Through this paper, we present the initial steps for the creation of an integrated platform for the provision of a series of eHealth tools and services to both citizens and travelers in isolated areas of thesoutheast Mediterranean, and on board ships travelling across it. The platform was created through an INTERREG IIIB ARCHIMED project called INTERMED.The support of primary healthcare, home care and the continuous education of physicians are the three major issues that the proposed platform is trying to facilitate. The proposed system is based on state-of-the-art telemedicine systems and is able to provide the following healthcare services: i) Telecollaboration and teleconsultation services between remotely located healthcare providers, ii) telemedicine services in emergencies, iii) home telecare services for "at risk" citizens such as the elderly and patients with chronic diseases, and iv) eLearning services for the continuous training through seminars of both healthcare personnel  and persons supporting "at risk" citizens.These systems support data transmission over simple phone lines, internet connections, integrated services digital network/digital subscriber lines, satellite links, mobile networks (GPRS/3G), and wireless local area networks. The data corresponds, among others, to voice, vital biosignals, still medical images, video, and data used by eLearning applications. The proposed platform comprises several systems, each supporting different services. These were integrated using a common data storage and exchange scheme in order to achieve system interoperability in terms of software, language and national characteristics.The platform has been installed and evaluated in different rural and urban sites in Greece, Cyprus and Italy. The evaluation was mainly related to technical issues and user satisfaction. The selected sites are, among others, rural health centers, ambulances, homes of "at-risk" citizens, and a ferry.The results proved the functionality and utilization of the platform in various rural places in Greece, Cyprus and Italy. However, further actions are needed to enable the local healthcare systems and the different population groups to be familiarized with, and use in their everyday lives, mature technological solutions for the provision of healthcare services. Th. ThTelemThese patient units can be portable or not depending on the use case , while they are responsible for collecting and transmitting in real time several biosignals and images of the patient to the central unit. Each unit consists of a biosignals acquisition device, an image acquisition device, a communication device and the central processing device .2, HR, NIBP, invasive blood pressure (IBP), TEMP and RESP.○ The biosignals acquisition device is the device responsible for collecting several biosignals from the patient, like 3 to 12 lead ECG, SpO○ The image acquisition device is responsible for collecting images of the patient that help doctors have visual contact with the patient.○ The communication device is responsible for controlling the communications with the central unit. This can be a GSM/GPRS/UMTS modem, a satellite modem or a network communication device if it is not on a portable setup.○ The central processing device is actually a personal computer, netbook, laptop or desktop, depending on the case. This device facilitates the software that controls real time acquisition of biosignals and images and real time transmission to the central unit. Furthermore, the software supports automated continuous communication of the telemedicine units with the central unit; this means that a connection will be automatically re-established in case of connection failure. The connection and communication procedures are all automated on the site of the telemedicine unit so as not to disturb the paramedics or any other personnel handling the patient.The central unit consists of a dedicated workstation  which facilitates the software for receiving all data coming from the telemedicine units. On this site, the expert doctor is able to see in real time biosignals and images of the patient. The telemedicine unit can be remotely controlled by asking for images or by changing the kind of biosignals received. In general, this unit allows the doctor to be visually present near the patient and give proper instructions to the non-specialized personnel handling the patient.Telemedicine System 3 (TS3): The TS3 is used mainly for the provision of home care telemedical services in the Samos Island. It consists of components that permit the acquisition and transmission of the patient's biosignals and weight. TS3 has been presented in detail in [• etail in .Telemedicine System 4 (TS4): TS4 is used for emergency telemedicine services onboard Blue Star Ferry II. The service is provided using the TraumaStation system [2signals all in a suitcase. Further, it offers tools for 2D/3D image acquisition and handling  included the acquisition of 2D/3D ultrasound data and the management of images in DICOM format. In addition, the system is equipped with all available telecommunication gateways. Text messages and online-mode interactive communication via usage of a chat window are also available.• n system  and coveTelemedicine System 5 (TS5): TS5 installed in Italy i) is designed following a human-centered design approach [• approach  ii) is bapproach , and morapproach -29, in oapproach . The extapproach . Additio© eLearning platform http://moodle.org/. The Moodle is an open learning management system (LMS) which permits the creation and organization of online courses and monitoring of the user's performance, and offers a series of tools for collaboration such as email, wikies, online forums, discussion boards and chats.For the continuous training of the people who will use the platform, a series of distance learning courses has been prepared. The courses are provided through an appropriate website, where healthcare professionals and telemedicine experts have uploaded multimedia materials (audio and video files) and links to external knowledge sources. This material, which is compatible with the sharable content object reference model (SCORM) standard , can be The electronic health record (EHR) created under the INTERMED platform is a longitudinal electronic record of patient health information generated by one or more encounters in any care delivery setting. Included in this information are patient demographics, progress notes, problems, medications, vital signs, past medical history, immunizations, laboratory data and radiology reports . The EHRAs mentioned earlier, it was the scope of the project not only to provide standalone telemedicine services at various sites, but also to validate the concept of eHealth. In order to achieve this, the project proposed a high-level integration of the described telemedicine services at EHR level. Namely, the project aspired to develop a common-reference medical record to which various telemedicine systems could store patient-specific data, and from which medical consultants could retrieve and evaluate patient-specific data  during or after a monitoring session, regardless of when and where other medical instances had occurred.If, for example, a Greek citizen with a chronic condition that was being monitored at home using one of the telemedicine systems, travelled to Cyprus or Italy and happened to be involved in a car accident. If teleconsultation was required during the transportation to a hospital, the medical experts responsible for it could retrieve information from the patient's short EHR, regardless of the locality of acquired data or the system from which this data had been retrieved, thus achieving continuity in care.It has however to be stressed at this point that it was out of the scope of the project to achieve integration and interoperability between the developed EHR and local healthcare systems, for a variety of reasons. The most important of these  is perhaps the (unfortunate) fact that even though most medical centers claim to support interoperability, the vast majority of them currently utilize closed-architecture systems based on proprietary protocols.Nevertheless, even though information could not and was not shared with current EHR systems, the project tried to develop an open architecture that would facilitate future interconnection with other systems.In this sense, connection to and interaction with the developed EHR was made feasible through the development of secure web services and the definition of solid "Get" and "Store" procedures for the retrieval and storage of data to the EHR respectively. For the deployment of the INTERMED common reference EHR, an XML schema that operates as an interface between different heterogeneous patient records was utilized. The use of the XML scheme facilitated the interoperability and interaction between geographically distributed systems, thus allowing the aspired patient mobility. The developed EHR was patient-centric, in that it followed a tree-structure with each patient constituting the root, which in turn could host several telemedicine sessions (branches). Each EHR session supports a fragmented message structure, with each fragment containing information regarding critical biosignals of the patients and their attributes, whether these were waveforms (i.e. ECG), arithmetic values (i.e. TEMP and/or BP) or images.The services mentioned above are provided through a broadband telecommunication network that integrates three types of communication media: terrestrial, satellite and mobile Figure . The netThe overall networking infrastructure is divided into a core part and an access part. The core part of the network consists of i) terrestrial technologies of ADSL lines, the Greek research and technology network (GRNET) , the CypADSL was selected to be the primary technology for use in the patients' premises as well as in the rural health and medical centers . ADSL was chosen for the provision of i) home care telemedical services ii) teleconsultation and telecollaboration services and iii) telemedicine services in emergency situations, due to the low overall cost of usage compared to the other technologies available and the provision of high speeds needed for the provided services. Depending on the availability of ADSL lines, the patients and the health and medical centers are connected with speeds of 1.024 Mbps download and 512 kbps upload.The GRNET, CYNet and GARR are used to interconnect the various academic  and research  partners (T1 connections). All nets fulfill the broadband network needs of the platform.very small aperture terminal (VSAT) technology via which the ship communication (internet access) was established was the single channel per carrier (SCPC) technology. The network management has been undertaken by the EUTELSAT representative in Greece. A virtual private network (VPN) connection has been used to interconnect the application at the Blue Star Ferry II and the Sotiria Hospital. The VPN connection has been implemented using the OpenVPN [Satellite technology was considered only for the ferry due to the high cost involved in bandwidth rent and in some cases in equipment installation as well. The  OpenVPN  solutionFor the telecollaboration service, a 2 Mbps ADSL line between NCSR and Sotiria Hospital was re-activated and used. The Medical Center of Karlovasi was connected with the Hospital of Samos using ADSL. The physicians within the medical service of Karlovasi were using Wi-Fi (802.11.a) enabled PCs to connect to the medical center's router that terminated the ADSL. Mobile communication links (3G/GPRS) were used for the ambulance case in Cyprus. Mobile networks cover the whole area of Cyprus, enabling the connection of the ambulance vehicle to the Central Hospital for all cases.A summary of the various services provided per pilot site and the utilized connections is presented in Table The INTERMED project has implemented an end-to-end system for telehealth and teleeducation applications, integrating wireless broadband networks with terrestrial broadband technologies. The system's main purpose is to facilitate the sustainable provision of integrated eHealth and eLearning services and applications to an adequate number of distributed interconnected sites over a variety of telecommunication infrastructures.The platform has been tested and validated in 17 pilot sites in Greece, Cyprus and Italy. It has to be noted that the platform and the provided services were assessed by citizens, travelers, patients, crew members and physicians in the sites mentioned above.In the first publication of the INTERMED consortium, the initial architecture regarding involved sites, provided services and planned activities to meet the user requirements have been presented . This paINTERMED, which is based on the integration of terrestrial, satellite and mobile networks, provides to the direct beneficiaries  the services described in the Methods section.The final platform initially went through technical evaluation in order to ensure the correct and reliable operation of the several subsystems and the exchange of information between the subsystems from different countries. Following the technical evaluation, we tried to evaluate the acceptance of the final product from the users' point of view. This was done using questionnaires that helped investigate how the system can be used to improve the healthcare procedures followed in every use case.During the pilot trials, four different use scenarios of the INTERMED platform have been evaluated. That is (a) home care (b) rural health center (c) ambulance/emergency and (d) navigating ship. For all cases, the evaluation was performed by all involved users (being either at the site accepting the consultation advice or at the site providing consultation). In tandem with this evaluation, participants were also asked to examine the eLearning tools offered as an infrastructural service to INTERMED users.Keeping in mind that the INTERMED platform was using different subsystems, we had to create an evaluation scheme that could collect the results in a comparable way. In order to achieve this data was collected using two approaches:Technical evaluation: Including general results related to technical parameters of the systems collected during the pilot tests.