n and x as continuous (non-negative) numbers, for reasons that will become clear in “We start with a simple binomial coin tossing model, with We begin with the postulate that the EqS for this system can be described by the equation describing an ideal gas Eq. , Table 1E, we simply use the area under the LR curve (Eq. x ≤ n/2). While this complicates the arithmetic somewhat, it will simplify some aspects of the presentation. The one-sided case also plays a special role in statistical genetics, and we have investigated its properties in detail elsewhere  as the evidence goes up (or down), and in a manner unmatched by other standard approaches to quantifying evidence, such as the p-value or the maximum LR  and 2nd Law  on an ideal gas, then we can also express the EqS in terms of the entropy S  value of the binomial probability θ, which is in this case simply the maximum likelihood estimator x/n, relative to the information entropy evaluated at the unconstrained MaxEnt value θ = 1/2  to arrive at that state from some other state; and because we have defined it in terms of MaxEnt states, assuming that MaxEnt also corresponds to statistical equilibrium, the evidential system developed here can be said to be in an equilibrium state at all times.From Jaynes Jaynes  and Kull 1/2 Eq. , Table 1E and VE into Eq. E is defined with respect to the MaxEnt state, we expect this definition of E to relate directly to the parameter β of the Boltzmann distribution). Finally, substituting E as expressed in Eq. E , into an explicit EqS describing the LR graph in terms of , while tacitly imposing analogues of the 1st and 2nd Laws of Thermodynamics. We can now describe allowable transformations of the system in terms of any change in the LR graph that conforms to the underlying binomial EqS, without explicitly referencing changes in data. This shift from the usual statistical perspective is critical, because it allows us to view changes in the LR graph in terms of the in- or out-flux of evidential information, rather than in terms of changes in data . Thus, while we continue to assume that we are working with the EqS for  a single mole of matter, or what is probably best viewed as a fixed quantity of data, we will plot results as a function of changes in n. The rationale lies in the transitional nature of this section, illustrating properties of the system in familiar statistical terms, en route to thinking of changes as influenced not by the influx of data, but rather, by the influx of evidential information  pair, which depends on E, the TRansition Point (TrP(E)).A feature of this system that plays an important role in subsequent discussion is that it captures evidence either in favor of the numerator of the LR or in favor of the denominator.zed Fig. a. We calx/n, as n increases E increases; (ii) for fixed n and reading from left to right on the x/n axis, E decreases up to TrP(E), then increases. Figure x/n at TrP(E) over a broader range of n. This plot also illustrates sensible behavior: as n increases, TrP(E) moves towards x = n/2; i.e., for very large n, even a small deviation from x = n/2 constitutes evidence against θ = 0.5.n. We return to this point in the “n, x) in three-dimensional space for n up to 1,000, again showing consistent statistical behavior. We note also that as Fig. n, it is possible to have far stronger evidence in favor of “coin is biased” than in favor of “coin is not biased.” This reflects the fundamental asymmetry in the hypotheses, with the denominator specifying a single value (θ = 1/2), and the numerator allowing for any value θ < 1/2.The behavior shown in Fig. n, x) values corresponding to a single value of E . These isotherms also behave in accordance with our intuitions regarding evidence, e.g., consider  (not shown on figure). Whatever the value of the evidence for that point, we know that as n increases while holding x fixed, the evidence must go up. This implies that, were we to hold the evidence fixed and increase n, x would have to increase in order to compensate. Conversely, if we hold n fixed and increase x, the evidence will diminish, which implies that if we were to hold the evidence constant while increasing x, n would have to go up to compensate. We do not normally think of the dynamics of statistical systems in these terms, precisely because outside of this framework we have no way to hold the evidence constant in our mind’s eye while allowing the LR graph to change. Given a way to establish these isotherms, however, the behavior illustrated in Fig. n for each isotherm occurs at TrP(E). Figure E and PE, illustrating consistency between the behavior of E and a physical system.In aggregate, the behavior illustrated in Fig. f E Fig. a, b showEdVE correctly characterizes a transformation of the system from an information-transfer point of view, just as PdV does in physics from an energy-transfer point of view  for higher E. As in physics, we distinguish work being done by the system (WE) from work done to the system (−WE). The central importance of this notion of evidential work will become clear in the following section. See also Appendix Finally, we consider another quantity unfamiliar in traditional statistical frameworks, namely, the evidential equivalent of physical  work. We are interested in the effects of in- or out-flux of evidential information on the LR graph, characterized in terms of the fundamental features of the graph. We posit, therefore, that the quantity Pmi E Eq. , Table 1E and VE are inversely proportional), Charles’ Law , etc.Note that, because our evidential system follows the ideal gas EqS by design, it follows immediately that the system exhibits the characteristic properties of ideal gases, including Boyle’s Law  Heat is absorbed by the system from the warmer heat reservoir while maintaining constant temperature t2, with corresponding increase in V and decrease in P, for an isothermal change. (B) Heat transfer is stopped (the reservoir is removed from contact) and the system is allowed to continue to expand and cool down to temperature t1, through a process known as adiabatic change. (C) The system is compressed isothermally by application of external force (work) at constant t1, with corresponding reduction in V and increase in P, requiring a corresponding transfer of energy out of the system into the cooler heat reservoir. (D) The system is permitted to continue adiabatically, with no further transfer of energy (no further contact with the second reservoir), until it returns to its initial state. During the first two strokes work is done by the system (positive work), while during the second two strokes work is done to the system (negative work). A mechanical heat engine is effective insofar as more work is done by the system during the first two strokes than is required to be done to the system through external means during the third stroke to return it to its initial state, and this happens because less work is required to effect the same transformation (or its reverse) at lower temperatures.Following Kelvin, we make use of the Carnot engine, an abstract mathematical device for considering the relationship between physical heat and work.EVE) diagram. These cycles are readily seen to correspond to genuine Carnot cycles: in each cycle, work done during the two adiabatic strokes  is identical in magnitude but opposite in sign; work WA done in the first  stroke is greater in magnitude than the work −WC done in the third  stroke; and WC/WA = e1/e2, where e is the analog of t in the physical engine, that is, any “thermoscopic” measure of evidence. We now posit that evidential work is a transformation of evidential information, just as mechanical work is a transformation of heat in a physical heat engine. In physics, heat Q represents the quantity of energy transferred in or out of