The Great East Japan Earthquake caused a gigantic tsunami which devastated coastal areas of northern Japan on 11 March 2011. Despite the large number of ‘resident survivors’ who continued to reside in their damaged houses on the second or upper floors, research on the mental health of these individuals has been limited. This study explored the prevalence of depressive reaction and risk factors for depressive reaction among these resident survivors.A cross-sectional household health support needs screening was conducted for resident survivors in Higashi-Matsushima city, Miyagi prefecture, two to four months after the tsunami. The health interview that was conducted including mental status, assessed by the Patient Health Questionnaire-2 (PHQ-2).Of 5,454 respondents, 8.1% had depressive reaction. After adjustment by the number of weeks from the tsunami and the mortality rate at each respondent's place of residence, depressive reaction was significantly associated with house flooding below or above the ground floor , the unavailability of gas supply , being female , middle aged or elderly , regular intake of psychotropic medicine(s) since before the tsunami  and the presence of one to five or more than six cohabiters .The results suggest a considerable psychological burden (depressive reaction) following the tsunami among resident survivors. Special supports for families with psychiatric problems need to be considered among resident survivors. Restoration of lifeline utilities and the strengthening of social ties of persons living alone may help prevent depressive reaction among resident survivors after a tsunami. On the afternoon of 11 March 2011, a massive magnitude 9.0 undersea earthquake (the Great East Japan Earthquake), with an epicenter approximately 70 km off the Pacific coast, caused a gigantic tsunami that devastated the coastal areas of northern Japan. Tsunami waves reached a height of 40 m. By the end of 11 March 2013, 15,882 people had been confirmed dead, and 2,668 were missing The coastal city of Higashi-Matsushima in Miyagi prefecture had 65% of its urban areas engulfed by the tsunami, which travelled inland as far as 3 km from the coast. Inundation rates were highest in municipalities hit by the tsunami In the wake of the tsunami, evacuation centers were overcrowded with a large number of displaced people who accounted for up to one-third of the inhabitants To assess this situation, a household health support needs screening survey was conducted by the local health office in areas inundated by the tsunami, except those in which all homes had been disappeared Mental health issues are a significant concern after tsunamis, such as the one that occurred following a massive undersea earthquake along Sumatra's northwest coast in Indonesia in 2004. Researches have shown a greater prevalence of depression among displaced persons after a tsunami than non-displaced persons Previous studies have reported that social ties are linked to a lower risk of mental health problems A better understanding of the impact of tsunamis on the mental health of resident survivors is required for designing and implementing effective public health responses that meet underlying needs for care and support. Therefore, this study aimed to explore the prevalence and correlates of depressive reaction among resident survivors after the tsunami following the Great East Japan Earthquake in 2011.We conducted a cross-sectional household health support needs screening.The sites targeted for the household screening included 31 local administrative areas that had been completely or partially flooded by the tsunami. In total, 7,084 registered households were targeted, and 4,672 (59.9%) households were finally confirmed to reside by the screening The local health office started the household screening on April 26 and finished on July 29, 2011. Public health nurses in Higashi-Matsushima city conducted the screening, together with public health nurses from across the country who had come to assist local health officers. There was a tendency for areas with more severe destruction to be screened earlier in order to meet potentially greater demands there as rapidly as possible.The target population of the screening was composed of individuals who continued to reside in their damaged houses in tsunami-flooded areas. Because of the way in which the census was administered in the areas which were completely or partially flooded, participants whose houses were not flooded were included in the screening. People were included in the study if they resided in the targeted areas, were aged 15 years or above, and were contactable in person at home. The exclusion criteria included people who had evacuated to temporary shelters or moved outside the tsunami flooded areas, were below 15 years of age, or could not be contacted at home. Older adults who had difficulty forming answers to these questions on their own, e.g., dementia, were also excluded from this mental health screening.Although a total of 15,503 registered residents of all ages were screened, ultimately 5,455 residents 15 years old or above were contacted in person at home. More than half of the household members were absent at the time of the survey because of work or school. Therefore, the individuals included in the screening were also likely to have been persons who were home at the time of the tsunami (Friday afternoon).A questionnaire comprise of 11 categories that obtained demographic data such as age and gender; physical status ; mental status, including depressive reaction and/or posttraumatic stress reactivity; and the impact of the tsunami, including flooding in the house, destruction of the house, disruption of lifeline utilities , food intake frequency and direct exposure to sea water at the time of the tsunami was administered to participants. However, variables related to deceased or missing family members and lost jobs were not included in the questionnaire, as the public health nurses had determined that the survivors were reluctant to talk about such matters during the pre-visits they had conducted.The dependent variable in this study was “depressive reaction,” which we assessed with the Patient Health Questionnaire-2 (PHQ-2). The PHQ-2 has been validated with with general population We made adjustments to the response categories. The adjustments were put back to the PHQ-2's original questionnaire (PRIME-MD) Respondents were deemed to have depressive reaction if they agreed with both items and reported difficulty performing common activities of daily living.In the questionnaire, social tie indicators were addressed by numbers of cohabiters. Social ties are often provided by cohabiting families, communities, schools, and places of work, but the tsunami had destroyed many previously existing community links and resident survivors were now sporadically distributed across devastated areas. Therefore, the public health nurses decided not to ask questions regarding community, school, or workplace ties, which they had determined would distress the respondents. The number of cohabiters was categorised into tertile groups to explore if a bigger number of cohabiters was differently associated with the risk of depressive reaction.The impact of the tsunami was assessed by number of weeks from the tsunami to the screening and degree of flooding in the house. Data on flooding in the house was categorised into three groups, in descending order of severity: above the ground floor, below the ground floor, and no flooding.The availability of lifeline utilities  was also examined to determine whether each of these was available. Behaviour and attitudes were expected to be influenced by any limited availability of lifeline utilities under post-disaster conditions. We considered the availability of water, electricity, and gas in adjusting for the impact of the tsunami on mental health.The demographic information collected in this study included age and gender. Age was also categorized into three groups  according to the criteria outlined by the World Health Organization (WHO) for people of middle age and the elderly There may have been individuals that had developed depression before the tsunami and thought it would be desirable to exclude these people from the target population. However, as the majority of medical records were lost in the tsunami, we could not identify these people through the normal means. While many of those in the target population could not remember the exact names of the medicines they had been regularly taking, most were able to recall the broad categories of their medicines . Therefore, in order to understand the respondents' mental health status prior to the tsunami, we asked whether respondents regularly took or were regularly taking any kinds of psychotropic medicines, such as for epilepsy or schizophrenia, or a tranquilizer or sleep inducer, since before the tsunami.IBM SPSS Statistics version 21 for Windows was used to analyse the data. We conducted chi-square tests for univariate analyses. We also performed two logistic regression analyses to explore the association of the tsunami with depressive reaction using the forced-entry method, after examining multicollinearity.Logistic regression models were conducted for depressive reaction after adjusting for number of weeks since the tsunami and the mortality rate at each respondent's place of residence P-values of ≤0.05 were considered to be statistically significant.All participants were informed about the objectives, the screening procedures, the possibility that the results would be utilized for a study, and the confidentiality of the study, with the aid of a prepared information sheet. The participants were explained an opportunity to refuse inclusion at any time during the screening. Verbal consent was obtained prior to enrolment, although the Ethical Guidelines for noninterventional epidemiological studies without human specimen collection does not require informed consent stipulated by the Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Welfare, Labour and Welfare, Japan. Written consent was not obtained, as it was not the requirement for noninterventional epidemiological studies without human specimen collection. For subjects aged below 18 years, we conducted the screening after obtaining parental agreement and that of their children. We prepared and retained a name list of the participants who agreed to participate in the screening. All household screening protocols and procedures, including the informed consent procedure, were reviewed and approved by the Research Ethics Committee of the National Center for Global Health and Medicine, Japan . The National Center for Global Health and Medicine acted in collaboration with the city of Higashi-Matsushima with regard to the restoration of public health. A total of 87 household members declined to participate in the screening. Numerical codes were used in place of names at the time of analysis to ensure confidentiality.p = 0.009), age (p<0.001), regular taking of psychotropic medicine(s) since before the tsunami (p<0.001), the height of house flooding (p<0.001), the number of cohabiters (p = 0.012) and the unavailability of gas supply (p = 0.002).The results of this study demonstrated that 8.1% of the resident survivors had depressive reaction from two to four months after the 11 March tsunami. To our knowledge, this is the first study to report on depressive reaction among resident survivors after a tsunami.The results showed a much higher prevalence of depressive reaction among respondents than in the general population . That study showed that, within the previous year, the prevalence rates of depression were 2.9%  The prevalence of depressive reaction decreased along with the increase in the number of weeks from the tsunami. These results were consistent with previous studies The height of house flooding was a significant predictor of depressive reaction. The result suggested that the level of house damage would reflect the level of distress among resident survivors, who continued to live in their damaged houses. Since it is common for Japanese to put off their shoes in the house, the resident survivors whose houses were flooded above the ground