Substantial research demonstrates the importance of online health communities (OHCs) for patient empowerment, although the impact on the patient-physician relationship is understudied. Patient empowerment also occurs in relationship with the physician, but studies of OHCs mostly disregard this. The question also remains about the nature and consequences of this empowerment, as it might be based on the limited validity of some information in OHCs.The main purpose of this study was to examine the impact of social processes in OHCs  on functional and dysfunctional patient empowerment in relationship with the physician (PERP). This impact was investigated by taking into account moderating role of eHealth literacy and physician’s paternalism.An email list–based Web survey on a simple random sample of 25,000 registered users of the most popular general OHC in Slovenia was conducted. A total of 1572 respondents completed the survey. The analyses were conducted on a subsample of 591 regular users, who had visited a physician at least once in the past 2 years. To estimate the impact of social processes in OHC on functional and dysfunctional PERP, we performed a series of hierarchical regression analyses. To determine the moderating role of eHealth literacy and the perceived physician characteristics, interactions were included in the regression analyses.P=.02), information exchange with users , and giving social support , but negatively predicted with receiving social support . Functional control is also predicted by information exchange with health professional moderators . Dysfunctional control and competence are inhibited by information exchanges with health professionals , whereas dysfunctional self-efficacy is inhibited by self-expressing . The process of finding meaning likely leads to the development of dysfunctional competences and control if the physician is perceived to be paternalistic . Under the condition of high eHealth literacy, the process of finding meaning will inhibit the development of dysfunctional competences and control .The mean age of the respondents in the sample was 37.6 years (SD 10.3) and 83.3% were females. Factor analyses of the PERP revealed a five-factor structure with acceptable fit (root-mean-square error of approximation =.06). Most important results are that functional self-efficacy is positively predicted by information exchange with health professional moderators (beta=.12, Social processes in OHCs do not have a uniform impact on PERP. This impact is moderated by eHealth literacy and physician paternalism. Exchanging information with health professional moderators in OHCs is the most important factor for stimulating functional PERP as well as diminishing dysfunctional PERP. Social support in OHCs plays an ambiguous role, often making patients behave in a strategic, uncooperative way toward physicians. Online health communities (OHCs), one of the most important eHealth Internet applications , play anAlthough the above-mentioned studies provide us valuable information regarding the impacts of OHCs on patient empowerment in relationship with the physician (PERP), little is known about how some potentially problematic facets of patient empowerment in OHCs ,17,18 arIn this study, we propose that the positive and negative aspects of PERP can be systematically conceptualized by leaning on the theory of psychological empowerment by Zimmerman  and the Therefore, PERP is a form of communicative orientation and behavior that is an important determinant of a relationship with the physician and of high-quality health care ,33. ThisThis assumption is based on the main premise of one of the most influential sociological theories: the theory of communicative action . This thIf we merge Zimmerman dimensions of empowerment and the two types of patient orientations, we arrive at the typology of 6 components of the PERP, of which 3 are forms of functional empowerment and 3 are forms of dysfunctional empowerment . A functThe main goal of this study was to investigate how social processes, in which patients are involved in OHCs , are associated with patient’s functional and dysfunctional PERP. An investigation of this association needs to consider the moderating role of dominant factors of the patient-physician relationship, such as the physician’s willingness to give up the paternalistic role ,9,19 and1: What is the impact of social processes in OHCs on functional and dysfunctional PERP?RQ2: Do eHealth literacy and perceived physician characteristics moderate the impact of social processes in OHCs on functional and dysfunctional PERP?RQThe data for this study came from a Web survey of users of Med.Over.Net (MON), the largest OHC in Slovenia. MON was established in 2000 and offers around 200 online discussion forums. Most of these are moderated by different types of voluntary moderators, among whom are around 150 health-related professionals. In general, the studied OHC covers the following three types of online interactional spaces: (1) online counseling forums in which health professional moderators answer user queries, (2) social support groups forums focused on specific symptoms or health conditions, and (3) general social forums dedicated to topics that are indirectly associated with health issues . MON registers more than 400,000 visits monthly and has more than 70,000 registered users.This study was conducted in collaboration with the providers of MON as a part of their annual survey on user experiences and satisfaction with the OHC. The survey, in which respondents participate voluntarily and anonymously, was administered during June 2016 by the OHC provider, who followed ethical standards for administering scientific surveys. The OHC provider invited potential respondents to participate in the Web survey via its email newsletter service. After clicking the link for the Web survey in the email, potential respondents were taken to an informed consent Web page with information about the purpose of research and the length of the survey, an assurance that the data would be dealt with in accordance with national and EU laws, information on who the investigator was, a contact information and a statement that they were under no obligation to participate, and that the aggregated results may be published.After giving their informed consent and clicking ‘Next’ button respondents could start to fill in the survey. The survey was conducted on platform english.1ka.si, which has mechanisms that disallow multiple entries by the same users. MON is a reputable Web service that treats all personal information (emails) in accordance with national and EU laws and protects data with standard security procedures, which include the deidentification of locally held data files, physical protection of hardware and, strong password protection. The authors of this study had no access to the emails of respondents and received an anonymized dataset containing no identifiable personal information. As per the code of ethics for researchers at the University of Ljubljana , no instThe OHC provider first designed a random sample of 40,000 users from the list of all registered users who visited MON at least once in past 6 years. Approximately, 25,000 of these users were randomly assigned to the first Web survey used for this study, whereas the remaining 15,000 users were assigned to a second survey, which mostly focused on service quality and did not provide data for this study. Of approximately 25,000 potential respondents, 4106 16.42%) clicked the link to the Web survey and 2587 (10.35% participation rate) viewed the informed consent page and clicked the button to start the survey. Of these 1572 finished the survey, which lead to a 60.77% completion rate. The survey took 15 minutes in average. The total response rate of 6.29%  is small, but not uncommon for Web surveys of this length [% clickedThe sample consisted of 16.7% men and 83.3% women , whereasThe theoretical background for developing items is summarized in Following the standard procedure for scale construction , 3 experItems were developed on the basis of an empowerment processes scale ,13 whichThis eHealth Literacy measure was adopted from the eHEALS Scale . As NormThe perceived paternalism of physician measure was adapted from the STAR Scale , which rA series of exploratory factor analyses were conducted to explore the factor structure of the scale to measure functional and dysfunctional PERP and to determine what items of the scale should be retained. Factors were extracted using Principal Axis Factoring with oblimin rotation as we didn’t expect orthogonal factor solution. The number of factors was selected on the basis of eigenvalues higher than 1. This decision was also supported by inspection of the scree plot. The obtained factor solution was put into a confirmatory factor procedure, which resulted in several statistics that estimate goodness of fit of the factor model to the study data. Since the statistics showed good fit of the model, no modifications were needed.1 and RQ2, we conducted a multiple regression analysis. As our factor analysis revealed 5 dimensions (factors) of dependent variable (PERP), a regression analysis had to be conducted for each dimension separately. More precisely, a hierarchical ordinary least squares multiple regression analysis approach [1, whereas comparison of the models in step three and the models in step two allowed us to analyze RQ2. All variables that appear in interactions were a priori centered to avoid collinearity. A logarithm of a scale for dysfunctional competences and self-efficacy was used because the original variables were highly skewed.To analyze RQapproach  was usedAmong the 5 dimensions of the PERP, the predominant one was functional competences . We also noticed an above-average presence of functional self-efficacy  and functional control  in relationships with the physician. All components of dysfunctional PERP were present to a lesser extent. Comparatively, the one predominantly present was dysfunctional self-efficacy , followed by dysfunctional competences and control . The latter variable was highly skewed because only 5% of all respondents on average responded to items with agree or completely agree values, which shows that only a small proportion of respondents obtained power by taking an explicitly manipulative, disrespectful, and generally negative stance toward the physician.Among the social processes, the predominant  in the s2adj=.002, P=.78). In step two, predictors that pertain to social processes in OHC were entered and this model significantly fit the data . Moreover, in comparison with the model in step one, the increase in R2 was also significant , thus suggesting that the model in step two is more valid for interpretation. In step three, moderating variables were entered together with interactions with predictors in step two. A significant increase in R2  was noted, making the model in step three the most valid for interpretation. Such a hierarchical regression analysis approach was repeated for the other 4 dimensions of PERP, and the results consistently showed that the best-fitting models were those in step three , except for the model on dysfunctional self-efficacy where the fit was nonsignificant . We nevertheless considered regression coefficients for interpretation.Five hierarchical regression analyses were conducted for each one of 5 dependent variables that correspond to the 5 dimensions of PERP. Results of hierarchical regression analyses, where functional PERP is the dependent variable, are reported in 1, the regression coefficients of the predictors of the model in step two needed to be investigated. Among all social processes on OHC, exchanging information with health professional moderators proved to be the most important factor of PERP. It had a weak but statistically significant impact on functional self-efficacy  and functional control , and negative impact on dysfunctional competences and control , thus enabling a more cooperative relationship with the physician. Exchanging information with users also proved to be a predictor of functional self-efficacy  but had no impact on the