the system. Following this convention, we consider evidential energy, QE, to be the amount of evidential information being transferred. In what follows, we use Q2 to indicate the evidential energy transferred into the engine during the first stroke at e2, and Q1 to denote the evidential energy transferred out of the engine during the third stroke at e1.We too can run evidential Carnot cycles using our binomial system.A = Q2. Thus defining the efficiency η of the engine as the ratio of the work performed by the cycle to the evidential information absorbed at the higher evidence level , we have η = (WA + WB − WC − WD)/WA = (WA − WC)/WA = 1 − WC/WA = 1 − Q1/Q2. Carnot proved that reversible cyclic engines have maximal efficiency, and by direct application of his reasoning we also have the result that all such evidential engines operating between the evidence levels e1, e2 share the same ratio Q1/Q2. In other words, the ratio of evidential energies depends only on the ratio of evidence levels and on nothing else specific to the particular system. Thus we can write Q1/Q2 = f, where (paraphrasing Fermi) f is a universal function of the two evidence levels. From here we can directly follow the arithmetic in Fermi to show that f = f/f, for e0 any arbitrary level of evidence. Fixing e0 at a constant value we can, therefore, consider f to be a function of e only, thus, K f = g(e), where K is an arbitrary constant. This gives, finally, Q1/Q2 = g(e1)/g(e2).For a cyclic, reversible transformation, there is no net change in energy from the initial to final state of the system, since by stipulation the system is returned to its initial state. In this case and for an ideal gas, W is a direct measure of heat, and in particular, We) to be the evidence E, we see that we have converted our “thermoscopic” measure e onto an absolute scale in the following sense: first, it is immediately apparent that E is on a ratio scale  relationship in an evidential Carnot cycle. In principle then, we can use any “thermoscopic” measure of statistical evidence, such as VE itself , as an evidence measure, and calibrate it against this absolute scale. Of course, different functions g must be derived for each different type of statistical outcome measure to accomplish this; and beyond the context of the highly stylized Carnot cycle, myriad practical issues complicate actual measurement calibration. Additionally, the statistical outcome measure must itself behave thermoscopically, properly tracking up and down with the evidence.As in physics, we did not define QThus we have not so much solved the evidence measurement problem, as reformulated it in a way that makes it amenable to solution for the first time. Any remaining skepticism regarding the probability of success in practical applications may be offset by an appreciation of how difficult the corresponding practical problems were in physics Chang . It is aE. UE can be thought of as a form of information if that seems more comfortable, but to begin with we did not define UE, nor did we propose any particular device for directly measuring it. .cs Chang , we firsevidential energy, with the unit of E having fixed meaning as described above. This opens an entirely new line of research into the manner in which evidential energy is transformed into evidential work as data accumulate, including investigation of relative efficiencies of different mechanisms  for so doing. We speculate that this shift in perspective will have numerous ancillary benefits, allowing us to extend Jaynes’ program of connecting the laws of inference with the laws governing physical systems through the shared concept of information, or evidential energy. . First and foremost, however, we envision this paper as merely a prelude to the difficult empirical work of aligning evidence measures across applications in biomedical research, so that results can be properly interpreted across the measurement scale within any one application, across disparate applications, and across different types and levels of analysis.Under this new formalism, E is a measure of evidential information, or what we might now preferably call While it may seem odd, although we have derived an absolute scale for evidence measurement we have in fact not yet specified the units of that scale. In thermodynamics too, the size of the degree is an arbitrary choice, set by convention. Thus, we can say that E, as it occurs in all Figures in this paper, is on the absolute scale; yet at the same time, the numerical values of E shown here may not correspond to what we will eventually settle upon as the actual values of the evidence, once a decision has been made regarding the size of the standard measurement unit.n in statistical systems. Initially, we had supposed that the accumulation of evidence based on two sets of data, with n1 = n2 observations, respectively, would be the analogue of doubling the number of particles (or moles of matter) in the system. However, the new framework invites us to view n ) as an index of evidential energy, not of the number of particles. Once we see that E measures energy UE and that in the context of an evidential Carnot cycle this energy can be directly measured through the work WE, it becomes clear that n as it appears in our equations must relate to the units of energy, not matter:  is what changes as energy flows in and out of the system, and it is changes in  that correspond to evidential work. This is built into the thermodynamic equations that form the basis of the system. In thermodynamics too, it is possible to effect equivalent changes in macroscopic properties of a system  by either the input of energy or the input of particles (under suitable conditions for each). Indeed, our own previous work on evidential “thermoscopes” has highlighted the distinction between “pooling” data  and “sequentially updating” the evidence across data sets (Vieland n considered as the number of observations (pooling) or as changes in n considered as an index of energy . Virtually all asymptotic theory in statistical inference is based on pooling as the fundamental operation as n increases, but we have argued elsewhere  or an arbitrarily large family, which might correspond to gases of different atomic structures. Another tantalizing connection relates to the characterization of energy in our system by the  pair, with x being bounded by n. Possibly even a simple statistical system would be more appropriately modeled through the Van der Waals EqS  will prove to be a phase transition boundary point, at which E remains constant regardless of energy input into the system. See also Appendix We also view it as likely that future work will need to carefully consider the units of qS Fermi  as a funOne further aspect of our system that may strike both statisticians and physicists as implausible is the assumption of evidential analogues of the 1st and 2nd Laws of Thermodynamics, which are generally thought of as essentially physical in nature. In Appendix Theoretical matters aside, the ultimate intent of this project is to be useful in practice. Measurement is not, after all, an end in itself, but rather a sine qua non of rigorous scientific activity. When completed, our formalism would not replace other statistical investigations, but it would ideally provide a basis for reporting results of statistical analyses on a unified scale for purposes of meaningful comparison across the range of the measurement scale and across disparate applications. Considerable hard work remains to be done, however, before this framework can be usefully applied to real data analyses. To begin with, we have considered only a simple, discrete distribution. . We will need to establish the validity of corresponding treatments of more complex statistical models involving nuisance parameters, approximating likelihoods, and disparate data structures, along with two-sided LR contrasts, before the framework can be deployed in target areas such as biomedical research. Finally, as a practical matter, we will need ways to indicate whether a given value of E is to the left, directly at, or to the right of TrP(E). This information is readily recovered from the underlying calculations, but forms a kind of meta-data that would need to be associated with the value of E in applications. Again, this might be equivalent to wanting to know whether a substance is in its liquid or gaseous state, which depends not just on temperature, but also on the volume and pressure of the system.The practical challenges to deploying the new framework are substantial, but no more so than the challenges physicists faced in making practical use of the Kelvin thermal scale itself Chang . Just as