• Users' satisfaction: Including data collected from the final users based on their experience during the pilot tests.• In order to assess the technical performance, the INTERMED systems were evaluated as follows:Module Testing: For this type of testing, each individual module was tested to determine whether all the system's modules are logically and functionally correct. If an error occurred, a suitable debugging procedure was followed.Integration Testing: This form of testing was applied to all interfaces among modules to ensure that transfer of both data and control were performed correctly. This testing method included the run-time evaluation of all variables that are passed from one module to another.Function Testing: The results and outcomes were evaluated after the execution of the program in which every functional menu selection had been activated systematically in turn.Final System Testing: The objective of this type of testing was the full test of the entire system on completion of the system development period. In order to achieve this and get comparable results, the INTERMED subsystems were evaluated on a number of technical factors that were selected as the most important for the platform's correct operation. These factors, which monitor the system's correct operation and adequate quality of service (QoS), were chosen in order to cover the various scenarios. Each technical test was repeated five times for the duration of 15 minutes. The five tests for 3G network transmission were repeated twice: a) five tests with the transmitting station moving at an average speed of 40 kmph and b) five tests with the transmitting station stable in one place. Three healthcare professionals from each clinical pilot site conducted the clinical evaluation of the system from the expert side, while a varying number of "patient-test subjects" provided feedback regarding the user acceptance. Finally, the technical evaluation of the system was conducted by the personnel that took part in the actual implementation of the INTERMED system and its services. The results are shown in Table connection loss rate. This is defined as the rate of disruptions, when connected to several telemedicine systems related to the total number of connections. The overall scores were very good in this area, with a low failure rate of less than 2% in the "home care" and "rural health center" scenarios while, as expected, failures for "ambulance/emergency" had the highest failure rate of around 10% and "navigating ship" of around 5%.In detail, the first technical factor is Ease of data transmission and data exchange was the second evaluation factor. It accounts for the ease of data transmission of biosignals and all other necessary data (e.g. ultrasound video) for effective diagnosis over the INTERMED network, the ease of data entry by users into the INTERMED system, as well as the ease of data exchange between the several subsystems. Given the trial results in the above technical factor (connection loss rate), the outcome of ease of data transmission follows the same pattern. In the "home care" and "rural health center" scenarios there were no problems with ease of data transmission. During the "ambulance/emergency" scenario, no problems were observed for this parameter. There were some connectivity failures recorded during the trials - however they did not affect transmission of biosignals to the server. Data was transmitted successfully during each repetition of the test. During the "navigating ship" scenario, the main problem recorded in this factor is linked to the limited bandwidth of the satellite network deployed by the Blue Star Ferry II during the trials. The bandwidth was not adequate for the transmission of biosignals and ultrasound data. No problems were recorded regarding the exchange of data between the systems from different countries.integrity of data transmission examines a parameter of paramount importance in telemedicine as suggested by the relevant literature [The third factor, terature . Anythin2 waveform• Biosignals such as ECG 3-12 leads and SpO2, RESP and TEMP• Numerical data like NIBP, HR, SpO• Image files: Pictures of the patient  and medical images like X-rays• Video-conferencing files: These were recordings automatically captured by the video-conferencing softwareintegrity of data transmitted. The data was 100% accurate and there were no complaints from either consulting (server) or consulted (client) units. During the "ambulance" scenario, despite a couple of times when connectivity failed, data has been transmitted successfully. Users did not express any problems regarding the procedures of data transmission. On the contrary, they were quite satisfied with the interface and the sequence of data entry. Successful transmission signified high quality of the relevant data. The reasons for this high success rate are the same as the ones analyzed in the "home care" and "rural health center" scenarios. The "navigating ship" scenario entailed the transmission of data through a satellite network. The purpose was to simulate the conditions of teleconsultation when the ship is at large and see whether this type of data transmission presents a better alternative to the standard procedures of radio-communication. Unfortunately, this scenario produced some problems in the quality of data transmitted. According to the data recorded by the INTERMED server, the satellite connection was poor. In the majority of instances, the data recorded by the ultrasound and the portable devices could not be transmitted properly since the connection failed before data could be transferred into the server. Obviously, this resulted in partially transmitted data that was unreadable by the client. When the satellite connection failed, both ultrasound data and biosignals were not transmitted correctly and the physician at the main hospital could not assess the situation of the patient.According to the data recorded by INTERMED servers for the "home care" and "rural health center" scenarios, in all four types of data there has been no problem with the interference to other medical equipment, where for all cases no interference effects were reported.The fourth factor recorded during the pilot tests is user requirements fulfillment. In general, users were satisfied with the final appearance of the systems. The systems were according to a detailed analysis of user requirements but, as expected, we had several requests for minor amendments on the systems used in the "home care" and "rural health center" scenarios.Finally, the fifth factor recorded is Following the technical evaluation, a small-scale qualitative evaluation of the systems was performed. The evaluation was focused on the usability and acceptance of the provided services by physicians, paramedics and "at-risk" citizens/carers. Whitten et al  point ouThe users' satisfaction evaluation included collection of data on perceived benefits of the services provided. Specifically, the three types of users from both Monitoring Stations and Clients were given access for a limited period to the INTERMED systems in order to run the different scenarios. Then they were asked for narrative comments regarding their experience during the interaction with the system. Their views, from both Monitoring Station and client perspective, are summarized in Table The evaluation showed that INTERMED services are generally reliable from a technical perspective. Technical problems were recorded mainly during the "navigating ship" scenario where signals and ultrasound video could not be easily transmitted due to bandwidth limitations. During the "ambulance" scenario, some problems with line failures due to the movement of the vehicle were reported, but this was expected and since the systems could revive quickly (in approx. 1.5 to 2 minutes), it did not cause problems. During the "home care" and "rural health center" scenarios there were no actual problems recorded. Although the user satisfaction was not systematically evaluated, the general interaction with INTERMED was characterized as a positive experience that makes them consider use of such a system in the future. The importance of qualitative and contextual parameters has been noted by both users and observers of the trials.The future research direction is aiming towards the involvement of end users in the evaluation of the developed platform regarding usability and improvement of healthcare. The goal of this task will be to create systems that can be integrated to users' daily routine without disturbing or needing major changes. This will help the effort to persuade users about the usefulness of such systems. Further, emphasis will be given to the quality of life of individuals living or traveling in isolated regions. Other challenging research areas that the involved research groups are currently working on are related to the enhancement of the platform with intelligent features in terms of computational decision support.This paper presents a new concept of an integrated broadband communication platform that might be able to serve the population in hard-to-access areas of the southeast Mediterranean and could also be used on naval vessels without medical services on board. It utilizes terrestrial, mobile and satellite communication infrastructures ensuring bidirectional communication between specialized and non-specialized medical personnel or civilians. The platform has been installed in several sites in Greece, Cyprus and Italy. The overall architecture of the platform has been technically tested, while a series of scenarios has been evaluated. The evaluation results showed the feasibility of the INTERMED platform to be successfully used by physicians, paramedical personnel and civilians. Encouraged by these results, the optimization of the platform for a wider delivery of telemedical services in the near future is under consideration. What we can expect from such a platform is the improvement of healthcare services in remote areas through telemedicine and teleconsultation, which can lead to a reduction in costs by limiting medical transfers to an absolute minimum, reducing morbidity and mortality of patients, and increasing quality of life due to better quality healthcare.The authors declare that they have no competing interests.SGM and EK drafted the manuscript, KP and AA designed and developed the EHR, HP designed and carried out the study for the network, while all of them designed, developed and evaluated the services in Greece and Cyprus. RT, LP and UB designed and developed the services in Italy. GK supported drafting the manuscript. CP provided advice on the project and revised the draft manuscript. DK managed the project and revised the draft manuscript. All authors read, reviewed and approved the final manuscript.


