Over the last three decades, a lot has been achieved in the control of trachoma worldwide. New assessment techniques, effective evidence-based control strategy with new methods and drugs, and an aggressive global partnership for the control of the disease have evolved. As such the number of people with the disease and blindness due to the disease had drastically reduced. Trachoma is now only responsible for about 4% of blindness worldwide down from 12% some few decades ago. Some countries are on the verge of eliminating the disease as a public health problem. Despite these achievements numerous challenges remain for achieving trachoma control in endemic communities. This article highlights the challenges faced in one of the known trachoma endemic areas – northern Nigeria. Aspects on the dearth of complete situational data on trachoma, fragmented implementation of the SAFE strategy, community apathy, difficulties faced in ensuring safe, and quality lid surgery in the most difficult terrain where the disease thrives are discussed here. Other unique challenges like managing children with severe trichiasis, curbing the high rate of early-onset recurrence of trichiasis after lid rotation surgery and challenges to maintain supply of antibiotics and implementation of facial cleanliness and environmental improvement components of the control strategy are presented along with the learnt experiences and recommendations. These challenges and their remedies are likely to be shared by other trachoma endemic areas in Africa. Chlamydia trachomatis—such as household crowding and limited access to and use of water.5Trachoma is an infective condition of the eyelid that results in in-turned eyelashes, thus damaging the cornea and subsequently leading to blindness. In the 80s, trachoma was one of the major causes of blindness worldwide, when it constituted about 12% of world blindness.The concerted efforts by stakeholders including WHO, Non-Governmental Organizations (NGOs), governments, and other agencies, coupled possibly by improvement in general socioeconomic conditions, has resulted in a decline in the incidence of the disease. The latest WHO estimates report that trachoma is only responsible for about 3% of blindness. There are currently estimated to be 40.6 million people with active trachoma, which has decreased from an estimated 84 million less than a decade ago. Despite this progress, the physical and economic burden of trachoma is even higher than previously projected. An economic assessment had asserted that trichiasis in itself may result in an economic burden comparable to trachomatous low vision and blindness.6Every year, a critical meeting of the World Health Organization, the Alliance for the Global Elimination of Trachoma by 2020 (GET2020), is held to chart the progress toward this goal. Country representatives and their partners report on national programs, progress and/or constraints encountered, and plan for the coming year. Success is being reported from Morocco, Ghana, and Mexico, and likely success will soon follow in Vietnam, Oman, and others.7Until 1999 when a population-based survey reported trachoma of public health significance in parts of northern Nigeria,However, trachoma control in Nigeria is facing numerous challenges, many of which may be similar to other trachoma endemic areas in Africa.2, with a population of over 80 million people. As such undertaking district by district population-based surveys to cover this vast area will require enormous resources and time. And NGOs as the main advocates and implementers of trachoma control in the country, are unable to provide such resources. A dearth of this comprehensive data had been a constraint for national trachoma control planning and resource utilization. Some states have a trachoma control program but most of them are not implementing the full SAFE strategy as recommended by WHO. Some states like Sokoto, Zamfara, and Kebbi have initiatives based mostly on the interest of the partnering NGO to provide community-based lid surgery only, while other states like Plateau and Nassarawa implement the personal and environmental hygiene components only. Local/Federal Governments and NGOs need to mobilize resources to complete the mapping of the entire trachoma belt of northern Nigeria. This can be integrated with the ongoing mapping of other NTDs. For optimal effect of the trachoma control program service providers, especially NGOs, should collaborate with other agencies and organizations to implement a full scale SAFE strategy.Many districts  of northern Nigeria have some data on trachoma, which is based on either trachoma rapid assessment or an epidemiological survey. However, other districts of the region are yet to be mapped Figures  and 2. TThe ambivalent attitude of people to health services appear to be a universal phenomenon in many local communities in Africa, and perhaps hinges on the local people’s perspective of the disease, which varies from place to place. A study conducted in The Gambia concluded that for any intervention strategy to achieve the set goals of eliminating trachoma in spite of other constraints, community support and participation is essential, and in order to achieve this, the healthcare provider needs to have a better understanding of the community perspectives of the disease.13Although we could not access any paper reporting community perspectives in Nigeria, it is observed that aspects of community participation are essential for optimal uptake of services like lid surgery and antibiotics usage. This was observed during a focused group discussion conducted in some districts with poor uptake of lid surgery.15The study identified stakeholders’ commitment to program implementation as the major challenge. There is a decline in stakeholders’ commitment to the program after 4 years of implementation. Problems identified included poor motivation (including per diem) and support to the primary healthcare workers ; lack of mobility to the lid surgeons to reach communities for service delivery; poor communication between service providers