This systematic review updated and extended the "UK evidence report" by Bronfort et al.  with respect to conditions/interventions that received an 'inconclusive’ or 'negative’ evidence rating or were not covered in the report.A literature search of more than 10 general medical and specialised databases was conducted in August 2011 and updated in March 2013. Systematic reviews, primary comparative studies and qualitative studies of patients with musculoskeletal or non-musculoskeletal conditions treated with manual therapy and reporting clinical outcomes were included. Study quality was assessed using standardised instruments, studies were summarised, and the results were compared against the evidence ratings of Bronfort. These were either confirmed, updated, or new categories not assessed by Bronfort were added.25,539 records were found; 178 new and additional studies were identified, of which 72 were systematic reviews, 96 were randomised controlled trials, and 10 were non-randomised primary studies. Most 'inconclusive’ or 'moderate’ evidence ratings of the UK evidence report were confirmed. Evidence ratings changed in a positive direction from inconclusive to moderate evidence ratings in only three cases . In addition, evidence was identified on a large number of non-musculoskeletal conditions not previously considered; most of this evidence was rated as inconclusive.Overall, there was limited high quality evidence for the effectiveness of manual therapy. Most reviewed evidence was of low to moderate quality and inconsistent due to substantial methodological and clinical diversity. Areas requiring further research are highlighted. Manual therapy is a non-surgical type of conservative management that includes different skilled hands/fingers-on techniques directed to the patient’s body (spine and extremities) for the purpose of assessing, diagnosing, and treating a variety of symptoms and conditions-4. ManuaSpinal manipulation and mobilisation are commonly used treatment modalities for back pain, particularly by physical therapists, osteopaths, and chiropractors. Back pain is an important health problem with serious societal and economic consequences for the developed world. It is estimated that in the USA 80% of people will experience back problems at some point during their lifetime. Back paThe use of chiropractic, osteopathic, and other forms of services delivering various types of manual therapies has been steadily increasing in the Western World. For exaOne descriptive review summarised surveys reporting rates of use of complementary and alternative medicine (CAM) therapies for management of low back pain and other musculoskeletal and non-musculoskeletal conditions. ResultsPrevious research has shown short-term benefit of spinal manual therapy  especially in reducing back pain-20. TherThe annual incidence of major harms or complications associated with the use of manipulative procedures is low. In general, manipulations using thrust techniques carry a greater risk of major complications than the non-thrusting, low-velocity, low-amplitude soft-tissue approaches. SystemaThe current review builds on the "UK evidence report" by Bronfort, Haas, Evans, Leininger and Triano on the eBronfort et al. referred• Synthesise evidence in addition to the randomised controlled trials (RCTs) and systematic reviews captured by Bronfort et al. such as • Synthesise evidence additional to Bronfort et al.  to those of Bronfort et al. focusingThe PRISMA checklist for the current paper can be found in Additional fileWe used a varied range of sources to identify relevant literature. A comprehensive literature search was undertaken in the major medical, health-related, science and health economic electronic bibliographic databases. We paralleled the comprehensive searches undertaken by Bronfort et al. through Search terms were restricted to terms related to manual therapy and broader terms like ‘physiotherapy’ were not included. The search included both free text and MeSH terms, as well as terms for the eligible study types (from pretested search strategies). To keep the search as broad as possible, no condition terms were included. There was no language restriction in the searches but due to limited resources only studies published in English, French, German, and Spanish were included. The main search was carried out in August 2011 , cohort studies with a comparison group, or qualitative studies of patients' views on manual therapy. Primary studies had to include at least 20 participants. Studies had to include participants of any age and in any setting treated for any musculoskeletal or non-musculoskeletal condition who were treated with any manual treatment/therapy were included . To provide an overall picture, any condition was included for which a trial documenting manual treatment was available. Interventions had to include an element of manipulation or mobilisation, and emphasis was on interventions typically carried out by a manual therapist/chiropractor/osteopath. Comparison was against any other therapy. Outcomes assessed included pain intensity, pain-related disability, analgesic use, function, mobility, activities of daily living, characteristic symptoms or indicators of disease, patient satisfaction, quality of life, views/themes from qualitative data, adverse events , and mortality. The focus of the present review was on evidence rated as ‘inconclusive’ or ‘negative’ by Bronfort et al.[Two independent reviewers applied the inclusion/exclusion criteria to the studies identified through the searches, screened the titles/abstracts and then the full text of any records appearing to fulfil the inclusion criteria. Any disagreements over the inclusion of records were resolved by discussion.a priori developed data extraction forms. The data extracted included: a) study characteristics , b) types of participants , c) types of interventions including comparators , d) outcomes .Data were extracted by two reviewers using The following assessment tools were used for appraising any new and additional evidence: AMSTAR (for systematic reviews);-32 CochrUsing the same criteria as Bronfort et al. . Of these, 178 were summarised in more detail , see Figure Tables The following section provides a summary of the conditions/interventions rated ‘inconclusive’, ‘negative’ or not covered in the UK evidence report. Details of study characteristics and study quality can be found in Additional filesTables Sciatica and back-related leg-pain Two new/additional medium[l medium to high l medium RCTs rell medium. The medl medium randomisl medium randomisSummary: Inconclusive (favourable) evidence for spinal manipulation/mobilisation in treating sciatica and back-related leg-pain (no change from the UK evidence report). The evidence suggests that chiropractic or orthopaedic manipulation may be effective in reducing symptoms of sciatica in adults, however, it is not clear due to the small sample