Patients with age-related macular degeneration (AMD) have difficulty recognising people’s faces. We tested whether this could be improved using caricaturing: an image enhancement procedure derived from cortical coding in a perceptual ‘face-space’. Caricaturing exaggerates the distinctive ways in which an individual’s face shape differs from the average. We tested 19 AMD-affected eyes  monocularly, selected to cover the full range of vision loss. Patients rated how different in identity people’s faces appeared when compared in pairs , at four caricature strengths . This task gives data reliable enough to analyse statistically at the individual-eye level. All 9 eyes with mild vision loss (acuity ≥ 6/18) showed significant improvement in identity discrimination (higher dissimilarity ratings) with caricaturing. The size of improvement matched that in normal-vision young adults. The caricature benefit became less stable as visual acuity further decreased, but caricaturing was still effective in half the eyes with moderate and severe vision loss . We conclude caricaturing has the potential to help many AMD patients recognise faces. It causes central vision loss, reduction in visual acuity, and a visual experience that can include blur, missing parts of the image and distortions4. As a result, even when vision loss remains mild, AMD impairs recognition of facial identity7, an ability essential for successful social interactions11.Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment in the developed world13. Until now, image enhancement procedures shown to improve face identity perception in AMD have included magnification6, and increasing the contrast of medium- and high-spatial frequency components in the face image16. These manipulations are targeted at improving processing in early stages of the visual processing stream . Our approach here is to ask whether there might also be benefit in image enhancement methods that target mid- and/or high-level vision areas where shape information is coded20  may be narrower, have closer together eyes, a larger chin, and a more tilt-tipped nose than the average young adult Caucasian male (the average face image). With caricaturing, these differences from the average are exaggerated so that the narrow face becomes even narrower, the close together eyes become even closer together, and so on. Caricaturing of photographic images is achieved using morphing software, which stretches and compresses the distances between corresponding landmark locations  marked on the target and average faces21.Specifically, we test whether benefits can be obtained from face e24 Fig. . For exa22 29.The effects of caricaturing on face perception are explained with reference to a mental face-space22 Fig. . In thisces Fig.  and also30. More recently, we have applied caricaturing to a partial simulation of AMD — specifically, normal-vision observers shown faces blurred to mimic resolution at different distances into peripheral vision corresponding to AMD disease progression. In these simulated-AMD studies32 we have shown that caricaturing is effective at improving face recognition accuracy  and increasing perceptual discrimination of identity between faces , across a wide range of circumstances. These include young adult observers, older observers (64–86 years) in the age-range relevant for AMD, and multiple levels of blur simulating different levels of vision loss in AMD32.Caricaturing improvements in face identification are well established in normal vision for high resolution faces33. In this task . We chose this task because, in addition to evidence that its results show good generalisation to recognition tasks , it offers excellent measurement reliability and thus high statistical power33. This allowed us to evaluate whether caricature improvements were present or absent in individual patients—indeed, individual eyes—rather than merely when averaging over a group. We were then able to efficiently test a wide range of vision loss levels, ranging from extremely mild to legally blind, across 19 AMD-affected eyes (tested monocularly) from 12 patients.In the present study, we provide the first test of caricaturing directly in AMD patients. We assess perceptual discrimination ability for unfamiliar faces, using a dissimilarity rating taskask Fig. , observe33.Our research questions were: (a) do caricature improvements in face identity discrimination occur in AMD, (b) if so, are these benefits found only at milder levels of vision loss or do they survive even severe vision loss , and (c) how does the size of the mild-vision-loss caricature improvement compare to previous studies of young adults with normal visionMean = 81.4 years, range 66–93), from whom 19 individual eyes were tested. To be eligible to participate, patients had to: (a) be diagnosed by a qualified ophthalmologist as having AMD in at least one eye (eyes with other diagnoses or without AMD were not tested); (b) not have dementia (and demonstrate good ability to comprehend task instructions); and (c) be Caucasian, to match the race of the face stimuli (and thus avoid poor perception due to the other-race effect34).Participants were 12 AMD patients .Recruitment targeted eyes covering the full range of vision loss severity from extremely mild to legally blind Table . Best CoRecruitment was via The Canberra Hospital Eye Clinic and private ophthalmologist’s rooms, using a study brochure or approach whilst patients were waiting for their consultation. Patients were not paid, beyond reimbursement of travel to the university. Participants gave informed written consent after explanation of the nature and possible consequences of the study. The research methods of the study adhered to the Declaration on Helsinki and were approved by the Australian National University (ANU) and ACT Health Human Research Ethics Committees.et al.31. Two faces were shown simultaneously on the screen, and the 4 images of each person varied in viewpoint and lighting ; thus patients are being required, deliberately, to rate dissimilarity of the face information, not the low-level attributes of the pictures .The task was a minor variant on that developed by Irons res Fig. . ObserveTime to test a single eye ranged from 1–3 hours. Total testing time was 2–6 hours per patient (longer durations for patients tested on both eyes), split into sessions of maximum 2 hours conducted on separate days to minimise fatigue.et al.33. The veridical faces were colour photographs of 26 people , with neutral expression and hair covered. Viewpoints were: frontal; 10° rotation left; 10° rotation right; 30° rotation left . Faces were assigned 147 landmark points by hand .Creation of the caricatures is described in full in Irons eft Fig. . Each faeft Fig. , previou32). Within a given face sex, the 13 faces were split into two sets, comprising 7 faces  and 6 faces (for block 2) of different identity.For each eye tested, the full experiment comprised four blocks, two showing male faces and two showing female faces. Half the patients did male blocks first, and data were combined across face sex ; each target face appeared on screen-left and screen-right equally often; and each face pairing was shown in each of the 4 caricature strength conditions (intermixed and in different random order for each eye tested). For patients who completed all four blocks of trials for the given eye, this gave 72 trials per caricature strength condition across which to average ratings , and a total of 288 trials . Across all the patients, 15 of the 19 eyes had complete data for the full four blocks. The other 5 eyes had data for a reduced number of trials ; this occurred where patients were slow (spending a long time viewing the faces) and/or when they stopped participating for that eye .more or less different in identity. Before testing each eye, a demonstration slide showed images of the types of faces they would see  and participants practiced pointing to face-pairs they found most similar (and thus might award a low rating), most different (and thus might award a high rating), and pairs that would be rated in the middle of the scale.Patients were encouraged to use the full range of the rating scale (1 through 9) as much as possible. Instructions (Supplement S2) explained face pairs were always of different people, but the task was to rate, within the upcoming block of faces, which pairs looked ms interval between trials. Patients were monitored for fatigue or discomfort, and offered regular breaks.Patients viewed the faces for as long as they wished, and gave their rating response verbally; the experimenter entered this using a keyboard. There was a 300 Face images were made as large as possible on a 68.5 cm computer screen Fig. . Average31.All testing was monocular, with the other eye covered by an eye patch. Some patients could be tested only on one eye, because: their vision in the other eye was so poor they reported they could not make any judgement about the face pairs; or their other eye did not have AMD. For patients tested on both eyes, we always tested the weaker eye first, to ensure any caricature advantages found with lower-acuity vision could not be attributed to having previously seen the caricatured faces at higher acuity. When subsequently changing to the stronger eye, patients were shown the demonstration slide again to accustom them to how the faces would now appear to them in terms of resolution, and were instructed to recalibrate their use of the rating scale Testing both eyes separately allowed us to test a wider range of acuity values with the number of patients we had available. Also, in some patients, the monocular testing provided data relevant to whether any failures to show caricature improvements could be attributed specifically to the severity of vision loss in a given eye, as opposed to inadequate cortical coding in the shared brain tapped by both eyes (see Results).within each eye separately. Some aspects of the analysis differ from statistics averaged over multiple participants. We conducted one-way ANOVA  using just the data from the individual eye being analysed. Because each face pair was repeated across the four caricature levels, statistical analysis on caricature strength (even within a single patient/eye) was repeated measures — but, repeated measures across items, not participants. Finally, statistical effect size measures (eta-squared) describe proportion of across-item-variance explained, rather than the usual proportion of across-participant-variance explained, which limits their usefulness (see Supplement S3 for further explanation).We had sufficient score reliability to perform statistical analysis 37. Pairs of eyes that come from the same patient are indicated by matched participant code. To assist with concrete interpretation of acuity values, poorer than 6/12 (binocularly) results in loss of standard driver’s licence and <6/60 is legally blind .Figure If caricaturing improves identity discrimination, the prediction is that dissimilarity ratings should increase as the strength of caricaturing increases . For each eye separately, we also conducted a statistical test for linear trend; results are in Table p < 0.05 . For the mild-vision-loss AMD patient group, our mean increase in dissimilarity ratings from Veridical to the maximum 60% caricature strength is 0.504 ± 0.063 (mean ± SE). Comparison values from the three previous young-adult studies were 0.699 ± 0.085 using exactly the same 26 faces seen by the AMD patients, and 0.504 ± 0.090 and 0.684 ± 0.120 using a subset of 20 of the faces; note none of these three differed significantly from the caricature advantage for AMD patients . Overall, the size of the caricature improvement in mild vision loss AMD was similar to that shown by young adults with normal vision.The benefit of caricaturing was clearest for eyes with mild vision loss. For this category, all 9 eyes—which came from 9 different patients—showed a significant caricature improvement. We also compared the size of this caricature improvement to that shown by young adults with normal vision in previous studies using the same task and stimuliTurning to higher levels of vision loss, caricature improvements were less consistent Fig. , Table 1p < 0.001; E5 from Pe, p < 0.001; E7 from Pg, p < 0.001; E8 from Ph, p = 0.028) as it was in the five cases with prior testing . This argues that it is acuity per se that drives the reliability of the caricature improvement.The greater consistency of the caricature improvements for mild vision loss eyes than for the moderate-and-severe vision loss eyes cannot be attributed to any kind of carryover effect from earlier testing of the other, weaker eye . Table lack of caricature improvement in the 5 cases where it was absent, results show that in 3 cases  this can unambiguously be attributed to the severity of vision loss in the relevant eye: this is because these eyes came from three patients  who were also tested on their other eye which had mild vision loss and showed a significant caricature improvement . Methodologically, results show the lack of caricature improvements cannot be attributed to reduced statistical power arising from reduced number of trials for some eyes: of the 5 eyes without caricature improvements, 3 received the full number of trials ; and, of the 5 eyes that received a reduced number of trials, 3 revealed significant caricature improvements .Similarly, concerning what might explain the both eyes, yet a caricature improvement was still observed. Specifically, patient Pk had moderate (6/24) and severe (<6/360) vision loss, and showed a caricature improvement in both these eyes  in one eye. These patients are cases where vision loss was moderate-or-severe in es Table . And patstrength of caricaturing was most effective. Averaging across the 14 eyes that showed a caricature improvement, perceived difference in identity increased progressively with increasing caricature strength , with 60% caricature strength most effective. 