other two components of functional empowerment. In addition, it demonstrated a positive, if marginally significant, impact on dysfunctional competences . Significant predictors of functional self-efficacy proved to be self-expressing  and giving social support . Self-expressing also had marginally significant impact on competences  and a negative impact on dysfunctional self-efficacy . Interestingly, receiving social support had a significant but negative influence on functional self-efficacy , whereas it had a positive impact on dysfunctional competences .For a detailed analysis of RQ2, the regression coefficients of the predictors that were entered in the model in step three needed to be investigated. In all models, except for dysfunctional self-efficacy, the perceived paternalism of the physician had a moderate influence on the functional components of empowerment  and a strong impact on dysfunctional competences and control . These estimates showed that the more physicians were perceived to be paternalistic, the less the patients were able to develop functional empowerment and the more they developed dysfunctional competences and control in relation to physicians. The eHealth literacy, as another moderating variable, demonstrated a significant impact on all 3 components of functional empowerment  but not on the dysfunctional ones.For a detailed analysis of RQP=.06). Conversely, this condition likely leads to the development of dysfunctional competences and control . High eHealth literacy intensified the effect of exchanging information with health professional moderators on functional control , but it surprisingly also led to more dysfunctional self-efficacy . People who found meaning in the OHC and had high eHealth literacy were less likely to develop dysfunctional competences and control . Finally, receiving emotional support under the conditions of a paternalistic physician were less likely to lead to the development of dysfunctional competences and control .The main goal of this research was to investigate whether social processes in which users are involved in OHCs have any impact on the patient empowerment experienced in relationships with the physician and, if so, what is the nature of such an impact. Beginning from the limitations of previous studies, we conceptualized the PERP and on this basis we developed a relatively valid and reliable scale. As this is a proposal of a new scale, it has some issues with reliability. Nonetheless, it demonstrates a meaningful factor structure, indicating that PERP should be investigated along at least two dividing lines: (1) two types of communicative orientation of a patient toward the physician and the associated functional or dysfunctional outcomes for the patient-physician relationship and (2) 3 components of patient empowerment in relationship with the physician: self-efficacy, control, and competence. Such conceptualization might be useful for further research on the dynamics of patient-physician relationships in the online era.To claim that empowered patients are emerging solely due to processes in OHCs would be a gross overstatement, as the results clearly show that it is foremost patient’s eHealth literacy and physician’s personality and communication style that are driving PERP. However, even after controlling for these 2 determinants, we could show that some social processes in which users of OHCs are involved do have an impact on how patients relate to their physicians.The most important factor pertaining to activities in the OHC was the involvement in exchanging information with health professional moderators. This influenced patients to (1) become more efficient in their relationships with the physician, so that they knew what to ask and were motivated to have collaborative and efficient meetings and (2) get more control in terms of having confidence to ask questions and participate in decisions. The impact on control was attenuated under the condition of high eHealth literacy. Furthermore, respondents exchanging information with health professional moderators were less likely to develop overconfident and strategically self-interested stances toward their physicians. The results reveal, however, that exchanging information with health professional moderators for those with high eHealth literacy can be somewhat problematic. People who know a lot and talk a lot with experts in OHCs might learn communication skills  to stratExchanging experiential information with users had a conflicting impact on PERP. On one hand, it had a positive impact on self-efficacy, suggesting that interaction with other users helps develop skills for more efficient communication with physicians. However, it can also lead to overconfidence in one’s own competences in relation to the professional competences of the physician, as already suggested in previous research ,20. The Our results revealed a surprising finding about the role of receiving social support, something often hailed as one of the most important processes in OHCs in terms of leading to individual empowerment ,15. In pReceiving emotional support does not have negative impacts in all cases. The problematic effects of social support are diminished if a patient’s physician is perceived as paternalistic, since social support in OHCs in this case lowers dysfunctional competences and control. This might be connected to the finding that the more the patients exchange social support in OHCs, the less likely it is that they will discuss information found online with the health professionals . We coulAlthough receiving social support seems to have an ambivalent role in the PERP, giving social support demonstrated a positive impact. Providing other users with help and advice bestowed patient’s confidence and competence in asking the right questions to physicians and making meetings more efficient. Those who gave support to other OHC users were also more likely to engage in shared decision making with their physicians. This is in line with the general finding from online community research that people who are active contributors in online environments are usually also more proactive in their offline environment . WritingPatients who found meaning in their life and made sense of their situation with the help of other users and who at the same time perceived their physicians as paternalistic through OHC were less likely to develop competences for more understanding relationships with the physician. As such, they will be more likely to develop dysfunctional competences and control, opening possible conflicts between the 2 partners. One possible explanation for this result might lie in the finding from previous studies that information received from external resources like OHC is often perceived to be superior to that provided by the medical staff . This coFinding meaning can on the other hand be a positive empowerment process, as under condition of high eHealth literacy, finding meaning had an inhibiting effect on dysfunctional competences and control. More precisely, people who are digitally literate in health issues and use OHCs to find meaning in exchanges with other users will be less likely to develop a problematic stance toward their physicians.Although not a central focus, it needs to be pointed out that this study confirms an important role of eHealth literacy in the dynamics of patient-physician relationships . People This study has some methodological limitations that warrant further research. First, because the respondents in this study were recruited from a single OHC, generalizations of any findings should be made with caution because OHCs can vary greatly in their membership, focus, and role structure . IdeallyFinally, in this study, we proposed a theoretical model in which social processes in OHCs have an impact on PERP, but it needs to be stated that, empirically, the association between variables can also go in the opposite direction. Moreover, the 2 phenomena are probably in a recursive relationship, where processes in OHCs are influencing relationships with the physicians and patients’ experiences with physicians can impact how they use OHCs and other online tools. To address this issue, we may have to undertake a random control trial type of research design.On the basis of these results, several important messages can be discerned for OHC managers, users, patients, and health care practitioners. First, strong empirical evidence for the importance of health professionals being visibly present in OHCs should stimulate online community managers to invest energy in attracting physicians and other health experts to actively participate and moderate discussions in OHCs. They are not only carers of high-quality information in OHCs, but they also stimulate processes that can ease patients’ relationships with their physicians  . Second,We believe that a better understanding of such aspects of patient-physician relationships is required because it has implications for how physicians are trained and health care is organized. We know that if physicians surrender their control, they can create an atmosphere of respect that facilitates the positive aspects of empowerment . Now we To our knowledge, this is the first study with a quantitative approach to empirically demonstrate the problematic aspects of patient empowerment that should be considered when investigating the impact of a patient’s engagement in online environments, both as an information seeker and as an active coproducer of online environments. Patients can feel psychologically empowered, and this sort of acquired internal power can translate into a cooperative relationship with the physician, thus bringing positive outcomes for both. We termed such empowerment functional. However, a patient’s feelings of empowerment can also be transformed, especially under conditions of low eHealth literacy and the presence of a paternalistic physician, into a manipulative, disrespectful, and generally negative stance toward the physician. Such empowerment is not productive for the relationship and possibly leads to conflicts as well as worsens the health outlooks for the patient.Online environments can have many benefits for patients, but unchecked information, under conditions of poor literacy, can lead to social contagion processes  that can


The European Alliance against Depression (EAAD) program is to be introduced in The Netherlands from 2017 onwards. This program to combat suicide consists of interventions on four levels: (1) increasing the awareness of suicide by local media campaigns; (2) training local gatekeepers, such as teachers or police officers; (3) targeting high-risk persons in the community; and (4) training and support of professionals in primary care settings. The implementation starts in seven Dutch pilot regions. Each region is designated as a Suicide Prevention Action NETwork (SUPRANET). This paper describes the SUPRANET program components and the evaluation of its feasibility and impact. The findings will be used to facilitate the national implementation of EAAD in The Netherlands and to add new findings to the existing literature on EAAD. Suicidal behaviour is a global health problem, with over 800,000 people a year dying by suicide . SuicideIn 2004, the European Alliance against Depression (EAAD) was founded. The goal was to create a network of experts from different European countries to implement action-focused, community-based public health interventions aimed at depression treatment and suicide prevention .The shared multilevel approach that is currently being disseminated by the EAAD consortium is based on a successful regional intervention in Germany called the Nuremberg Alliance against Depression (NAAD). NAAD was a two year action program combatting depression and suicide in Nuremberg and consisted of interventions on four levels: (1) increasing the awareness of depression by local media campaigns; (2) training local gatekeepers, such as police officers; (3) targeting high-risk people in the community; and (4) training and support of professionals in primary care settings. NAAD resulted in a sustainable decline in suicidal acts (completed