size of the trials, if these manual treatment techniques are more beneficial compared to surgery, McKenzie method, or advice only.Neck pain  One low quality,[quality, four medquality,-43 and tquality,,45 examiquality,-46.A medium quality RCT comparedSummary:Inconclusive (favourable) evidence for cervical spinal manipulation/mobilisation alone in treating neck pain (no change from the UK evidence report). Inconclusive (favourable) evidence for manipulation and mobilisation with/without soft tissue treatment . The evidence suggests there are similar improvements in the manipulation and/or mobilisation intervention groups compared to active treatment, however, some trials also found no improvement in comparison to a control group.Non-specific mid-back pain One additional low quality systematic review[c review and one c review were idec review eligibleSummary:Inconclusive (favourable) evidence (no change from the UK evidence report). It cannot be established from the current evidence whether manual therapy is more effective than non-treatment, placebo, or other treatments for the treatment of non-specific mid-back pain.Ankle and foot conditions Three additional systematic reviews[ reviews-52  and six reviews-58  a reviews were ideA high quality Cochrane review examined the effect of rehabilitation interventions for ankle fractures. With reA low quality RCT examinedSummary:Inconclusive (favourable) evidence that manipulation, mobilisation, and a muscle energy technique are of benefit in the treatment of ankle sprains . Inconclusive (favourable) evidence for Kaltenborn-based manual therapy for rehabilitation following ankle fracture . Inconclusive (favourable) evidence for hallux abducto valgus that mobilisation/manipulation is more effective in leading to improvements in the intermediate term than night splints (no change from UK evidence report). Inconclusive (favourable) evidence for trigger point therapy in treating plantar fasciitis treatment (no change from the UK evidence report). Inconclusive (favourable) evidence for manual therapy (manipulation/mobilisation) of the ankle and/or foot combined with multimodal or exercise therapy (no change from the UK evidence report) in treating Morton’s neuroma, metatarsalgia, hallux limitus/rigidus.Carpal tunnel syndrome Three additional medium quality systematic reviews,[reviews,,61 one hreviews, and threreviews,-65 on threviews,,61 and areviews, did not reviews,,64 were reviews,. Only onThe medium quality systematic review summarisA medium quality RCT was and Summary:Inconclusive (favourable) evidence for carpal bone mobilisation and for trigger point therapy in the treatment of carpal tunnel syndrome (no change from the UK evidence report). Inconclusive (unclear) evidence for neurodynamic treatment, soft-tissue mobilisation (with or without Graston instrument), and diversified chiropractic care in the management of carpal tunnel syndrome .Lateral epicondylitis (tennis elbow) Eight additional low to moderate quality systematic reviews,[reviews,,67-73 eireviews,-81 one oreviews, and threreviews,-85. Fourreviews,,77-79 weOne systematic review of medium quality evaluateIn one pilot study of low quality, the authIn one observational cohort study of low quality, the authSummary:Inconclusive (non-favourable) evidence was found for the treatment of lateral epicondylitis (tennis elbow) with manipulation alone (no change from the UK evidence report). The reviewed evidence indicated some benefits of manual therapy in reducing symptoms in patients with lateral epicondylitis, when in combination with other treatments , when compared to no treatment, or baseline values (within-group change), however, the evidence was still rated inconclusive (favourable) evidence (no change from the UK evidence report). When comparing manual therapy to other treatments , there was inconclusive or inconsistent (favourable) evidence (no change from the UK evidence report).Shoulder conditions Fifteen new or additional systematic reviews[ reviews,86-99 we reviews-112. How reviews-93,95-99 reviews,104-110. reviews,94. The  reviews,111 and In one of the new systematic reviews, the authA medium quality systematic review examinedA low quality RCT examined the effects of manual therapy  in 30 patients with chronic rotator cuff injury. The durSummary:Moderate (positive) evidence for use of manual therapy combined with exercise in the treatment of rotator cuff disorders (change from inconclusive (favourable) evidence in UK evidence report). Inconclusive (favourable) evidence for the effectiveness of mobilisation with movement  or osteopathy (Niel-Asher technique)  or manual therapy with exercise in the treatment of adhesive capsulitis . Inconclusive (favourable) evidence for the effectiveness of cervical lateral glide mobilisation and/or high velocity low amplitude manipulation with soft tissue release and exercise in minor neurogenic shoulder pain . Moderate (positive) evidence for using myofascial treatments  for soft tissue disorders of the shoulder .Temporomandibular disorders One systematic review protocol[protocol and fiveprotocol-118  werCraane et al. conducteSummary: Results on the comparative effectiveness/safety of manual therapy for temporomandibular disorders remain inconclusive (favourable) evidence for mobilisation, massage, myofascial or osteopathic manipulation (no change from the UK evidence report).Table Cervicogenic headache Two new high quality systematic reviews,[reviews,,120 one reviews, and one reviews, were ideA high quality systematic review evaluateSummary:Moderate (positive) evidence for mobilisation techniques in cervicogenic headache (change from inconclusive (unclear) evidence in the UK evidence report). Inconclusive (non-favourable) evidence for friction massage and trigger points in cervicogenic headache (no change from the UK evidence report).Tension-type headache Four new and additional RCTs[nal RCTs-127  assessenal RCTs did not A low quality RCT comparedSummary:Inconclusive (favourable) evidence for manual therapy  in treating tension-type headache . Inconclusive (unclear) evidence for spinal manipulation in treating tension-type headache (no change from the UK evidence report).Miscellaneous headaches Two medium quality systematic reviews[ reviews,130 and  reviews,132 wereThe systematic review by Bryans et al. investigA medium quality RCT comparedSummary:Moderate (positive) evidence for manipulation and mobilisation for miscellaneous headache (change from inconclusive (favourable) evidence in the UK evidence report).Fibromyalgia Three medium quality systematic reviews[ reviews-135 asse reviews,134 did  reviews 1 low qu reviews) not incThe medium quality RCT assessed the effects of cranio-sacral therapy in 92 women with fibromyalgia. After 2Summary:Inconclusive (favourable) evidence for the use of chiropractic spinal manipulation in fibromyalgia (no change from the UK evidence report). Inconclusive (favourable) evidence for effectiveness of cranio-sacral therapy and massage-myofascial release therapy for fibromyalgia.Table Asthma We identified three additional systematic reviews on manual therapy for asthma,[ asthma,-140 one  asthma, and one  asthma,. Only on asthma, includedThe review investigated chiropractic treatment for asthma and included eight studies, of which three were RCTs and one was a CCT, while the rest were uncontrolled studies. Three of the included studies were in children. In the comparative studies, no significant differences between comparison groups were seen in respiratory parameters, symptoms or subjective measures. In the uncontrolled studies, improvements were generally seen in subjective measures – however, improvements in subjective measures were also seen in the control groups of comparative studies. Only one study reported on adverse events (none reported). The