and program management, and sometimes communal conflicts between neighboring communities. This demonstrates the importance of periodic review and studies to identify obstacles in program implementation, so as to address such problems.The WHO recommended strategy for the control of trachoma-SAFE is an effective control strategy but there are challenges to its application. Lid surgery and antibiotics distribution are two common intervention strategies used by trachoma control programs.The lid surgery involves out-turning of the in-turned upper eyelid in a community setting. This intervention is more commonly undertaken by NGOs and governments because it is easy to demonstrate its impact compared to other components of the intervention. However, even this intervention has many challenges. These include questions about who does the community-based lid surgery, how to sterilize surgical instruments in a community setting, how to ensure high quality of surgery in a community setting, and the universal issue of recurrences of trichiasis after lid surgery.In most trachoma endemic areas, there is a dearth of eye care personnel. Often, it is difficult to identify the available cadre to appropriately provide lid surgery. In northern Nigeria with limited number of ophthalmologists to be able to provide lid surgery services at community levels, ophthalmic nurses have been trained to do lid rotation surgeries based on the available evidence elsewhere that a non-ophthalmologist can perform the surgical procedure satisfactorily Figures  and 4. IThe issue of maintaining the sterility of operating instruments is a big challenge, especially in this age of HIV pandemic and other blood borne transmissible diseases. An evaluation of the trachoma control program in two states of north-west Nigeria in 2008Recurrence of trichiasis after lid rotation surgery has been reported in various parts of the worldP < 0.01).In view of plausible linkage of postoperative recurrence of trichiasis with recurrent infections or intensity of infections, the use of preoperative antibiotics has been advocated. However, the effect of such perioperative antibiotics to reduce re-occurrence has not been proven. In fact, a study in a low trachoma intensity area of the Gambia showed no difference in the recurrence between patients treated with azithromycin immediately after surgery and those not treated.One of the difficulties faced by lid surgeons is the decision on which severity of trichiasis to operate on adults and the issue of children with trichiasis. Most people with one or two offending eyelashes are encountered in the field and different control programs have differing approaches to such mild trichiasis. Basically, important considerations in deciding the approach will include the backlog of severe trichiasis in the area, expertise of surgeons, effectiveness and efficiency of the control program to provide services later to such cases when the trichiasis becomes severe. In many control programs in Nigeria, mild cases are given palliative treatment in the form of epilation in order to concentrate on the many severe cases. Children as young as aged 6 years have been seen with severe trichiasis in some trachoma endemic communities of northern Nigeria Figures . This isUse of mass antibiotics distribution or targeted treatment is a major component of trachoma control program. Traditionally, tetracycline eye ointment has been used, but the use of azithromycin had been adopted by many programs because of its similar efficacy as the ointment and higher compliance, as it is an oral preparation given once in 6 months or per year. The major challenge to this control component is the cost of the drug. Even though the International Trachoma Initiative (ITI) in conjunction with Pfizer is donating azithromycin to some countries, the trachoma control programs in Nigeria have been unable to obtain the drugs, until recently, when approval was given for pilots in 17 districts in northern Nigeria in 2010. For now most NGOs involved in trachoma control in Nigeria use tetracycline eye ointments in few communities, as they are unable to provide the drug to all endemic communities. Although this effort is laudable, it has limited effect because of the expected cross-infections that can occur between neighboring villages. Furthermore, the oily nature of tetracycline and its daily usage for several weeks gives rise to limited compliance rate. One NGO provided azithromycin and used it in its control program in a district but had to abandon this approach due to high costs., The program could only be implemented in instances when ITI/Pfizer donation was obtained.A multi-country evaluation also reported insufficient antibiotic distribution compared with the magnitude of the disease burden. In some countries, the trachoma control program covered only a small proportion of the population in need.22A more sustainable and probably more effective control strategy for the trachoma control program is improvement in personal and environmental hygiene. However, it is more difficult to attain, as it takes time for the effect to be visible and requires attitudinal and often sociocultural changes. These parameters may take generations to change, especially in isolated communities with no modern social and educational facilities. The primary school enrollment in Nigeria is about 68% and 58% for boys and girls, respectively.Furthermore, hygienic practices are closely related to use of water. In Nigeria, less than 50% of adequate water sources is available for people; and in rural areas where trachoma thrives, this is even less than 30%.Addressing the issue of water scarcity and sanitary conditions in vulnerable communities requires higher investment, which neither the governments nor NGOs are often ready to undertake. The difficulty in undertaking these projects is compounded by the fact that it is not solely a health issue but one that needs multi-sectoral approach linking ministries and agencies concerning water, environment, education, women affairs, etc. Awareness about trachoma, the SAFE strategy