floor would be inconvenient in their houses. Even if the distance from the coast was the same, the level of flooding in the house could be different depending on the landscape. Therefore, the data obtained through the household screening could provide substantial information on levels of flooding in houses, which would reflect the eventual impact of the tsunami more accurately.However, direct exposure to sea water at the time of the tsunami was not associated with depressive reaction in this study. Future studies to be conducted if an approach can be found to assess the height of exposure to sea water with less burdensome to respondents.We found a significant association between the female gender and depressive reaction among the resident survivors. These results were consistent with the results of most previous reports A higher risk was found for depressive reaction among persons aged 40 to 64 years and 65 years or older than those aged 15 to 39 years. Approximately 140,000 to 200,000 persons were estimated to have lost their jobs as a result of the Great East Japan Earthquake A significant association was found between depressive reaction and regular intake of psychotropic medicine(s) since before the tsunami. We used “regular intake of psychotropic medicine since before the tsunami” instead of “developed depression since before the tsunami”, as we could not identify persons who had developed depression before the tsunami by medical records. Given that persons engaged in “regular intake of psychotropic medicine since before the tsunami” included those with depression, a significant association between “depressive reaction” and “regular intake of psychotropic medicine since before the tsunami” would be expected.According to anecdotal reports, some resident survivors had hoped to continue staying at the evacuation centers but could not due to conditions their family members had, such as autism and schizophrenia. Therefore, it would be necessary to consider special support for such families coping with psychiatric problems to further ensure the efficacy of public health programs geared toward survivors of the tsunami.The results of this study offer insight into the protective effects of social ties provided by cohabiters in terms of the incidence of depressive reaction among resident survivors. Associations between weaker social ties and the development of depression have been also reported after a terrorist attack The effect exerted by the presence of cohabiters might be due to the following two reasons. First, the cohabiters might play an important role in allowing the survivors to share their traumatic experiences, and thus provide critically needed emotional support in the form of person-to-person contact. It is reasonable to speculate that cohabiters helped mitigate the sense of loneliness and isolation felt by resident survivors through their reactions in the aftermath of the crisis. As mentioned earlier, the resident survivors exhibited noticeable difficulties in retelling their experiences at the time of screening. Anecdotal reports by international counsellors, who had immediately been dispatched to the scene after the tsunami, also described how profound their sense of helplessness was, and the survivors' inability to talk about what had happened or how they felt.Second, cohabiters could have shared crucial information on the social context with each other in the post-disaster situation. Given the circumstances, this information is potentially more critical for resident survivors than for refugees at the evacuation centers. This is because the tsunami destroyed their community links and communication networks which had existed previously; therefore, support depended to a large extent on the resources available via social ties. For example, food supply and/or medical services were mainly available at the evacuation centers, and resident survivors needed to know the schedules for these services as well as their locations. Cohabiters, even children, can help obtain more information and establish more dense social networks Further, the characteristics of social ties of residents of Miyagi prefecture may have worked supportively after the tsunami. In general, the people living in Miyagi tend to participate more frequently in civic activities such as volunteer work and be associated with people at school or the office, but perform fewer activities with others in the neighbourhood or society Finally, the prevalence of depressive reaction was also associated with the disruption of lifeline utilities, particularly gas supply. As of 31 March 2011, the rate of restoration was more than 90% for electricity and 70% for water, but only 30% for gas in Miyagi prefecture In conducting this study, we noted several limitations which may have had an effect on the scope and generalizability of the results. First, a greater percentage of elderly women were included in this study than that in the city's population. These elderly female residents were also more likely to have been affected by the tsunami while at home, as the earthquake happened at 14:46. Second, the screening was conducted earlier in areas where destruction was greater, so the regression analysis was adjusted for the number of weeks since the tsunami. Third, the questionnaire did not include any variables about deceased or missing family members, lost jobs because of the tsunami, or other variables related to the survivors' social networks other than the number of cohabiters, or variables related to peritraumatic distress The results suggest that there is a considerable psychological burden (depressive reaction) among resident survivors after a tsunami. The predictors of depressive reaction were being female, middle-aged or elderly, regular intake of psychotropic medicine(s) since before the tsunami, house flooding , an unavailability of gas supply, and living alone. Special supports for families with psychiatric problems need to be considered among resident survivors. Strengthening of social ties for persons living alone and restoration of lifeline utilities to their normal state would ameliorate the development of depression among resident survivors who continue to reside in their homes in the aftermath of a tsunami.


Postgraduate training in medical and surgical specialties has been further developed in a constructive and inclusive way with support of American universities.4 Although postgraduate training in family and community medicine has been temporarily halted, the need to develop and enhance undergraduate training in social and community medicine was identified and efforts have since commenced. This raises the question whether postgraduate training was developed too early, at a time when undergraduate training did not yet embrace the concept of primary health care.Globally there is a need for well-trained primary health care physicians at the district level. Physicians who focus on ambulatory care will be in greater demand in addressing the global burden of chronic disease and multi-morbidity, which are on the increase in Africa. Not surprisingly, family medicine has grown stronger on the African continent in the past decades.5 The majority of the population live in rural areas. The 2010 Demographic Health Survey showed dramatic gains in life expectancy, although infectious diseases were still the leading cause of death.6 Chronic non-communicable diseases are on the rise and presently constitute 25% of Rwanda's burden of disease, which makes the need for chronic care urgent.7Rwanda is a small, landlocked, low-income country in central East Africa and the most densely populated country on the continent.9 Faced with a similar shortage of health workers as in other African countries, Rwanda has successfully embarked on pre-service and in-service training programmes at all levels of care delivery.At present Rwanda has four national referral hospitals, over 40 district hospitals and about 450 health centres. In addition, approximately 45 000 community health workers provide health promotion activities as well as preventive and curative care to rural communities.10 Rwanda already had a robust structure and organisation in primary care through a network of community health worker teams and health centres. The FAMCO department, working with external partners, saw this as an opportunity for preparing a generation of well-trained, expert generalists able to work at the district level. However, by 2011 the programme was facing difficulties owing to stakeholders, from undergraduate students to policy makers, being unfamiliar with the new model of ‘African family medicine’. Faced with a national need to focus resources on training hospital-based specialists, the FAMCO residency programme was suspended in 2012.In 2008, the then National University of Rwanda (now University of Rwanda) started the postgraduate family and community medicine (FAMCO) training programme. The objective was to train family physicians capable of providing comprehensive, continuous health care of good quality, which is person centred, family oriented and community based, using the biopsychosocial model of care at the district level.11 Both training content and teaching methods, which involved peer education, reflection and mentorship, were highly appreciated by the students.When the postgraduate training started in 2008, primary health care was not part of the undergraduate medical curriculum, except for a module in public health. Students had little exposure to district health care. In 2011, the FAMCO department developed a programme aimed at teaching community medicine as part of the undergraduate curriculum. The training consisted of a two-week theoretical module in the fourth year and a four-week practical module in the fifth year. The objective of this training was to prepare students, in small groups, to understand the unique issues and challenges of health in the community and medical care at the community level through experience at community health centres and district hospitals to enable them to function more effectively in the Rwandan health system.12 which includes e-learning methods. iSOCO aims to prepare each future Rwandan medical doctor to be patient centred and community oriented, to provide health care in a biopsychosocial way, to understand the importance of and having skills in communication, collaboration, advocacy, management, being a scholar and developing a professional attitude.13 Graduates will also appreciate the role of clinical information systems, decision support systems and referral pathways, the virtues of planned and coordinated care, and the role of self-management through exploration and appreciation of commonly held health beliefs.During their review of the undergraduate curriculum in 2014, the Discipline of Primary Health Care (formerly the FAMCO department) advocated for students to be exposed to the concepts of social and community medicine earlier. In the emergent five-year curriculum, a new approach to social and community medicine (referred to as iSOCO) was developed and integrated from the first year of training. According to this training approach, students are taught in a multidisciplinary way (together with pharmacy and dentistry students) using the flipped classroom model,13 These doctors will be able to use the principles of primary health care in later medical or surgical specialisation or other career development paths.The new curriculum will use the biopsychosocial approach to develop a new generation of Rwandan doctors who are patient-centred and community-oriented change agents and are able to practise interpretive medicine and support patients to maintain their health. These attributes are described as the making of the desired Rwandan doctor.To train postgraduate residents in primary health care and family medicine, it is essential to create awareness already at the undergraduate level so that there will be a critical mass of physicians who are able to apply these principles in their daily work at any level of the health care system. The new approach will prepare physicians to work in the primary health care setting to serve the needs of the Rwandan community and to mitigate the burden of disease at a lower level of care.