and attempted suicides combined) of 24% compared to baseline ,7,8. ThiAs part of the Dutch National Agenda for Suicide Prevention of the Dutch Ministry of Health, 113 Suicide Prevention, the Dutch suicide prevention centre, is introducing the EAAD model in The Netherlands from 2017 onwards. The implementation starts in seven Dutch pilot regions. Each region is designated as a Suicide Prevention Action NETwork (SUPRANET). This paper describes the SUPRANET program components and the evaluation of the feasibility and impact of SUPRANET.From January 2016 to August 2016, 113 Suicide Prevention has selected seven pilot regions within The Netherlands to implement the Dutch version of EAAD, called the Suicide Prevention Action NETwork (SUPRANET) Community. A SUPRANET Community is defined as a network of local multidisciplinary teams and organizations with shared ownership and responsibility for preventing suicide within a geographical area. The participating communities are committed to embark on a population-focused approach based on the EAAD model to prevent suicidal acts within their population. Members of the network acknowledge that reducing suicidal acts successfully requires concerted action.Commitment to suicide prevention expressed by the city council, which is prepared to invest financially;Commitment of local stakeholders in and outside health care to be part of the local network and implement the EAAD components and measure progress;○General practitioner (GP) practices, including GPs and their mental health support staff (POH)○social community teams○mental health care organization○emergency department○citizens/consumer/carer representation○schools and/or employment/social care agencies depending on the high-risk groups targeted by the community.The potential to create a steering group, local project leader and project teams consisting of at least the following key players:Initially, eight regions participated in the selection. One region decided not to continue the selection process because of the lack of commitment and funding. The SUPRANET communities  were selFurthermore, based on international experiences with the EAAD model, each region had to cover a substantial population, preferably of at least 150,000 inhabitants .In January 2017 SUPRANET was launched in seven regions in The Netherlands. The intervention of SUPRANET will consist of the implementation of the EAAD model, a two year multi-component multi-setting suicide prevention package with the four components as shown in The public awareness campaigns in the SUPRANET communities will be based on the national campaign launched by 113 Suicide Prevention from February 2017 onwards. This campaign aims to encourage the general public to talk about suicide and to break the taboo. The core message of the Dutch campaign is “Ask the question of your life”. The campaign has three waves in 2017: the first started in February, the second will start in May and the third in September. Based on this national awareness campaign of 113 Suicide Prevention, the SUPRANET communities will start additional, tailored, regional public awareness campaigns in their own communities in May 2017. This includes the release of more posters, flyers, and (radio/online) presentations, specifically tailored to the community. Regions order the materials at 113 Suicide Prevention, which makes the monitoring of the number of ordered materials feasible. The text on the spreading material is specifically tailored to each community. For example the title is altered, containing the name of the region, or the language or dialect is altered to the most common language or dialect in that region.Gatekeeper training programs are recognized as a successful component in multiple intervention projects . CommuniThis program component also covers collaboration with stakeholders, especially those at suicide hotspots  and implementing interventions to reduce access to means, such as providing professionals information about hot-spots for suicide and (the risks of) medication. This important aspect is based on strong evidence for restricting access to means in prevention of suicide .Within each community, specific attention will be dedicated to high-risk groups. Examples of high-risk groups are people who received care in the emergency room after a suicide attempt or middle-aged persons  between 40 and 65 years of age without paid work who receive social assistance or incapacity benefits. In The Netherlands this latter group has a five- to eight-times higher risk of suicide as compared to persons with paid work [SUPRANET has a strong focus on change in recognition and treatment of suicidal behaviour in Dutch primary care. Therefore, crucial to each community, is the participation of general practice, notably the general practitioners (GPs) and their mental health support staff (POH). This is a relatively new professional in most Dutch general practices, most often with a nursing or psychological background, providing brief coaching sessions to patients after being diagnosed by the GP. We aim to recruit at least five GP practices within each region. As part of the intervention, a suicide prevention training package is offered to primary care staff in 2017–2018, stimulating the exploration of suicidal ideation and concrete suicide plans among patients. In addition, the practices will work on continuity of care by improving collaboration with social community teams, emergency rooms, and mental health care.The four-level intervention will be implemented in each SUPRANET community, specified and tailored to local circumstances and to pre-existing suicide prevention structures or interventions. As such, it can be seen as a combination of a top-down and bottom-up approach. This is in line with the EAAD literature, which states that a participatory approach that maximizes and complements what was already in place, is an incentive for participants to become involved in the process .Tailoring includes the option for each region to fine-tune each of the four SUPRANET components and enrich them with local strategies, based on an analysis of the local situation, thus developing a context-specific suicide prevention plan. An example of such fine-tuning is the selection of gatekeepers with whom one might want to work. These could include teachers, youth workers, and sports coaches in an area where the focus is on suicide prevention among youth. When focusing on middle-aged persons without employment, selected gatekeepers could be professionals within employment agencies, social security agencies, debt, counsellors or clergymen. Examples of tailoring the program component in general practice primary care are: the add-on of a depression prevention e-learning module, or the availability of a case manager to ensure continuity of care after hospitalisation.The purpose of the evaluation is to investigate the activities of SUPRANET by examining its feasibility and impact on suicidal ideation and behaviour.(1)(a)Reduced suicidal ideation and behaviour and psychological distress?(b)Reduced stigma and taboo and improved attitude towards seeking help?(c)Increased help seeking behaviour to the helpline of 113 Suicide Prevention? Does the implementation strategy of SUPRANET lead to the expected EAAD outcomes ,7,8,9 in(2)(a)What is the reach on each SUPRANET program component ?(b)What are the barriers and facilitators when implementing the SUPRANET approach?(c)What is the impact of the interventions on professional performance?Is SUPRANET implemented as intended, in terms of:This study aims to answer:The evaluation of the feasibility and impact on the Dutch SUPRANET communities will be carried out by the research department of 113 Suicide Prevention, NIVEL , and local Public Health Services in the participating communities.The multilevel SUPRANET intervention requires a multilevel evaluation approach. Each SUPRANET program component is part of a multi-layered intervention program, therefore, the effect of one component itself is impossible to discern. Since the primary focus of SUPRANET is on preventing suicide, our primary outcomes studying the impact of SUPRANET are on (attitudes toward) suicidal ideation and behaviour. The outcomes and measurements are described in The outcomes are analysed using a non-randomized controlled pre-post design; i.e., the outcomes are analysed compared to a baseline and to national data not involved in the SUPRANET communities. The process evaluation requires qualitative research with stakeholders in all participating regions.Suicidal ideation and behaviour of the general public will be measured in two ways: First, while challenging, because of the low base rate of completed suicide , suicide rates will be analysed using data from Statistics Netherlands. Trends in suicide rates during 2017–2019 in the seven SUPRANET communities will be compared to the national suicide trends. In 2015, the number of suicides in the SUPRANET communities was 166, on a population of 1,407,331 . Differences in suicide rates at baseline and after each implementation year will be calculated using incidence rate ratios. The hypothesis is that the multilevel intervention approach of SUPRANET will lead to a reduction in the suicide rate in the general population, as was found in other EAAD studies [n = 100). The sample will be stratified by gender, age, education, region, and social class. The first measurement, the baseline, took place in January 2017. The second will take place just after the first wave of the public awareness campaign, the third in January 2018, and the fourth in January 2019. A fresh sample is taken for each of the four measurements to prevent learning effects and keep the comparison pure over time. Given an alpha of 0.05 and a power of 0.8, the sample will allow us to detect a small effect size of 0.08. The Suicidal Ideation Attribution Scale (SIDAS) consists of five items that are scored from 0 to 10 and assesses the frequency and controllability of suicidal thoughts, as well as the closeness to a suicide attempt, distress and interference with daily activities. We will investigate, using General Linear Model (GLM) repeated measures, if the changes measured in the SUPRANET communities are more improved than the changes measured nationally.Secondly, the scores on the Suicidal Ideation Attribution Scale  in an onFurthermore, a secondary analysis will be performed on data of the cross-sectional survey Health Monitor 2016. This survey was carried out by all Public Health Services in The Netherlands between September and December 2016 to provide insight into the physical and mental health and lifestyle risks of adults and senior inhabitants. Participants were randomly sampled from municipality registries. Individuals were excluded if they lived in nursing homes, mental health institutions, or if they were imprisoned or were staying in asylums. Based on a sample calculation which took into account the size of the total target population, as well as the expected response rate, approximately 1.1 million inhabitants of 19 years and older were approached. Mental health was assessed by using the validated Dutch version of the 10-item Kessler Psychological Distress Scale (K10). The K10 uses a five-point Likert scale to measure psychological distress, whereby a higher score indicates more distress [The online survey among the general public partly replicates the baseline questionnaire for the general public of the Optimising Suicide Prevention Programmes and Their Implementation in Europe (OSPI-Europe) study , with DuChanges in help-seeking behaviour, stigma, talking about suicide, and taboo around suicide will be analysed using GLM repeated measures. We will compare the results over time, as well as time × effect interactions to reveal if a SUPRANET community is differently (more) effective than the nationally-observed changes.In addition to measuring an intervention effect within the general public with self-reporting, an intervention effect will also be measured by analysing the volume of crisis calls to the helpline of 113 Suicide Prevention. A significant increase in monthly calls during and just after the three