40.A final question is what The key results were as follows. All eyes with mild vision loss showed improvement in identity discrimination with caricaturing. In mild vision loss, the size of the caricaturing benefit was as large in AMD patients as in young adults with normal vision. The caricaturing advantage became less stable as visual acuity further decreased. Despite this, caricaturing was still effective in half the AMD cases we tested even with moderate and severe vision loss. Finally, caricature improvements do not require the patient to have one “relatively unaffected” eye  but can occur even when high quality visual input from either eye has been absent for some time in the patient’s day-to-day experience (which in turn implies the patient’s brain has retained accurate face-space representations despite the lack of recent “topping up” with any high resolution face input). Together, these findings are encouraging for caricaturing as a potential real-world method for improving face identity recognition in AMD, in terms of both breadth of applicability across patients, and the size of the likely caricature improvement.perception, as tapped here by dissimilarity ratings, would translate into the presence of caricature improvements in memory.The rating task used in the present study — selected because of its high reliability allowing individual-eye analysis — does not provide a direct measure of the amount by which caricaturing improves performance accuracy . In future studies, it would be valuable to test recognition directly, while noting this would require averaging 30+ participants within a tight range of visual acuity to obtain error bars of acceptable size to determine whether caricature effects are present (at that one acuity level). Importantly, however, there are strong reasons to believe that the presence of caricature improvements in patients’ identity 33. Second, there are strong theoretical links between caricature improvements in perceiving differences in pairwise identity (our task) and caricature improvements in recognition memory via well-established properties of face-space coding . Third, we have shown that caricature improvements in memory occur specifically in the age range relevant to AMD: our findings in normal-vision older adults include a faster face-name learning rate, more accurate subsequent recognition of novel images of the learned faces, and no reduction in size of the caricature improvement with increasing age (up to 86 years)32. These findings argue that the specific properties of face-space that improve memory remain functional in the brains of older adults of similar age to AMD patients. Overall, given that caricature effects on perception remain despite impaired patient vision (present article), and caricature effects on memory occur in similar-age brains32, there seems little reason to doubt that the caricature improvements in memory will survive the combination of impaired vision and an elderly brain.First, in every circumstance our lab has tested to date, we have found that caricature improvements in our dissimilarity rating task translate to caricature improvements in recognition ; these circumstances include young adults, older adults, own-race faces, other-race faces, blurred faces, other types of low-resolution faces (a ‘bionic eye’ simulation), and high-resolution faces33 using the same face stimuli shows that caricaturing in young adults produces a 5–10% improvement in recognition accuracy, using old-new recognition and face-name learning tasks. Thus, our present results predict a similar performance improvement of 5–10% in mild-vision-loss AMD patients.Concerning the likely size of improvement in recognition tasks, a conversion can be made, using the fact that, on dissimilarity ratings, mild-vision-loss AMD patients had a similar level of caricature improvement to young adult observers. Other research from our laboratoryincremental improvement. Caricaturing can be combined with other image enhancement procedures targeting other stages of visual processing of faces  that also produce incremental improvements, to produce the greatest total benefit to patients’ functional vision. Translation to patients would then involve potentially several stages of software manipulations to a face image. Note that, currently, computer science is getting fairly close to being able to implement real time caricaturing. Solved steps of the problem include: initial face detection and isolation of the face from the background of a complex natural image41; the caricaturing stage itself23; and also real-time assignment of landmark points . There are also some remaining difficulties .An improvement of 5–10% in recognition accuracy in patients is large enough to be of some practical value in the real world. At the same time, it will not get patients back to normal-vision performance. We thus argue that caricaturing should be viewed as a technique that provides useful 44 . Another limitation is that we caricatured only shape information in the face. It is possible that caricature benefits for patients could be larger if shape + reflectance information is caricatured, given that reflectance/texture caricaturing can produce performance benefits in normal-vision observers47 . A final limitation is that we tested patients monocularly, while real world viewing is binocular. In some cases, binocular vision can improve acuity and functional vision48. This suggests that perhaps some people with AMD, who have acuity too poor to show a caricature improvement with either eye tested independently, might show a caricature improvement with binocular vision.A limitation of the present study is that we test perception of unfamiliar faces only. In future studies, it would be valuable to test whether caricaturing also improves AMD patients’ recognition of pre-experimentally familiar faces, such as friends, family, and famous faces. Of potential relevance to low-vision patients, familiar-face caricature advantages occur in normal vision using impoverished face stimulibodies. Human bodies are used in recognising other people , and, like faces, show evidence of coding relative to an average50. It is thus possible that exaggerating an individual’s body shape away from the average may further improve AMD patients’ perception of people’s identity. .Another question for future research is whether caricaturing might be able to improve AMD patients’ perception of information other than faces. A class of wide relevance is 32; actual AMD patients who commonly experience blur-plus-distortions; and a simulation of prosthetic vision (bionic eye) where images appear as a grid of separated phosphenes of light33. Theoretically, this broad generalisability across very different low-resolution formats arises because caricaturing targets high-level visual processing . Practically, it implies caricaturing should improve identity perception in any vision disorder that produces low vision.A final question of interest is whether face caricaturing might be useful in other vision disorders beyond macular degeneration. We predict it will. Across studies, we have shown face caricaturing produces very similar sized benefits for: a blur-only partial simulation of macular degenerationSupplementary Materials


In global health discussions, there have been widespread calls for health policy and programme implementation to be informed by the best available evidence. However, recommendations in the literature on knowledge translation are often decontextualised, with little attention to the local systems of institutions, structures and practices which can direct the production of evidence and shape whether or how it informs health decisions. This article explores these issues in the country setting of Cambodia, where the Ministry of Health has explicitly championed the language of evidence-based approaches to policy and planning.Research for this paper combined multiple sources and material, including in-depth interviews with key informants in Phnom Penh and the analysis of documentary material and publications. Data collection and analysis focused on two key domains in evidence advisory systems: domestic capacities to generate health policy-relevant evidence and institutional mechanisms to monitor, evaluate and incorporate evidence in the policy process.We identified a number of structural arrangements that may increasingly work to facilitate the supply of health-related data and information, and their use to inform policy and planning. However, other trends and features appear to be more problematic, including gaps between research and public health priorities in the country, the fragmented nature of research activities and information systems, the lack of a national policy to support and guide the production and use of evidence for health policy, and challenges to the use of evidence for intersectoral policy-making.In Cambodia, as in other low/middle-income countries, continued investments to increase the supply and quality of health data and information are needed, but greater attention should be paid to the enabling institutional environment to ensure relevance of health research products and effective knowledge management. There is widespread recognition that policy and planning in the health sector should be informed by the best available evidence; however, our understanding of the institutional and structural arrangements that can promote improved knowledge utilisation is limited, especially in low/middle-income countries (LMICs).Our study takes an institutional approach to examine the local systems of structures and practices influencing the production and utilisation of health evidence within the country setting of Cambodia.We found that increasing availability of health data and research products, combined with recent reforms of the health system, may increasingly serve an evidence advisory role in the health sector.However, lack of clear guidelines and weak domestic research capacities make the use of evidence in line with best practices less likely.In Cambodia, as in other LMICs, continued investments to increase the supply and quality of health policy-relevant data and information are needed, but more attention should be paid to the underlying structural arrangements including the strengthening of local research organisations as well as the development of policy and local institutions that can facilitate knowledge management and translation.et al, p54).4In current global health policy discussions, there has been increasing emphasis on the importance of promoting the use