Obtaining data without the intervention of a health care provider represents an opportunity to expand understanding of the safety of medications used in difficult-to-study situations, like the first trimester of pregnancy when women may not present for medical care. While it is widely agreed that personal data, and in particular medical data, needs to be protected from unauthorized use, data protection requirements for population-based studies vary substantially by country. For public-private partnerships, the complexities are enhanced. The objective of this viewpoint paper is to illustrate the challenges related to data protection based on our experiences when performing relatively straightforward direct-to-patient noninterventional research via the Internet or telephone in four European countries. Pregnant women were invited to participate via the Internet or using an automated telephone response system in Denmark, the Netherlands, Poland, and the United Kingdom. Information was sought on medications, other factors that may cause birth defects, and pregnancy outcome. Issues relating to legal controllership of data were most problematic; assuring compliance with data protection requirements took about two years. There were also inconsistencies in the willingness to accept nonwritten informed consent. Nonetheless, enrollment and data collection have been completed, and analysis is in progress. Using direct reporting from consumers to study the safety of medicinal products allows researchers to address a myriad of research questions relating to everyday clinical practice, including treatment heterogeneity in population subgroups not traditionally included in clinical trials, like pregnant women, children, and the elderly. Nonetheless, there are a variety of administrative barriers relating to data protection and informed consent, particularly within the structure of a public-private partnership. Primum non nocere”, “first do no harm”, and provides protection to human subjects of medical research by establishing ethical principles to ensure that medical research can never take precedence over the rights and interests of individual research subjects [The Declaration of Helsinki extends the ancient medical tenet of “subjects . While lConsider, as an example, the importance of understanding which medications can be safely used during pregnancy, especially during the first trimester, since some exposures at this time may have teratogenic potential ,3. IncluHere, we describe the legislative challenges in data ownership and barriers to approval faced by a public-private partnership in conducting an observational study of self-reported maternal medication use and pregnancy outcomes.This observational study of direct-to-consumer data collection on various exposures during pregnancy was conducted through a public-private partnership known as the Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT) , which wWhile other PROTECT work packages focused on methodological challenges using existing data sources, we explored digital technologies for frequent and timely data collection from consumers for the purposes of determining whether this is a viable alternative as a pharmacovigilance tool.This study was conducted according to the current best practices for noninterventional drug safety research including full protocol, specification of analytic methods and data to be collected, and a description of the plan for protecting human subjects . PregnanThere was substantial variation in the requirements for ethical review. Denmark did not require ethical review for an observational study. In the Netherlands, a waiver  was granted since the personal identifiers were securely retained and maintained separately from study analysis files. In Poland and the UK, ethics submission required submitting the study protocol and all study documents  and other administrative information.It is also worth noting the differences between countries in enrollment requirements and informed consent. Although the study was designed to give the choice of participating by phone or Internet to facilitate recruitment of low-income women, one country required all participants to enroll on the Internet before being able to respond by phone, and another required printing and mailing written informed consent in addition to consent by phone or Internet.Formal notifications were required for data protection. The European Medicines Agency, as required under Article 27 of Regulation (EC) number 45/2001, submitted a notification for prior check with the European Data Protection Supervisor (EDPS) in October 2010. The EDPS opinion was that, since all study partners were involved in the development of the protocol and all could decide on the “means and purposes of the processing of personal data” and review results, all study partners effectively determined the purposes of the collection of the data and were “joint controllers”. As a result of this ruling, a formal memorandum was prepared detailing each partner’s role and participation in the study, responsibilities to the study and other partners, and to data protection. It took about 14 months to get these agreements in place, since they required agreement from all study partners. After these provisions were in place, the EDPS confirmed that the processing operations would not involve any breach of Regulation (EC) No 45/2001.In the Netherlands, approval of data protection was granted on the same day the request was submitted, and review was also relatively quick in the UK and in Denmark. However, review by the Polish Data Protection Agency took 9 months and required submission of special items including the characteristics of the Personal Data Administrator, the technical and organizational conditions, and how those conditions would be fulfilled to comply with Polish legislation.Data collection for this study closed in the first quarter of 2015. Analyses examining the type of information reported by respondents are in progress, including comparisons of self-reported data with that available from electronic medical records and with the Danish National Prescription Registry. Analyses will be completed in 2015.Using direct reporting from consumers to study the safety of medicinal products allows researchers to address a myriad of research questions relating to everyday clinical practice, including treatment heterogeneity in population subgroups not traditionally included in clinical trials, like pregnant women, children, and the elderly. Internet-based studies such as this may also be useful for studying illicit drug use and other risky behaviors, since there is some evidence suggesting that patients will tell computers things that they might not tell health care professionals . These sThere were substantial barriers due to the nature of the funding structure, in addition to the challenges typically encountered in conducting direct-to-patient medical research. Public-private partnerships like this IMI project are becoming more prevalent as desirable funding mechanisms for research on the safety of medications and medical devices used in everyday clinical practice, for example, IMI Get Real  in EuropThe text of the proposed data protection regulation, which was endorsed by the European Parliament at its first reading in March 2014, if adopted into law, will do little to improve the situation . The joiData protection legislation is intended to allow freedom of movement of data, while protecting people from the theoretical harm of disclosure of personal data. This theoretical harm of disclosure of data that could be linked to an individual needs to be balanced against the potential for actual harm that could result from failure to identify safety signals in a timely fashion. Further, issues of data protection which require joint controller status to be shared among multiple parties may discourage participation, and might even drive health research away from regions of most interest to areas with potentially weaker protection of patient privacy and medication use that is quite different ,12. The


The associations between several measures of low employment quality and some specific health and safety outcomes have become the subject of more recent investigation. The main objective of our study is to examine the relationships between irregular work arrangements indicators including contract type, long working hours, multiple jobs, shift work, and occupational injuries, taking into account several sociodemographic and work characteristics.The study was based on the data of the fifth European working condition survey (EWCS), carried out by Eurofound from January to June 2010. For the purpose of this analysis, the analytical sample was restricted to a subgroup of 26.839 respondents from the 27 countries of the European Union, who were all workers with either a permanent contract, a temporary or a fixed contract. Associations between irregular work arrangements and occupational injuries were studied with multilevel modeling techniques.About 9% of the workers suffered from an occupational injury over the past twelve months. An increased injury risk is observed for those working long hours , having multiple jobs  and shift work . However, the relationship between contract type and work injuries was not significant .This study confirms that indicators of irregular work arrangements, with the exception of contract type, were significantly associated with occupational injuries. More attention should be paid to workers with low employment quality. Further efforts on the workplace, the organizational and political level are needed to avoid irregular work arrangements in order to improve workers' health and safety.