Unmet needs for mental health treatment in low income countries are pervasive. If mental health is to be effectively integrated into primary health care in low income countries like India then grass-roots workers need to acquire relevant knowledge and skills to be able to recognise, refer and support people experiencing mental disorders in their own communities. This study aims to provide a mental health training intervention to community health workers in Bangalore Rural District, Karnataka, India, and to evaluate the impact of this training on mental health literacy.A pre-test post-test study design was undertaken with assessment of mental health literacy at three time points; baseline, completion of the training, and three month follow-up. Mental health literacy was assessed using the interviewer-administered Mental Health Literacy Survey. The training intervention was a four day course based on a facilitator's manual developed specifically for community health workers in India.70 community health workers from Doddaballapur, Bangalore Rural District were recuited for the study. The training course improved participants' ability to recognize a mental disorder in a vignette, and reduced participants' faith in unhelpful and potentially harmful pharmacological interventions. There was evidence of a minor reduction in stigmatizing attitudes, and it was unclear if the training resulted in a change in participants' faith in recovery following treatment.The findings from this study indicate that the training course demonstrated potential to be an effective way to improve some aspects of mental health literacy, and highlights strategies for strengthening the training course. Mental disorders are both disabling and costly for affected individuals, their families and the community. Mental disorders are increasingly recognised as a major contributor to the global health burden, including in low income countries (LICs), and they are often co-morbid with communicable and non-communicable diseases ,2. MentaIn India, approximately 6% of the population have a mental disorder such as schizophrenia . SuicideThe World Health Organization (WHO) advocates the need to integration of mental health into PHC as the optimal strategy for addressing the global burden of disease ,8. In InIf mental health is to be successfully integrated into PHC in low-income countries like India then grass-roots workers need to acquire relevant knowledge and skills so that they are able to recognise, refer and support people experiencing mental health disorders in their own communities. Task shifting of effective mental health interventions to non-specialist health workers has been proposed to increase the coverage of mental health care in both low and high-income settings -25.Mental Health Literacy (MHL) is defined as 'knowledge and beliefs about mental disorders which aid their recognition, management and prevention' (p.396) . StudiesA small number of studies investigating various components of integrating mental health into PHC settings in India, have been conducted ,32-36 anThis study involved an evaluation of a mental health training program using a pre-test post-test design. Assessment of participants' MHL was undertaken at baseline, at completion of the course and three months later. The training and data collection was conducted between May and October 2010. Ethics approval was obtained from the University of Melbourne Health Sciences Human Ethics Sub-Committee.Training participants were community health workers sourced through Gramina Abrudaya Seva Samstha (GASS), an NGO operating in Doddaballapur Taluk, Bangalore Rural District, Karnataka, India. The types of community health workers included Junior Health Assistants, Village Rehabilitation Workers, and ASHA workers. These are all categories of government-funded community health workers operating in Doddaballapur Taluk, that each have a range of tasks to undertake from the provision of maternal and child health care, to building community awareness about communicable and non-communicable diseases, to disability rehabilitation. The participants were trained in three separate groups of between 23 and 24 participants by the same two facilitators who were both local health professionals with a moderate level of experience and understanding of community mental health. The level of experience of the facilitators reflected a 'real world' scenario given that experienced mental health professionals are rare in rural settings in India.The mental health training program is a four-day course that aims to increase recognition of mental disorders, enhance appropriate response and referral, support people with mental disorders and their families, and improve mental health promotion in communities. It is not intended as a training program for mental health practitioners, but rather as an introduction to mental health for uninitiated community health workers. The training program is based on a facilitator's manual  developeTo assess changes in the participants' level of MHL, we adapted a MHL survey previously used in rural India -29 and iTo ensure the MHL survey was appropriately translated for the local setting, the English version was reviewed with local psychiatrists, and the relevance of concepts and categories and the appropriate form of translation into the local language (Kannada) were extensively discussed. The survey was then translated and back-translated into English to check for equivalence of meaning, and subsequently piloted.Based on a change in the percentage of respondents who were able to correctly recognise a mental disorder in a vignette, we estimated that we would require a total of 63 training participants to detect a medium effect size  with a power of 80%, alpha of 0.05, and making the conservative assumption of no correlation between pre-test and post-test . The samStatistical analysis was performed with SPSS version 18. Dichotomous variables were analysed using the Cochran's Q test to test for variation between the three points of measurement; baseline, post-course, and three month follow-up. McNemar's test for two paired proportions was used to specifically examine changes between baseline and post-course, and between baseline and three month follow-up. All tests were performed separately for responses to questions about each of the two vignettes (i.e. depression and psychosis) in the MHL questionnaire. Respondents who didn't complete all three points of measurement were omitted from the analysis.There were 70 participants recruited for the study and only one participant did not complete the training. A further three participants were not available at the three month follow-up leaving 66 (94.3%) participants who had completed the MHL survey at all three points of measurement. Table Participants were read the two vignettes and asked to name the problem (more than one response was possible). Only "depression", "schizophrenia" or "psychosis" were considered correct responses to the relevant vignettes. A substantial improvement in the participants' ability to recognise mental disorders was observed at the completion of the training and sustained for the three-month follow-up assessment Table . Prior tParticipants were asked about the helpfulness or otherwise of a range of possible pharmacological and non-pharmacological interventions for the problems identified in the vignettes Table . RegardiThere were no clear and sustained changes in the endorsement of various non-pharmacological interventions, other than a decrease in the percentage of participants endorsing a special diet as helpful for the psychosis vignette. At baseline, psychosocial interventions such as physical activity, distraction, love and affection and listening were strongly endorsed as being helpful for both vignettes, and this was sustained across both points of follow-up.There was a statistically significant change in the percentage of participants endorsing hospital admission as a helpful response for the depression vignette between the three points of measurement, however, the greatest difference was between post-course and follow-up measurement. The decreased endorsement of hospital admission for the depression vignette between baseline and follow-up (60.6% to 43.9%) was not statistically significant .There was a substantial reduction in the percentage of participants endorsing marriage as a helpful intervention for the person in the psychosis vignette between baseline and post-course measurement , however this change was not sustained at the three month follow-up. The decrease in the endorsement of marriage for the psychosis vignette between baseline and follow-up (72.7% to 65.2%) was not statistically significant .Participants were asked structured questions about the anticipated recovery of the persons described in the vignettes if appropriate help is received Table . For theParticipants were asked whether they agreed with a range of attitudinal statements relating to the persons described in the vignettes, and while some improvements in attitudes were observed, others remained largely unchanged Table . For botWith respect to the depression vignette, the training resulted in a marked decrease in the percentage agreeing that it is best to avoid people with these problems. Additionally, there was a reduction between baseline and follow-up (84.8% to 62.1%) in the percentage who agreed that the problems described in the depression vignette were a sign of personal weakness ; however, there was no statistically significant change between baseline and post-course measurement .In the case of the psychosis vignette, there were no sustained changes in responses to the attitudinal statements that could be clearly attributed to the training intervention. Fewer participants agreed that the person could 'snap out of it' at post-course (42.4%) measurement than at baseline (67.2%) , however the decrease between baseline and follow-up (51.5%) was not statistically significant  indicating that the improved attitude had not been sustained. The Cochran's Q test indicated a statistically significant change in the percentage of participants agreeing that the problem is a sign of personal weakness; however, this was due to the change between the results at post-course and follow-up measurements. There was no statistically significant change in the proportion agreeing with this statement between baseline and post-course measurement  