waves of the public awareness campaign is hypothesized compared with the same months in the previous year . FurtherIn addition to evaluating the impact of the SUPRANET intervention in the ways described above, we will conduct an evaluation with the aim to: (1) generate an overview of the actors, situations, sites, and contexts involved in the SUPRANET implementation process and the main implementation activities undertaken within the regions; (2) create an insight into the degree to which suicide prevention is actually embedded into routines, or “normalized” in daily practice and routines, identify the barriers and facilitators to and in implementing the four-level intervention, and illuminate recommendations for broader dissemination of the EAAD approach in The Netherlands; and (3) study the impact of the SUPRANET interventions on professional performance.To generate an overview of the reach of SUPRANET, and to reveal intermediate effects on the outcomes, all specific actions and interventions related to the four components of the SUPRANET approach in each of the intervention regions are monitored. For the public awareness campaign, the amount of posters, flyers, etc., for each region is registered, as well as the location. Furthermore, questions on awareness and recognition  the media campaign are asked in the general public in the online survey. Another example of monitoring the reach of each SUPRANET component in each region is the number of community facilitators that are trained as gatekeepers.Every six months  we will ask the regional implementer of each SUPRANET community to fill in an online survey, with questions about the actors, sites, and contexts involved in the SUPRANET implementation process and the main implementation activities undertaken within the regions according to the Re-Aim Model . Since it is possible for each region to fine-tune each of the four SUPRANET components and enrich them with local strategies, thus developing a context specific suicide prevention plan, the survey also monitors additional local strategies and interventions. Additional local interventions will be monitored by 113 and evaluated by the epidemiologists working at the local Public Health authorities.During the process evaluation the Normalization Process Theory (NPT ) will guNPT helps to classify complex implementation work that people do around four conceptual constructs: coherence, cognitive participation, collective action, and reflexive monitoring. Coherence refers to how people individually and collectively make sense of the situation when they are faced with the problem of operationalizing complex interventions, in our case suicide prevention activities. It implies that the actors have a shared understanding of what constitutes the suicide prevention work. Cognitive participation is the relational work that people do to build and sustain a community of practice around the suicide prevention work. Collective action is about how suicide prevention is organized and what factors constrain and structure the activities. The fourth mechanism of reflexive monitoring is about the appraisal of the suicide prevention work and the modifications the actors may propose to make the suicide prevention activities workable in practice.We will purposefully select settings and individuals within the SUPRANET communities to participate in the process evaluation. This means that we will select respondents beyond the “usual” respondents, like the health professional or patient. We will focus on others who are vital within suicide prevention, those that are less visible and often omitted from implementation studies. For example, receptionists in GP practices, debt counsellors, clergymen, and sports coaches. They have to accommodate and realise aspects of adequate suicide prevention. NPT also recommends selecting a large range of sites and contexts, beyond the usual situations, times, and contexts of health care research. We will follow the regional networks for 18 months during their implementation journey in different situations and places: the local project management table, local health authorities or mayor’s offices, GP practices, social community teams, the benefits payment offices, and so forth. We will also pay attention to the diffuse situations where suicide prevention work is discussed, complained about, or praised.(1)Every three months semi-structured interviews will be conducted with the seven project managers in charge of the overall coordination within each SUPRANET community, and (at least) three other relevant participating stakeholders (to be selected purposefully at every interview period) per community. The interviews will focus on the implementation processes and activities and the facilitators and barriers of and to the implementation process per program component. Over the course of the intervention, we will interview and survey SUPRANET participants from different backgrounds and settings: those involved in the local implementation/project teams and those involved in the organisations that will actually implement the suicide prevention interventions. The interviews will be analysed using the NPT framework.(2)During the period of the SUPRANET community program (2017–2018) relevant documents supporting the implementation process of the regions will be analysed .Methods of data collection for this part of the evaluation are as follows:Since, the interviews will be conducted every three months with 3–5 persons per region, surveys will be held every six months with all seven local project leaders, and every six months the project environment will be screened for relevant documents regarding the implementation process; after 18 months this will lead to a total of approximately 125 to 200 interviews, 21 surveys, and a number of documents produced by the regions.We will use all data sources to perform the analysis and answer our research questions (triangulation). The surveys will be analysed by listing actors and settings, barriers and facilitators, and by thematic analysis of the qualitative information. The interviews will be coded using thematic analysis, and grouped under the various NPT constructs and components. Thematic analysis consists of a process of coding in six phases to create established, meaningful patterns. These phases are: familiarization with data, generating initial codes, searching for themes among codes, reviewing themes, defining and naming themes, and producing a scientific publication and recommendations for broader dissemination of the program in The Netherlands .The gatekeeper intervention will be evaluated within the SUPRANET communities with measurements before and after the gatekeeper training sessions. We will use a baseline questionnaire prior to the start of the training and a follow-up questionnaire six weeks after. This is already a standard procedure for the gatekeeper training sessions given by 113 Suicide Prevention.Gatekeepers’ identification of people with suicidal thoughts, referrals to professional care, knowledge of suicidal behaviour, and confidence in their abilities to talk about suicide will be evaluated with an instrument based on other gatekeeper training surveys , added bUsing the NIVEL primary care database (NIVEL-PCD) we can extract incidence and prevalence rates of depression and suicide (attempt) for individual general practice. NIVEL-PCD is one of the largest primary care databases in Europe, covering more than 500 GPs with a total practice population of 1.6 million individuals. NIVEL-PCD collects routine electronic health record data, including health problems, consultations, prescriptions, and referrals. Health problems are ICPC coded  . The datAnalysis will be carried out using multilevel regression techniques, with the incidence of depression and suicidal thoughts as the dependent variable and the condition (intervention or control) as the independent variable. Covariates will be the characteristics of the practices  and the incidence of depression and suicidal thoughts before the intervention. The different levels are the region, the general practice and the patient.Furthermore, to measure change in guideline adherence, we will look at the key recommendation of the Dutch guidelines, i.e., the exploration of suicidal ideation and concrete suicide plans by GPs and/or primary care nurses ,27 withiWe hypothesize that, within the intervention practices, suicide ideation will be more often explored within depressed patients after the suicide prevention training offered to primary care staff (2017–2018) as part of the intervention, when compared to the period before the training (2016) and when compared to those sentinel practices who are not part of the intervention group and did not have the training.113 Suicide Prevention has the ambition to implement SUPRANET nationwide. The results of this study will help other regions to more effectively tailor the program to their context, important for the national implementation of the EAAD in The Netherlands. The results will be of high relevance for countries in and outside of Europe.As suicides have been rising since 2007 in The Netherlands, 113 Suicide Prevention believes it is time to really tackle the problem, and directly target suicidal behaviour. While the focus of the public awareness campaign of the EAAD lies on depression, with the secondary aim to reduce suicidal behaviour, in SUPRANET we decided to directly focus on suicide. We believe the specific focus fits well in the Dutch culture, since the Dutch expect others to be open and direct. Furthermore, general practitioners and gatekeepers in The Netherlands are confronted with suicidal behaviour more often than before. Therefore, they understand the need for an intervention with a specific focus on suicide prevention. Regarding the public awareness campaign, we know from the literature that properly communicating about suicide can actually result in less suicidal behaviour (Papageno effect). 113 Suicide Prevention appoints to the subject suicide direct and encourages people to talk about it. Still, as it is a novum to offer a public campaign on suicide prevention in The Netherlands, a safety procedure is built in. As soon as any rise in adverse events are reported, either via the national railways or via other monitors, such as social media, the campaign will immediately be aborted.Compared to existing studies on the EAAD, our study has a strong focus on change in recognition and treatment of suicidal behaviour in Dutch primary care. Since GPs play a crucial role in Dutch mental health care and in our suicide prevention intervention, and because the NIVEL primary care database provides good research opportunities in terms of reliable data collection, our project provides a unique chance to assess the effectiveness of the program within primary care. Ideally, we would also be able to collect data from other health care partners, such as social community teams or specialized  health care. However, the results will offer unique insight in the way GPs deal with suicidal ideation and behaviour in depressed patients and will learn how to optimize the training of GPs. Additionally, once the NIVEL depression module has been constructed, it can be used for a longer period of time with only limited funding, allowing us to assess changes in suicide prevention within primary care over years to come.Regarding the qualitative analysis, previous studies have done quite a large amount of work analysing the success and barrier factors of the EAAD program. Still, no overall list of success and barriers factors has been published. By doing so, our study hopes to facilitate the further implementation of the EAAD across Europe and beyond.This paper describes the implementation of the European Alliance against Depression (EAAD) by creating local Suicide Prevention Action Networks (SUPRANET) in seven Dutch pilot regions and how we plan to evaluate it. The evaluation consists of both quantitative and qualitative analyses. The findings will be used (1) to facilitate the national implementation of EAAD in The Netherlands; and (2) to add new findings to the existing literature on EAAD.