The ‘external validity’ of randomized controlled trials is an important measure of quality, but is often not formally assessed. Trials concerning mass drug administration for helminth control are likely to guide public health policy and careful interpretation of their context is needed. We aimed to determine how representative participants in one such trial were of their community. We explore implications for trial interpretation and resulting public health recommendations.The trial assessed was the Entebbe Mother and Baby Study (EMaBS), a trial of anthelminthic treatment during pregnancy and early childhood. In a novel approach for assessing external validity, we conducted a two-stage cluster sample community survey within the trial catchment area and compared characteristics of potentially-eligible community children with characteristics of children participating in the trial.A total of 173 children aged three to five-years-old were surveyed from 480 households. Of children surveyed, we estimated that mothers of 60% would have been eligible for recruitment, and of these, 31% had actually been enrolled. Children surveyed were compared to 199 trial children in the same age group reviewed at annual trial visits during the same time period. There were significant differences in ethnicity between the trial participants and the community children, and in socioeconomic status, with those in the trial having, on average, more educated parents and higher maternal employment. Trial children were less likely to have barefoot exposure and more likely to use insecticide-treated bed nets. There were no significant differences in numbers of reported illness events over the last year.The trial had not enrolled all eligible participants, and those enrolled were of higher socioeconomic status, and had lower risk of exposure to the parasitic infections targeted by the trial interventions. It is possible the trial may have underestimated the absolute effects of anthelminthic treatment during pregnancy and early childhood, although the fact that there were no differences in reported incidence of common infectious diseases (one of the primary outcomes of EMaBS) between the two groups provides reassurance. Concurrent community surveys may be an effective way to test the external validity of trials.ISRCTN32849447, registered 22 July 2005The online version of this article (doi:10.1186/1745-6215-15-310) contains supplementary material, which is available to authorized users. The rise of evidence-based medicine has seen much emphasis placed on the internal validity of clinical trials but less attention has been given to external validity. Measures adopted for ensuring internal validity include the design of a trial which is appropriately powered to detect a clinically significant effect, the use of a control group selected by randomization and the ‘blinding’ of both participants and investigators to the intervention. Statistical analysis of the trial results then allows the classification of data on the basis of generally accepted levels of ‘significance’ , 2. HoweWe aimed to assess the ‘external validity’ of the Entebbe Mother and Baby Study (ISRCTN32849447), a trial designed to investigate the effects of anthelminthic treatment in pregnancy and in childhood . The priThere are relatively few studies which aim to assess the external validity of clinical trials. Most published studies focus on assessing the number of people included in the trial, as a proportion of those who would have been eligible for participation in the trial given the trial’s inclusion and exclusion criteria –27. OtheThe catchment area for the Entebbe Mother and Baby Study (EMaBS) was comprised of the Entebbe Municipality and Katabi sub-country, a peninsula on the northern shore of Lake Victoria, Uganda. Entebbe town is located approximately 40 km southwest of the capital, Kampala, has a population of approximately 90,500 and is the site of Uganda’s main international airport. Katabi sub-county borders Entebbe Municipality, has a population of approximately 59,000 and consists of semi-urban, rural and fishing communities. The EMaBS trial recruited pregnant women between April 2003 and November 2005. At the time of this investigation (between July and August 2008), EMaBS cohort children were aged three, four and five years. We therefore conducted a survey within the same catchment area, consisting of three, four and five-year-old children, both male and female.The community survey used a sampling strategy designed to reduce bias within a setting with limited prior demographic data. The study area comprised 47 administrative units known as wards. Census data detailing the number of households in each ward was available. A sample of 15 wards within the survey area was selected by random number generation, with probability of selection being proportional to the number of households. It was possible for one ward to be selected twice. Each ward was then mapped onto satellite imagery of the area with the help of locally available maps. Uninhabitable areas were excluded from mapping. The wards were divided into segments of equal geographical size  based on lines of latitude and longitude . These segments were then numbered and four segments from each ward were randomly selected using random number generation. The midpoint of each segment was identified by its coordinates and this was used as the starting point for sampling. The starting point was identified using a geographic information system (GIS) device  and the nearest house selected for sampling. Eight houses were then surveyed sequentially from this point, the next house to be sampled being the nearest to the previous house. A household was defined as a habitable roofed structure whose primary function was residence or, if used for dual purposes, had at least one active resident using the structure as their primary residence. In selected households that included a three, four or five-year old child, the parent or guardian was counselled and provided with written information in English and the vernacular of the area prior to obtaining written consent. If two or more eligible children lived in the same house, they were all surveyed if possible.A questionnaire was then administered for each child. This was designed to match with data collected at the yearly trial visits undertaken by children enrolled in the Entebbe Mother and Baby Study, in order to obtain comparable information from both sources. In addition, during the period of the community survey supplementary information sheets were completed by trial participants during these yearly visits. These covered questions asked in the community survey but not routinely asked in the trial, or which had been asked in screening at enrolment into the trial, but were felt likely to have changed since that time.EMaBS trial participants were recruited at the antenatal clinic at Entebbe Hospital over a two and a half year period. At the same time, the community was sensitized to the study. The mayor of Entebbe and sub-county chief of Katabi were informed and the research team visited all villages in the catchment area and held meetings with the local council (LC) leaders. LC leaders were asked to select community field workers, who were trained in simple data collection and subsequently followed up on participating children every two weeks until they were five-years-old. They met monthly and provided the main link between the research team and the community throughout the study period.Inclusion criteria for the EMaBS trial required women to be resident in the study area, attending the Entebbe Hospital antenatal clinic and intending to give birth at the hospital, with no age limits. The exclusion criteria for the trial included not wishing to participate, not being willing to receive an HIV result, bloody diarrhoea, previous adverse reaction to anthelminthics or sulfadoxine-pyrimethamine (Fansidar™), already having a child in the trial, antenatal abnormalities, failure to complete screening or re-attend for enrolment, not being pregnant and anaemia (hemoglobin <8 g/dL).In the survey, we first aimed to assess what proportion of community children would have been potentially eligible for EMaBS trial participation. Children were deemed to have been potentially eligible if, at the time of the child’s birth, the mother was resident within the study area and attended the Entebbe Hospital antenatal clinic. We then aimed to estimate what proportion of potentially eligible children had actually been enrolled in the trial. We were unable to directly assess the impact of the other EMaBS inclusion and exclusion criteria.Socio-demographic characteristics: The outcomes assessed were primary carer/s, maternal and paternal age and health status, level of maternal and paternal education, maternal employment and wage, maternal tribe and other socioeconomic parameters . These factors are unlikely to have been affected by the trial intervention and therefore reflect inherent characteristics of the study population.Disease risk factors and comorbidities: Outcomes assessed were barefoot exposure, lake exposure (both risk factors for helminth infection), mosquito net usage and insecticide-treatment of household nets .Diseases and anthropometry outcomes were as follows: we recorded self-reported disease episodes of malaria, diarrhoea, pneumonia, measles and tuberculosis. We did not ask directly about HIV because of the limitations placed on confidentiality in the field setting and concerns over the reliability of any results obtained. We also measured height, weight, mid to upper arm circumference and head circumference. These outcomes may have been influenced by the trial interventions.Data were analyzed using Stata version 12 . Data from the youngest of each pair or group of siblings in the community survey were excluded from the analysis, in order to make the inclusion criteria comparable with EMaBS . Clustering at the ward and segment level was taken into account in the analysis. Clustering at the household level was not allowed for in the analysis due to the small number of households remaining with multiple children after younger siblings were