of health data and research findings to inform policy formulation and implementation. Particular concerns have been expressed about the need for a "culture of evidence" in low/middle-income countries (LMICs), where "the pressure to extract the most out of funds is particularly great, as the gap between the resources available and those that are needed to address the burden of preventable diseases is larger than elsewhere"  and the analysis of three specific case studies of evidence use (reported in a previously published paper).23 24n, date.Data collection and analysis were informed by the principles of exploratory case study research, an approach commonly used in policy studies which combines multiple sources and material to gain a better understanding of a particular issue within a given context, and generate insights and concepts for further inquiry.In the early 1990s, Cambodia embarked in a process of political reform and state reconstruction following two decades of civil conflict. In 1993, the first general elections, overseen by the United Nations Transitional Authority in Cambodia, laid the foundation for democratic transition and the peaceful resolution of conflicts. After the elections, the new government drafted the Constitution of the Kingdom of Cambodia, which established a constitutional monarchy, based on a bicameral legislative system and multiparty elections.27Cambodia’s political transition ended a long period of isolation, opening the country to greater engagement with the international community and the inflow of foreign aid assistance. Subsequently, significant investments have been made to rebuild and reform institutions for national planning and state administration, including structures for the collection and management of basic demographic data.In the health sector, the development of a national information system was a priority in the reconstruction agenda. A pilot system for the collection of basic data on illness and service utilisation from public health facilities was established in 1993 with the support of the WHO and the Unicef.The MoH has recognised the importance of strengthening the NHIS as a necessary requirement to support evidence-based policy-making, identifying gaps and challenges that should be addressed to improve the reliability and policy relevance of the system. As reported in the second national health sector strategic plan, however, the lack of comprehensive information technology (IT) coverage, human resources and capacities remains a national challenge.The NHIS is also unable to capture data from the private sector , which altogether account for 67.1% of first treatments in Cambodia.Société Royale de Médicine du Cambodge, which published scholarly proceedings in its periodical bulletin.The development and current status of domestic research capacities in Cambodia has also been shaped by pivotal events in its modern political history. The establishment of national universities was initiated after independence by Prince Sihanouk, who founded the Royal Medical School (1953) and the Royal Khmer University (1960). As part of the project of nation building and modernisation, efforts were subsequently made to promote the professionalisation of medical research in the country such as the foundation of the It is difficult to attract good researchers, as they prefer to work in the private sector or move abroad. (…) Staff can top up their salaries with grant money, up to USD 1000 a month. Still, this is not competitive enough to attract good researchers, because the market standard is around USD 3,000 .From the early 1990s, a diverse range of international actors has filled this gap in domestic research capacity, generating research products on different aspects of health and healthcare in Cambodia. International actors that have financed or conducted health research include NGOs, academic institutes, private foundations, aid agencies, UN agencies and other international bodies such as the European Commission, research institutes or companies and private consultants. Some organisations have established offices in Cambodia ; others have conducted short-term projects. Prominent global health actors such as the Global Fund have also provided large grants to the health sector in Cambodia, further contributing to the generation of evidence, often in the form of reports and programme evaluations.As a result of these developments, there has been a significant increase in health research output. However, some informants noted that the research landscape is fragmented, with little coordination between research projects sponsored by different organisations . Further, discrepancies were reported to exist between donor-funded research and health priorities in the country. As one high-level manager in the MoH remarked, “many times research is driven by funding, not demand. And this type of research is less relevant to the country” . Similarly, two other local informants, with many years of experience in the conduct and management of research programmes in Cambodia, complained that research and data collection efforts tend to focus on vertical programmes that receive donor support, but other important public health priorities for the country or wider health system analyses are neglected:I believe hepatitis is a big problem in Cambodia; however, we have no data on this (…) What is the actual burden of hepatitis? No-one can answer this question, because we have no data. But we know everything on TB, HIV, and malaria .The most active in research are the programmes like maternal and child health or HIV because there is external support and they are very specific. It is rare we have research from the perspective of the wider health system .These perceptions are reflected in the results of a recent literature review, which found an increase in research output on communicable diseases , but under-representation of other important health issues in the country such as non-communicable diseases  as well as implementation and health system research.www.nchads.org).In addition to the need for both health data and research in Cambodia, it is important to consider the systems through which pieces of evidence can inform decisions. Over the past 15 years, following the reform of the health sector and the MoH, a number of institutional arrangements have been put in place, which appear well situated to provide evidence to key decision-making points. One notable example is the integration of the management of the NHIS and technical responsibility for strategic planning into a single structure of the MoH, the Department of Planning and Health Information. Specialised centres under the MoH also have organisational structures that may be conducive to the use of evidence. For example, the technical bureau of the National Centre for HIV/AIDS, Dermatology, and Sexually Transmitted Diseases incorporates a data management unit, a research unit and a planning unit, which are mandated to interact at various stages of data collection, reporting and planning  is a forum for policy dialogue and information sharing across a wide range of stakeholders, which was established in 2004 by the government of Cambodia to improve aid effectiveness, harmonisation and alignment with development partners. The TWG-H has a broad and inclusive membership, with subnational and civil society representation, and is based on monthly meetings, co-chaired by the Minister of Health (or a Secretary of State) and the WHO Country Representative. Directors of Provincial Health Departments (PHDs) are regularly invited to attend the meetings, where they usually provide a presentation on health progress and challenges in their administrations.There was some consensus among participants that these mechanisms have created a well-functioning space for debate and coordination, contributing to the circulation of health information and knowledge among a wide range of stakeholders:It is good to have forums such as the TWG to avoid duplication of efforts and find synergies between partners. Also, those meetings are crucial to promote an evidence-based culture because people meet and when they discuss they must support their arguments in a rational way, presenting evidence .Participation of representatives from grassroots organisations and managers of provincial departments was mentioned as an important feature of the TWG-H, with the potential to enhance the visibility of local perspectives at the highest level of policy-making. In addition, the existence of consultative mechanisms at the village level might further support the generation and use of what has been termed "community-based evidence".Despite the existence of enabling structures, our investigation found gaps in the local context that make direct or widespread applications of evidence in line with best-practice expectations less likely. As informants pointed out, there are no clear guidelines about the way in which evidence should be appraised and used in policy processes. As a result, evidential practices were reported to be highly variable across different sectors and health issues, depending on the initiative and skills of individual managers and political will . High-ranking bureaucrats or politicians may require technical departments of the MoH or international organisations to provide evidence in support of policy-making and parliamentary debates. Yet, the lack of clear procedures, combined with power imbalances and the pressure of hierarchies, may constrain the ability of technical officers to act on, or even communicate, policy-relevant knowledge and information; one manager in the MoH explained, “we present evidence, but if a politician says, ‘I don’t believe it’, we cannot argue (…) we can present new evidence or clarify only if they request us to do so” . Further, mechanisms such as the TWG-H may serve well as a platform to share data and expertise. However, some informants noted that meetings tend to be very formal, especially when high-ranking politicians are present, and therefore their value as a forum to appraise and discuss evidence critically is limited . Similarly, an evaluation of the TWG-H found that meetings could be informed by "more substantive, strategic and open debate on policy, strategy and problem-solving, underpinned with evidence" .36The use of evidence to inform decisions that require multisectoral coordination was seen as particularly problematic, especially for health policy decisions which have significant implications for the national budget, impinge on different agendas and require agreement across the political board. Interministerial committees have been established to promote dialogue on complex health policy issues such as tobacco control and nutrition, but the idea that health evidence alone can guide decision-making in these fora was questioned:Anything inter-sectoral, like nutrition is very hard to get policy shift on. Because the Ministry of Agriculture says “well, look, we do what we can but our priority is food security” (…) And then you have to convince the Ministry of Health with technical evidence but, more importantly, it’s the business case to the Ministry of Economy and Finance, unless it’s a revenue neutral decision, but very few of them are .The case of tobacco is a good illustration of these challenges. In April 2015, the Cambodian National Assembly approved the first ever Tobacco Law in the country, which introduced new restrictions on the import and sales of tobacco, smoking in public places and ban on most advertising. The approval of the Tobacco Law was a major step towards the implementation of the Framework Convention for Tobacco Control in Cambodia. However, the legislative process was very slow and unwieldy, destabilised by conflicting mandates of the MoH , the Ministry of Economy and Finance  and the Ministry of Agriculture, Forestry, and Fisheries , in addition to pressures of tobacco corporations .In the process, the advocacy of the National Center for Health Promotion of the MoH, the WHO and two NGOs was crucial to keep the issue on the agenda of the government and mobilise resources, including the production of evidence in the form of qualitative studies and surveys.Sometimes you need to present the same evidence in a different way (…), also because policy