review authors concluded that some patients may experience chiropractic care as beneficial, but overall there were no significant effects in any outcomes versus sham treatment. However, the quality of the evidence was generally poor and more evidence is required using valid and reliable outcome measurements.The medium quality RCT includedIn the qualitative study, 50 patieSummary:Inconclusive (unclear) evidence for use of spinal manipulation in treating asthma (change from moderate (negative) evidence in the UK evidence report). Inconclusive (favourable) evidence for osteopathic manual therapy in treating asthma (no change from UK evidence report). Inconclusive (favourable) evidence for cranio-sacral therapy in treating asthma .Attention Deficit/Hyperactivity Disorder (ADHD)/Learning disabilities One medium quality systematic review[c review and two c review,145 wereOne systematic review sought tSummary: Given the severe methodological limitations of the included studies, there is inconclusive (unclear) evidence regarding the effectiveness of osteopathic treatment for ADHD .Cancer care One low quality systematic review[c review assessedc review,148 one c review and one c review assessedc review assessedCantarero-Villanueva et al. comparedWith respect to adverse events, one moderate quality controlled cohort study (Wu 2010) assessedSummary:Moderate (positive) evidence for the effectiveness of massage techniques involving manual therapy elements in breast cancer survivors and terminal cancer patients but inconclusive (unclear) evidence for use of chiropractic care for cancer care . In some types of cancer such as osteosarcoma, manipulative therapy may have significant adverse effects and was contraindicated.Cerebral palsy in children Three RCTs  werquality, on interA low quality trial assessedSummary:Inconclusive (unclear) evidence for the effectiveness of osteopathic manual therapy in the treatment of cerebral palsy .Cervicogenic dizziness/balance One high quality systematic review was identified on the effects of manual therapy with or without vestibular rehabilitation in the management of cervicogenic dizziness,[zziness, as well zziness, and a przziness,.The high quality systematic review includedA low quality RCT comparedSummary:Inconclusive (favourable) evidence for the effectiveness of manipulation/mobilisation for cervicogenic dizziness . Inconclusive (unclear) evidence for diversified chiropractic treatment in the improvement of balance in elderly people .Chronic fatigue syndrome/myalgic encephalomyelitis One high quality systematic review was identified that studied the effects of alternative medical interventions  on patients with chronic fatigue syndrome or fibromyalgia[omyalgia. The autSummary:Inconclusive (favourable) evidence for osteopathic manual therapy improving symptoms of myalgic encephalomyelitis .Chronic pelvic pain Two high quality systematic reviews[ reviews,160 and  reviews,162 and  reviews,164) werA high quality systematic review assessedOne medium quality RCT,162 compSummary:Inconclusive (favourable) evidence for the use of osteopathic treatment in female urination disorders . Inconclusive (favourable) evidence for the use of myofascial therapy in interstitial cystitis/painful bladder syndrome or chronic prostatitis/chronic pelvic pain . Inconclusive (favourable) evidence for distension of painful pelvic structures in chronic pelvic pain in women and for osteopathic manual therapy in men with chronic prostatitis/chronic pelvic pain .Cystic fibrosis One small medium quality RCT assessed the effects of musculoskeletal treatments including mobilisations to the rib cage and thoracic spine in 20 adults with cystic fibrosis[fibrosis. PatientSummary:Inconclusive (unclear) evidence for the use of mobilisations (rib cage and thoracic spine) in patients with cystic fibrosis .Paediatric dyfunctional voiding One low quality RCT was identified that assessed manual therapy in paediatric dysfunctional voiding[ voiding. ChildreSummary:Inconclusive (favourable) evidence for osteopathic manual therapy improving symptoms of paediatric dysfunctional voiding .Gastrointestinal disorders One additional medium quality systematic review[c review and two c review,169 wereThe systematic review includedOne additional low quality RCT assessed the benefits and harms of osteopathy compared to standard care at 1, 3, and 6 months of post-baseline follow-up for 39 patients with irritable bowel syndrome. The posSummary:Inconclusive (unclear) evidence for spinal manipulation for gastrointestinal disorders . Inconclusive (favourable) evidence for osteopathic manual therapy for irritable bowel syndrome .Hypertension We identified one new medium quality systematic review[c review and one c review on the uA systematic review examinedA non-randomised clinical trial examinedSummary:Inconclusive (favourable) evidence for upper cervical NUCCA manipulation for stage 1 hypertension (no change from the UK evidence report). Inconclusive (unclear) evidence for instrument assisted spinal manipulation for hypertension . Inconclusive (unclear) evidence for effectiveness of Gonstead full spine chiropractic care or osteopathic manipulative therapy for hypertension .Infantile colic Four potentially relevant new systematic reviews[ reviews,172-174  reviews,172,174. reviews. Overall reviews of chiroSummary:Inconclusive (favourable) evidence for cranial osteopathic manual therapy in treating infantile colic. Inconclusive (favourable) evidence for spinal manipulation in treating infantile colic (change from moderate (negative) evidence reported in the UK evidence report).Insomnia One low quality systematic review[c review assessedSummary:Inconclusive (unclear) evidence on the benefits of manual therapy in people with primary insomnia .Menopausal symptoms One small low quality RCT[lity RCT assessedSummary:Inconclusive (favourable) evidence for the effectiveness of combined use of Fox’s low force osteopathic techniques and cranial techniques in the treatment of menopausal symptoms .Myofascial pain syndrome Two additional medium quality systematic reviews assessing the effectiveness of manual therapy in myofascial pain syndrome were identified[entified,179. Howentified-182 and entified were ideTwo trials,181 onlySummary:Inconclusive (favourable) evidence for ischaemic compression  in the deactivation of upper trapezius trigger points . Inconclusive (non-favourable) evidence indicating that trigger point release is not as effective as ischaemic compression in deactivating active upper trapezius trigger points and improving associated neck pain . Inconclusive (favourable) evidence for an integrated neuromuscular inhibition technique in the management of neck pain with active upper trapezius trigger points .Otitis media One new high quality systematic review was identified on the treatment of otitis media in children with spinal manipulative therapy[ therapy. One ong therapy. One sys therapy did not The review by Pohlmann et al. summarisSummary:Inconclusive (unclear) evidence for osteopathic manual therapy in treating otitis media (no change from the UK evidence report).Parkinson’s disease One small low quality controlled trial[ed trial assesseded trial.Summary:Inconclusive (favourable) evidence for the effectiveness of osteopathic manual therapy in Parkinson’s disease .Paediatric nocturnal enuresis One high quality new systematic (Cochrane) review was identified that assessed the effects of complementary and miscellaneous interventions (including chiropractic) for nocturnal enuresis in children[children. Howeverchildren also didSummary:Inconclusive (favourable) evidence for spinal manipulation in paediatric nocturnal enuresis (no change from the UK evidence report).Peripheral arterial disease One medium quality RCT[lity RCT was idenOne medium quality non-randomised