or between baseline and follow-up .At baseline, approximately half the participants agreed that the problems described in both the depression and psychosis vignettes were not real medical illnesses. There was no real change in this belief in the case of the depression vignette, but there was some statistically significant variation over time in relation to psychosis as identified by the Cochran's Q test. However, this was due to the changes between the results at post-course and follow-up measurements. There was no statistically significant change in the proportion agreeing with this statement between baseline and post-course measurement  or between baseline and follow-up .The issue of providing practical mental health training for primary health care workers in low-income countries is of broad interest to many working in the field of global mental health. This study makes an important contribution to the related literature by conducting an evaluation of a training program for community health workers in rural India using an existing facilitator's mental health training manual .The findings suggest that the mental health training program had mixed success in achieving its stated aims, but there were some encouraging outcomes. Importantly, there was only one participant out of seventy who did not complete the training program despite the extensive travel required for many participants to attend, and the considerable demands of participants' daily working and living duties.The training increased the ability of the community health workers to recognize depression and psychosis in vignettes, and reduced their faith in unhelpful pharmacological interventions. There was evidence of a minor reduction in stigmatising attitudes, although the changes were very limited and largely isolated to the depression vignette. It was unclear if the training resulted in a change in the participant's faith in recovery.The percentage of respondents correctly identifying the disorders in the vignettes in the baseline questionnaire was low relative to a previous survey of village health workers in a rural area of Maharashtra, India  , and mucAt baseline, psychosocial interventions, including physical activity and listening, were widely viewed as helpful by participants, and there was moderately high endorsement of potentially inappropriate treatments like appetite stimulants, vitamins, tonics, herbal medicines, and sleeping pills. These findings are comparable to those from the rural Maharashtran MHL survey mentioned above . The sigLess than half the participants believed that, with appropriate help, the persons described in the vignettes could fully recover without further problems. Additionally, belief in full recovery with no further problems decreased in the case of the psychosis vignette, however, it appeared that the significant decrease happened after the training (i.e. between post-course measurement and three month follow-up) making it difficult to directly attribute this change to the training intervention itself. In any case, these negative outcome expectations are concerning and have the potential to impede access to potentially effective treatments. The result may also reflect the local context of the study setting where there are no local psychiatrists or highly skilled mental health practitioners. Additionally, the training intervention itself did not focus on evidence for the effectiveness of treatments for mental disorders. This is an important consideration given that there is evidence indicating that belief in the effectiveness of treatments can help to reduce stigmatising attitudes towards people with mental disorders ,49.The training had a small impact on stigmatising attitudes towards people with mental disorders. Perhaps most importantly, after participation in the training fewer participants thought that the mental disorder described in the depression vignette was a sign of personal weakness, and only a small percentage agreed that it is best to avoid the person described in this vignette.The concepts of stigma and discrimination in the context of mental disorders have been well documented ,51. StigCulture influences the experience, expression and determinants of stigma, and the effectiveness of different approaches to stigma reduction, and further research on attitudes toward mental illness is required in India and other non-Western cultures. Results from a study on patients with schizophrenia and their caregivers in Bangalore  indicateThe content of the mental health training manual in this study incorporated a brief educational activity regarding the topic of stigma and discrimination that was focused on exploring the impact of stigma and identifying some common stigmatising attitudes. Our findings indicate that the effectiveness of the training in relation to stigma reduction was limited, and that it would be worthwhile exploring opportunities to have a greater impact in this area.Research has highlighted the importance of contact with people experiencing mental disorders as a strategy for changing stigmatising attitudes about mental illness ,59-65. AA second useful strategy for improving stigmatising attitudes as identified by Corrigan et al  is to prThere are several limitations to this study, including the lack of a control group. Whilst there is no obvious reason for knowledge and attitudes to change over time without having had the training, it is plausible that repeated testing alone may produce some change or that the participants gave certain responses to please the researchers due to a social desirability bias. It is also possible that a relevant event occurred in the general community  in-between points of measurement that may have caused participants to change their responses to the questions in the MHL survey. The lack of a control group makes it difficult to confidently explain some of the changes in participant's responses, particularly those changes between post-course measurement and three month follow-up. However, we believe the pre-test post-test design was appropriate for this evaluation study, and acknowledge that further research in this area would benefit from using a randomised controlled trial design with a control group who could be wait-listed to receive the training after data collection was completed.There are potential limitations to the cultural transportability of the MHL questionnaire. Despite careful and consultative adaptation, translation and piloting of the training program as well as the MHL questionnaire, we must be cautious in presuming an equivalence of meaning across cultures and languages. Certainly explanatory models of mental health and illness are culturally determined and therefore not equivalent across cultures, and this may effect the utility of the MHL survey, even though it was locally adapted. Subtleties of meaning and cultural factors may have influenced the way in which the facilitators interpreted the content of the training manual, the messages taken away from the training by the participants, and the interpretation of the questions in the MHL survey.A comparison of findings between this study and similar evaluations of mental health training conducted elsewhere should be interpreted with caution. Firstly, the community health worker participants had minimal knowledge of mental health as explained by the Western model of psychiatry. Terms such as depression and schizophrenia do not easily translate linguistically or culturally. Secondly, rather than using facilitators who were very experienced in the field of mental health, our study sought to replicate a "real world" situation involving facilitators who were local community health leaders and who had minimal prior experience in delivering mental health training of this nature. They were required to work with a manual written in English and translate complex concepts in a coherent way, whilst managing group conversations about the cross-cultural understanding of the material. The outcomes may well have been different if the facilitators were more experienced in both the field of mental health and the effective use of active-learning methods of training as designed in this manual.Finally, the training in this study was provided to participants in four consecutive days for logistical reasons, despite the recommendation in the training manual that it be spread out. Ideally, participants would have time to reflect on the material in-between sessions, particularly given that the material was new for most participants and complicated by the cultural issues that arise when discussing mental health in India.The impact of the training on the self-confidence of the community health workers, the rates of mental health consultations and referrals, and benefits for people experiencing mental health problems including improvements in pathways to treatment and recovery, remain unknown. To achieve substantial improvements in community mental health, it is likely that a comprehensive suite of interventions including community awareness programs and improved integration of mental health into primary health care is required.The mental health training facilitator's manual demonstrated potential to be an effective way to improve some aspects of mental health literacy among community health workers, including the recognition of mental disorders in vignettes and the perceived helpfulness of inappropriate pharmacological interventions. The training had a limited positive impact on attitudes towards people with mental disorders. Strategies for improving the training could include facilitating contact with consumers of mental health services, including stories of recovery, and providing information on the effectiveness of interventions for mental disorders.The authors declare that they have no competing interests.All authors contributed to interpretation of the findings and development of the manuscript. GA and SS coordinated the study implementation. GA and MK undertook the statistical analysis and wrote the first draft of the manuscript. SR and MK assisted with the study implementation. PC provided expertise on the local context of mental health and reviewed the questionnaire for appropriate translation of key concepts. AFJ designed the original mental health literacy questionnaire that was adapted for this study, and provided expertise on study design and data analysis. All authors read and approved the final manuscript.