is multi-sectoral. It’s not that one minister decides. For example, they say that if you want to increase [tobacco] tax, this is not an issue of the Ministry of Health. We don’t have the power to do this. We can do a smoke-free policy, but tax is under the Ministry of Finance. So, you have to work closely with the Ministry of Finance… invite them to international workshops (…) Also, we have to explain that farmers do not rely on one crop only, so reduced tobacco production will not significantly affect them .And when the Tobacco Law was approved in 2015, 12 years after the presentation of the first draft bill, the Prime Minister Hun Sen reportedly commented: “an individual cancer patient costs the government $10 000 per year, and the cost of treatment to the country is significantly higher than the $100 million spent by Cambodians on tobacco products” . This kind of reasoning suggests that, at the highest level of decision-making, arguments about the economic impact of tobacco consumption were crucial to advancing the legislative process. This may not be surprising in a developing country that has placed economic growth at the centre of the development agenda and illustrates the limitations of oversimplified assumptions that health-related evidence not only speaks for itself but also will have an obvious political priority.This study aimed to provide a broad mapping of challenges to, and opportunities for, the promotion of evidence-informed health policy-making in Cambodia, an approach which has been explicitly endorsed by the MoH and the global community alike. Our findings document a number of institutional and structural developments which may be conducive to meaningful and effective use of evidence for health policy and planning in the country; these include improved health information systems, increasing availability of institutional surveys and research products, the existence of participatory policy mechanisms in which evidence can be presented to local and international stakeholders and channels for the circulation of evidence across different levels of the MoH. However, other trends and features seem to be more problematic, including gaps between research areas and public health priorities, the fragmented nature of research activities and information systems, the lack of a national policy to support and guide the production and use of evidence for health policy, challenges to the use of evidence in support of intersectoral policy-making and the influence of external donors on research priorities. Some of these issues are known in health policy studies. For example, a recent literature review showed that development actors in many LMICs continue to operate research models that are not in line with widely accepted views of best practices, including a preference for vertical approaches to research capacity development, donor-led research agendas and fragmentary research programmes.Further reflecting on our results, we can draw out general insights and recommendations, which can be useful to inform the process of resource allocation in the country as well as the wider debate in global health policy. First, as described, recent investments in Cambodia, as in many other LMICs, have tended to focus on knowledge generation, but little investments have comparatively been made to support local research organisations so that they can initiate, conduct and disseminate research findings independently. As emerged during the symposium "Building research capacity in Cambodia" , a new generation of qualified researchers is ready to contribute to social development and innovation in the country, but more investments will no doubt be needed to provide them with the means to shape the research agenda. In particular, the strengthening of higher education institutions would be a key driver of innovation and development in the country, with potential spillover effects on the establishment of a culture of evidence. It would likely contribute to enhancing the status and recognition of the academic community in Cambodia, providing a critical mass of local experts. The development of research-oriented universities would also train a new generation of managers in public administration that are more familiar with research methods and practices, and thus in a better position to consider and evaluate evidence in policy processes. Efforts to achieve this will want to consider not just research training but also the development of a national research policy that increases the supply of local evidence and aligns research programmes with decision-making points and local needs to create the most favourable conditions for knowledge utilisation.et al pointed out a greater level of institutionalisation and regulatory support would enable stronger foundations for a continued and sustainable use of evidence.52Second, as we have seen, there are no clear guidelines and structures to support the use of evidence for health policy in Cambodia. Experiences in other LMICs indicate that dedicated committees, platforms and networks for knowledge management and translation can facilitate the regular and effective exchange of information between researchers and policy-makersThe development of enabling mechanisms and the strengthening of a culture of evidence will take time. Resources to support institutional development are still limited in Cambodia and partly dependent on international aid.Lastly, we should note some study limitations. Given the exploratory nature and broad scope of the research design, we could generate hypotheses and identify emerging issues and potential solutions, but further research is needed to verify or explore them in-depth. For example, (participant) observations at key meetings of technical working groups would provide a thicker description of dynamics and interactions between local and international stakeholders, and specific ways in which different types of evidence are presented, discussed and valued, including local data and surveys, findings from other countries and experiences from the communities. It would also be relevant to explore in detail such interactions in the conduct of research projects and the extent to which the involvement of local researchers can facilitate the generation of findings that are tailored to the local context and knowledge translation. Second, we could identify a number of institutional, political and structural features which may affect how and what evidence is used for health policy and planning. However, a detailed examination of the complexity of competing actors and interests influencing policy directions (in ways that are not necessarily informed by evidence) was beyond the aim and scope of this study and would require the in-depth analysis of specific case studies. Finally, when investigating policy issues and the views of government officers in particular, a tendency to provide socially desirable accounts, disengaged from controversial issues, can potentially result in biased accounts. In our interviews, we tried to minimise the potential for such bias by prioritising "how" questions rather than "why" questions, as these are known to create a more defensive attitude.This study highlights a number of developments in Cambodia that may increasingly work to facilitate the supply of health-related data and information, and their use to inform policy and planning. It also identified ways in which the institutional framework could be strengthened to create more favourable conditions to support evidence-informed policy-making. The issues we have discussed here are complex, intertwined and shaped in multidimensional ways by contextual factors. Yet, lessons from Cambodia can be useful to explore and better understand the environment for evidence-informed policy in many other contexts, especially in transitional economies where national structures for the generation and use of policy-relevant evidence are not yet fully developed and where research priorities have been directed by external actors.


Quality improvement (QI) initiatives should be based on sound evidence to be effective since human resources, efforts and a lot of time is invested into the process.Continuous quality improvement is crucial for patient satisfaction which subsequently leads to financial viability. Quality improvement (QI) initiatives should be based on sound evidence to be effective since human resources, efforts and a lot of time is invested into the process. Also, quality improvement processes affect the financial health of an organisation.Sackett et al defined evidence-based medicine (EBM) as “the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients, integrating individual clinical expertise with the best available external clinical evidence from systematic research”.Quality improvement initiatives should lead to improvements in patient outcomes that are, ideally, both clinically important and cost-effective.Quality improvement initiatives should be based on sound evidence of what works to implement these products or approaches.Evidence-based quality improvement (EBQI) requires an evidence-based problem that needs assessment. Also, guidelines governing the process to be improved are essential and there has to be sufficient relevant evidence regarding potential methods for improvement . A team of experts is needed for the propagation of EBQI. EBQI aims to systematically insert evidence, knowledge, and data at all points in development of a QI intervention.In a reputed National Accreditation Board for Hospitals (NABH) accredited eyecare hospital in North India various EBQI measures are taken in a continuous manner.A set of quality indicators  are monitored in the hospital regularly  which deThe standard operating procedures of all the departments of the hospital are reviewed and updated each year by the technical experts. Latest national and international guidelines are used for this purpose as evidence.The quality team of the hospital also takes up various lean Six Sigma projects for continuous quality improvement. These initiatives are based on the evidence and effectiveness of DMAIC strategy. DMAIC is a data driven quality strategy used to improve processes. It is an integral part of a Six Sigma initiative, but in general can be implemented as a standalone quality improvement procedure. DMAIC is an acronym for five phases that make up the process 4:Define the problem, improvement activity, opportunity for improvement, the project goals, and customer  requirements.Measure process performance.Analyse the process to determine root causes of variation, poor performance (defects).Improve process performance by addressing and eliminating the root causes.Control the improved process and future process performance.In the year 2016, continuous quality improvement projects were on:Project Chakshjyoti: to improve the quality of optical services and optical conversion rate ;Project to improve surgical conversion rate;Project to reduce patient waiting time in out patient department (OPD)These projects were taken up and successfully accomplished with evidence-based DMAIC strategy leading to improved quality of services, patient care and sustained the financial health of the hospital.The hospital also uses EBQI tools like “audit and feedback” to improve its quality of services. A prescription error audit was also done at the hospital in the last financial year taking MCI  guidelines as evidence. The results were communicated to the clinicians and post intervention a re-audit was done which showed significant improvement in the system.Operating theatre starting time is also monitored at all the secondary centres of the hospital. At one of the secondary centres it was showing higher non-compliance consistently. NABH guidelines make it mandatory to have hospital committees to ensure patient safety and prevention from hospital-acquired infections. Evidence suggests that these committees are essential and play an important role in patient care.Hence, such examples illustrate that quality and evidence-based practice are mutually linked. To make quality improvement interventions effective, evidence-based methods are essential. This ultimately leads to improved patient care along with patient satisfaction and sustained financial health of the organisation.