The present study aimed to determine the relationship between human dignity and medication adherence in patients with heart failure. This was a cross-sectional study. A total number of 300 patients with heart failure admitted to the Mazandaran Heart Center, Iran, participated in this study by census. Samples were selected based on inclusion criteria such as an HF diagnosis by a cardiologist for a minimum of 6 months, and taking at least one cardiac medication. Data were collected through demographic, clinical, human dignity, and medication adherence questionnaires over a period of three months in 2016. This study was approved by the Ethics Committee of Mazandaran University of Medical Sciences. Consents were obtained from patients and the medical center, and necessary explanations were given about the confidentiality of information prior to completing the questionnaires. The mean score of medication adherence was 5.82 suggesting low medication adherence among the patients, and the mean score of human dignity was 81.39. There was a negative relationship between medication adherence and threat to human dignity , i.e., the higher the scores of threat, the lower the medication adherence of the patients. After adjusting the effects of potential confounding variables, there still was a correlation between medication adherence and the variables of human dignity and its dimensions. Based on the findings, an increase in patients’ dignity can enhance medication adherence, which can theoretically improve patients’ health and reduce frequent hospitalization. Medication adherence is a behavior that is influenced by several factors, and maintaining patients’ dignity is an important issue that needs to be considered in the course of treatment Heart failure (HF) is a disorder of the heart structure and function that leads to failure in the transport of proper amounts of oxygen to tissues according to their metabolic needs. Clinically, HF is a syndrome in which patients demonstrate symptoms such as dyspnea, swollen ankles and fatigue, and signs such as jugular venous pressure, and crackles in the lungs as a result of abnormal heart structure and function . HF is aAdherence to medication regimen is a disease-related behavior that predicts successful treatment outcomes and reduces the adverse effects and severity of the disease . MedicatHuman dignity is considered one of the most important features and ethical concerns in healthcare and nursing care. There are two types of human dignity: absolute and relative dignity. The former pertains to the essence of each creature, and the latter is influenced by the society and human relations . DignityThis cross-sectional study recruited patients with heart failure on their first day of admission to CCU wards of Mazandaran Heart Center in 2016. Census sampling method was used to select all patients with heart failure that met the inclusion criteria. In order to determine the sample size, the number of patients admitted with heart failure in a month per year was first established through hospital medical records. Sampling was carried out based on that figure for three months. Then, the sample size  was determined at 300 patients using GPOWER software. Inclusion criteria were: being older than 18 years, Iranian nationality, residing in Sari, Mazandaran province, speaking Persian, HF diagnosis from a cardiologist for a minimum of 6 months, taking at least one cardiac medication, classes II and III of the New York Heart Association classification, ejection fraction higher than 30%, lack of sensory perception disorder or mental retardation, full consciousness and the ability to answer questions.Data were collected by demographic and clinical questionnaires, Patient Dignity Inventory, and the Morisky Medication Adherence Scale (MMAS-8) revised in 2008. Clinical and demographic questions included age, sex, marital status, income, number of children, education, occupation, location of residence, comorbidities including diabetes and hypertension, and the number of pills consumed per day. In order to measure human dignity, the Patient Dignity Inventory (PDI) developed by Chochinov et al. in 2008 was used. The reliability and validity of the PDI were reported as Cronbach’s alpha coefficient of 93% and 0.85 . Abbas-ZMedication adherence was calculated by Morisky Medication Adherence Scale . The 8-iAs the first step of the research, the participants were briefed on the purpose of the study, received instructions on how to complete the questionnaires, and were assured of the confidentiality of their responses. Subsequently, the questionnaires were completed after obtaining patients’ consent. Data were analyzed in SPSS version 16 using descriptive statistics and Pearson’s correlation test.Based on the results obtained in this study, the participants’ mean age was 64.15, men and women equally comprised the study population, most (50.3%) were illiterate, and 49.3% had poor income . P < 0.001), , . In other words, the higher the score of threat to dignity, the lower the medication adherence. Even after adjusting the potential confounding variables in this study , there still was a correlation between the variables of human dignity and its dimensions, and medication adherence .The main finding in this study was the significant relationship between medication adherence and human dignity and its dimensions , so that even by eliminating potential confounding variables, the relationship still existed. The patients in this study had reduced human dignity, and consequently low levels of medication adherence were reported.Even though studies have been conducted on the dimensions of human dignity and medication adherence separately, none were found on the connection between the two on available databases. This research revealed a significant relationship between medication adherence and distress symptoms, which is in line with the findings of previous studies on the relationship between psychological distress and medication adherence. The following authors have worked in this regard: Alosco et al. studied the relationship between cognitive dysfunction and treatment adherence in patients with heart failure . Gehi etIn this study, there was a significant relationship between the peace of mind dimension of patient dignity and medication adherence in HF patients. This is consistent with the findings of another study, which showed that respect for the patients and their experiences and interests increased their confidence and consequently medication adherence . There was a significant relationship between the dependency dimension and medication adherence in this study. Similarly, Maeda et al.  and CrisThe present study showed that there was a significant relationship between social support and medication adherence, which is backed by studies on different patients , 44-50. The findings of this study demonstrated a significant relationship between the existential distress dimension of patient dignity and medication adherence. This dimension is associated with the reduced ability of patients to do their daily activities as a major threat to human dignity. A study showed that diminished performance and activity had a significant effect on medication adherence in patients with HF . SimilarThis study was conducted in only one medical center, and it is recommended to perform further studies in multiple centers in order to investigate the generalizability of the findings. . Medication adherence is a multidimensional behavior influenced by several factors. Therefore, care providers need to first identify these factors and then consider them in training and treatment planning for patients in order to increase their medication adherence. Based on the results, it is recommended to maintain patients’ dignity as an important factor that should be considered in the course of treatment, and can improve patients’ recovery and their return to normal lifeIt is therefore recommended to study the effects of dignity therapy on patients with heart failure, and the role of education in improving medication adherence further. Also, it is suggested that similar studies be conducted on patients suffering from other chronic diseases such as diabetes or multiple sclerosis, and those who have undergone surgery or are receiving hemodialysis.