and use of water should be promoted. The government and NGOs should encourage such activities and build local capacity for the management of water and sanitation resources in affected areas. Each country needs to adapt the elements of the SAFE strategy to its own unique conditions.25Many NGOs may not be willing to address the problem because it is capital intensive and does not show results immediately, as the impact manifests many years after. Furthermore, there is limited clear scientific evidence that FE intervention really works to prevent trachoma. Although a study reported disappearance of trachoma in a village without a control program, this was attributed to improvements in sanitation, water supply, education, and access to healthcare in the village.2829All the same, some NGOs like The Carter Center and the Sightsavers have been involved in the FE control of trachoma in Nigeria, where they have been encouraging building of Ventilated Improved Pit (VIP) latrines in communities through limited cost of materials and labor. The objective is to enhance personal and environmental hygienic practices through multi-focal health education activities and provision of sanitary ware to endemic communities. Sanitary wares  were provided to 30 communities in one of the Sightsavers supported projects. These items are being used by communities to keep the environment clean, thereby improving environmental hygiene. Water and sanitation committees have been formed in each of these 30 communities to encourage, monitor, and promote environmental cleanliness in communities. Masons were also trained in 30 communities on construction of pit latrines. They also worked with local government staff to construct demonstration latrines.Advocacy to local government and communities for involvement in construction of pit latrines resulted in the support by the government for construction of latrines.This project promoted the desirability and demand of household latrines and environmental cleanliness in the communities with government support. This also helped improve environmental and personal hygiene and hopefully reducing the prevalence of active trachoma. Of significance is that the exercise had opened up a channel of collaborative efforts in health matters between the community and local governments.Any control program will need a good monitoring system to supervise and administer. In Nigeria, trachoma, as many other blinding diseases, does not have a unified and standardized reporting system and a chain of transmission of information in the health information system. Although trachoma is listed in the HMIS diseases of the Ministry of Health, no concerted efforts have been made to document and report this neglected disease.Trachoma control program or other programs  within which trachoma is domiciled, in the Ministry of Health, needs to strongly advocate for inclusion and enforcement of data collection on trachoma from all trachoma-endemic regions of the country. This is necessary for planning and monitoring of control programs.th country in budgetary allocation to health per person, of the 133 countries assessed in 1998, spending only $30 per capita (PPP).30A sustainable and effective trachoma control requires a good health system with strong primary healthcare built upon an efficient multi-sectoral collaboration. However, many trachoma-endemic countries have a weak health system with even weaker primary healthcare. The health budget is often less than the UN recommended health budgetary allocation, and there are competing demands like HIV, malaria, tuberculosis, other sporadic infectious diseases like meningitis, gastroenteritis, including cholera. Most of the trachoma-endemic countries have the least health budget. Nigeria ranks 95Endemic countries must make more budgetary allocation to health and strengthen their health system, especially primary healthcare, to curb not only trachoma but many other associated diseases. Stakeholders most advocate strongly for full integration of primary eye care into the primary health care and emphasize to governments that elimination of blinding trachoma in the short term could free up resources for other conditions and at the same time improve the standard of living for society’s most vulnerable populations.22The setting up of trachoma control programs with the community-based mobilization and services in some states of Nigeria seems to have spurred the interest of local governments and other stakeholders with regard to eye care as wells as reactivated the dormant primary health centers in the states. In Sokoto state, these factors might have impressed the governments and played a significant role in encouraging the state government to set up a comprehensive eye care program. Other trachoma control states like Zamfara and Kebbi states may soon commence comprehensive eye care programs.For its support of the global effort to eliminate blinding trachoma, the International Trachoma Initiative (ITI) builds coalitions with partners and agencies to implement the full SAFE strategy. The ITI works with Ministries of Health and other partners from basic planning and program development through implementation and evaluation. In less than 4 years, some of the world’s countries with the least resources have planned and implemented successful programs and demonstrated measurable short-term impact. These early successes point to the feasibility of implementing SAFE in a variety of program conditions, namely, geographic regions, population densities, and economic disparities.Unless more efforts are geared toward addressing various exceptional challenges facing local trachoma control programs, the hope of global elimination of one of the oldest causes of blindness by the year 2020 may prove a mirage. Various national and international trachoma control groups like GET 2020, NTD, need to keep up the momentum to sustain the achievements. The current momentum in reinvigorating primary healthcare with integration of eye care and health system strengthening provides opportunity to harness toward trachoma elimination.