excluded from the analysis. The svy commands in Stata were used to allow for the clustering. Distributions of parental and child characteristics in the two groups were first compared using simple tabulations, with design-based Pearson’s F statistics calculated to test for differences in characteristics between the community survey and EMaBS children. Logistic regression was used to calculate crude and adjusted odds ratios (ORs) and associated 95% confidence intervals (CIs), allowing for the sampling design. Multivariable logistic regression analysis was conducted to control for potential confounding. A hierarchical approach was used to decide which variables should be treated as potential confounders in the multivariable analysis. Maternal and paternal sociodemographic parameters were considered as potential confounders for each other, for household characteristics, for disease risk factors and comorbidities, and for diseases and anthropometry. Household characteristics were considered as potential confounders for each other, for disease risk factors and comorbidities and for diseases and anthropometry. Finally, disease risk factors and comorbidities were considered as potential confounders for diseases and anthropometry.Both EMaBS and the community survey received ethical approval from the Science and Ethics Committee of the Uganda Virus Research Institute (GC/127), Uganda National Council for Science and Technology (MV 625) and the London School of Hygiene and Tropical Medicine ethics committee (07/303).In total, 480 households were surveyed; eight households from each of four locations in 15 wards. The breakdown of these is provided in Figure Of the 173 children seen in the community, 104 (60%) had mothers who would have been potentially eligible for recruitment into the trial. Of the remaining children, 38 (55%) had mothers who were not resident in Entebbe or Katabi at the time of delivery, an additional 28 (41%) had mothers who did not receive antenatal care at Entebbe Hospital and were therefore not available for recruitment, and there was no information available on where mothers had received antenatal care for 3 (4%). Of the 104 children who were potentially eligible for inclusion, 32 (31%) were in the trial.There were significant differences between the ethnic makeup of the two populations, based on the mother’s tribe. Of particular note only half the mothers in the trial were Buganda compared to 65% in the community, and being a member of the Banyankole, Batoro or Banyarwanda tribes was twice as common in the trial mothers Table .Table 1Levels of both maternal and paternal education were, on average, higher amongst trial children Table . There wP = 0.33). There were no significant differences in roofing materials, electricity or water source between the two groups . Reported measles, although rare, was more common in community children  than children in the target population for the trial. However, we found no differences in reported episodes of common childhood diseases between trial participants and children in the community survey. We estimate that 31% of eligible children in the community were enrolled in the trial, and although it was not possible to assess all trial exclusion criteria in the community survey, refusal and exclusion criteria are unlikely to account for the lack of enrolment of all the remaining children.Under a fifth of children in the community had been enrolled in the trial. Approximately 22% of children were ineligible on the basis of non-residency at the time of birth, and these children may have differed in important ways from those who had not recently migrated. This is an unavoidable factor when considering the non-representativeness of trials to their community. It is possible that migration into a trial area, particularly if large and sustained, may account for a significant proportion of any non-representativeness and this highlights the need to interpret the results of trials carefully in the light of shifting demographic patterns. A similar proportion of children were ineligible because their mothers received antenatal care outside of the hospital setting, a group previously noted to differ from those who did receive hospital-based antenatal care in this area . Our surApproximately 60% of mothers of children in the community survey would have been eligible for recruitment into EMaBS on the basis of residence and of antenatal care in Entebbe Hospital, and 31% of these were enrolled in the trial. Non-participation could have been secondary to refusal, exclusion on the basis of trial exclusion criteria or not having been approached for recruitment into the trial. In comparison, data from the EMaBS trial itself Figure  shows thData from the EMaBS trial Figure  give an Whilst the majority maternal tribe in both groups was the local Baganda, the proportion within the trial participants was 15% less than within the community at large. The difference was largely made up by a higher proportion of mothers from the Banyankole and Luo tribes. The Banyankole are a Western Ugandan tribe and the Luo are from Northern Uganda . The posChildren enrolled in the trial were more likely to be from families of higher socioeconomic status. Maternal employment status and income were higher, as was the level of both maternal and paternal education. There was a difference in crowding status, with trial children more likely to live in crowded circumstances. It is suggested that increased crowding may be a function of increased wealth in some circumstances. In particular it may be the case that families with increased income remain in their current property, but members of extended family or friends may move into the residence. This is consistent with findings from other settings, where in general, trial participation is more likely amongst those of higher socioeconomic status , 35, 40.In general, disease exposure risks were fewer amongst the trial children with more bed-net use and less barefoot exposure. This difference persisted after adjustment for parental socioeconomic status. It may be the case that a systemic bias in selection for children in the trial resulted in selection of children with lower risk exposure status . Alternatively, health education as part of the trial may have led to less exposure prone behaviour in the families of the trial children. However, importantly, with the exception of measles, there were no differences between the two groups in terms of reported episodes of infectious diseases, one of the EMaBS primary outcomes. This suggests that the sociodemographic differences we have observed between trial and community survey participants would not have led to biased intervention effect estimates on this primary outcome in the EMaBS trial.We were unable to select participants at the level of the child due to the lack of sampling frame and therefore used a multi-stage sampling survey approach. This was done using a predefined random sampling approach and was taken into account in the analysis, however, it is possible that our sampling strategy will have over-represented children in less populated areas. There may be important differences between these children and children in more populous areas, hence potentially biasing our results. The fact that we used a random sampling approach should have reduced bias in the sample, however the clustered nature of our design means we may have misrepresented variables which are geographically confined. For example, there was one sampled area (a military barracks) which we were not permitted to enter, whereas children enrolled in the trial do live in this area. Indeed, this may explain the higher proportion of abodes constructed from metal amongst the trial children, as this is the predominant material used in military barracks in Entebbe.The high response rate in the community survey means that selection bias should be minimized, and data completeness for the community survey was high. For the trial children we used several different sources of information, meaning the completeness of the data for each variable differed. In particular, a number of variables that were assessed from the supplementary forms for EMaBS children are limited because out of the 199 children assessed, only 128 supplementary forms were completed. There is no reason to believe this introduced bias since characteristics of the children who completed forms were similar to those of the children who did not, however, it limited the study’s power to detect differences between the groups for these variables. It is possible that responses to the questions may have been systematically different between the trial and community-surveyed groups. This may have occurred because the interviewers in the trial clinic and the community were different throughout. Also, the parents or guardians of the non-trial children may have responded to questions on recent childhood illnesses differently to the parents or guardians of the trial children, for instance, participation in the trial may have sensitized them to keeping a more accurate record of their child’s illnesses. We included trial children in our community survey  and whilst this was intended in the survey design on the basis that they are part of their community and thus not as such a limitation, it could have led to a slight underestimation of the differences between the groups.Recruitment at the level of the antenatal clinic did not achieve enrolment of all eligible participants into this trial and this was unlikely to be fully explained by refusal or exclusion criteria. The study population was significantly different from the community at large on the basis of ethnic composition and socioeconomic status. There appeared to be increased disease risk factors in the community survey group but little difference in terms of reported disease episodes. To our knowledge, this is the first study of its kind using a community survey to assess the external validity of a randomized controlled trial. External validity is a very important component of the assessment of trials and this approach offers a cost-effective, practical and robust method of assessing the validity of a trial.