The relationship between diabetes and academic performance have been of great interest to researchers during the year to date. Many studies have been conducted to discover this relationship during three recent decades. But, evaluation of the structural changes of brain in the context of diabetes is of paramount importance especially in children and adolescents.This study is a systematic review conducted to investigate the structural changes in the central nervous system in children and adolescents living with diabetes. Among about 500 papers published in this area in Pubmed and SCOPUS, 13 articles in the field of assessing structural changes in the central nervous system in children and adolescents with diabetes mellitus were entered into the evaluation process.As can be seen in these studies, a huge proportion of structures of the central nervous system have been affected by diabetes that include different areas of gray and white matters. In the majority of these studies, it has become clear that high glycemic changes, especially recurrent hyperglycemic attacks are very seriously associated with structural changes in the brain.It seems the findings of this review can positively aid other researchers to develop medical guidelines to prevent or resolve the brain changes in central nervous structure and consequently cognitive impairments in children and adolescents. The relationship between diabetes and academic performance have been of great interest to researchers during the year to date. Many studies have been conducted to discover this relationship during three recent decades . Also, oHowever, with the development of functional imaging techniques in recent years, the changes in the performance of different areas of the central nervous system in children and adolescents with diabetes are evaluated with a greater precision . But, evPediatric neuroimaging is faced by major challenges, among which one can name having no tendency of children for different imaging devices due to some fears . On the Therefore, aiming at evaluating the relationship between diabetes and structural changes in the central nervous system in children and adolescents, the authors of this paper decided to conduct a systematic review to provide a response to the research question. By this systematic review and also considering executive and ethical issues, they hope there is no need to design and run further researches in order to evaluate the relation between diabetes and brain structural changes in children and adolescents.For certain, finding the answers to these questions may be an effective step in alleviating the diabetes complications on the brain structure and subsequent cognitive functions in children and adolescents with diabetes.This study is a systematic review conducted to investigate the structural changes in the central nervous system in children and adolescents living with diabetes.In order to search the published research until the beginning of November 2016, the authors used all articles published in national and international journals indexed in the scientific databases of Pubmed and SCOPUS, as two large and prestigious sources of biomedical and life sciences journal literature. The articles were found using key words or their combinations in English including, neuroimaging, brain change, brain structural, brain map, and diabetes.The inclusion criteria used to select articles were publication in the last 10 years, publication in English, research on humans, sample aged between 0 and 18 years (in PubMed) and Category of children and adolescents (in SCOPUS).A list was prepared by the researcher including the relevant titles and abstracts of all papers available in the above mentioned databases, and each were independently studied in order to select the relevant topics. Afterward, the repeated studies were eliminated followed by checking for titles, author(s) names, publication year, Number, and name of journal. Also, based on the titles of the articles, irrelevant unrelated articles to the subject of the present study were excluded from further assessment.Followed by determining the relevant studies in terms of titles and abstracts, the researchers used STROBE checklist  which is a standard checklist to evaluate the selected papers. Articles given at least score 40 points according to the checklist questions were entered into the research, and their associated data were extracted for the systematic review.In order to extract data from the selected studies, the researchers evaluated them in terms of some details, including titles, first author’s name, year of study, type of study, age group, sample size, type of imaging tool used, and the structural changes observed in the imagingUsing relevant keywords and making a search with high sensitivity, 503 papers published until the beginning of November 2016 were identified. Of these articles, 58 articles were deleted due to duplication from the former evaluated banks. After the removal of titles unrelated to the subject of the study, 16 related articles remained. It should be noted that a large number of published articles on the subject of diabetes insipitus were excluded at this stage. For this reason, a considerable number of articles were excluded at this stage. Also, those articles examining the structural changes in the brain due to diabetic ketoacidosis, as one of the most important neurological complications in pediatric diabetes, were also excluded. Three other papers were eliminated due to lack of access to the full-text of article despite sending email to the correspondence author. Finally, 13 articles in the field of assessing structural changes in the central nervous system in children and adolescents with diabetes were entered into the evaluation process. The flowchart of search strategy and the evaluation of papers are presented in Fig. A summary of the key findings are as follows Table :Table 1MIn the majority of conducted studies so far, a group of children and adolescents with diabetes have been compared with a healthy peer where in the majority of them several differences in neural structures have been reported in patients with diabetes compared to the healthy individuals. In the study of Rofey et al. conducted on 15 male adolescents aged 12–21 years in three groups including, diagnosed with type 2 diabetes, obese non-diabetic, and normal- weight nondiabetic, it was found that the volume of caudate in the group with normal weight was significantly higher compared to the obese and diabetic groups. Thalamic volumes in both normal and obese were higher in comparison with diabetics. Although not statistically significant, but such differences were found in some other regions, including the hippocampus, nucleus accumbens, amygdala, putamen, and pallidum. In evaluating white matter, diabetic group were reported to have the highest deficit in terms of functional anisotropy volume (FA). However, such differences were not significant .In another study on 142 children with diabetes aged 4 to 10 years and 72 healthy subjects, Mauras et al. evaluated the structure of the central nervous system using MRI during two separate phases, at baseline and after 18 months. They drew the conclusion that children with diabetes showed a slower growth rate in parts of the gray and white matters volume compared to healthy subjects. Gray matter areas included left precuneus, right temporal, frontal and parietal lobes and right medial-frontal cortex, and white matter areas included splenium of corpus callosum, bilateral superior-pareital lobe, bilateral avterior forceps, and inferior-frontal fasciculus. After 18 months, diabetic children revealed significant differences compared to their healthy peers in the development of white and graymatters involved in the process of sensorimotor and cognition [In another study on 142 children with diabetes and 68 healthy controls with an average age of 7 years (1.7), Marzelli et al. reported the reduced volume of gray matter in the bilateral occipital and cerebellar regions and increased volume of gray matter in left inferior prefrontal, insula, and temporal pole in children with diabetes compared to their health peers . Also, iIn a similar study conducted by Antenor-Dorsey et al. to evaluate the microstructural changes of white matter in children with diabetes, lower fractional anisotropy in the superior parietal lobule and reduced mean diffusivity in the thalamus in the diabetic group were observed compared to healthy subjects . Also, AIn another study, they also explored the structural differences in the brains of children with diabetes and evaluating 28 children with diabetes reported that after controlling for age and sex. The volume of white matter in diabetics didn’t show the expected growth rate according to age compared with controls. The same trend was observed in hippocampal volume. But nothing was reported in the gray matter and the amygdala .Developing a cohort study, Perantie et al. compared 75 diabetic children and adolescents with an average age of 12.5 years with 25 healthy subjects in terms of structural central nervous system at two time intervals in the framework of a two year study. Finally, they reported no significant differences in the overall brain volume and voxel-wised changes between the groups in two years . In anotIn a different study, Yau et al. conducted a different study to analysis the brain structure of 18 obese adolescents with type 2 diabetes and 18 healthy obese adolescents in gray matter volume where no difference in the gray matter volume was observed. However, a smaller white matter, and larger CSF space was observed in the whole and in frontal lobe of people with diabetes compared to healthy subjects .In addition, Hershey et al. in their study of diabetic children aged 7–17 years showed that after matching for the age and sex no significant difference in the whole brain and the hippocampus of diabetic and healthy children were observed . The redThis study was conducted on 106 diabetic patients aged 20.5 on the average diagnosed with diabetes since 12 years ago and 75 healthy subjects aged 21 (3.8) on the average. And in this respect, this research has important differences with other studies in which the long-term complications of diabetes on brain structures can be well demonstrated . But, HoIn the majority of studies been made to evaluate the relationship between diabetes and the structural changes in the central nervous system its attempted to study the structural changes in the brain and the status of glycemic control in diabetic patient in addition to comparing diabetic children with healthy subjects. These studies, has put forward a clear illustration on the important facts regarding the role of glycemic control on the brain changes.In their study, Mauras et al.along with assessing differences in brain structure among children with diabetes compared to healthy subjects, showed that these changes are related with cumulative hyperglycemia and notable changes in glucose levels; however, not correlated with hypoglycemia . MarzellSimilarly, the volume of gray matter in areas of bilateral medial orbitofrontal, rectal gyri, and the anterior cingulate are inversely associated with the duration of diabetes. In addition, the volume of white matter in the left anterior frontal lobe has been shown to be negatively correlated with duration of disease . Also, iDuration of diabetes revealed a significant inverse correlation with the size of axial diffusivity (AD) and radial diffusivity (RD) and a significant positive correlation with Fractional anisotropy (FA) values in widespread brain regions. No significant difference has been seen in the volume of white matter in children with diabetes who experience severe hypoglycemia and seizures and the rest of diabetics without such experiences. On the other hand, younger ages of developing diabetes showed a positive correlation with lower FA and higher RD . In anotIn the study of Aye et al., a direct and significant correlation between HbA1C and RD was found which was observable in the inferior fronto –occipital fasciculi, uncinated fasciculi, subgenual WM, anterior forceps, right internal capsule, superior middle, inferior temporal gyri, splenium of corpus callusome, superior longitudinal fasciculi, and occipital WM. In this study, a negative correlation between the level of HbA1C and FA in right internal capsule, anterior forceps, inferior fronto-occipital fasciculi and splenium of CC have also been reported .In another study, Aye et al. showed that diabetic children with a history of seizures developed a reduced volume of gray and white matters compared to those with diabetes who had no history of seizures. But, the history of seizures did not show any impact on the volume of the hippocampus. As well, HbA1C levels showed no correlation with changes in the volume of brain structures . Also, iIn another study on diabetic children, he also reported that patients with history of hypoglycemia had a lower volume of gray matter in the superior temporal, occipital cortex, and left inferior occipital cortex compared to the group without a history of hypoglycemia.In diabetes, recurrent hyperglycemia was found to be associated with less gray matter volume in the right cuneus and precuneus. As well, it was associated with higher volume of gray matter in the right frontal middle gyrus and lower volume of white matter in the right superior parietal (WM). Also, its indicated that the early onset of the disease was related with greater white matter volume in the left precuneus region . In the Northamet al. also claimed in their research that hypoglycemia is a predictor of gray matter loss in the thalamus. This survey also revealed an association between poorly controlled metabolic and T2 reduction in the thalamus .Several evidence is available indicating the structural changes in the central nervous system as a complication of diabetes in adults . Also, iThe authors of the present study have attempted to make a comprehensive review of the efforts of other researchers to explore the association between diabetes and brain structural changes. Of course, neurological changes in the context of some severe complications of diabetes, such as ketoacidosis have been the subject of several studies which were not included in this study. This is mainly because the subjects in these studies were merely children with diabetes who had these complications and may not be a perfect example of the diabetic children population.As can be seen in these studies, a huge proportion of structures of the central nervous system have been affected by diabetes that include different areas of gray and white matters. Of these studies, only two longitudinal studies have evaluated the developmental changes in the central nervous system in diabetic patients over times, which have not reported consistent results with together. Other studies reviewed in this paper are cross-sectional and case–control studies which the majority have reported various brain structural differences in children and adolescents with diabetes compare to healthy subjects.This could explain the cognitive changes in diabetic children who have been investigated in several studies. Also, newer researches on children and adolescents with diabetes conducted by the application of functional brain imaging techniques have presented new evidence regarding this association.Of other important aspects that should be taken into account in these studies is the association of glycemic control and the structural changes in the central nervous system of children and adolescents with diabetes. In the majority of these studies, it has become clear that high glycemic changes, especially recurrent hyperglycemic attacks are very seriously associated with structural changes in the brain.Now, if one takes into consideration the fact that a significant proportion of children and adolescents with diabetes lack good glycemic control parameters , it mustThis issue must be well taken into account and the families of children with diabetes must be well understood by the health care providers.One of the considerations that must be made when reviewing these studies is that apart from two studies on children and adolescents with type 2 diabetes, other studies had been conducted on patients with type 1 diabetes. Moreover, none of the studies have compared the changes in brain structure in children and adolescents with type 1diabetes and those with type 2, and in this respect, the difference between these two types of diseases affecting the central nervous system is not well illustrated. On the other hand, given the growing trend of developing type 2 diabetes among adolescents, further evidence indicating the association between type 2 diabetes and the structural changes of brain is needed .Of the limitations observable in related studies are the lack of prospective studies exploring this association. Surely, design and implementation of prospective studies can provide answers to serious questions in this area including whether adequate glycemic control after the structural changes of the nervous system can resolve the changes or not, and or the brain structural changes seen in children and adolescents with diabetes compared to healthy peers is merely due to diabetes or other effective factors have created such differences. The answers to these questions can positively aid therapists to develop medical guidelines to prevent or resolve the changes in nervous structure.