Network Tools and Applications in Biology (NETTAB) Workshops are a series of meetings focused on the most promising and innovative ICT tools and to their usefulness in Bioinformatics. The NETTAB 2011 workshop, held in Pavia, Italy, in October 2011 was aimed at presenting some of the most relevant methods, tools and infrastructures that are nowadays available for Clinical Bioinformatics (CBI), the research field that deals with clinical applications of bioinformatics.In this editorial, the viewpoints and opinions of three world CBI leaders, who have been invited to participate in a panel discussion of the NETTAB workshop on the next challenges and future opportunities of this field, are reported. These include the development of data warehouses and ICT infrastructures for data sharing, the definition of standards for sharing phenotypic data and the implementation of novel tools to implement efficient search computing solutions.Some of the most important design features of a CBI-ICT infrastructure are presented, including data warehousing, modularity and flexibility, open-source development, semantic interoperability, integrated search and retrieval of -omics information.Clinical Bioinformatics goals are ambitious. Many factors, including the availability of high-throughput "-omics" technologies and equipment, the widespread availability of clinical data warehouses and the noteworthy increase in data storage and computational power of the most recent ICT systems, justify research and efforts in this domain, which promises to be a crucial leveraging factor for biomedical research. Clinical Bioinformatics (CBI) can be defined as "the clinical application of bioinformatics-associated sciences and technologies to understand molecular mechanisms and potential therapies for human diseases" . Being sMore specifically, CBI is aimed at providing methods and tools to support two different decision-makers. On the one hand, it should assist clinicians in dealing with clinical genomics (biomarker discovery), genomic medicine (identification of genotype/phenotype correlations), pharmacogenomics and genetic epidemiology at the point of care  Workshops are a series of meetings focused on the most promising and innovative ICT tools and to their usefulness in Bioinformatics . They aiIn this paper, the viewpoints and opinions of three world CBI leaders, who have been invited to participate in a panel discussion of the NETTAB workshop on the next challenges and future opportunities of this field, are reported.Looking at CBI from the technological side, these experts have identified three areas that need advancement and further research. These include the development of data warehouses and ICT infrastructures for data sharing, the definition of standards for sharing phenotypic data and the implementation of novel tools to implement efficient search computing solutions. In the following of the editorial we report such opinions and discuss their relevance to the field.i2b2 (Informatics for Integrating Biology and the Bedside) is an NIH-funded National Center for Biomedical Computing based at Partners HealthCare System that is an integrated framework for using clinical data for research .The back end of i2b2 has a modular software design, called the 'Hive,' that manages everything having to do with how data is stored and accessed. The front end of i2b2 is the i2b2 Web client, a user interface that allows researchers to query and analyze the underlying data. The software is open source and can be extended by users once the core cells of the Hive are included and correctly configured.To date, i2b2 has been deployed at over 70 sites around the world, where it is being used for cohort identification, hypothesis generation and retrospective data analysis. At many of these sites, additional functionality is being developed to suit the needs of the researchers.Several aspects of i2b2 contribute to its rapid adoption by the clinical research community. The first is that it is open source and therefore not only is it free to try, but there is a built-in set of collaborators - other users - with whom to engage both to get help with any questions and to foster innovation. The open source, self-service nature of i2b2 allows investigators to try out ideas stepwise at their own pace and at no financial cost. The online documentation and community wiki are kept up-to-date and greatly assist in user support. Secondly, both the fact that it is open source and the modularity of the design enforce backward compatibility with existing research, so that it is added to the i2b2 platform and does not become obsolete.But perhaps the key to the utility of i2b2 is the simplicity of its database design. A research data warehouse typically includes data from disparate sources, such as electronic health records, administrative systems, genetic and research data, and lab results, to name a few. The structure of the i2b2 database allows this data to be aggregated and optimized for rapid cross-patient searching in a way that is transparent to the user. The specific design and flexibility of the data model supports new research data being added to the database as it is amassed, while allowing users to construct complex queries against the multiple source systems.i2b2 data is stored in a star schema, first described by Kimball . A very The star schema is optimized for analytic querying and reporting. Its design tends to mirror the way users think about and use data, which is important since users must understand what data is available in order to formulate queries. The straightforward connections between the fact and dimension tables mean that navigation through the database via joins and drilling into or rolling up dimensional data is simple and quick. The design allows the fact table to grow to billions of rows while maintaining performance. Another advantage of the fact table design is that it is well suited to handle "sparse" data; data that has many possible attributes , but with only a few that are applicable. In this model, only positive facts are recorded, thus resulting in more efficient storage.Perhaps the most powerful aspect of the i2b2 database design is the design of the metadata. In i2b2, metadata is the vocabulary, all the medical terms that describe the facts in the database. Metadata is what allows users to interact with the database. A typical clinical data warehouse may have 100,000 to 500,000 concepts, including ICD-9 , SNOMED-Maintaining and updating the metadata is a significant, but workable challenge. New medical codes are constantly being created, and old codes are discarded or changed. The structure of the metadata must be able to seamlessly absorb new codes while remaining backward compatible with old coding schemes. The hierarchical classification scheme of i2b2 makes it easy to map new codes to