Social epidemiology seeks in part to understand how social factors--ideas, beliefs, attitudes, actions, and social connections--influence health. However, national health datasets have not kept up with the evolving needs of this cutting-edge area in public health. Sociological datasets that do contain such information, in turn, provide limited health information.Our team has prospectively linked three decades of General Social Survey data to mortality information through 2008 via the National Death Index. In this paper, we describe the sample, the core elements of the dataset, and analytical considerations.The General Social Survey-National Death Index (GSS-NDI), to be released publicly in October 2011, will help shape the future of social epidemiology and other frontier areas of public health research. As new knowledge is accumulated, the field of public health periodically undergoes paradigm shifts. For instance, the sanitation and clean water revolution was brought about in part by our understanding of the germ theory. This, aThis new paradigm required an entirely new way of thinking about health and disease intervention. This challenge was met with longitudinal studies, such as the Framingham Heart Study, which ultimately showed that smoking, drinking, poor diet, and a sedentary lifestyle were major risk factors for poor health. This reHowever, a dataset has not yet been built that allows researchers to study the relationship between these characteristics and mortality. The General Social Survey-National Death Index (GSS-NDI) is an important first step toward creating a dataset that will help researchers understand how such social environments shape health.Social risk factors for poor health, such as poverty, failing schools, community characteristics, and weak social ties, appear to be powerful determinants of one's health and life expectancy-12. SuchPsychological risks also extend outward into the social spheres around us. Perceived racism may cause health problems among minorities who feel stigmatized,,21 but ith century, for instance, Rudolf Virchow posited that poor social policies were a major root cause of diseases such as typhus[The idea that social risks cause disease go back well over a hundred years, but has only recently taken root. In the as typhus. HoweverAs they stand, our national health datasets were designed to identify basic correlates of disease, so that these risks can be better described and tracked. But they lack critical information on one's social position, social networks, thoughts, feelings, attitudes, beliefs, and participation in civil society.If the GSS had been designed as a health dataset from the start it would have had the potential to advance social epidemiologic studies of health disparities beyond mere identification and description to a deeper understanding of the underlying mechanisms. It does contain a few health measures, such as self-rated health and basic information on behavioral risk factors such as smoking . However, it was primarily designed to answer traditional questions in sociology and political science. Fortunately, it is possible to link the GSS to prospective mortality data by cause of death for the years 1978 onward via the NDI, so it can be used to answer many new health questions. The GSS-NDI is rich in sociological variables and can provide some of the critical information necessary to better explore the relationship between mortality and social position, beliefs, social cognition, and social relationships.The GSS-NDI linked data from 18 waves of the GSS (1978 through 2002) to death certificate data from 1979 through 2008. We have not yet linked more recent years of the GSS to the NDI because very few deaths occur among subjects in the 4- to 6-year period following the survey. It is straightforward and inexpensive to create further linkages as additional mortality data becomes available.Up through 2006, the GSS sampled only English speaking subjects 18 and over in the non-institutionalized population. Spanish was added as a survey language that year onward, but will not be available in the current GSS-NDI dataset. The GSS employs a multi-stage probability sample. Interviewers conduct face-to-face canvassing after 3 PM on weekdays and on weekends and holidays. Over thEach subject within the GSS from 1978 through 2002 has a paper record securely stored with identifying information at NORC. To generate a matching file for the NDI, it was necessary to pull paper records for the GSS. Quality control checks included a comparison of names in household enumeration file with names in the questionnaire and a comparison of entered values with GSS public use data. NORC submitted 33,091 records from the GSS to the NDI for linkage. Of these records, 38 were outright rejected and dropped from the dataset because of incomplete or inaccurate information. An additional 223 records were dropped because there were multiple matches between GSS and NDI records. The final sample was therefore 32,830 subjects.The NDI utilizes a probabilistic matching algorithm to link identifiers from user provided data with death certificate information. This algorithm is designed to maximize the number of correct matches between a survey record and a death certificate, and minimize the number of incorrect matches. The NDI is capable and willing to conduct multiple matches between record files and death certificates. By attempting various permutations of potential errors in a given record file, the probability of a match is increased.Therefore, prior to submission of GSS records to the NDI, NORC created duplicates of the 660 GSS subject records that had an incomplete birth month, incomplete birth year, or a possible inconsistency in spelling of first or last name of the respondent, yielding a total of 9,824 duplications. These inconsistencies were identified only for those cases in which the paper record was initially entered incorrectly into the computer system (and subsequently caught on the second round of cross-checking), under the assumption that these permutations were common. In cases where the month of birth was missing, NORC created 12 copies of the original record, one with each of the twelve months inserted. Where the age did not match the birth year on the GSS, both birth years were entered.One issue that affected the match between the GSS identifiers and those in the NDI is that the GSS does not have Social Security numbers for the majority of its subjects. In the GSS, the provision of one's Social Security number was voluntary, and only collected from 1993 onward. Of the GSS records returned as potential death certificate matches, only about 21% had a valid Social Security number.Roughly 83 to 92 percent of deceased individuals, and 92 to 99 percent of living persons, would be expected to be correctly identified for datasets missing Social Security numbers. The preRecords flagged by the NDI as potential matches were not necessarily interpreted as deaths. Rather, because the NDI utilizes a lenient set of criteria to identify potential matches, these matches are regarded as a set containing both true and false death certificate matches. Of the 22,062 GSS records  that the NDI identified as having at least one potential death record match, 5,561 GSS records were matched with a single NDI record. However, 16,501 of the GSS records matched more than one NDI record, with one GSS case being linked to as many as 1,200 NDI records.To guide the user in assessing the death record matches, the NDI provides a probabilistic matching score. This score was generated by the NDI using previous matching data in which the decedents were known, and provides a reliable way of ascertaining each participant's vital status. Using this algorithm, the NDI generates a suggested vital status  for each matched NDI record along with the probabilistic matching score.However, the NDI's matching algorithm uses a weighed set of key identifiers  to assign the probabilistic matching score. This procedure disproportionately weighs the number of correct digits in the Social Security number, which was not appropriate for matching GSS records (because many such numbers were missing).After providing a probabilistic matching score, the NDI produces a class rating that includes five possible classes, dependent on the level of agreement on specific identifiers Table . AccordiFor the GSS-linked records there were no class 1 matches and a limited number of class 2 matches due to the lack of Social Security information and the fact that the GSS did not collect data on participant's state of birth. Subsequently, even for those few records that matched exactly on Social Security number, lack of state of birth information demoted those from class 1 to class 2, and matches that would have met criteria for class 3 were assigned to class 4.To correct for our missing matching variables, we used a modified cutoff score that lowered the threshold for obtaining a status 1 match  by the exact amount that the NDI gives records matching on seven or eight digits of the Social Security number. Where the GSS records had Social Security number available, the NDI's suggested cutoff score was accepted as accurate.To identify the correct match, we first selected the match with a combination of the highest class and score provided by the NDI. Of the 22,062 GSS records that the NDI linked with one or more NDI records, we identified 9,285 GSS records (or about 42% of matched records) as having a vital status of deceased. Of these GSS records identified as deaths, the score plus class evaluation flagged 6,504 NDI records (about 70%) as an exact match, but 30.5% of GSS records were linked to more than one NDI record with precisely the same score and class combination. To resolve these multiple matches, we examined the degree to which GSS identifiers agreed with NDI identifiers, and flagged those with the highest number of agreeing identifiers.The final version of the GSS-NDI dataset contains 32,830 total records, of which 9,271 are deaths. Table Of the 9,271 GSS records determined to have a vital status of 'deceased', 99.84% were linked to underlying cause of death information. Until the year 1999, the NDI provided users with cause of death using codes from the Ninth Revision of the International Classification of Diseases (ICD-9) and Tenth Revision (ICD-10) codes thereafter. In order to unify the different coding schemes, we collapsed cause of death into 285 mutually-exclusive categories using the single-level Clinical Classification Software (CCS) system.Whereas the NDI's method for evaluating matches relied heavily on the Social Security number, our algorithm places emphasis on identifiers used in the match. Our objective was to ensure that our technique was conservative enough to eliminate false positives and provide an accurate record matching. We tested this by utilizing a sub-sample of our matches - the 927 records that were qualified as 'class 2' matches by the NDI's algorithm and thus had a valid Social Security number.To perform our comparison, we took these matches and modified them to appear as though these records were missing Social Security numbers. This was achieved by reducing the probabilistic score of each match by the Social Security number weight. Next, we re-ran our evaluation method and selected the best match according to the criteria described above. This method identified 784 deaths out of the 927 records that were initially categorized as class 2 matches, proving to be somewhat more stringent than the NDI's evaluation scheme, which designates 860 of the class 2 matches as 'deaths' (a difference of about 8.2%). In effect, this test demonstrates that although the Social Security number provides important information for the linking process, it is not essential for match evaluation. When techniques are undertaken to de-emphasize Social Security number in the match evaluation process, as is the case with our methods, NDI record matches can be assessed so as to maximize sensitivity without sacrificing specificity.The GSS-NDI represents a new and essential tool to be used by social epidemiologists. The GSS-NDI will have time trends available for roughly 1000 variables, which will allow researchers to examine relationships between social factors and mortality over time. Because the sample is nationally-representative, repeated variables also open the door to the creation of synthetic cohorts.  Several thousand other variables are available in the GSS-NDI, although many of these were asked during a particular wave of the GSS, and therefore do not have potential for time trend analyses.In addition, the primary sampling unit information  can be used for hierarchical linear models. We are currently in the process of setting up a unit that can manage requests for spatial data that cannot be released due to concerns surrounding the possibility of identifying a subject.One variable, a four-point self-rated health scale  is available for all years of the GSS-NDI in the public release. This will allow researchers to better probe questions of causality. For example, if we wished to examine the relationship between wealth and mortality, we could limit the analysis to respondents who report excellent or good health at the time of survey. This way, we would be more certain that we were measuring the effect of wealth on illness and not illness on wealth.We plan on releasing the GSS-NDI to the general public in October of 2011. The dataset will be de-identified, and available for use by researchers everywhere. It has been granted approval from the Institutional Review Board at Columbia University. To ensure that subjects cannot be identified, only the year of the subject's birth and the de-identified primary sampling unit (rather than the subject's city or state of residence) will be available in the public release dataset.In the meantime, a team of inter-disciplinary researchers is testing the dataset and developing statistical code that can be used as a toolkit for future analyses. Already underway are studies surrounding how changes in discrimination against lesbians and gays may be influencing their health, how the falling academic performance of males is influencing their health, and various research questions surrounding social capital and mortality, variations in mortality with economic cycles, and the underlying nature of the religion-mortality association.The newly constructed GSS-NDI dataset was designed to meet the needs of social epidemiologists investigating emerging areas of public health. Researchers who have exhausted the capabilities of our currently available national health datasets ought to find the dataset invaluable in furthering their studies.The dataset is expected to be publicly available in October 2011 from NORC.The authors declare that they have no competing interests.PM conceived of the paper, wrote the primary text, and contributed to the paper's ongoing development. JK and TS assisted with data preparation and contributed to the development of the paper, GJ conducted the data analyses and contributed to the development of the paper, and ZR helped conceptualize the paper and contributed to its development. All authors read and approved the final manuscript.