The EDL microstructure is represented by number densities of cations and anions, and the potential drop near neutral and charged electrodes reveal that the supercapacitor model with a single electrode has the same EDL structure as the model with two opposite electrodes. Nevertheless, the employment of the one-electrode model without tuning the bulk density of RTILs is more time-saving in contrast to the two-electrode one. With the one-electrode model, our simulation demonstrated that the shapes of anions significantly imposed effects on the microstructure of EDLs. The EDL differential capacitance vs. potential (C-V) curves of [Emim][CNPyr] electrolyte exhibit higher differential capacitance at positive potentials. The modeling study provides microscopic insight into the EDLs structure of RTILs with different anion shapes.Room-temperature ionic liquids (RTILs) are an emerging class of electrolytes for supercapacitors. In this work, we investigate the effects of different supercapacitor models and anion shape on the electrical double layers (EDLs) of two different RTILs: 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([Emim][Tf The limited availability of fossil fuels and the urgent demand for environmentally friendly and sustainable energy resources bring about an intense need for efficient energy storage devices, leading to widespread research efforts into electrochemical capacitors, especially into supercapacitors, in the past decade ,2,3. In The structure of the electrical double layers (EDLs) at the interfaces of RTILs and the electrode has been intensively studied in experiment, theory and modeling. Ohsaka and co-workers studied the EDL capacitance near carbon and gold electrodes with imidazolium tetrafluoroborate RTILs by the impedance technique and found that the capacitance-electrical potential (C-V) curves were parabolic-like shaped at the glassy carbon electrode . Lockett4]−) or elliptical  anions. However, it is still intriguing how the EDL structure and C-V curve will be modified when replacing anions with planar aromatic ones. In addition, the commonly adopted supercapacitor model in simulations consisting of two parallel electrodes with the in-between space filled by RTIL electrolytes, requires tuning the number of ion pairs in the channel repetitiously until the density fits the bulk properties; in contrast, one-electrode supercapacitor model, comprised of one charged electrode and RTIL electrolytes, with one end in contact with electrode surfaces and the other end of RTILs in contact with the vacuum, is facile to establish for molecular simulations and generally costs fewer computation resource. Thus, in this work, we used two different supercapacitor models including single-electrode model and two-electrode model  in simulations to compare the RTILs behaviors in EDLs. The main goal of this work is to investigate how the simulation model and anion shape could influence the microstructure and capacitance of the EDLs at the RTIL-electrode interfaces. The rest of this paper is organized as follows: the results on the EDL structure and capacitance are given in A vast majority of studies have focused on RTILs consisting of planar imidazolium-based cations and spherical  and B (20.2#/nm3) are very close to each other. Moreover, similar tendency is observed in their space charge density near electrodes (shown in Both one-electrode (Model A) and two-electrode (Model B) models as shown in ous work . The numshown in c,f as we2N] and [Emim][CNPyr] consisting of identical [Emim]+ cations and anions of different shapes were obtained using one-electrode supercapacitor models by MD simulations. 2N] and [Emim][CNPyr] near neutral electrode. There are several noticeable features in this figure. Two peaks of [Emim]+ are observed and the first peak is located at ~0.350 nm for both ILs. Their second peak is slightly different, i.e., the second peak of cations in [Emim][Tf2N] is further away from the electrode in contrast to that of [Emim][CNPyr]. Comparing the number density profiles of [Tf2N]− and [CNPyr]−, there is only a single peak located at ~0.430 nm observed for [Tf2N]−, while twin peaks of [CNPyr]− with the first peak located at ~0.330 nm are present, and the height of the first peak is lower than that of [Emim][Tf2N]. Such observations can be attributed to the strong interaction between planar [CNPyr]− and graphene electrodes, especially the dominant van der Waals force between the electrode and ions [The EDL structures of [Emim][Tfand ions . To vali+ and the graphene wall [+ ions were packed closer than [Tf2N]−, as shown in 2N] and [Emim][CNPyr], the van der Waals energy between [Emim]+ of the first ion layer at 0.350 nm and graphene is −62.6 kJ/mol. The strongest van der Waals interaction energy between the [Tf2N]− and graphene electrode is located at z = 0.430 nm, accounting for the first ion layer of [Tf2N]− packed at ~0.430 nm. Regarding [Emim][CNPyr], the van der Waals interaction energy depth between [CNPyr]− and graphene is slightly lower (−49.7 kJ/mol) and [CNPyr]− is closer (0.330 nm) towards graphene compared with that between [Emim]+ and graphene, which can be explained by the missing methyl and ethyl groups in planar [CNPyr]− in comparison with [Emim]+, leading to more efficient packing of ions in the first layer. The second layer peaks of [CNPyr]− can be resulted from the densely-packed cations in the first layer adjacent to the electrode, facilitating the formation of the second [CNPyr]− layer to compensate the positive charges of the first cation layer and preventing the formation of second [Emim]+ layer [Due to the strong π-π interaction between the planar [Emim]ene wall ,33, [Emi]+ layer .2N] and [Emim][CNPyr] near neutral and charged electrodes, respectively. The cations in both [Emim][Tf2N] and [Emim][CNPyr] exhibit similar behavior at electrode surface regardless of the charge status of electrode. There is a significant accumulation of [Emim]+ ions at neutral electrode within the first counter-ion layer, which accounts for the strong affinity of the imidazolium ion toward the π-electronic graphene electrode + ions presents two peaks at z = 0.320 nm and z = 0.440 nm from the planar electrodes, similar to our previous work [2N] and [Emim][CNPyr] exhibit dissimilar behaviors at electrode surfaces. [CNPyr]− anions are located closer towards electrode surfaces than [Tf2N]− at varying charge densities, which could be attributed to the specific orientation of [CNPyr]− in EDLs as illustrated below.lectrode ,34,35,36ous work . It is a+ cations or [CNPyr]− anions and the normal vector of the electrode, was computed as shown in + cation is parallel to the graphene electrode, while at higher surface charge density, the orientation of [Emim]+ changes from parallel to random alignment. We attribute this transition to that lessening the overlapping of the π orbital of the imidazolium cation with the vacant orbital of the graphene electrode leads to more efficient packing of cations to compensate the negative charges − anions are more parallel to the positive electrode as the electrode is more positively charged, which can be explained by the reduced steric effects resulting from the absence of methyl and ethyl groups in [CNPyr]− in contrast to [Emim]+.To elucidate the arrangement of ions in RTIL-based EDLs, the ion orientation, defined by the angle formed by the normal vector of the plane of [Emim] charges ,24. On t2N] and [Emim][CNPyr] are quite different and [Emim][Tf2N] exhibits a camel-like shaped C-V curve, whereas [Emim][CNPyr] displays an incomplete camel-shaped C-V curve. Similarly, Smith’s group [2N] electrolytes-based supercapacitors using flat graphene electrode by MD simulations, consistent with the experimental measurement with similar cations by Lockett et al. [CNPyr] is higher than that for [Emim][Tf2N]. However, at highly negative potentials, anions are gradually squeezed out from the EDL by cations, and more cations of [Emim][Tf2N] accumulated to replace anions than those of [Emim][CNPyr] in EDLs due to the relative larger space occupied by [Tf2N]−, leading to the higher capacitance of [Emim][Tf2N] at negative potentials than [Emim][CNPyr].To better understand the influence of the anion shape of RTIL electrolytes on the EDL capacitance, the differential capacitance (C) vs. electrical potential drop (V) across EDL was shown in ’s group  also rept et al. ,38. The 2N] and [Emim][CNPyr] of the first layer at varying charge densities can also explain the origin of the shape of C-V curves. According to 2N] at different charge densities, indicating the more efficient packing of ions with planar geometry in EDLs, resulting from the π-π interaction. Moreover, as the surface charge density increases, the number of counter-ions is increased while the number of co-ions is decreased in EDLs for both RTILs, consistent with previous observations [2N] at fixed positive surface charge densities of the electrodes. In addition, the variations in negative net charges of EDLs per unit charge density for [Emim][CNPyr] are steeper than [Emim][Tf2N], leading to the higher capacitance at positive potentials of the C-V curve. Furthermore, the positive net charges of [Emim][CNPyr] are lower than those of [Emim][Tf2N] at higher surface charge densities, resulting in the smaller capacitance.The number of accumulated co-ions and counter-ions in EDLs of [Emim]−) composed of a planar ring, and bis(trifluoromethanesulfonyl)imide ([Tf2N]−) anion were included. The force fields for all ions were taken from − and planar [CNPyr]− anions on the capacitive performance of [Emim][Tf2N]- and [Emim][CNPyr]-based supercapacitors. The results demonstrate that [Emim]+ cations in EDLs of both RTILs exhibit similar behaviors. Nevertheless, there are obvious differences in the interfacial properties of [Tf2N]− and [CNPyr]− anions across EDLs. [CNPyr]− anions are located closer to electrode surfaces in contrast to [Tf2N]− due to the π-π interactions with graphene. It was further verified that [CNPyr]− anions prefer to align parallel to graphene with the increase of electrode surface charge density, similar to planar [Emim]+ cations at moderate potential. Accordingly, different C-V curves of [Emim][Tf2N] and [Emim][CNPyr] are present, especially at positive potentials. The more efficient packing of [CNPyr]− anions within the EDLs results in higher capacitance of [Emim][CNPyr] than [Emim][Tf2N] at positively-charged electrodes. The corresponding number of ions accumulated in EDLs also evidenced the origination of the shape of the C-V curves of two RTILs. It is noteworthy that the planar ion geometry plays a similar role to the small-sized ions [In this work, MD simulations were performed to study the effects of different supercapacitor models and anion shapes on the EDL microstructure and capacitance of RTIL’s electrolyte. It was revealed that either the single-electrode supercapacitor model or the two-electrode model gave rise to nearly identical EDL structure. Thus, single-electrode model with low computational cost was adopted to investigate the effects of [Tfzed ions ,26 in tezed ions . Accordized ions , the simzed ions ,37,38 ca


To critically appraise, compare and synthesise the quality and acceptabilityof multi-item patient reported outcome measures for adults with chronic orepisodic headache.Systematic literature searches of major databases (1980–2016) to identifypublished evidence of PROM measurement and practical properties. Data onstudy quality (COSMIN), measurement and practical properties per measurewere extracted and assessed against accepted standards to inform an evidencesynthesis.From 10,903 reviewed abstracts, 103 articles were assessed in full; 46provided evidence for 23 PROMs: Eleven specific to the health-related impactof migraine (n = 5) or headache (n = 6); six assessed migraine-specifictreatment response/satisfaction; six were generic measures. Evidence formeasurement validity and score interpretation was strongest for two measuresof impact, Migraine-Specific Quality of Life Questionnaire (MSQ v2.1) andHeadache Impact Test 6-item (HIT-6), and one of treatment response, thePatient Perception of Migraine Questionnaire (PPMQ-R). Evidence ofreliability was limited, but acceptable for the HIT-6. Responsiveness wasrarely evaluated. Evidence for the remaining measures was limited. Patientinvolvement was limited and poorly reported.While evidence is limited, three measures have acceptable evidence ofreliability and validity: HIT-6, MSQ v2.1 and PPMQ-R. Only the HIT-6 hasacceptable evidence supporting its completion by all “headache”populations. Headache disorders are common in the adult population; the most common – tension-typeand migraine – have a one-year prevalence of 40% and 11% respectively ,3. BetweAn individual’s self-report of the presence, severity, frequency, and impact ofheadache is crucial to understanding the effectiveness of therapeutic interventions.Patient-reported outcome measures (PROMs), which seek to provide a patient-basedassessment of the impact of headache on how people feel, function and live theirlives, are now available. While recommendations to include PROMs in headacheclinical trials are available ,9, speciIn this systematic review, we critically appraise, compare and synthesise publishedevidence of essential measurement and practical properties for clearly defined PROMsevaluated in adult headache populations. The review provides a transparent summaryof the evidence base with which to inform PROM selection for future application inheadache-specific research.The search strategy was developed by experienced reviewers  andwith expert librarian support to retrieve references relating to the developmentand/or evaluation of multi-item PROMs used in the assessment of adults (aged 18years and above) with chronic or episodic headache including migraine.Medical subject headings (MeSH terms) and free text searching were used toreflect three characteristics: a) population – headache and migraine; b) type ofassessment – patient-reported outcome measures (PROMs); and c) measurement andpractical properties ,13,14.TTwo databases were searched (MEDLINE (OVID), EMBASE (OVID); 1980 to December2016) . AsubseThe citation lists of included articles and existing reviews were also reviewed,16. NameTitles and abstracts of all articles were independently assessed forinclusion/exclusion by two reviewers  and agreement checked. Publishedarticles were included if they provided evidence of development/evaluation forclearly defined, reproducible, multi-item PROMs, following self-completion byadults who self-reported or had been diagnosed by a clinician as having aheadache disorder. Articles relating solely to the application of measureswithout some evidence of measurement and/or practical properties were excluded.Articles describing the translation of PROMs and/or evaluations in non-Englishspeaking populations were also excluded. Conference papers and abstracts wereexcluded.Included PROMs had to be in use in research published between 2000–2016. PROMswere categorised as: Generic  or condition-specific . Clinician-reported, diagnostic and screening measures were excluded.Domain-specific measures that were not specific to the impact of headache, andmeasures that were not clearly reproducible, were excluded.A data extraction form was informed by guidance for PROM evaluation ,11,17, pOne experienced reviewer (KH) applied the COSMIN checklist to assess themethodological quality of included studies ,21. MethA similar checklist for PROM quality does not exist. Therefore, a pragmaticchecklist informed by a synthesis of various recommendations was adopted ,19,21,24A qualitative synthesis of evidence per reviewed PROM per reported measurementproperty informed the overall judgement of quality and acceptability. Thesynthesis combined four factors: a) study methodological quality (COSMINscores); b) number of studies reporting evidence per PROM; c) results permeasurement property (Appendix 3: Table 2); and d) evidence of consistencybetween evaluations ,27.Two www.prisma-statement.org). Forty-six articles providedevaluative evidence for 23 PROMs (Appendices 4 and 5 (Tables 3 and 4)). Sixassessed impact of headaches overall: The EUROLIGHT  , SF-12 , SF-8 4, EuroQoLhttp://www.ihs-klassifikation.de/en/. However, for many,patients were self-diagnosed, and a wide range of diagnostic criteria weredescribed. Most studies were cross-sectional or longitudinal surveys. Nine wereclinical trials or involving data secondary analysis. Fourteen studies werespecific to PROM development and/or initial evaluations. Most evaluations werewith US populations.Patient populations ranged from 18 to 83 years, were largely white, often withlarge proportions of female participants. Sample sizes ranged from 25 to morethan 8,500. Populations included mixed, chronic, and/or episodic headache ormigraine. Where clinician-based diagnosis was described, most adopted theInternational Classification of Headache Disorders (ICHD-II), available atStudy methodological quality per measurement property per reviewed PROM ispresented in Appendix 7 (Table 6). The overall evidence synthesis is presentedin PROMs assessing migraine and headache-specific impact (n = 11)Apart from the FAIM, MSQ v2.1, MSQoL and HIT, all measures lack a cleardescription of aim, the concepts being measured, or the process of itemgeneration. The FAIM , MSQ v2.The HIT “item bank” was informed by four legacy measures – the MIDAS, MSQ (v1.0),Headache Disability Index (HDI) and Headache Impact Questionnaire (HIMQ) – andconsultation with clinicians . Apart fThe shortest measures are the MIDAS (five items) and HIT-6 (six items); thelongest is the 103-item EUROLIGHT (Table 2). Apart from the FAIM, all assessheadache/migraine symptomology. While five headache-specific measures assesspain, the migraine-specific measures do not. Only the HANA, MSQv2.1 and HIT-6assess fatigue.All assess the impact of headache/migraine on social function, activities ofdaily living and/or work. Seven – FAIM, HANA, MSQv2.1, MSQOL, HIT, HIT-6, andEUROLIGHT – assess the emotional burden of headache/migraine; five of these –FAIM, MSQv2.1, HIT, HIT-6, and EUROLIGHT – plus the HADLI, assess the impact oncognition and difficulty with thinking.andinternal consistency – FAIM  in physicalactivity, level of frustration or daily activities following a three-monthfollow-up period of “usual care” .Large and moderate effect size statistics were reported for the MSQv2.1  and HIT-Following completion of the HIT-6 by patients with chronic daily headache in atrial of usual medical care (UMC) versus UMC plus acupuncture, an anchor-basedestimate of the MIC was calculated as approximately 3.7; the MID was estimatedas 2.3 . ChangeBoth anchor-based ,61and dPROMs assessing response to or satisfaction with migraine-specifictreatment (six measures)Four of the six measures – the CORS, M-TOQ, MTSM and PPMQ-R – have acceptabledescriptions of the measurement aim, conceptual underpinning and itemgeneration. Although detail is limited, three measures – CORS, MTSM and PPMQ-R –involved both expert clinicians and patients in item generation (the MTSMinvolved US and UK participants), supporting a positive rating of contentvalidity; the M-TAQ utilised patient interviews and focus groups, withadditional reference to established treatment optimisation measures.Item generation for the M-ACT  and the The shortest measures are the M-ACT (four items) and M-TOQ-5 (five items); thelongest is the 45-item MTSM (Appendix 4). Apart from the M-ACT and M-TAQ, allassess migraine symptomology, including pain severity, and the wider impact onactivities of daily living and/or work; the PPMQ-R also assesses limitations insocial functions (Appendix 6). The CORS, M-TOQ-15 and PPMQ-R assess theemotional burden of migraine; only the CORS and PPMQ-R also assess cognition anddifficulty with thinking. Three measures assess if the patient has “returned tonormal” – CORS, M-ACT, and M-TOQ. All assess confidence in/or satisfaction withtreatment; the M-TOQ assesses treatment side-effects.and internal consistency reliability from studies of atleast moderate methodological quality  was calculated for the PPMQ-R, as areflection of the within-individual minimal change in score (MIC) . Apart fEstimates of the minimally important change and minimally important differencewere reviewed for three headache-specific measures: MSQ v2.1 , HIT-6 , PPMQ-R Generic PROMs (n = 6)Evaluations of all generic measures in the headache population were very limited.There was no evidence exploring the content validity or relevance of the sixreviewed generic measures with the headache population. There was no evidence ofactive patient collaboration.Where applicable, there was no evidence of measurement dimensionality or internalconsistency reliability . Just onAcceptable evidence of construct validity from several studies judged to be offair or good methodological quality was reviewed for both the SF-36 ,65 and tHigh quality, relevant and acceptable PROMs provide patient-derived evidence of theimpact of headache and the relative benefit of associated healthcare at both thetime of the headache and the intervening period. The importance of capturing thepatient perspective is reflected in the large number of measures included in thisreview. However, apart from two condition-specific – HIT-6 and MSQv2.1 – and onetreatment-response – PPMQ-R – measures, for which strong evidence was reviewed,evidence was largely limited or not available.This is the first systematic review to include a methodological assessment of bothstudy and PROM quality in the headache population. Clarity in PROM focus is anessential, but often overlooked aspect of PROM development ,80. ExceExcept for two condition-specific (MSQv2.1 and MSQoL) and four treatment-responsemeasures , the extent of patient participation waslimited and poorly detailed. Moreover, except for three measures  PROM relevance, content and face validity was not explicitly exploredwith patients and/or expert panels. Item content for the remaining measures wasinformed by a mix of qualitative research with clinicians, reference to existingmeasures, published literature and/or completed questionnaires. Successful treatmentfor headache disorders should seek to improve both overall quality of life, as wellas an individual’s quality of life during the attack ; assessmAlthough varying in length, there was a similarity of item content acrosscondition-specific measures. Most assessed headache/migraine-related symptomology;pain severity was commonly assessed by headache-specific and treatment-responsemeasures, but not by the migraine-specific measures. Just two measures (MSQv2.1 andHIT-6) assessed fatigue. Measures with a primary focus on symptomology have beencriticised for failing to take into consideration the longer-term consequence of, orfear associated with, a potentially-severe headache or migraine, such as evadingcommitments or making plans ,82.NeveThree condition-specific  and one treatment-response(PPMQ-R) measures have strong evidence of both structural validity and reliabilityof internal consistency. Factor analysis supported the uni-dimensionality of theFAIM following completion by migraineurs, and the HIT-6 as a measure of “headachedisability” following completion by mixed populations. The three-domain structure ofthe MSQv2.1 was supported – Role Restriction (RR), Role Prevention (RP) andEmotional Function (EF) – following completion in both chronic and episodic migrainepopulations. However, for most measures, evidence of structural validity orreliability of internal consistency was limited, from methodologically-poor qualitystudies, or not available. Evidence of temporal stability was also limited, andavailable only for the HIT, HIT-6, M-ACT, M-TAQ, M-TOQ and PPMQ-R. There was noevaluation of measurement error.a priori the expected association between variables. Asreported in other reviews , twotreatment-response (MTSM and PPMQ-R) and two generic (SF-36 and SF-8) measures haveacceptable evidence of construct validity from good quality studies. For theremaining measures, evidence was limited, of poor methodological quality, or notavailable. Methodological inadequacies included small sample sizes and a failure tohypothesise  reviews ,19, ther reviews ,38 proviWhile a limitation of the review is that we have only included evaluations inEnglish, the context, setting and population are important in appraising evidence ofPROM measurement and practical properties . MoreoveAll data from included studies was double extracted and agreement checked .However, the COSMIN grading and synthesis score was applied by a single, experiencedreviewer (KH). Although applied in several recent reviews ,84, the The lack of reporting guidance and significant heterogeneity in outcome assessmentdetailed in this review highlight the importance of establishing guidance on outcomereporting in this population. Future research should seek to establishinternational, multi-perspective guidance for a core set of outcomes to include infuture headache research and across routine practice settings. The first step inthis process is to seek consensus on which outcomes should be assessed, as aminimum, in future clinical trials or routine practice settings . InformeAlthough many PROMs were reviewed following their evaluation in the headache and/ormigraine population, study methodological quality was often poor and evidence ofessential measurement properties largely unavailable or limited. Such limitationshinder PROM data interpretation from clinical trials, audit, or quality assuranceinitiatives. However, three measures – HIT-6, MSQv2.1 and the PPMQ-R – hadacceptable, and often strong, evidence of reliability and validity followingcompletion by patients with headache (HIT-6) or migraine ,and are recommended for consideration in future clinical research and routinepractice settings as measures of headache-specific impact, migraine-specific impact,or migraine-treatment response respectively. However, the similarity of item contentacross all three measures suggests that a further exploration of the attribution,relevance and acceptability of the measures with representative members of thepatient population is warranted. Further comparative evidence of widely-used genericmeasures and evidence of measurement responsiveness of all measures is urgentlyrequired.