controlled trial was identified of osteopathic manipulative therapy in patients with intermittent claudication. Thirty Summary:Inconclusive (favourable) evidence for the effectiveness of osteopathic manual therapy in the treatment of intermittent claudication and of myofascial release manual therapy combined with kinesiotherapy in the treatment of venous insufficiency.Pneumonia and COPD One high quality Cochrane review[e review was idene review which ale review of osteoe review which wae review. Anothere review did not A Cochrane review includedThe trial by Zanotti et al. comparedSummary:Inconclusive (favourable) evidence for osteopathic manipulative treatment of pneumonia in older adults (no change from the UK evidence report). Inconclusive (favourable) evidence for osteopathic manipulative treatment in patients with COPD .Pregnancy/obstetric care/neonatal care Two systematic reviews  and thrquality,-200 werequality,.One systematic review of medium quality evaluateThe medium quality RCT randomisSummary:Inconclusive (favourable) evidence for spinal manipulative therapy for back pain during pregnancy . Inconclusive (unclear) evidence for manual therapy during labour or delivery . Inconclusive (unclear) evidence for manual therapy in the care of preterm infants .Rehabilitation There were three new and additional RCTs  andquality,-207  on manuquality, abdominaquality, knee/hipquality, and coroquality,.A medium quality RCT randomisA retrospective cohort study of low quality explored the effect of osteopathic manipulative treatment on the length of hospital stay in adults who had developed ileus after abdominal surgery. The recSummary:Inconclusive (favourable) evidence for osteopathic manual therapy for surgery rehabilitation . Inconclusive (unclear) evidence for mobilisation for stroke rehabilitation .Systemic sclerosis Two small low quality RCTs by the same research group,[h group,,209 examThe emphasis was on hand involvement, although one of the studies also examined parameters related to face involvement. Both trials did not report any formal comparisons between intervention and control groups. In both trials, some mobility parameters (Hand Mobility in Scleroderma Test) were improved both after the nine week intervention and after a nine week post-intervention follow-up. Some quality of life measures (SF-36) were only improved after the intervention but not at the nine week follow-up. In one trial, disability measures were improved in the intervention group both after the intervention and at follow-up, while in the other trial the disability improvement did not persist at the follow-up measurement. However, as these results were not statistically compared with those of the comparison group (results reported as unchanged) any benefits of the intervention have to remain unclear.Summary:Inconclusive (unclear) evidence for McMennell joint manipulation used in a complex rehabilitation programme in systemic sclerosis .No new or additional studies were found for the following conditions: coccydynia, dysmenorrhoea, premenstrual syndrome.Adverse events Seven systematic reviews[ reviews,210-213  reviews-220 wereThe current report summarised new and additional systematic reviews, RCTs and non-randomised primary studies not included by Bronfort et al. focussinThe majority of conditions previously reported to have ‘inconclusive’ evidence ratings by Bronfort remained the same. Evidence ratings changed in a positive direction from inconclusive to moderate (positive) evidence ratings in only three cases . New moderate (positive) evidence was identified for soft tissue shoulder disorders using myofascial treatments  not reported in the UK evidence report. In addition, evidence was identified on a large number of non-musculoskeletal conditions that had not previously been considered by Bronfort, most of this evidence was rated as inconclusive; although moderate (positive) evidence was identified for the use of massage including myofascial release/strain/counterstrain for cancer care.Despite a noted shortfall in the quality of the evidence, the current review also supported the "moderate (positive)" evidence ratings by Bronfort for the use of:• Manipulation/mobilisation (with movement) for shoulder girdle pain/dysfunction;• High grade mobilisation for adhesive capsulitis;• Myofascial treatments  for soft tissue shoulder disorders;• Manipulation/mobilisation (with exercise) for plantar fasciitis;• Self-mobilising apophyseal glides for cervicogenic headache;• Self-mobilising apophyseal glides for cervicogenic dizziness; and• Massage including myofascial release/strain/counterstrain for cancer care.Both Bronfort et al. and the • Asthma using osteopathic manual therapy;• Paediatric nocturnal enuresis using spinal manipulation;• Infant colic using cranial osteopathic manual therapy ;• Premenstrual syndrome using spinal manipulation;• Stage 1 hypertension using upper cervical (NUCCA) spinal manipulation;• Stage 1 hypertension using instrumental assisted spinal manipulation;• Otitis media and pneumonia in elderly adults using osteopathic manual therapy; and• Pneumonia in elderly adults using osteopathic manual therapy.The clinical effectiveness review was limited by the extent of information provided in the included primary studies and clinical/methodological diversity of the included evidence. Most studies had small sample sizes and methodological limitations. For the majority of RCTs it was not clear if the methods for randomization were adequate and the treatment allocation was appropriately concealed. In many cases, either the studies were not blinded or the blinding status of outcome assessors could not be determined. It should be noted that in most situations where physical treatments were applied, blinding was very difficult or impossible to achieve. The lack of description of adequacy of randomisation methods, treatment allocation concealment, and blinding in the studies complicated valid interpretation of the review results. Furthermore, there was a substantial clinical and methodological diversity across the included studies that may have contributed to the observed inconsistencies in the results. For example, there has been a large variation in types of manual therapy and their modes of application across studies, which was compounded by differences in control treatments thereby limiting comparability between the study results. Moreover, the therapy provider’s experience, training, and approaches used varied across the trials and this variation may have additionally impacted on the trial results. The above-mentioned clinical diversity limited the extent of statistical pooling of trial results. Poorly and scarcely reported harms data limited our ability to make meaningful comparisons of rates of adverse events between the treatments.We attempted to take into account a user perspective by considering qualitative studies, however, we only identified a very limited number of studies reflecting patient views of manual therapy.One of the main strengths of the clinical effectiveness review is its broad scope in terms of reviewed interventions, populations/conditions, and outcome measures. This review identified, appraised, and summarised a large amount of relevant literature. The review authors employed systematic, comprehensive, and independent strategies to minimise the risk of bias in searching, identifying, selecting, extracting, and appraising the evidence. The broad search strategy, not restricted by the language or year of publication, was applied to multiple electronic and other bibliographic sources.The current research has highlighted the need for long-term large pragmatic head-to-head trials reporting clinically relevant and validated efficacy outcomes. If ethically justifiable, future trials need to include a sham or no treatment