Attention and inhibition are core executive-function deficits in FRagile X syndrome (FXS). This pilot study evaluated the feasibility, reproducibility, and clinical relevance of the KiTAP, a computer-based pictorial measure of attention and inhibition with an enchanted-castle theme, in an FXS cohort.The 8-subtest KiTAP battery (as many subtests as each could perform) was given to 36 subjects with FXS, of variable age and cognitive/behavioral functioning, and 29 were retested, with an interval of 2 to 4 weeks between sessions. Subjects were rated by parents on the Aberrant Behavior Checklist-Community Edition (ABC-C) and Behavior Assessment System for Children, Second Edition (BASC-2). Feasibility, ceiling and basal effects, and data range and distribution analyses were used to eliminate outliers and invalid data points. Reproducibility of scores was analyzed using intraclass correlation coefficients (ICCs) and validity/clinical relevance was assessed by correlating KiTAP scores with ABC-C and BASC-2 scores.P < 0.01). Only minor differences in performance on the KiTAP were seen between mental age-matched cohorts of subjects with FXS and non-FXS intellectual disability.Most of the participants with FXS were able to complete the Alertness, Distractibility, Flexibility, and Go/NoGo subtests.About 50 to 60% completed the Visual Scanning and Vigilance subtests, and 20 to 25% completed the Sustained Attention and Divided Attention subtests. A panel of seven scores from four subtests were identified as feasible for most subjects, lacked excessive ceiling, basal, or learning effects, exhibited an acceptable range and distribution of scores, had good reproducibility (ICC > 0.7), and correlated with behavioral ratings for hyperactivity or attention (The KiTAP can be administered to cohorts with FXS over a wide range of function with valid reproducible scores. With additional validation, it could represent a useful outcome measure for assessment of attention/executive-function abilities in clinical trials targeted to these core deficits in FXS. FMR1 , which leads to transcriptional silencing of FMR1, and loss or significant reduction of expression of the gene product, the Fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that acts as a negative modulator of dendritic translation. Loss of FMRP results in excessive and dysregulated dendritic translation, producing aberrant dendritic morphology and synaptic plasticity, and leading to abnormal development and cognition [Fragile X syndrome (FXS) is the most common known inherited cause of intellectual disability (ID), learning disability, and autism, with an estimated frequency in the range of about 1:2500 to 1:4000 [ognition .Recent advances in the neurobiology of FXS have suggested that many of the phenotypic features of the disorder arise from enhanced activity of translational activation pathways regulated by metabotropic glutamate receptors 1 and 5 , as a result of absence of FMRP . In suppThus, there is an urgent need to develop objective and well-validated outcome measures that assay core FXS phenotypes. Boys with FXS show larger attention and executive function (EF) deficits than do mental age (MA)-matched boys with Down syndrome or typically developing boys, particularly in areas involving switching attention and inhibiting repetitious behavior . Thus, EThe Test of Attentional Performance for Children  is a computer-based CPT and EF battery  that hasIn this study, we sought to determine the feasibility , reproducibility (consistency of scores in a test/retest setting), and validity  of the subtests of the KiTAP in a population with FXS. Additionally, scores were compared with those of MA controls with ID as a means of evaluating specificity of performance patterns on the KiTAP in FXS.The study was approved by the institutional review board at Rush University Medical Center (RUMC), and all participants or their parents signed informed consent according to an approved protocol.± 10.24 years of age, range 7 to 50) with the full Fragile X mutation confirmed by standard testing using Southern blot combined with PCR. All participants were tested using the computer-based KiTAP test.Participants with FXS were recruited through the Fragile X Clinic and Research Program at RUMC, In total, 36 participants  18.0 Subject participation was not limited by age, gender or IQ score because the intent of the study was to evaluate a wide range of subjects to determine the age and functional range over which the KiTAP could be used as an outcome measure in clinical trials with subjects with FXS. It was important to evaluate the KiTAP in both genders, and in both children and adults, given that trials of new targeted treatments for FXS would probably involve all these groups. However, all subjects tested were verbal and able to speak at least in phrases, and all had sufficient receptive language to follow basic directions.When available, cognitive (IQ) assessments were obtained from previous tests  performed at RUMC or from psychological assessments at the participant's school. Subjects for whom IQ test results were not available were not precluded from participating in the study. IQ assessments represented scores from the Wechsler Intelligence Scale for Children (WISC), Wechsler Adult Intelligence Scale, or Stanford-Binet tests, and were available for 24  participants with FXS. MA was calculated from IQ using the formulawith a maximum value of 15 used for chronological age.The comparison cohort, consisting of 25 individuals with ID , was recruited and tested using identical protocols at the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute at UC Davis. This group consisted of 12 subjects with idiopathic ID, 8 with Down syndrome, 2 with fetal alcohol syndrome, 1 with 17q21.31 deletion syndrome, 1 with 22q11.2 deletion syndrome, and 1 with ID and autism. IQ measures, performed with the WISC or Stanford-Binet tests, were available for all ID participants. Although the FXS and ID subjects were tested at different sites, the methods for administration of the KiTAP were standardized as much as possible through phone conferences and a face-to-face meeting. The ID group was examined to see if there were differences in performance patterns that might be attributed to the FXS phenotype alone rather than to general ID. For this purpose, retest was not necessary, and so the ID group was not retested.Distribution of psychotropic medication use in the FXS group was as follows: no drug (14 subjects); one drug (10 subjects), two drugs (8 subjects), and three drugs (2 subjects). Medications used were stimulants (15 subjects), selective serotonin uptake inhibitors (SSRIs)/antidepressants (10 subjects), antipsychotics (4 subjects), and lithium (1 subject).. Distribution of psychotropic medication use in the ID group was: no drug (18 subjects), one drug (3 subjects), two drugs (3 subjects), and three drugs (1 subject). Medications used were stimulants (2 subjects), SSRIs/antidepressants (2 subjects), antipsychotics (4 subjects), valproic acid (1 subject), and clonidine (2 subjects).The KiTAP is composed of eight subtests designed around a theme (an enchanted castle) specifically designed to be accessible to young children, thus providing more motivation to sustain interest in testing than CPTs and other EF batteries based on abstract symbols. Each subtest measures a different aspect of cognition: alertness, distractibility, divided attention, flexibility, reaction control (inhibition), sustained attention, vigilance, and visual scanning. The Alertness subtest (The Witch) requires subjects to tap a button every time a stimulus (a witch) appears on the screen. The Distractibility subtest (The Happy and Sad Ghosts) requires subjects to tap a button when a target stimulus (a sad ghost) appears on the screen while ignoring distracters that appear shortly before the stimulus; subjects are supposed to 'cheer up' the sad ghost by pushing the button and must not respond when the happy ghost because it does not need cheering up. The Flexibility subtest (The Dragons' House) requires subjects to alternate between identifying blue and green dragons which seem on random sides of the screen by tapping one of two buttons. The Go/NoGo or inhibition subtest (The Bat and the Cat) requires subjects to tap a button when the target stimulus (a bat) is presented, while refraining from hitting the button for the non-target stimulus (a cat). The Visual Scanning subtest (The Witches' Parade) requires subjects to scan a grid of 25 witches; subjects press one button if all witches are flying in the same direction, and hit a second button if one of the witches is flying in the opposite direction. The Vigilance subtest (The Mirror) is similar to Go-NoGo, but the target stimulus (a ghost with orange eyes) appears infrequently, and the test is much longer (approximately 10 minutes). The Sustained Attention subtest  features a sequence of different-colored ghosts; subjects press a button when two ghosts of the same color appear sequentially. The Divided Attention subtest (The Owl) is the only task requiring processing of an auditory stimulus in addition to visual stimuli, and requires subjects to simultaneously listen to a series of high and low owl sounds and watch for target stimuli (owls with closed eyes). Subjects must press a button either when a sound is repeated or when the target stimulus appears.Subjects spent up to 90 minutes completing all KiTAP subtests if they were able to perform the entire test (only five subjects). Most subjects spent about 30 minutes doing the test, in which they completed 4 to 5 subtests, but were unable to focus upon, or did not understand what to do in subsequent longer subtests. Subtests were administered in the order: Alertness, Distractibility, Flexibility, Go/NoGo, Visual Scanning, Vigilance, Sustained Attention, and Divided Attention. Because the last four are much longer tasks, and based on previous experience of the length of task that typically functioning individuals with FXS can tolerate, a decision was made to begin with the subtests most likely to be completed by a wide range of participants, and to leave the most difficult and longest subtests (Sustained Attention and Divided Attention) until