However, the overwhelming evidence shows that the quality of reporting of prediction model studies is poor. Only with full and clear reporting of information on all aspects of a prediction model can risk of bias and potential usefulness of prediction models be adequately assessed. The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Initiative developed a set of recommendations for the reporting of studies developing, validating, or updating a prediction model, whether for diagnostic or prognostic purposes. This article describes how the TRIPOD Statement was developed. An extensive list of items based on a review of the literature was created, which was reduced after a Web-based survey and revised during a 3-day meeting in June 2011 with methodologists, health care professionals, and journal editors. The list was refined during several meetings of the steering group and in e-mail discussions with the wider group of TRIPOD contributors. The resulting TRIPOD Statement is a checklist of 22 items, deemed essential for transparent reporting of a prediction model study. The TRIPOD Statement aims to improve the transparency of the reporting of a prediction model study regardless of the study methods used. The TRIPOD Statement is best used in conjunction with the TRIPOD explanation and elaboration document. To aid the editorial process and readers of prediction model studies, it is recommended that authors include a completed checklist in their submission  and will be also published in BJOG, British Journal of Cancer, British Journal of Surgery, BMC Medicine, British Medical Journal, Circulation, Diabetic Medicine, European Journal of Clinical Investigation, European Urology, and Journal of Clinical Epidemiology. The authors jointly hold the copyright of this article. An accompanying Explanation and Elaboration article is freely available only on www.annals.org; Annals of Internal Medicine holds copyright for that article. In medicine, patients with their care providers are confronted with making numerous decisions on the basis of an estimated risk or probability that a specific disease or condition is present (diagnostic setting) or a specific event will occur in the future (prognostic setting) Figure . In the In both the diagnostic and prognostic setting, estimates of probabilities are rarely based on a single predictor . DoctorsPrediction model studies can be broadly categorized as model development , model vQuantifying the predictive ability of a model on the same data from which the model was developed (often referred to as apparent performance) will tend to give an optimistic estimate of performance, owing to overfitting (too few outcome events relative to the number of candidate predictors) and the use of predictor selection strategies . StudiesAfter developing a prediction model, it is strongly recommended to evaluate the performance of the model in other participant data than was used for the model development. Such external validation requires that for each individual in the new data set, outcome predictions are made using the original model  and compared with the observed outcomes ,14. ExteStudies developing or validating a multivariable prediction model share specific challenges for researchers . SeveralPrediction models in medicine have proliferated in recent years. Health care providers and policy makers are increasingly recommending the use of prediction models within clinical practice guidelines to inform decision making at various stages in the clinical pathway ,31. It iWe describe the development of the TRIPOD  Statement, a guideline specifically designed for the reporting of studies developing or validating a multivariable prediction model, whether for diagnostic or prognostic purposes. TRIPOD is not intended for multivariable modeling in etiologic studies or for studies investigating single prognostic factors . FurtherReporting guidelines for observational  , tumor mTo address a broader range of studies, we developed the TRIPOD guideline: Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis. TRIPOD explicitly covers the development and validation of prediction models for both diagnosis and prognosis, for all medical domains and all types of predictors. TRIPOD also places much more emphasis on validation studies and the reporting requirements for such studies. The reporting of studies evaluating the incremental value of specific predictors, beyond established predictors or even beyond existing prediction models ,42, alsoAnnals of Internal Medicine, BMJ, Journal of Clinical Epidemiology, and PLoS Medicine) to develop recommendations for the TRIPOD Statement.We convened a 3-day meeting with an international group of prediction model researchers, including statisticians, epidemiologists, methodologists, health care professionals, and journal editors .Twenty-five experts with a specific interest in prediction models were invited by e-mail to participate in the Web-based survey and to rate the importance of the 76 candidate checklist items. Respondents (24 of 27) included methodologists, health care professionals, and journal editors. . During the 3-day meeting, each of the 76 candidate checklist items was discussed in turn, and a consensus was reached on whether to retain, merge with another item, or omit the item. Meeting participants were also asked to suggest additional items. After the meeting, the checklist was revised by the steering committee during numerous face-to-face meetings, and circulated to the participants to ensure it reflected the discussions. While making revisions, conscious efforts were made to harmonize our recommendations with other reporting guidelines, and where possible we chose the same or similar wording for items ,41,45,46D, items relating solely to a validation of a prediction model are denoted by V, whereas items relating to both types of study are denoted D;V.The TRIPOD Statement is a checklist of 22 items that we consider essential for good reporting of studies developing or validating multivariable prediction models Table . The iteThe recommendations within TRIPOD are guidelines only for reporting research and do not prescribe how to develop or validate a prediction model. Furthermore, the checklist is not a quality assessment tool to gauge the quality of a multivariable prediction model.An ever-increasing number of studies are evaluating the incremental value of specific predictors, beyond established predictors or even beyond existing prediction models ,42.The rIn addition to the TRIPOD Statement, we produced a supporting explanation and elaboration document  in a simThere was no explicit funding for the development of this checklist and guidance document. The consensus meeting in June 2011 was partially funded by a National Institute for Health Research Senior Investigator Award held by Dr. Altman, Cancer Research UK, and the Netherlands Organization for Scientific Research. Drs. Collins and Altman are funded in part by the Medical Research Council. Dr. Altman is a member of the Medical Research Council Prognosis Research Strategy (PROGRESS) Partnership. The funding sources had no role in the study design, data collection, analysis, preparation of the manuscript, or decision to submit the manuscript for publication.Many reviews have showed that the quality of reporting in published articles describing the development or validation of multivariable prediction models in medicine is poor –27,29. IThe TRIPOD Statement does not prescribe how studies developing, validating, or updating prediction models should be undertaken, nor should it be used as a tool for explicitly assessing quality or quantifying risk of bias in such studies . There iTRIPOD encourages complete and transparent reporting reflecting study design and conduct. It is a minimum set of information that authors should report to inform the reader about how the study was carried out. We are not suggesting a standardized structure of reporting, rather that authors should ensure that they address all the checklist items somewhere in their article with sufficient detail and clarity.We encourage researchers to develop a study protocol, especially for model development studies, and even register their study in registers that accommodate observational studies  ,54. The To help the editorial process; peer reviewers; and, ultimately, readers, we recommend submitting the checklist as an additional file with the report, indicating the pages where information for each item is reported. The TRIPOD reporting template for the checklist can be downloaded from .Announcements and information relating to TRIPOD will be broadcast on the TRIPOD Twitter address (@TRIPODStatement). The Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Network  will helMethodological issues in developing, validating, and updating prediction models evolve. TRIPOD will be periodically reappraised, and if necessary modified to reflect comments, criticisms, and any new evidence. We therefore encourage readers to make suggestions for future updates so that ultimately, the quality of prediction model studies will improve.