Dirofilaria immitis) in a wild non-human primate, the mouse lemur (Microcebus rufus). Zoonotic D. immitis infection has been associated with clinical pathology that includes serious and often fatal cardiac and pulmonary reactions. With human encroachment and associated increases in free-roaming dog populations in Madagascar, we examined lemurs for zoonotic canid pathogens. D. immitis presents a new potential conservation threat to lemurs. We highlight the need for wide-ranging and effective interventions, particularly near protected areas, to address this growing conservation issue.The lemurs of Madagascar are threatened by human activities. We present the first molecular detection of canine heartworm (  •Dirofilaria immitis) in lemurs.Molecular evidence of canine heartworm (•D. immitis, in a wild non-human primate.The first detection of •Free-roaming dogs spatially overlap with lemurs. Between 2000 and 2010 the country lost 9,700 km2 of forest, which is almost three times the area of loss in the previous decade  spillover from dogs to wild mouse lemurs (Microcebus rufus), non-human primates with known co-occupancy with dogs , Madagascar, where free-roaming dog populations are high (occupancy estimated at 0.78 ± SE 0.08) . Mouse lIn addition to the collection of blood from mouse lemurs, 5 μL of whole blood was also collected from 18 dogs living in and around RNP during a spay-neuter-vaccination campaign for community dogs. As described above, these samples were collected on TropBio Blood Spot cards.2O, 5 μl of 5× Phire Reaction buffer, 0.5 μL dNTPs (10 μM), 1 μL of each primer, 0.5 μL of Phire Enzyme, and 1 μL of DNA template, for a total volume of 20 μL. Thermal cycling conditions were 95 °C for 30 s, then 35 cycles of denaturing (30 s at 95 °C), annealing (40 s at 55 °C) and extension (1 min at 72 °C); a final extension (5 min at 72 °C) and a hold at 4 °C in a Veriti 96 well Thermal Cycler . PCR products were then run on a 1.5% agarose gel and visualized for the presence of bands. The expected size of an amplicon resulting from the amplification of a D. immitis target was 542 bp and two samples produced distinct bands appearing to be approximately this size. These samples were subjected to cycle sequencing, using 4 μL of Big Dye, 2 μL of primers (0.8 pMol/μL), and 4 μL of PCR product. Two sequencing reactions were prepared for each positive sample (i.e. those giving a band appearing to be 542 bp) using forward and reverse primers. The cycling protocol was set at 25 total cycles of 96 °C for 30 s, 50 °C for 15 s, and 60 °C for 4 min. Reaction products were purified using EdgeBio columns  according to the manufacturer's protocol. Purified products were then sequenced using an ABI 3130xl Genetic Analyzer (Applied Biosystems) and resulting sequence reads underwent BLAST analysis. BLAST results indicated the unambiguous presence of D. immitis in both analyzed samples .All samples  were extracted using the Qiagen DNEasy Blood and Tissue Kit  and screened for the presence of filarial parasites using a “pan-filarial” primer set  designedD. immitis positive samples were also amplified using a D. immitis-specific nested PCR detection protocol . Unfortunately, nested PCR failed to produce sequence-quality product from the other “pan-filarial” positive sample, at which point extracted DNA was exhausted, preventing further analysis. However, the lack of sequencing results from the nested PCR analysis of the second sample does not preclude the detection of D. immitis confirmed by sequencing of the “pan-filarial” assay products. When compared in GenBank to other known Dirofilaria spp. and other nematode outgroups, our samples matched specifically to D. immitis , sea lions , beavers (Castor canadensis (Nyctereutes procyonoides), , . Clinicaeactions , althougmyopathy . Since cD. immitis DNA in two samples of mouse lemur blood may indicate the presence of microfilariae in this host species and suggests that adult worms are active and breeding in mouse lemurs; however, given that no cases of patent D. immitis infections are known in primates or other aberrant hosts, this is unlikely. The detection of D. immitis DNA in a region where dogs are also positive for D. immitis does suggest contact between a mosquito vector infected with canine heartworm and wild mouse lemurs, highlighting the potential for exposure of native wildlife to canid pathogens from invasive carnivores. Mouse lemurs could be a sentinel species of emerging zoonotic infections in Madagascar due to their broad habitat usage and the detection of many pathogens in these populations (Pathogen spillover events from invasive species are an underappreciated threat to the beleaguered island fauna of Madagascar, and will likely increase with increasing encroachment into what remains of Madagascar's forests. Our findings add pathogens from dogs to the list of potential threats facing lemurs. The unambiguous presence of ulations .


There is international recognition of the need for service user and caregiver involvement in mental health system strengthening. However, little is known about how best to integrate this approach into the mental healthcare system; what works to advance involvement, under what conditions, how and when does involvement bring added value, and how can it work in resource-poor settings in low and middle-income countries.To describe the methodology for a realist systematic review protocol to synthesise the evidence to explain the contexts, outcomes, and underlying mechanisms for involvement of service users with severe mental health problems and their caregivers in mental healthcare policy-making and planning, advocacy, service development, monitoring and improvement.The proposed realist systematic review will involve five steps: (i) clarifying the review scope, (ii) a systematic search for evidence, (iii) evidence appraisal and data extraction, (iv) data analysis, (v) synthesis of evidence and formation of revised programme theory. Inputs from a formative qualitative study, consultative Theory of Change meetings with key stakeholder groups, and scoping reviews will be used to identify candidate theory/theories that will guide the selection, appraisal and analysis of studies, and refine the Theory of Change model that will be piloted and evaluated. Synthesis of data will be undertaken using realist logic, constant comparison and thematic analysis. In a consultative meeting with stakeholders the Theory of Change model will then be situated with respect to relevant programme theories and adapted to incorporate the synthesized evidence of relevance to the local context. The finalized Theory of Change model will be piloted and evaluated in a primary health care setting in rural Ethiopia.Realist review methodology has not been applied to the area of mental health service user involvement in low- and middle-income country settings. In this protocol, we describe how this contextualized approach will be applied to identify and refine a theory-driven and transferable model of involvement of service users, embedded in ongoing work in Ethiopia.Systematic review registration PROSPERO CRD42018084595The online version of this article (10.1186/s13033-018-0220-4) contains supplementary material, which is available to authorized users. Service user and caregiver (SU/CG) involvement in mental health systems has become a mainstream policy expectation in many countries and has attracted growing research interest internationally –4. SU/CGThere is wide recognition of the benefits of involving SU/CGs at all levels within mental health systems –9. InvolDespite the rhetoric and the wide recognition of the value of SU/CG involvement in strengthening mental health systems in policy documents and academic literature, involvement is limited. A gap remains about how meaningfully to involve SU/CG, the impact of their involvement in different contexts, when and how participation works, and why , 7, 18. … the active and meaningful involvement by service user, caregivers, and their representatives in decision-making and participation in a range of activities  starting from the ‘expertise by experience’ of the person, in collaboration with and as equal partners of professionals to improve health and health care quality’’.‘‘However, SU/CG involvement is a complex process, a multifaceted construct with multiple meanings, involving different approaches, various levels, and numerous processes , 22, 23.Systematic reviews of SU/CG involvement in mental health have usefully described the context, type, barriers and facilitators to involvement, general lessons for good practice, and to a lesser extent the impact of involvement , 12, 18.The general objective of the proposed study is to synthesize evidence about the theoretical and empirical basis of involvement strategies for SUs with severe mental disorders and their CGs to inform the development, testing and evaluation of Theory of Change model (ToC) underpinned by programme theory for integration of SU/CG involvement in mental healthcare scale-up within primary health care setting in rural Ethiopia.develop a range of initial programme theories, and draft a ToC model that describe how SU/CG involvement works, for whom, in what circumstances and why;synthesise evidence on the contextual factors, mechanisms and outcomes of existing models and strategies for involvement of SU with severe mental disorders and their CG;refine the programme theory or theories that explain the relationships between the mechanisms underlying these involvement strategies, the particular outcomes of the mechanisms and the contextual factors that may influence these relations; anduse the programme theory and evidence synthesis to inform the locally embedded ToC model, and test and evaluate the resulting model for the integration of SU/CG involvement in a rural LMICs setting.The specific objectives of the proposed realist review are to:Given the complexity of SU/CG involvement, a realist review can offer key methodological tools and the theoretical basis to facilitate the exploration of learning, accumulation of evidence and the transfer of lessons in different contexts –28. The what works best, how, for whom and when and why, under what conditions” .Additional file 2. Initial search terms to inform search strategy (Service user and caregiver domain) AND  AND  AND (Models domains).