last. We continued to administer subtests of increasing length and difficulty until the subject refused to do any more, until it became clear to the examiner that the participant was not making any real attempt to perform the task, or until the subject was not able to show that they understood the sample pretest. Although there is the possibility that this testing order may have introduced bias into the analysis of the ability of subjects with FXS to complete the subtests, the testing order was necessary, based on initial experience with pilot subjects, as administering the longer and more difficult tests first was likely to lead to refusal, thus precluding later administration of the tests the subjects would be most likely able to complete. The order of test administration was therefore driven predominantly by the length of the task and the restrictions posed by the limited attention of subjects with FXS. Further, it is important in clinical trials or for interventions in the clinic to use the same test order before and after administration of the intervention, and the most important focus of this study was to determine the reliability of the KiTAP subtests for intervention and longitudinal studies that would involve multiple testing sessions.During the tests, subjects were aided by a research assistant (RA). Before the start of each subtest, the RA explained the goal of the test. The subject then took a short pretest to allow their understanding to be evaluated, and if necessary repeated the pretest after further explanation, up to a maximum of three pretests. If the subject was ultimately able to perform the pretest for a given subtest correctly, and the RA perceived that the subject understood the test, the subtest was then administered. If the subject could not show that they understood what to do on the subtest, the subtest was listed as 'not feasible' for that subject. The RA also encouraged subjects to continue working, and gave positive reinforcement about performance during subtests, provided breaks between subtests when necessary, and dismissed subjects when they finished all subtests or were judged unwilling or unable to continue testing. The administration method was consistent between both centers (Rush and UC Davis), including the scripts used to explain tests to subjects and the prompting strategies. The scripts used to explain the task for the pretest were those in the KiTAP instruction manual, but these were repeated and rephrased in simpler language (same content) when subjects did not understand and were unable to perform the pretest correctly. Prompts to encourage the subjects to continue working on the task were given when they stopped paying any attention to the screen and started to do something else or were clearly no longer engaged in the testing . Subjects were given non-specific positive feedback for continuing to work regardless of whether they were giving accurate responses or not . Subjects were not helped with the test or told to push the button when stimuli appeared. As would be expected, the number of prompts required varied depending on the subject.Of the 36 subjects with FXS who were tested with the KiTAP, 29 were retested 2 to 3 weeks later by the same tester in the same setting. The other seven subjects  were not retested because of scheduling issues. No changes in psychotropic medication were allowed between testing sessions. IQ data were available for 22  subjects who completed retesting.At the initial session, parents of all participants, including adults who consented for themselves, filled out both the Behavior Assessment System for Children-Second Edition (BASC-2)  and Abert-test. Because this was a pilot study, significance was set at P = 0.05 for all comparisons, without adjustment for multiple comparisons.Data analysis was performed using a spreadsheet . Several measures from each KiTAP subtest were analyzed including number correct, errors, omissions, median reaction time, and SD of median reaction time. Raw scores were used because the normalized scores on the KiTAP previously generated from a typical population of children would not be relevant to individuals with FXS. For each of these measures, the distribution of the scores was plotted, and the intraclass correlation coefficient (ICC) was computed in SPSS for measures that had an acceptable distribution  after outliers and non-valid data points  were eliminated. To examine clinical relevance, Pearson correlations between KiTAP scores and eight behavior checklist scores  were calculated. For all subjects with FXS and ID who had completed IQ testing, MA values from the assessments were used as estimates of cognitive level to allow determination of the minimum ability required for valid testing in both children and adults  and to allow MA-matching in the FXS/ID comparisons. Correlations between MA and scores on KiTAP measures shown to be valid and reliable were calculated. KiTAP subtest scores in FXS and ID groups were compared using the P = 0.01 for age comparison with both total FXS cohort and retested FXS cohort).Demographic information is shown in Table In the feasibility analysis for the FXS group Table , the AttBasal and ceiling effects were related to MA for the subjects with FXS for whom we had valid IQ scores Table . Basal eICCs were calculated for measures that did not show significant basal, ceiling, or learning effects, using data from subjects who successfully completed both trials Table . After aPearson correlations between KiTAP subtest scores and clinical ratings of behavior as measured by the ABC-C and BASC-2 are shown in Table P = 0.25). Mean scores on KiTAP subtests were compared, and a significant difference was found for only two: the FXS group had fewer errors on the Distractibility (P = 0.053), and more errors on the Flexibility (P = 0.03) test.Relationships between performance on the four KiTAP subtests that could be completed by most subjects (first testing session for subjects with FXS) and level of function were compared for the FXS and ID groups Table . This anIn this study, we sought to determine the feasibility, reliability, and validity of the KiTAP in FXS. Our data demonstrates that several measures from the KiTAP show an adequate range and good feasibility, are relatively stable over time, and are correlated with clinically meaningful behavioral constructs. The KiTAP subtests had different ranges of MA for which there were no ceiling, basal, or learning effects, and thus subjects of all MAs received a valid score on at least some of the subtests. In general, however, a significant minority of subjects with FXS could not perform the Vigilance and Visual Scanning subtests, and the large majority could not perform the Sustained Attention and Divided Attention subtests; the former because of the subjects' inability to maintain attention and motivation long enough to complete the task, and the latter because of the high level of task complexity and the subjects' inability to remember directions for both auditory and visual stimuliEach of the subtests that were feasible for the majority of subjects with FXS had specific measures with an acceptable range and distribution of scores, and good test/retest reproducibility (ICC < 0.6). Finally, each of these feasible and reproducible measures showed some correlation with clinical behaviors, with the exception of Go-NoGo reaction time, and these correlations were mostly in the expected direction with respect to the clinical behaviors. For example, subjects who scored higher in Hyperactivity on ABC-C and BASC-2 tended to commit more impulsive errors, and subjects who scored worse on Adaptability tended to commit more errors on the Flexibility subtest. However, reaction time data was more difficult to interpret. Indeed subjects showing shorter reaction times on flexibility had higher hyperactivity ratings. This may reflect a relationship between more impulsive responding (and therefore shorter reaction time) and hyperactivity on the BASC-2, although other reaction time scores on KiTAP subtests seemed to be positively correlated with hyperactivity, suggesting that hyperactivity may result in more off-task behavior and slower reaction time. These results are difficult to reconcile, but may be just an effect of small sample size that do not reflect a clinical pattern. Our data suggest that some scores on the KiTAP may reflect the severity of aspects of the FXS phenotype, but this will require more study in a larger sample.It is difficult to know in the FXS population whether the subtests of the KiTAP were specifically measuring the EFs they were designed to measure. Despite the correlations with the behavioral forms, which represent a crude screen for clinical relevance, there is no validated EF measure or CPT for cohorts with FXS, and therefore there is no standard for comparison to evaluate the specificity of the subtests in FXS. Previously, CPTs have been used in FXS cohorts in a clinical trial setting, and to measure medication effects on EF and attention in patients treated in clinical practice. When administered to 48 adults with FXS in a clinical trial, the IVA produced data that were impossible to analyze . In thisWe found that many, but not all, KiTAP measures correlated with MA, both in the FXS group and the ID group. There was no association between chronological age and KiTAP performance in either group, and for the MA-matched FXS and ID groups used to compare the KiTAP subtest scores, there was no significant difference in chronological age, so age should not have been a factor limiting the comparisons. For most KiTAP measures there were no significant differences in score distributions between the two groups for the different subtests, suggesting that KiTAP gives a general measure of executive-function ability both in subjects with FXS and in those with other causes of cognitive impairment. The difference in flexibility scores, with worse performance in the FXS group, is not unexpected given that perseveration is a prominent feature of the FXS phenotype. However, it was unexpected that the FXS group made fewer errors on the Distractibility sub-test; this may be due to the high demand for rapid visual processing inherent in the test (stimuli are presented