existing folders and to create new folders as needed. Entire new coding systems can be added just by creating a new folder. Discarded codes can remain in the hierarchy next to newer ones and used to reference older data, or hidden to discourage their usage in new queries.One goal of i2b2 is to help integrate data from the many different sources that exist in modern day healthcare institutions in order to present a comprehensive view of patient care for research. The simple and intuitive design of the i2b2 database enables users to construct complex queries over these disparate data sources.The success of Personalized Medicine (PM) at the point of care is dependent on the effective use of PM knowledge  while considering the complete patient's medical history .In order for PM knowledge to be effectively applied to the patient medical records, representations of data and knowledge need to be standardized due to the heterogeneity of their original formats. Both data and knowledge are generated nowadays by a variety of sources, each of them using proprietary formats and idiosyncratic semantics, often not represented explicitly .Interpretation of clinical data typically starts at parsing the metadata, e.g., the predefined schemas of clinical information systems. However, these schemas  cannot accommodate the complexity of contextual data representation. Thus, it is important to have a richer language allowing the explicit representation of patient-specific context of each discrete data item and of how it relates to other data items, as well as how it fits within the entire health history of an individual.Dispersed and disparate medical records of a patient are often inconsistent and incoherent. A patient-centric, longitudinal electronic health record (EHR) based on international standards  standard . CDA docThe efforts to apply Natural Language Processing (NLP) to health information could be connected to healthcare information technologies through standards like CDA that uses the clinical statement concept. The NLP fundamentals can be reduced to the clinical statement constituents and the CDA can thus be a good "catcher" of the results of NLP running over unstructured health information.The continuously increasing amount of available data poses significant technological and computational challenges, both to their management  and effective use . This issue is becoming predominant in several fields and it is being addressed in different ways, according to each specific field peculiarities.The Web is a paradigmatic field for this aspect. A rapidly growing mass of data is flooding the Web. Yet, leveraging on the typical linked nature of Web data, technological and computational advancements are preventing (at least for now) drowning by Web data. Automatic robots have been implemented to crawl the Web resources, collect their huge key data and store them in powerful database management systems. Effective indexing and ranking techniques, such as the Google PageRank , have beat least one" or "the most evident" item that can answer his/her question. Current Web search technologies are not enough when search questions either become more complex, simultaneously involve different topics, or require the retrieval of most of  available items regarding the question, possibly ordered according to different user-defined features. Furthermore, only an estimated limited part of all data accessible through the Web can actually be found by current search engines: the vast "deep Web", including dynamic pages returned in response to a query or accessed through a form, resources protected by password, sites limiting access by using various security technologies , and pages that are accessible through link-produced scripts, remains unrevealed.Such ability, which is tremendously boosting the Web as an extraordinary easy-to-use source of information, is based on the assumption that user searches are mainly aimed at finding "Especially in the CBI field, the amount of collected data is continuously and rapidly increasing, in particular with the recent collection of -omics data. Also, compared to the Web, the current ability of extracting relevant biomedical information and of answering even common CBI questions is far less, due to many reasons.First, the biomedical-molecular data - which are of various types - are stored in several different formats within systems that are distributed, heterogeneous, and often not interoperable. Furthermore, a lot of important information is subjectively described in free texts, within chief complaints, discharge letters, clinical reports or referrals, which are intrinsically unstructured. The adoption of electronic medical or health records can significantly enhance the availability and sharing of clinical data and information, which are still only on paper in very many healthcare sites. Yet, the digitalization of health data alone is far from sufficient; having clinical reports and referrals in PDF format is evidently not enough to solve the information extraction and question answering issues. A standard data and information representation according to a shared reference model has to be adopted, together with controlled terminologies and ontologies to objectively describe medical and biomolecular findings. Moreover, the use of advanced Natural Language Processing techniques suited for the clinical domain to extract and structure information from previous medical textual descriptions can also greatly help.Second, usual biomedical-molecular questions are generally more complex than Web search questions. They often involve more types of data, as well as topics with usually several attributes. In many cases, retrieving only a few of the items related to a biomedical-molecular search question, or even the K top items according to some user-defined ranking, may not be enough for a proper answer, which can instead require the exploration of all available items and their attributes.Advanced search computing techniques are being developed to answer complex, multi-topic Web search questions involving the integration of possibly ranked partial search results . These tCBI goals are ambitious, but many factors, from the availability of high-throughput "-omics" technologies and equipment, allowing identifying "individual" genomes and proteomes, to the incredible increase in data storage and computational power that is allowed by most recent ICT systems, justify research and efforts in this domain.In this paper, we have reported some points of view on the current and future challenges in this domain that were discussed in a panel session at the NETTAB 2012 workshop on Clinical Bioinformatics.First, we presented what we believe are the most important design features of a CBI-ICT infrastructure, by taking into account some achievements of the i2b2 system. Data warehousing is essential in