arm to allow the assessment and separation of non-specific effects  from treatment effects. Furthermore, future research needs to explore which characteristics of manual therapies  are important in terms of their impact on clinically relevant and patient-centred outcomes. Also, strong efforts are needed to improve quality of reporting of primary studies of manual therapies.The following key research needs and recommendations were highlighted from the report findings:• Studies need to be developed that involve qualitative research methods to explore patient attitudes, satisfaction with and the acceptability of manual therapy treatments, this could also take the form of mixed methods studies exploring both effectiveness and patient views;• Greater consistency is needed across research groups in this area in terms of definition of participants, interventions, comparators and outcomes;• More research is needed on non-musculoskeletal conditions; and• High quality, long-term, large, randomised trials reporting effectiveness and cost-effectiveness of manual therapy are needed for more definitive conclusions.We consider that it is unlikely that the evidence which is available provides a reliable representation of the likely success of manual therapy as provided in the UK. The magnitude of the benefits and harms of all manual therapy interventions across the many conditions reported on cannot be reliably estimated due to the paucity, poor methodological quality and clinical diversity of included studies.The differences in the therapy providers’ experience, training, and approaches may have additionally contributed to the inconsistent results. Limited research has been published on many non-musculoskeletal conditions. There were considerable gaps in the evidence, inconsistent reporting on techniques and interventions used (with often a lack of description of techniques), and many studies failed to consider the generalisability of the findings to the range of settings in which manual therapy is practised in the UK.http://www2.warwick.ac.uk/fac/med/research/hscience/pet/reportforcollegeofchiropractors/. The authors declare that they have no competing interests.This project is an extension of a report funded by The Royal College of Chiropractors, available from: PS and GLH developed the review. CC, AT and PS conducted the review, this included: screening and retrieving papers, assessing against inclusion criteria, appraising the quality of papers and abstracting data from papers for narrative synthesis. RC developed the search strategy and undertook searches. All authors were involved in writing draft and final versions of the review. All authors read and approved the final manuscript.CC, AT, PS, RC and AC all work in Warwick Evidence at the University of Warwick and undertake systematic reviews on the clinical and cost effectiveness of health care interventions for the National Institute for Health Research Health Technology Assessment Programme on behalf of a range of policy makers, including the National Institute for Health and Care Excellence (NICE). AC is a Professor of Public Health Research, Director of Warwick Evidence and Acting Director of the Division of Health Sciences. GLH is a Professor of Social Sciences in Health at the University of Warwick.PRISMA 2009 Checklist.Click here for fileSearch strategies.Click here for fileData tables for included papers – study characteristics, results and conclusions.Click here for fileQuality assessments of all included papers.Click here for file


The consistency of treatment recommendations of evidence-based medical textbooks with more recently published evidence has not been investigated to date. Inconsistencies could affect the quality of medical care.To determine the frequency with which topics in leading online evidence-based medical textbooks report treatment recommendations consistent with more recently published research evidence.Summarized treatment recommendations in 200 clinical topics  covered in four evidence-based textbooks–UpToDate, Physicians’ Information Education Resource (PIER), DynaMed, and Best Practice–were compared with articles identified in an evidence rating service  since the date of the most recent topic updates in each textbook. Textbook treatment recommendations were compared with article results to determine if the articles provided different, new conclusions. From these findings, the proportion of topics which potentially require updating in each textbook was calculated.χ23=65.3, P<.001). The time since the last update for each textbook averaged from 170 days (range 131-209) for DynaMed, to 488 days (range 423-554) for PIER .478 clinical topics were assessed for inclusion to find 200 topics that were addressed by all four textbooks. The proportion of topics for which there was 1 or more recently published articles found in PLUS with evidence that differed from the textbooks’ treatment recommendations was 23% (95% CI 17-29%) for DynaMed, 52% (95% CI 45-59%) for UpToDate, 55% (95% CI 48-61%) for PIER, and 60% (95% CI 53-66%) for Best Practice (In online evidence-based textbooks, the proportion of topics with potentially outdated treatment recommendations varies substantially. Online evidence-based textbooks such as UpToDate, Physicians’ Information Education Resource (PIER), DynaMed, and Best Practice aim to provide high quality, frequently updated, evidence-based recommendations for clinical practice, enabling clinicians to provide care to their patients, meeting the most recent evidence-based standards , 2. If tIt is very costly and time consuming for evidence-based textbooks to seek out, appraise, and incorporate new information in a timely manner, using only their own resources . ImproveThe McMaster Premium Literature Service (PLUS) database is a continuously updated, searchable database of primary studies and systematic reviews. Each article from over 120 high quality clinical journals and evidence summary services, such as the AHRQ Technology Assessment Program, is appraised by research staff for methodological quality, and articles that pass basic criteria are assessed by practicing clinicians in the corresponding discipline . ClinicaThe primary objective of this investigation was to determine the proportion of topics in UpToDate, PIER, DynaMed, and Best Practice that predated articles in PLUS with findings different from those reported in the topics. We also assessed the number of topics available in each evidence-based textbook compared with the topic coverage in the PLUS database and the recency of updates for these publications.An analytic survey of 200 clinical topics across four online evidence-based textbooks was performed based on their most recent update to determine how frequent these topics omitted evidence in PLUS that was published since the most recent textbook update. The four textbooks, UpToDate, PIER, DynaMed, and Best Practice, were selected based on their performance in a study which assessed their evidence-based standards of preparation, timeliness of updating, and breadth of topic coverage . These fArticles in the PLUS database are indexed for over 700 topics, 502 of which had at least one corresponding article in the database in June 2011. A randomized sequence for the 502 topics was generated for topic selection. To permit comparisons of the textbooks, topics from the randomized sequence were included if each of the four textbooks had a corresponding chapter or section, and each included treatment recommendations. Searches were conducted using the textbooks’ search engine via a federated search platform  that seaCorresponding chapters for each topic in each textbook were captured as PDFs at the identical time for a given topic to provide a common baseline capture date for all texts, from July 2011 to November 2011. Any