Toxoplasma gondii. The disease is usually appeared as asymptomatic in immunocompromised individuals but its most common symptom is lymphadenopathy. Shortly before or during the first trimester of pregnancy, this disease can be transferred to the fetus and cause serious infection in the fetus. In late pregnancy (third trimester), the complications of this infection is very low or unsigned. Due to the absence of non-specific clinical symptoms or slight infection in pregnant women, prenatal diagnosis is often impossible.Toxoplasmosis is the most common disease in humans and animals (zoonosis) caused by the protozoan parasite Since no research compared these two methods, we decided to compare these methods and determine which method works better for diagnosis of toxoplasmosis.Toxoplasma gondii by both ELISA and Chemiluminescence methods.In this study, 50 pregnant women who referred to the Chalus Health Center laboratory were included and the blood samples were tested for presence of IgG and IgM antibodies of Of the 50 samples tested by the ELISA method, 26 samples (52%) were positive for IgG . No samples were positive for IgM. Of the 50 samples tested by the Chemiluminescence method, 28 samples (56%) were positive for IgG. No samples were positive for IgM.A significant relationship between the age of the youngest child and the infection rate was seen. No significant correlation between age, number of individuals in the household, number of children, location, type of construction, consumption of greens, the way of greens and meat consumption, drug use, history of stillbirth and infection levels was seen. Toxoplasma gondii  caused by the protozoan parasite a gondii , 2.. Thia gondii . In prega gondii , but infa gondii .Prevalena gondii -11. For a gondii . Variousa gondii , 14.Overa gondii .There ara gondii .QuantitySince no research compared these two methods, we decided to compare these methods and determine which method works better for diagnosis of toxoplasmosis.Subjects were women who referred to the laboratory of Health center in Chalus city from 2012 till 2013 and had IgG and IgM in their blood. Pregnancy and place of residence were the only criteria for entry in the study. All the blood samples were tested by the CLIA (chemiluminescence) and ELSA (Enzyme-linked immunoadsorbent assay) methods.This is a simple and highly sensitive biochemical method that analyzes a large number of samples simultaneously. This immunological method detects antibodies or antigens in a sample.When energy of an excited electron decreases from high to low, the energy released in the form of light and the reaction is known as luminescence. Types of luminescence include fluorescence, phosphorescence and chemiluminescence. Chemiluminescenceis different from other luminescence phenomena in which chemical or electrochemical reactions (not the photoluminescence phenomenon) cause excitement, but this excitement is similar to fluorescence and during electron’s return to baseline energy, light is emitted .Toxoplasma infection. We compared IgG ELISA and IgG Chemi with variables such as education, number of individuals in a household, parity and number of children. The results demonstrated that there is no significant relationship between IgG ELISA and IgG Chemi and different variables (P > 0.05). All results summarized in In this study, fifty patients with mean age of 27.4 were entered whose highest education was upper diploma (8 patients). The number of patients from Urban and the country were 21 and 29, respectively. These results summarized in According to our results from the ELIZA method, the frequency of IgG in patients was 26 out of 50 individuals, and there was no frequency of IgM. Therefore, the results of chemiluminescence method are the same as the results from ELIZA. These results demonstrate that toxoplasmosis had a high frequency in the studied area. In this study, infection was diagnosed in more than half of the subjects; but fortunately, none of them showed acute infection. If there are not factors weakening the immune system and made Igm negative, so there is no risk for disease transmission from mother to the fetus.Toxoplasma. The results demonstrated that antibody which used ELISA and IFA methods in infected cases was detected after three and nine days, respectively. Also, the frequency of IgM and IgG was different in these two methods. Detection of antibodies using the ELISA test is more sensitive than ones using the IFA test  were used for detection of IgM and IgG antibodies of IFA test , therefoIFA test ; this istibodies .However, not PCR ;this res not PCR ; this st


Strabismus associated with high myopia is a rare abnormality of ocular motility, leading to the impairment of abduction and supraduction. Loop myopexy of the superior rectus (SR) and lateral rectus (LR) muscles is now the most preferred surgery for restoring the dislocated eye globe back into the muscle cone. Various procedural modifications have been made based on this concept, and satisfactory outcomes have been reached in most cases. In this paper, we review various surgical modifications published in the literature that are based on the loop myopexy surgery in patients with high myopic strabismus and summarize the applicable scope of different surgical procedures for patients with different degrees of strabismus. Three major surgical procedures are identified and different modifications have been applied based on their concept. Most of these modifications have been proven to be safe and effective and result in good ocular alignments. The selection of such modifications is of great importance in different patients. Careful evaluation before surgery should be made not only to make the correct diagnosis but also to choose an appropriate surgical procedure and offer individualized modifications in the surgery. Strabismus associated with high myopia is a rare abnormality of ocular motility characterized by the presence of esotropia and hypotropia, with restricted abduction and supraduction . In lateWith the evolving understanding of the pathogenesis, consensus has now been reached that strabismus with high myopia is usually the consequence of the supertemporal protrusion of the elongated eye globe through the muscle cone, leading to an inferior displacement of the lateral rectus muscle and nasal displacement of the superior rectus muscle , 4. In aBased on the updated pathogenetic mechanism, the traditional recession-resection surgery, which aimed at altering the forces of the muscles, is no longer popular due to its limited effects, especially in some severe cases , 3. ManyIn this paper, we review the various surgical management techniques published in the literature that are based on the procedure of loop myopexy for treating patients with strabismus associated with high myopia. We also summarize the applicable scope of surgical procedures for patients with different degrees of strabismus.Recession-resection surgeries have been traditionally applied to alter the forces of the muscles. Hayashi et al.  and LouiIn the past, most attention has been paid to the management of the horizontal muscles because some researchers claimed that it was the dislocation of only the LR by the elongated eyeball that caused the corresponding strabismus , 3. HoweBased on this hypothesis, Yokoyama et al. proposed a loop myopexy surgery of the muscle bellies of the SR and LR to restore the dislocated globe back into the muscle cone . This suYamada's procedure, a hemitransposition of the SR and LR, cannot be strictly included as a loop myopexy surgery because it merely secures the muscle bellies to the sclera without actual union of these two muscles . HoweverAll studies regarding loop myopexy in high myopic strabismus in the literature were reviewed and the main surgical procedures were determined. Eighteen studies of strabismus associated with high myopia treated with the procedure of loop myopexy were eligible for our review. The clinical characteristics, surgical management, and outcomes of eighty-nine patients, with ages ranging from 5 to 78 years, are described in Three main surgical management techniques were found in the literature, namely, Yokoyama's procedure, Yamada's procedure, and the partial Jensen's procedure. Other studies found in the literature were performed based on these three procedures, with modifications in various details of the surgery, such as being with or without medial rectus (MR) muscle recession, scleral fixation, or the use of materials for muscle union. All three surgical procedures were based on the concept of pathogenesis described by Yokoyama et al. .Yokoyama's procedure, first performed in 2000, has drawn wide attention because of its satisfactory postoperative ocular alignment and the concept that there is no abnormality of the muscle forces but abnormality of the muscle paths , 10, 26.In 2002, Yamada et al.  performeThe partial Jensen's procedure was first performed by Larsen and Gole in 2004 –24.In other studies, various modifications have been performed based on the three surgical procedures mentioned above . To eliminate the risk of scleral perforation, some authors preferred not to suture the muscle bellies onto the globe , 20–24. Δ of esotropia [Δ when combined with recession of the MR muscle [Δ, also have satisfactory outcomes after surgery [The selection of a surgical procedure is based mainly on the surgeon's preference and proficiency in a certain technique. All three procedures discussed above have been proven to be effective in the treatment of high myopic strabismus. However, there exist some differences in the applicable scope of each procedure, which is a consideration that might be beneficial when planning a surgery. Shenoy et al. found that full loop myopexy of the SR and LR alone can correct up to 40sotropia . After aR muscle , 15. Fur surgery , 24. BecMyopic strabismus fixus is an extreme condition in which the affected eye is fixed inferomedially with restricted ocular motility. The elongated globe is dislocated from the muscle cone, and the posterior portion of the globe is blocked by the SR and LR, thus leading to restriction in abduction and sursumduction. The main purpose of surgery is to eliminate the mechanical limitation in ocular motility.Δ esotropia in individual cases. Thus, all three surgical procedures mentioned above  have been proven to be effective in the treatment of myopic strabismus fixus.Hayashi et al. classified patients with high myopic strabismus into four groups, and the surgical management of patients who presented with fixed eye in the extreme position was considered a great challenge . Basmak The MR recession is not necessary in all patients. If forced duction test confirms tight muscle or if restricted abduction exists for several years, contracture of the MR muscle is likely to have occurred . In thesIn patients with strabismus associated with high myopia in both eyes, we recommend that bilateral strabismus surgeries be performed simultaneously to correct the muscle paths, not only to eliminate the disparity between the two eyes but also to avoid the potential risk of having the patient undergo a second general anesthesia, especially in the elderly. In those severe cases, large MR recession is usually needed because some residual esotropia will remain after union of the SR and LR bellies. The MR recession will be helpful to further correct the eye position. Morad et al. held a similar opinion that bilateral myopexy of the SR and LR is the preferred method, after comparing the surgical results of patients with high myopic strabismus unilaterally and bilaterally . If a unΔ of esotropia [Δ to 60Δ of esotropia [A thorough eye examination and imaging of the patient before surgery will be helpful for the surgical strategy. Patients are suggested to have an MRI or CT scan of the orbit, which can give a clear demonstration of the rectus muscle paths, the relationship between the globe and muscle cone, and also the shape of the globe to exclude thyroid eye disease , severe sotropia . Yamada'sotropia , 20, 22.Loop myopexy is a safe and effective surgical treatment in patients with high myopic strabismus. Different modifications of this surgical procedure can be applied based on its concept, most of which have been proven to have good surgical outcomes. The selection of such modifications is of great importance in different patients. Careful evaluation before surgery should be made not only to make the correct diagnosis but also to choose an appropriate surgical procedure and offer individualized modifications in the surgery.