CBI because of the great amount of clinical and biomedical information that needs to be generated and managed within health organizations. Indeed, CBI depends on information that is gathered from single individuals, usually patients, and thus it cannot exclusively depend on general population or species oriented databases that are available on-line from main data providers. On the contrary, these general resources may only be used as a general reference, while the most important data is provided by individual's clinical and molecular information.Some of the most relevant features of a data warehouse for CBI have been identified by examining the i2b2 experience. Simplicity of the database schema is a key factor, facilitating the modularity and flexibility of the system, that support its continuous development and improvement, and making optimization of queries and searches possible. Modularity is indeed essential also because of the various and heterogeneous data and sources that may be usefully included in the data warehouse, thus leading to a multiplicity of goals and application domains for the system.The open source approach is also extremely important, since it is able to fully exploit collaboration among users both for software development and for new features design. Collaborative development is especially important for the maintenance and update of shared metadata that, being used by the users as the main means to interact with the database, determine in fact its real usefulness and success.Of course, individuals are moving, and information is being accumulated in many health organizations and information systems, that need to interoperate so that all possible information on each patient is made swiftly available when it is needed. This is a precondition for the clinicians in order to be able to deal at the point of care with all needed information for a proper, molecular-enabled, diagnosis, prognosis and optimized treatment selection.Moreover, CBI data analysis may be greatly facilitated and improved when the population under analysis is the greatest possible. Such clinical-related processes as biomarker discovery and identification of genotype/phenotype correlations may only be carried out when a sufficient amount of data is available. So, interoperation of information systems should support both integration of data on single individuals and coming from many patients. Hence, it is of extreme relevance.In this paper, we have therefore also faced the interoperability issue, and we have discussed about some of the most recent standards for data modelling and data interchange and their possible use in CBI to overcome heterogeneity of original data and knowledge formats, as well as modelling of arising information. In this case, international standards exist and should be adopted, with the provision that new evidence arising as a result of genomic medicine efforts be also properly included. We also highlighted that the application of a shared reference model could lead to a standard, semantics rich, processable representation of clinical statements.CBI is not limited, however, to the analysis of the information on a given individual by the health care personnel that provide him/her assistance. As previously said, it must also support researchers in the reuse of clinical data for research purposes. Many new applications are being developed by researchers in the field, who can largely benefit from making access and searching information resources through Web services. It is often from such free access to data that new associations may be identified, possibly leading to hypothesis for new biomarkers validation and assessment.In this paper, we have therefore also tried to point out which currently are the main difficulties in making access and searching CBI related information sources.First, we addressed the idea that the adoption of common data models could be the best starting point for the implementation of a set of data marts, optimized representations of data included in warehouses for performing specific research tasks. New data marts, each devoted to a different task, could easily be created and made available.Current techniques and technologies aimed at searching data on the Web, even the most advanced, do not seem completely adequate for CBI needs, where queries are complex, involving many data sources simultaneously and, often, requesting from each resource more results than the first that are usually returned. One of the most demanding issues remains access to a lot of information that is included, and subjectively described, in free texts, which are intrinsically unstructured. The use of controlled terminologies and of ontologies, whenever possible, together with the adoption of NLP tools suited for the clinical and biological domains can indeed support extraction of information from medical textual descriptions.We finally moved to the issue of searching and extracting information from big data amounts. Queries which are relevant in CBI often require retrieving result sets bigger than usual and the exploration of all available items and their attributes because of possible correlations among data in the results that could change, even sensibly, their relevance to the overall query. Of particular interest are those advanced search computing techniques, which are aimed at integrating ranked search results from multiple sources.The integrated search and retrieval of CBI data from multiple sources and its comprehensive analysis constitute in our opinion one of the biggest challenges for the future. The NETTAB 2013 workshop will be devoted to this theme.CBI: Clinical Bioinformatics; CDA: Clinical Document Architecture; CEN: Comité Européen de Normalisation (European Committee for Standardization); CPT: Current Procedural Terminology; EHR: Electronic Health Record; HCPCS: Healthcare Common Procedure Coding System; HL7: Health Level 7; i2b2: Informatics for Integrating Biology and the Bedside; ICD-9: International Classification of Diseases rel. 9; ISO: International Standard Organization; LOINC: Logical Observation Identifiers Names and Codes; NDC: National Drug Code; NETTAB: Network Tools and Applications in Biology; NIH: National Institute of Health; NLP: Natural Language Processing; RIM: Reference Information Model; RM: Reference Model; SNOMED: Systematized Nomenclature of Medicine; TBI: Translational Bioinformatics.The authors declare that they have no competing interests.RB and PR conceived the work, wrote the background and introduction and drafted the conclusions. MM, SM, and AS contributed by identifying and specifying issues in one of the three main chapters, respectively on data search and extraction, data warehouse platform, and standardization and interoperability. All authors revised, discussed, and amended the manuscript and approved its final version.