Evidence-based practice (EBP) arises from evidence-based medicine (EBM). The latter represents a movement of thought born in the second half of the 19th century, while the EBP is born since the new millennium, represented by different scientific figures and professional associations. The EBP is the research for the best practical and clinical strategies, with the ultimate goal of determining guidelines. The improvement of manual osteopathic practice derives from the balanced mix of scientific research, operator experience and patient experience. The text reviews the benefits and limitations of EBP in the osteopathic field. We must remember that knowledge, both theoretical and practical, is always evolving and we must not stop at what appears to be a dogma. Science and knowledge are always evolving, and hence, we must always study and update ourselves. The evidence-based practice (EBP) arises from evidence-based medicine (EBM). The latter represents a movement of thought born in the second half of the 19th century, whose principles have been distorted over time [Physicians David Sackett and Gordon Guyatt have laid the modern foundations of this movement born in the 1950s and 1960s, through various articles published since 1981 , seeking the applicability of the data obtained based on the patient's need . Guyatt In 1996, Sackett, given the difficulty in reconciling the daily clinic with the ever-evolving scientific knowledge, wrote an article to explain, once again, the real meaning of EBM: “The practice of evidence-based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research. By individual clinical expertise, we mean the proficiency and judgment that individual clinicians acquire through clinical experience and clinical practice…..and in the more thoughtful identification and compassionate use of individual patients' predicaments, rights, and preferences in making clinical decisions about their care.” . The artIn 2008, Montori and Guyatt wrote an article to emphasize how, in addition to the importance of scientific evidence and the clinician's experience, the patient's experience of treatment has the same importance in the final curative decision . EBP is There are some assessment tools to understand if there is an acceptable level of knowledge that coincides with clinical quality, such as the Berlin questionnaire (self-administered test on 15-item), the Fresno tool  and the Assessing Competency in Evidence-based medicine (ACE) tool  . The EBPThe benefits of EBP in osteopathyOsteopathy considers the systemic relationships of the human body, during both evaluation and manual practice . Like alIn a cardiovascular field, one of my recent studies has demonstrated how osteopathy with indirect techniques for patients undergoing cardiac surgery, not only decreases the pain perceived by the patient, but the general clinical picture improves in early times and with a more rapid discharge . We knowAnother randomized trial with a follow-up of five years demonstrates how a manual osteopathic approach can significantly improve the symptoms of patients with chronic prostatitis with chronic pelvic pain . In patiThe limitations of EBP in osteopathyThe use of EBP in the osteopathic field is still a practice not followed in a decisive manner -21. The EBP is an important resource for a manual approach, a tool that must be used based on the patient's needs and weighing the scientific information with respect to the experience of the operator and patient. In fact, the manual best practices are based on other more loose principles: “Identify and develop clinical models that integrate evidence-based nonpharmacologic therapies…. Develop, optimize, incentivize and coordinate care across disciplines with nondiscriminatory access to evidence-based nonpharmacologic therapies, as a stand-alone first line of care and as an essential part of comprehensive care.” . It is tImplications or relevance of EBP in osteopathyHow can we apply scientific information in the osteopathic field? Probably, we must remember that the results in literature do not include all types of patients and that even simple case reports are important to understand and improve the daily osteopathic practice -27. The To conclude with examples of how a revision can be useful to change the manual approach, other texts highlight that the cranial articulation between the sphenoid bone and the occipital bone from adolescence merges, and all the meaning of cranial primary breathing must change, as well as practice -37. EBP The EBP derives from the EBM, currents of thought with the ultimate goal of improving the osteopathic clinical decision. This can happen, thanks to a balanced mix of scientific research and operator experience and the patient's experience. Literature in recent decades has misrepresented the meaning of EBP/EBM, creating hierarchies of different studies, putting randomized controlled research on top of this erroneous evaluation, which is considered the only source of error-free information. In reality, the tendency of this vision of literature has brought to light the limits, or rather, the not easy applicability of the results coming from these researches and wrongly obscuring the validity of other types of articles. The osteopathic practice must be able to take advantage of all the scientific information available in the literature, as the manual clinic is full of facets not always found in the trials.


Human breast milk (HM) is the physiological nutrition during an infants' first few months of life, a crucial period for immune system development, metabolic and endocrine programming for growth, development, and lifelong health. HM is a complex and variable mixture with a multitude of constituents each contributing either singly or in combination to health outcomes . This ReRajani et al. focuses on variations in immune active components that have been reported to be associated with allergic risk in children, providing insight into potential mechanisms of action. Although cytokines and growth factors have been mostly investigated in relation to allergy development, some authors studied associations with growth patterns  rather than single time-point concentration, reporting lower TGF-β1 ratio to be associated with the development of eczema. This indicates that innovative approaches to data analysis coupled with more extensive use of serial data could unveil links between the TGF-β and allergic diseases development.Transforming growth factor beta (TGF-β) is one of the best-studied immune regulatory cytokines and often is investigated with regards to allergy development. A recent systematic review failed to find convincing evidence of associations between HM TGF-β and allergic outcomes . Most ofHsu and Nanan present a critical analysis of potential associations between breastfeeding and the development of thymus, playing a crucial role in T lymphocytes maturation and output.To further understand how breastfeeding can influence immune development, Ayechu-Muruzabal et al. provide an overview of the HMOs diversity and impact on early life immune development, while Triantis et al. discusses potential effects of HMOs on infectious and non-communicable diseases and inflammation in general. This paper emphasizes the role of HMOs in altering immune responses through binding to immune-related receptors. There were very few attempts to systematically review available evidence on human milk composition and they are needed to guide future research and highlight gray areas in need of further investigation -III being associated with cow's milk allergy and that higher fucosyl-oligosaccharide levels provides some protection against infectious disease, however, the evidence is sparse and more studies are required.Human milk oligosaccharides (HMOs) are as a group the 3rd largest component of HM. More than 200 HMOs are present in HM, and diversity and complexity of HMOs are very specific to HM. Both, short-and long-chain oligosaccharides are found, at a unique ratio. HMOs play an important role in microbiome development and immune system maturation thereby having short- and long-term impacts on infant health. In this Research Topic, two reviews address HMOs importance for infant health and development. tigation . In viewMoossavi et al. provide a nice overview review of the latest evidence, mechanisms, and hypotheses for the synergistic and/or additive effects of milk microbiota and HMOs in relation to asthma development in children.Although HM has been considered sterile this concept has changed in the last decades with extensive research of HM microbiome. In a recent systematic review of published evidence, a total of 820 microbe species were identified in HM, mainly consisting of Proteobacteria and Firmicutes . Human mBardanzellu et al. They outline targets for the future research, suggesting a promising approach, of integrative assessment of metabolomics, microbiomics, and HM cellular composition, as the way toward better understanding the potential health promoting properties of HM.Metabolomic studies increase in numbers and provide complex analysis, with recent data showing distinct patterns associated with maternal lifestyle and the environment . ComplexLogan and Genuneit discuss the results of the systematic review in their commentary. In light of their subsequent original research (Attention to HM polyunsaturated fatty acids (PUFAs) in relation to health outcomes is based on the hypothesis that the modern diet has led to changes in ratio of n-6 to n-3 fatty acids which may result in increase in allergic diseases prevalence in children. This concept resulted in a number of studies assessing HM PUFAs profile association with atopy/allergy development. Recent systematic review of 18 papers from 15 study populations reported heterogeneity among studies with insufficient evidence to suggest that HM PUFAs influence the risk of childhood allergic diseases  may also play in important role in structural and functional maturation of infant gut. Comprehensive review of one of the less well-studied HM constituents, factors influencing its characteristics and potential role in gut immunity maturation presented by Lee et al.Diversity of HM constituents, such as immune active factors, oligosaccharides, and microbes contribute to complex interactions within the HM and associated with gut barrier function, the gut microbiota, and oral tolerance induction . It was Future of HM research is tightly linked with multi-disciplinary collaborations, aiming to approach HM as a complex and dynamic fluid, which will have various impact on the short and long-term of infant health. We hope that this compilation of articles accumulating existing evidence in the field of HM research will be of an interest to the readers and will inspire more state-of-the-art work on the topics described.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. The views expressed in the paper are those of the authors and not those of the NIHR or Department of Health (UK).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.