It has been suggested that the research priorities of those funding and performing research in transplantation may differ from those of end service users such as patients, carers and healthcare professionals involved in day-to-day care. The Kidney Transplant Priority Setting Partnership (PSP) was established with the aim of involving all stakeholders in prioritising future research in the field.The PSP methodology is as outlined by the James Lind Alliance. An initial survey collected unanswered research questions from patients, carers and clinicians. Duplicate and out-of-scope topics were excluded and the existing literature searched to identify topics answered by current evidence. An interim prioritisation survey asked patients and professionals to score the importance of the remaining questions to create a ranked long-list. These were considered at a final consensus workshop using a modified nominal group technique to agree a final top ten.The initial survey identified 497 questions from 183 respondents, covering all aspects of transplantation from assessment through to long-term follow-up. These were grouped into 90 unanswered “indicative” questions. The interim prioritisation survey received 256 responses , resulting in a ranked list of 25 questions that were considered during the final workshop. Participants agreed a top ten priorities for future research that included optimisation of immunosuppression , prevention of sensitisation and transplanting the sensitised patient, management of antibody-mediated rejection, long-term risks to live donors, methods of organ preservation, induction of tolerance and bioengineering of organs. There was evidence that patient and carer involvement had a significant impact on shaping the final priorities.The final list of priorities relates to all stages of the transplant process, including access to transplantation, living donation, organ preservation, post-transplant care and management of the failing transplant. This list of priorities will provide an invaluable resource for researchers and funders to direct future activity. Kidney transplantation is arguably the most successful treatment for end-stage kidney failure in suitable patients, with evidence that demonstrates cost effectiveness, improved survival and improved quality of life in comparison with patients remaining on dialysis ,2. Over Despite the success of kidney transplantation there are still challenges. The limited donor pool means that access to transplantation is not universal, with a median waiting time of 1,022 days for adult patients in the United Kingdom resulting in a waiting list of around 5,600 patients at any one time . FurtherGiven these challenges, it is perhaps not surprising that the field of kidney transplantation has a very active research community. The research agenda has typically been set by individual researchers or industry, with over one third of randomised controlled trials in transplantation receiving industry funding . It has Increasing recognition of a potential mismatch between the priorities of end service users and researchers/funders has led to a drive towards involving healthcare professionals, patients and carers in projects identifying and prioritising topics for research. This approach has been championed by the James Lind Alliance in the UK, a not-for-profit organisation now a part of the National Institute for Health Research (NIHR) Evaluation, Trials and Studies Coordinating Centre (NETSCC). These “Priority Setting Partnerships” (PSPs) have been successful in a number of areas of medicine, and have led to successful funding of many of the research questions identified –14.The aims of the present study were (i) to identify unanswered research questions in the field of kidney transplantation from end service users  and (ii) to prioritise these questions according to the needs of these groups, for use in future decision making by funders and researchers.The Kidney Transplant Priority Setting Partnership followed the methodology described in detail in the James Lind Alliance (JLA) guidebook . In keepNational patient and professional organisations and charities involved in kidney transplantation were contacted about the project and invited to contribute to a steering group. This group included representation from the Centre for Evidence in Transplantation (CET), British Transplantation Society (BTS), Renal Association (RA), British Renal Society (BRS), Kidney Research UK (KRUK), the National Kidney Federation (NKF) and the British Kidney Patient Association (BKPA). The group was chaired by an experienced advisor from the JLA (LM). The steering group developed the protocol for the project and was involved in all stages of its management. It included transplant surgeons, nephrologists, transplant recipients, living donors and carers. Additional partner organisations were invited to take part in the process by involving their members in the surveys and helping to promote the process. A full list of partner organisations is included in the Supporting Information .The steering group also defined the scope of the project. This incorporated all stages of the transplant process, including access to the waiting list and pre-transplant assessment, the transplant procedure itself, post-transplant care in the short and long-term, management of the failed transplant and issues surrounding retransplantation and living-donor transplantation. Scope included both adult and paediatric patients and their carers and clinicians. In order to maintain the focus of the process, it excluded management of end-stage kidney failure other than transplantation, donor selection and management (other than living donors) and issues specific to combined organ transplants.In order to identify potential research questions, an online survey was created to collect possible questions, along with the demographic details of the respondents. The survey was open-ended, simply asking “What unanswered questions about kidney transplantation and living donation would you like to see answered by research?” with space for up to three questions to be submitted. The survey was piloted by members of partner organisations and the wording refined according to feedback. It was also made available in paper format to improve access. The paper version included the same instructions and questions with the same wording as the online version, and was made available on request. The survey was open to responses between October and December 2014, and promoted via the steering group, partner organisations and other interested individuals. Methods of dissemination included websites, blogs, social media, society/organisation e-mailings and print newsletters distribution of flyers at conferences and events and display of posters and leaflets in transplant centres. The survey was open to all transplant recipients and those on the transplant waiting list, their carers, live kidney donors and professionals involved in the care of kidney transplant recipients in the UK. As the purpose was to collect as many potential research questions as possible, multiple submissions from the same respondent were allowed.The steering group also identified two recent previous surveys from the BTS and KRUK to which respondents were asked to submit potential research questions. Questions from these surveys that fell within the scope of the PSP were also included, although demographic information were not available.The raw submissions were imported into a custom designed MySQL database. Responses were reviewed by two researchers and those that were out of scope (as defined above), or that could not be translated into an answerable research question, were identified. These questions were reviewed by the entire steering group and only excluded if all members agreed.The remaining questions were grouped into similar themes using a pre-defined taxonomy to form a set of “indicative” research questions that covered the scope of all questions submitted. These indicative questions were expressed in the PICO  format as far as possible, although many questions were broad and all four parameters were not defined. Classification and grouping was initially performed by two researchers, with the results discussed in detail by the entire steering group to agree the final indicative questions.www.transplantlibrary.com), which includes all randomised controlled trials and systematic reviews  published in the field of solid organ transplantation between 1970 and present, identified from searches of MEDLINE the Cochrane Library and hand searches of conference proceedings. The purpose of the literature review was to identify any of the questions that were considered adequately answered by the existing literature. In order for a question to be considered answered, an existing up-to-date systematic review with a clear conclusion had to be identified. Questions with no available review, outdated reviews or with an existing review that expressed uncertainty in its conclusions  were considered unanswered. Questions considered answered were discussed in detail by the steering group prior to exclusion from the remainder of the process. A full description of the strategy and search terms used to identify existing reviews is provided in the Supporting Information (Two experienced systematic reviewers reviewed the transplant literature for each of the remaining indicative uncertainties in order to assess the extent of the existing evidence. The primary sources for this review were the Cochrane Library and the Transplant Library (ormation .In order to make a more manageable prioritisation survey (based upon previous JLA experience), remaining indicative questions submitted by three or more individuals to the initial survey were brought forward for prioritisation. A second online survey was designed and piloted in which respondents were asked to rate each remaining question on a five-point Likert scale from “Not at all important” to “Extremely important”. Following an initial pilot, a glossary of terms was also developed to help non-professional respondents understand some of the medical terminology used in the questions. Demographic characteristics of respondents were also collected, including age, sex, geographical region, ethnicity and role. The second survey was open from October to December 2015, and was promoted in a similar way to the initial survey. All respondents to the initial survey were contacted to participate in prioritisation, although this survey was also open to individuals who had not previously participated in the process. Only one response per participant was allowed.Responses to the prioritisation survey were collated and the Likert scale coded numerically from 1  to 5 (Extremely important). The overall mean score as well as the mean score for patients, donors and professionals were calculated for each question. Results were reviewed by the steering group, and the decision