Lymph node involvement is considered to be one of the most important independent prognostic factors in breast cancer. In patients without palpable lymphadenopathies, the method of choice for determining this involvement is the sentinel lymph node biopsy. In the presence of macrometastases, the current standard is to perform axillary lymph node dissection in spite of the knowledge that the involvement of non-sentinel lymph nodes is approximately 50%. When lymph node involvement is micrometastasic, the decision as to whether or not to proceed with lymphadenectomy remains in dispute. We set out, on the basis of the current scientific evidence and our own experience, to create guidelines that allow us to individualise each case and decide whether or not to perform a lymphadenectomy. We will discuss the arguments that support our position. Axillary involvement is considered to be the most important independent prognostic factor in breast cancer. In the last 15 years, the number of patients with breast cancer benefiting from sentinel lymph node biopsy (SLNB) has increased . When thThere are other elements that explain the growing interest in omitting ALND. The majority of patients with SLN involvement will receive adjuvant chemotherapy, and its indications do not depend on the number of lymph nodes with metastasis. In contrast, for a significant group of patients, the decision making in adjuvant treatment planning will be based on the immunohistochemical study of the tumour, which has a greater influence in the therapeutic decision than the ALND. Finally, during the years 2010 and 2011, the first results of clinical trials were published that specifically analysed the impact of ALND on local control and survival of women with SLN involvement. These have not shown any benefit in patients who had an ALND performed . In lighet al [The ACOSOG Z0011 multicentre clinical trial by Giuliano et al  shows thet al . The criIn the analysis of the results, it is noted that age (young patients) and small degree of differentiation were related to a greater percentage of locoregional relapse. Non-sentinel lymph node involvement was 27%, a fact observed in the arms of patients undergoing ALND, suggesting that in the group of patients under observation there was a similar trend. However, since there were no differences in relapse, the importance of the adjuvant treatments is highlighted as elements of locoregional control, suggesting that ALND does not improve this control.However, it is important to take into account the limitations of this work. The main being that the selection of patients was mainly among those in very early-stage cases with good prognostic factors . In addition, in all cases, radiation therapy to the entire breast bed was administered, which influences the possible extrapolation to less extensive radiotherapy fields. There was limited follow-up; 6.3 years being the median time. Ninety-six per cent of patients received chemotherapy. Recruitment of the expected number of patients (891 of 1900 planned) was not possible for reasons related to patients themselves or to the denial of some surgeons. Eighty percent of patients were hormone receptor positive, which skews the sample towards tumours with better prognosis, susceptible to hormonal manipulation. There was no identification of Her-2/neu at the start of the study as this was not a standard procedure. This limits the establishment of subgroups of patients, including the triple negative [There are other studies that have looked into sentinel node involvement. However, the majority have focused on the analysis of micrometastases. One of these is the MIRROR study, in which nearly 2600 patients with biologically favourable tumours, and no indication for systemic adjuvant treatment with chemotherapy, participated in a trial. These patients had negative sentinel lymph nodes PN0, isolated tumour cells pN0 (i+), or were positive for micrometastases pN1mi, and were separated randomly into ALND or axilla radiation therapy. In this study, omission of axillary dissection or radiotherapy in patients with a positive SLNB for micrometastases resulted in a higher rate of axillary relapse at five years .et al conducted a study in the European Institute of Oncology in which they omitted ALND in 377 patients with micrometastases in SLN; 2.1% (N = 8) of the patients had a recurrence at the axillary level. The only risk factor detected for axillary relapse was the size of the tumour [Galimberti e tumour .In the NSABP-B32 trial, analysing the clinicopathological factors associated with positive non-sentinel lymph nodes was one of the objectives of the study. The tumour size, presence of lymphovascular invasion, and SLN macrometastases were independent predictors. There was no cutoff point considered for the size of the tumour since this was considered to be a continuous variable  .In a study conducted in Barcelona, Spain, by Pernas and colleagues, 59 cases with SLN micrometastasic involvement in which ALND was not performed were analysed. There were no axillary recurrences in a median follow-up of 60 months . In anotP = 0.48), with an overall survival of 97.6% and 98% (P = 0.35) for the groups assigned ALND and not, respectively [Finally, in April of this year, the results of the IBCSG Trial 23-01 were published. This trial was conducted in 27 European centres in which 931 women with SLN micrometastases involvement were randomly assigned to ALND or not. The majority (85%) had one or two positive SNL. With a median follow-up of 57 months, the disease-free survival rate was 87.3% and 88.4%  that arise as alternatives to ALND in a subgroup of patients with SLN involvement.et al [In our Breast Pathology Department, we are continuously searching for solid foundations