very rapidly) coupled with the relative strength in visual processing in FXS , or to sThis pilot study had a number of limitations related to the sample of subjects examined.1) The sample size is relatively small, although the study was intended as a pilot study to help determine whether further work with the KiTAP in FXS should be pursued. Given the relative rarity of FXS, this study is similar in size to other pilot studies of measures in FXS.2) Not all subjects provided IQ results; however, subjects with missing IQ scores were generally well distributed across KiTAP scores and age. The one exception to this rule was that the four subjects who scored poorest on KiTAP across all subtests did not have valid IQ scores. One of these subjects was probably too low functioning to complete valid IQ testing. The other subjects had very substantial clinical issues with hyperactivity and distractibility, which probably contributed to their lower scores.3) Formal testing for autism was also not available for the majority of the subjects in the cohort, and thus the effects of autism status on performance could not be assessed; however, this analysis was outside the scope and purpose of the study in any case, and would be a topic for further research.4) Although medication overall did not seem to have a major effect on group performance levels, it is possible that differences in the FXS and ID groups in the fraction of subjects treated with medication (the FXS group had a higher level of medication use) could have affected the comparisons between the two groups. More definitive analysis of medication effects and an understanding of the effects of individual medications on performance will require further work with a larger sample size.5) Although females with FXS generally have a higher level of functioning than males, the number of females enrolled was insufficient to generate a sample size adequate to analyze their data separately from the males, hence we cannot be absolutely sure that the relationships between KiTAP performance and BASC-2/ABC-C scores would be the same in females and males.6) The FXS and ID groups were tested at different sites, and despite attempts to ensure similar protocols and administration methods, differences in administration technique could have affected the results.7) The KiTAP subtests were administered in a fixed order, which may have affected the assessment of subjects ability to perform the subtests administered later in the battery, and the examiner prompts, which were somewhat variably used across subjects, were not counted systematically for analysis of their effect on test feasibility and validity8) The BASC-2 has not been formally normalized or evaluated in FXS, and there may be better attention measures to use for KiTAP validity analyses, although no other parent-report attention measures have been formally validated for FXS, and understanding the optimal measure for use to assess cohorts with FXS will require further study.9) Another potential limitation of the KiTAP is the difficulty in defining a true floor for scores. Our criteria for failing a subtest only included refusal or inability to stay engaged. For a number of the subtests, subjects who are engaged in the subtest may receive a non-zero score, even if they do not understand the idea behind the test. This could lead to a situation in which a subject might have an improvement in cognitive function that was not measured by the test, if they remain beneath the threshold of actually understanding the test. However, the overall correlation of measures with MA and clinical behavior is reassuring that, in spite of this problem, KiTAP does serve as a good measure of function.10) Lack of immediate feedback during testing may be a further limitation of the KiTAP. Because no immediate feedback about incorrect or correct responses is given by the KiTAP program during the test, subjects might become confused about the purpose of the test or disinterested in participating. The RA administering the test addressed this problem by frequently encouraging the subject to continue to participate in the task and by giving positive feedback for participation.11) However, this strategy does have the disadvantage of adding another potential limitation: the subject performance is made somewhat dependent on the motivation and technique of the test administrator, and creates problems in interpretation of the subject's innate attention/EF skills as measured by the task. Such a limitation may be unavoidable with an FXS population because of the difficulty in getting subjects with FXS to finish the testing tasks at all without such encouragement. We attempted to at least keep the assessments consistent between subjects and trials by using the same test administrator for all trials of a given subject at each site, and creating a common protocol for administering the test. Lack of feedback about incorrect responses is likely to be helpful in that subjects do not really experience a sense of failure or frustration about their inability to perform.12) Finally, the KiTAP castle appears on first impression to appeal more to children than to adults with FXS. Although older adult subjects may have been less engaged by the castle theme than children, this did not seem to specifically affect performance, as many adults with FXS remain interested in and enjoy cartoon characters, and some of the adults in the study expressed interest in talking about the characters after the testing session. Regardless of age, the castle 'characters' seemed to sustain attention and to be of greater interest than the abstract stimuli used in the IVA and other standard CPTs. Validated computerized EF batteries with adult visual themes are an area that could be explored in future test development and validation.Specific measures on the KiTAP that emerged as feasible for the majority of subjects were Alertness reaction time, SD of Alertness reaction time, Distractibility errors, Go/NoGo errors, Flexibility errors, Flexibility reaction time, and Vigilance reaction time Table . These mIn this pilot study, some measures on at least some subtests of the KiTAP showed adequate feasibility, reliability, and clinical validity for subjects with FXS across a wide range of function. This is in contrast with previous CPTs which have not allowed meaningful administration to such a range of individuals with FXS without producing substantial ceiling and floor effects ,18. GiveThe authors declare that they have no competing interests.AK recruited and carried out testing with most of the FXS participants at RUMC, performed data and statistical analyses, and assisted with drafting the manuscript. AS assisted with data analyses. FA carried out testing with subjects at UC Davis. CH assisted with subject recruitment and carried out some testing with subjects at RUMC, and assisted with drafting the manuscript. CT assisted with recruitment and testing with subjects at RUMC. DH participated in the conception and design of the study, performed some data and statistical analyses, and assisted with drafting the manuscript. EBK conceived of, designed and coordinated the study, and participated in drafting of the manuscript. All authors read and approved the final manuscript.


Helicobacter pylori (H. pylori) is associated with gastrointestinal tract disorders, ranging from chronic gastritis to gastric adenocarcinoma; there is also evidence of a possible association with gastric lymphoma and peptic ulcer. Published reports support the existence of geographic regions where this bacterium is endemic and where H. pylori colonization occurs at a very early age in populations living in precarious sanitary conditions. For this reason, gastric cancer is one of the most common cancers in the world in low-resource countries and, as noted in the accompanying articles [One of the greatest areas of scientific progress has been the identification of certain infectious agents that are implicated in the carcinogenic process. This new knowledge has had broad repercussions not only in the application of new primary prevention options, such as prophylactic vaccines, but also in the definition of infection biomarkers that can be used as screening alternatives or as prognostic markers for neoplasia. We now know that chronic infection with the pathogenic bacteria articles , 2, one H. pylori and gastric cancer. On the one hand, we should gain a more precise understanding of the natural history of H. pylori infection and, as a consequence, learn about the triggering mechanism(s) related to chronic exposure in the development of gastric adenocarcinoma. However, we also know that reducing future incidence of gastric cancer is possible by improving the living conditions of the general population from a hygienic perspective, as confirmed by Porras et al. [H. pylori as a part of normal human microbiota [H. pylori [From a public health perspective, there are currently two major lines of research and action in regard to s et al.  in this crobiota . This licrobiota , which p. pylori , preventH. pylori research consortium was formed with the primary mission of evaluating effectiveness, feasibility, and cost of eradication using an antimicrobial regimen specifically for Latin America. Results are encouraging and demonstrate the technical and academic abilities of the participating groups [H. pylori infection [Research groups in Latin America have generated an invaluable scientific tradition for generation of new hypotheses , evidencg groups . They alg groups , ecologig groups , assessmg groups , confirmnfection , and a mnfection .The work presented in this special edition of the journal along with the recently formed consortium underscores the enormous potential that multi-centric regional studies have for addressing the magnitude of health problems, and even more important, identify solutions for prevention of future disease. These invaluable resources allow us to postulate new research hypotheses and to consolidate a regional group, which can contribute to improving therapeutic strategies for prevention and control of gastric cancer and build the foundation for evidence-based regional public policies aimed at improve the quality of life of the population.