was made to take the top 25 ranked questions overall through to the final workshop.A final one-day workshop was held in London in February 2016. The aim of the workshop was to agree a top-ten list of prioritised questions for future research. Professionals , patients and donors from partner organisations were invited to attend and contribute via contact details submitted to the two surveys, as well as organisation mailing lists, social media and websites. Participants were selected with the aim of broad representation of all involved groups and organisations. We initially planned to include around 25 participants in the final workshop, based upon optimal numbers for interaction during previous JLA PSPs, as well as budget and space constraints. Due to illness and unexpected work commitments, 20 individuals eventually participated.The workshop took the form of a modified nominal group process facilitated by experienced JLA advisors. Participants were asked to rank the remaining 25 questions prior to attending the workshop, and in an initial small group session these responses were discussed to identify any agreement in the top and bottom three priorities. In a second small group session the groups were asked to rank the uncertainties based upon this discussion. Groups were balanced to ensure equal professional and non-professional involvement and the facilitators encouraged all participants to take part and voice their opinions. Results of this ranking process from each small group were fed back to the meeting as a whole, with agreement in the top and bottom ranked questions highlighted. A further small group round (with different group composition) took place to revise ranking based upon this feedback. In the final whole group session, the results of the small group discussions were used to suggest a top-ten ranking, and discussion took place as to whether items should be removed or inserted into the top ten. Where there was disagreement, all participants were asked to vote in order to reach a decision. The results of the interim prioritisation survey  were made available on request throughout the meeting to help inform debate and decision making. At the end of the meeting, a final top-ten questions were agreed as priorities for future research.The initial survey received 440 potential research questions from 183 respondents. Responses were from a mixture of professionals (36.1%), patients (37.7%), carers (2.2%) and live donors (21.9%), although some donors also identified themselves as carers for a transplant recipient. Full demographic details of respondents are described in Submitted questions covered the breadth of kidney transplantation, and were categorised as relating to recipient assessment, recipient education, access to the waiting list, organ allocation, management of highly sensitised recipients, organ preservation and reconditioning, live donor transplantation, non-directed donation, tissue typing and immunology, ABO and HLA incompatible transplantation, surgical technique and intra-operative management, post-transplant complications, acute and chronic rejection, recurrent disease, psychosocial outcomes, diet and lifestyle, management of the failing transplant, immunosuppression and tolerance, paediatric and adolescent transplantation and organ bioengineering.The flow of questions through the PSP process is outlined in The interim prioritisation survey received 256 responses from a mixture of patients (30.5%), carers (4.3%), donors (10.9%) and professionals (54.3%). Full demographic details of those responding are described in There was evidence of a difference in priorities between patients, donors and professionals. Of the 25 top-ranked questions, there was a difference in rankings of greater than 5 places between patients and professionals for 16, between donors and professionals for 18 and between patients and donors for 17. Whilst all groups prioritised questions regarding improving long-term transplant outcomes, patients tended to prioritise questions about immunosuppression (including side effects), organ preservation and equity of access. Professionals prioritised questions about assessment of patient and organ suitability and management of antibody mediated rejection. Donors prioritised questions regarding assessment of organ suitability and promotion of living donation. The questions taken to the final workshop represented a mixture of those prioritised by all three groups.Twenty participants took part in the final workshop, representing patients (7), donors (4) and professionals (9). During the day, it was decided that two of the questions had some degree of overlap (regarding organ preservation and conditioning) and the group agreed to merge them together. The top ten research priorities agreed are listed in Of particular note was the desire of the participants in the final workshop to include realistic questions achievable in the short term (for example those relating to the management of immunosuppression) as well as questions that seem much further away from reality such as the development of bioengineered organs and induction of tolerance. The most highly prioritised question from the interim survey (“What is the best strategy to prolong the life of the transplant kidney?”) was felt by the group to be too generic and covered by many of the more specific questions under consideration, and so was not included in the final top ten.A number of questions considered during the process were submitted by non-professionals, and would not have been considered without their involvement. Of the 90 indicative questions 41 (45.5%) were submitted by professionals alone and 14 (15.6%) were submitted by non-professionals alone; the remainder were submitted by both groups. Four questions submitted by patients alone were taken through to the prioritisation stage. Of the final top ten questions, six were originally submitted by both patients and professionals, and four by professionals alone.The final top ten reflected the mixed priorities of all groups. Of the ten, five appeared in the patient top ten during the prioritisation survey, four in the professional top ten, and two in the donor top ten. Four of the final ten were ranked more than five places higher by patients than professionals, and four were ranked more than five places higher by professionals.www.transplantpsp.org/kidney) and the JLA website (http://www.jla.nihr.ac.uk). They were also disseminated to all partner organisations and participants involved in the process, many of whom are involved in or fund transplant research. The James Lind Alliance is part of the National Institute for Health Research (NIHR), one of the largest funders of health research in the UK. The results of the Kidney Transplant PSP have been discussed with NIHR representatives in detail with the aim of taking forward priorities for future specific funding calls.The final list of priorities, as well as all research questions identified, have been made available on the internet through both the PSP website , and the methodology used fulfils many of the criteria defined for good practice in priority setting [The JLA process followed has now been used to identify research priorities in over 35 areas of medicine . The final top ten included questions ranked highly by all groups during the prioritisation process, with an equal mixture of those ranked highly by professionals and non-professionals. It is likely, therefore, that patient involvement played an important role in the shaping of the final prioritised list.A recent systematic review identified four existing publications outlining research priorities with a scope including kidney transplantation . Of thesThe current process may under-represent certain groups affected by transplantation. In particular, very few responses were received from children and adolescents despite partnership with children’s renal charities and the British Association for Paediatric Nephrology. However, many respondents were parents of affected children or nephrologists involved in the treatment of these patients, and questions regarding child and adolescent transplantation were considered during the final workshop. The other patients under-represented in the current process are those from black, Asian and minority ethnic (BAME) groups. These groups made up around 9% of the responses to the initial survey, and 5% of those to the prioritization survey, yet represent around one quarter of the patients on the UK transplant waiting list. BAME patients have significantly higher waiting times to transplantation in the UK, and are less likely to donate . QuestioA further limitation of the current process is the relatively small number of participants in the final workshop. A group size of around 25 participants was determined to provide optimal interaction based upon experience from previous JLA PSPs, and within the budget limitations of the project. Unfortunately, due to illness and unforeseen work commitments the final number of participants was reduced to 20. Despite this, the final group had fair and balanced representation from all stakeholder groups including patients, donors and clinicians. Furthermore, discussions during the final workshop were informed by the rankings of all groups during the prioritisation survey, meaning that the final decision making was influenced by a broader group than just those involved in the workshop.Whilst the prioritised results of this PSP are most relevant to the UK healthcare setting, it is likely that the long-list of potential research questions has international relevance. The review process to check whether questions were truly unanswered by existing literature included evidence from all international healthcare settings, and so whilst it is conceivable that priorities may differ, the unanswered questions are likely to remain the same. This notion is supported by comparison of questions submitted to the current process and those submitted to previous prioritisation processes in other healthcare settings, with significant overlap seen despite differences in priority . One cavPriority setting should not be seen as a one-time exercise, and the priorities set in this process will require future re-evaluation to ensure continuing relevant or to identify new areas of important uncertainty . As yet,The Kidney Transplant PSP has provided an invaluable resource of prioritized, unanswered research questions to help in the design of future research studies. By increasing awareness of these topics, we hope to divert research effort and funding towards the design and implementation of high quality studies, including collaborative randomised controlled trials, with the goal of improving access to transplantation and the long-term outcomes for both donors and recipients.S1 File(DOCX)Click here for additional data file.S2 File(DOCX)Click here for additional data file.S3 File(DOCX)Click here for additional data file.