The hippocampus is believed to have evolved to support allocentric spatial representations of environments as well as the details of personal episodes that occur within them, whereas other brain structures are believed to support complementary egocentric spatial representations. Studies of patients with adult-onset lesions lend support to these distinctions for newly encountered places but suggest that with time and/or experience, schematic aspects of environments can exist independent of the hippocampus. Less clear is the quality of spatial memories acquired in individuals with impaired episodic memory in the context of a hippocampal system that did not develop normally. Here we describe a detailed investigation of the integrity of spatial representations of environments navigated repeatedly over many years in the rare case of H.C., a person with congenital absence of the mammillary bodies and abnormal hippocampal and fornix development. H.C. and controls who had extensive experience navigating the residential and downtown areas known to H.C. were tested on mental navigation tasks that assess the identity, location, and spatial relations among landmarks, and the ability to represent routes. H.C. was able to represent distances and directions between familiar landmarks and provide accurate, though inefficient, route descriptions. However, difficulties producing detailed spatial features on maps and accurately ordering more than two landmarks that are in close proximity to one another along a route suggest a spatial representation that includes only coarse, schematic information that lacks coherence and that cannot be used flexibly. This pattern of performance is considered in the context of other areas of preservation and impairment exhibited by H.C. and suggests that the allocentric-egocentric dichotomy with respect to hippocampal and extended hippocampal system function may need to be reconsidered. Spatial memory of both newly encountered and well-known environments is crucial to everyday life—it enables us to navigate and to locate objects, buildings, and landmarks, and it may provide the necessary backdrop for the unfolding of episodic memories. Theoretical attempts to accommodate cross-species similarities in spatial navigation, and within-species specialization in episodic memory, have focused on the hippocampus, a brain region that is highly preserved across species, including humans. Cognitive Map Theory 2). Tasks were constructed to assess memory for the visual identity, the locations, and the distance, direction, and routes between a set of 37 well-known landmarks dispersed throughout both environments. Based on previous findings, some tasks appear to rely to a greater extent on an allocentric framework and others on an egocentric framework, as detailed in Table Nine mental navigation tasks were adapted from previous studies  between the correct placement of each of the landmarks and the participant’s responses.In each of 10 trials, participants were presented with 3 photographs of well-known landmarks from the two environments, presented in a triangular configuration (a reference landmark at the top and two choice landmarks at the bottom) on a laptop computer screen with E-prime software . Participants were instructed to decide which of the two choice landmarks is closest in distance to the reference landmarks with a button press (left corresponding to the bottom left landmark and right to the bottom right landmark). The level of difficulty was manipulated by including nearly equivalent distances between each of the two choice landmarks and the reference landmark in some trials and by incorporating landmarks from both environments within the same trial. Accuracy (proportion correct) was calculated.Participants viewed 10 pairs of photographs, each depicting a well-known landmark from one of the spatial environments and asked to give their best estimate of the absolute distance between the two in their preferred unit of measurement . All of the participants’ responses were converted to km, and absolute distance error was calculated by subtracting the actual distance from the estimated distance. The error scores for each trial were then averaged, resulting in an average error score for each participant.Fifteen randomly ordered photographs of well-known landmarks from both environments, located along a north-south route, were combined and presented to participants. Participants were asked to imagine traveling from north to south and to sequence the landmarks in the order that they would be passed along the route. The total number of landmarks that were correctly sequenced with respect to an adjacent landmark was calculated for each participant and divided by 15, providing a Landmark Sequencing accuracy score.Each participant was given a set of 10 sheets of 8.5 × 11 inch paper, 5 depicting an outline map of the neighborhood and the other 5 depicting a map of downtown. In addition to the 4 boundary streets corresponding to one of the two environments, participants were provided with a dot indicating the actual location of a landmark and asked to draw a line depicting as accurately as possible the distance and direction from the given landmark to a second named landmark. Deviation of the line drawn between each pair of landmarks from the actual line was calculated separately for the length (distance) and angle (direction) of the line and averaged across trials.In each of 5 trials, participants were given the names of two landmarks, the first representing the start location and the second the goal location, from one or both of the environments. A name of a major street along the most direct route between the two landmarks was also provided and participants were informed that this particular street would be inaccessible for the trial—the street could be crossed but not taken. Participants were then asked to imagine traveling from the start landmark to the goal landmark, avoiding the inaccessible street while adhering to the rules of the road , and to describe the most direct detour to reach the goal. The correct route for each trial consisted of 4 key left and/or right turns. Proportion of correct turns across all 5 trials was calculated for each participant from a raw score out of a possible 20.This task does not measure the ability to represent spatial relations between landmarks, but rather measures the “what” of spatial memory—the participant’s ability to visually represent environmental features and navigational cues within the spatial environments. It also ensures that the participants did not have trouble identifying the well-known landmarks chosen for the study, which could have impeded their performance on the mental navigation tasks. Participants were presented with a randomly ordered set of 37 well-known landmarks from both environments and 37 closely matched, unfamiliar distractor landmarks gathered from other Canadian towns and cities that were similar in terms of age of building, architectural style, and function. For each landmark, participants were asked whether it is located in either of the familiar environments, and if so, to identify it. An accuracy score, calculated by subtracting the false alarm rate from the hit rate, was used in the statistical analysis for comparison of performance.t-test procedure established by Crawford and Howell , distance judgments , and vector mapping , and her performance was significantly impaired on the landmark localization task .Remarkably, despite a hippocampus and extended hippocampal system that did not develop normally, H.C. demonstrated intact performance compared to controls on several of the mental navigation tasks, namely proximity judgments . However, when the outlier is withheld from the analysis, H.C. appears to perform significantly worse than controls . It is important to note that responses were strictly scored based on the use of the most direct detour between two landmarks, for which H.C. demonstrated a deficit. However, this method of scoring did not take into account participants’ general ability to navigate between two landmarks using a detour, regardless of its length. For example, H.C. received a raw score of 0 (out of a possible 4) on one of the five routes tested, as she did not use the most direct route. She did, however, correctly navigate to the goal landmark, albeit along a longer route than necessary . Thus, H.C.’s overall route descriptions were feasible but limited in terms of flexible use of existing spatial representations.An outlier was identified in the data for the blocked route task. Control participant 004 performed much worse than other controls and H.C. only on this task. The reason for his poor performance is unknown, which is why we present the results with and without his data point. When the outlying data point is included in the analysis, the results suggest that H.C. did not differ significantly from controls  as did controls, which represents a significant difference , with abnormally rotated hippocampi that are reduced in volume by a minimal, yet significant amount (Olsen et al., To conclude, a person with congenital hippocampal system pathology and impaired episodic memory has managed to form spatial memories of large-scale, real-world environments. Despite an intact ability to represent distance and direction between pairs of landmarks, H.C.’s difficulties devising the most direct route between landmarks, producing detailed spatial features on maps, and accurately ordering more than two landmarks that are in close proximity to one another along a route are interpreted as symptomatic of a spatial representation that includes only coarse, schematic information that lacks coherence and that cannot be used flexibly. The current study adds to the literature by confirming early findings based on cursory measures of impaired spatial memory in developmental amnesia, and by explaining the possible basis of the impairment in greater detail while showcasing its limits. The original conclusion of impaired wayfinding in familiar, real-world environments in the seminal paper on patient Jon and two other developmental amnesic cases (Vargha-Khadem et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.