additional chapters linked to specific treatments for the topics of interest  were also captured. It was not feasible to conceal the textbook sources of the PDFs from research staff  doing assessments; however, the protocol was standardized and outcomes were objective to minimize bias introduced by this lack of blinding. The date of the most recent article cited for a topic was used as the update time since the textbooks did not consistently specify whether the posted date referred to the last literature search, the date the update was posted, or otherwise.A simultaneous search of the PLUS database was conducted, using the pre-assigned SNOMed indexing terms for each topic, and including only articles that reported randomized trials or systematic reviews of trials relevant to questions about therapy. Data captured included PubMed ID, article title and abstract, and the date the article was posted to PLUS. The PLUS posting date was compared to the last update for each textbook to determine which article was more recent.The treatments studied in the selected articles were compared to those recommended in the textbooks. If the study findings were qualitatively different from the textbook recommendation, the findings in the article were considered as potential update material for a textbook. For example, if a PLUS article reported a significant effect of nebulized epinephrine for croup and a textbook did not recommend this therapy, the article would be deemed a potential update for this topic. The term potential update was used to acknowledge the fact that clinical recommendations require the consideration of accumulated evidence, patients’ circumstances, and other variables such as the quality of the new evidence, in addition to the new evidence itself.Articles were assessed to determine if the findings of the study showed a benefit, harm, or no effect of the treatment on the clinical outcome reported in the study. This assessment was initially done in duplicate by 2 reviewers (RJ and TN) for 20 topics. The rate of agreement beyond chance (kappa statistic) was 91% (81%-99%). Subsequently, only 1 reviewer assessed each article for the other 180 topics.The proportion of topics in each textbook with the potential to update was the primary outcome of interest. A topic was in need of an update if there was at least one newer article in PLUS that provided information that differed from the topic’s recommendations in the textbook. Practical importance was defined as textbooks which require an update on 15% or more of the topics. The sample size of 200 topics was determined based on this parameter with a 95% confidence interval of ±5%. Chi-squared tests were performed to determine if the proportions of topics needing updates for each textbook were significantly different across the four textbooks. Analysis of variance was used for continuous data comparisons. Stata version 9.2  was used for statistical analysis.χ23=345, P<.001 for the differences across textbooks).During topic selection, 478 topics of the 502 were assessed for eligibility. 271 topics were excluded because they were not found in all evidence based textbooks while 7 were excluded because they had more than 5 topic links in a single textbook . Of the χ23=65.3, P<.001, Overall, 956 articles found in PLUS were more recent than the last update in at least one textbook over all 200 topics. 165 topics of the 200 had at least 1 article for at least 1 textbook that could be a potential update to that topic. All textbooks had >15% of topics with the potential for an update, ranging from 23% (46/200) for DynaMed to 60% (200) for Best Practice  was investigated . For artThe clinical relevance and newsworthiness for each article available in PLUS was also investigated, based on the score out of 7 for each category assigned to that article by PLUS raters. For the 406 accruing articles that reported new information on benefit of a treatment for at least 1 textbook, mean clinical relevance scores were 5.51  and mean newsworthiness was 4.98 . Mean clinical relevance scores were ≥ 6 out of 7 for 25% (101/406) of the studies; mean newsworthiness scores were ≥ 6 out of 7 for 9.4% (38/406) of these beneficial studies. For the 27 articles reporting harm, mean clinical relevance was 5.49 (5.24-5.74) and newsworthiness was 5.01 (4.72-5.31). Of the 27 articles reporting harm, 15% (4/27) were rated ≥ 6 for newsworthiness, 26% (7/27) were rated ≥ 6 for clinical relevance.We found that topic coverage varied substantially for leading evidence-informed electronic textbooks and generally a high proportion of the 200 common topics had potentially out of date conclusions, missing information from 1 or more recently published studies. PIER had the least topic coverage, while UpToDate, DynaMed, and Best Practice covered more topics, in similar numbers. DynaMed’s timeline for updating was the quickest and it had by far the least number of articles that needed to be updated, indicating that quality was not sacrificed for speed.These findings were similar to a recent study looking at updating systematic reviews . Our samEvidence-based textbooks are an important source of summary information and care recommendations for practicing clinicians . KeepingThe articles identified as potential updates reporting benefits and harms had a range of scores for clinical relevance and newsworthiness, with most articles rated as “probably” to “definitely” relevant to clinical practice across disciplines, and rated as “useful information” by practicing physicians .Studies have shown that patients often do not receive the best care, or may even receive harmful or unnecessary care, due to difficulties in updating information for practice . RecentlIt is important to note that no single study is likely to change a clinical recommendation on its own ,17. HoweThe study appraised only online textbooks, each with varying chapter headings and coverage. Comparing the textbooks for currency required finding topics common to all four textbooks, which was challenging. In most instances when a topic was not included in our sample, it was because PIER did not have a comparable chapter or section, making it unlike the other textbooks in terms of breadth of content. Importantly, topics were excluded if they were not included in all textbooks, thus all topics in our study were covered in PIER.Evidence-based clinical textbooks are in evolution, and we assessed them at only one timepoint, however we compared the updatedness of a large number of topics, allowing us to establish a clear picture of the updating practices of each textbook. We hope that they will continue to improve their coverage and timeliness in considering newly published evidence. All textbooks have access to the PLUS database to facilitate updates, and also use other sources of updates, such as practice guidelines. In this investigation, we looked only at studies published following the most recent textbook updates, and could not discern if the PLUS service is supplementary to other sources of appraised study reports. Redundancy abounds in evidence sources and resources, increasing the costs for publishers, editors, and authors to appraise, organize, and incorporate evidence in a timely fashion, unless ways of reducing redundancy are operationalized.Future research should investigate best methods of facilitating efficient updates of medical textbooks and uptake of these practice changes by health care professionals. Our study documents that these textbooks have some ways to go in keeping pace with high quality, clinically relevant new evidence. This new evidence has the capacity to impact their clinical recommendations, and potentially the quality of patient care. Follow-up studies to document the progress of these texts in keeping pace with new evidence would be informative.