for our medical practice that ultimately translate into benefit for patients. SLN involvement has been one of these fields of research. In 2011, a study was published by Zenzola et al  in whichet al, clinically negative node (cN0) patients with tumours up to 1.2 cm were randomised to receive either axillary radiotherapy or no axillary radiotherapy. With an average follow-up of 63 months, no differences were found between the working underarms in terms of local recurrences and disease-free survival [Given the possibility of residual disease in the underarm when the SLN is positive in patients selected for skipping ALND, most centres tend to prescribe radiation treatment at that level as a tool of local control. In fact, the incidence of axillary relapses in women with SLN (micrometastasis or macrometastasis) without ALND is the same as in women with ALND when combined with postoperative radiotherapy in the breast, and this is based on prospective randomised clinical trials , 16. Patsurvival . Howeversurvival .et al). Through these methods, attempts are made to establish quantitatively the probability of metastasis in non-sentinel lymph nodes, taking into account factors like tumour size, size of the metastasis in the SLN, number of positive SLNs, ratio between the number of positive SLNs and removed SLNs, lymphovascular invasion, extracapsular extension, among others [At least nine mathematical models have been developed to predict the status of non-sentinel lymph nodes in patients with breast cancer and SLN. Among them are included four nomograms , Mayo, Cambridge, Stanford), three scoring systems , and two recursive partitioning models , and in case, the report is positive for metastasis, to proceed to ALND. This avoids the possibility of a second surgical intervention since the procedure is completed in just one stage. However, we see that there is a series of clinical and pathological factors, some of the primary tumour  and others of the SLN  that are important for decision-making and that they are not considered but after the definitive anatomopathological study. This raises the question of whether to conduct a preoperative histological study of the SLN or to wait on a more exhaustive study to obtain more complete information and make the most appropriate determination. In both MD Anderson and MSKCC, as current everyday practice, they have the omission of the intraoperative study of the SLN, in patients who meet the criteria of the ACSOG Z0011, while waiting on the outcome of the definitive biopsy for decision-making , 24.The Venezuelan Mastology Society published its Consensus of Sentinel Lymph Node in Mammary Carcinoma in 2010. This recommends performing ALND in all cases of macrometastasis and leaves the decision in the hands of each working group in cases of micrometastasis. The American Society of Clinical Oncology (ASCO) recommends performing ALND in all patients with SLN, whether they have macro or micrometastasis.Tumours under 2 cm (T1).One or two affected sentinel lymph nodes.Absence of infovascular invasion.Guaranteed irradiation of Berg levels I and II.Guaranteed adjuvant systemic treatment.Positive hormonal receptors.In our Mammary Pathology Service, we conduct a presurgical discussion, individualising the decision for each case. We propose on the basis of existing evidence and our own evidence, the following criteria for omitting ALND, in cN0 patients:The absence of just one of the criteria indicates performing ALND.We recommend waiting for the outcome of definitive pathologic anatomy in cases where no sufficient elements are considered for deciding whether or not to perform ALND. We suggest not omitting ALND in cases of triple-negative tumours or overexpressed Her2/neu carcinoma that cannot receive treatment with trastuzumab. We also recommend performing axillary dissection in cases of patients who undergo total mastectomy (since the majority will not receive radiotherapy).These are the guidelines of the Mammary Pathology Service of the Dr Luis Razetti Oncology Institute for establishing therapeutic conducts in patients with mammary carcinoma and sentinel lymph nodes metastasis. They are based on the experience of our institution, on our own scientific evidence and on other global centres. Medicine is dynamic and these will continue to evolve as they continue to generate new evidence. We hope these guidelines are able to serve as a guide to other working groups.


Histoplasma capsulatum var. capsulatum is probably on the top of the list of AIDS-defining illnesses and AIDS-related deaths HIV/AIDS is not a neglected disease. Histoplasmosis is not considered a neglected disease in North America. However, in South America, it should be. It often affects neglected populations and represents a lethal blind spot of the HIV/AIDS data collection systems. Counts of new AIDS cases and AIDS-related deaths are useful to follow the epidemic; however, they overlook the exact cause of death. In the context of the South American pathogen ecology, the systemic mycosis due to Studies performed in the 1950s and 1960s on the histoplasmin skin test positivity in South America showed positivity rates around 30% from Trinidad and Tobago in the North, to Uruguay and Argentina in the South. The pathogen is there For too long, the absence of a simple, reliable, and affordable diagnostic test has made it difficult to determine the burden of this disease in HIV-infected patients in much of South America. The gold standard for diagnosis relies, so far, on the culture of fluid and tissue samples Histoplasma in clinical specimens Don't miss histoplasmosis!”In French Guiana, there has been a mycology laboratory since 1997 with a BSL 3 laboratory. The virtuous cycle between laboratory and clinicians has been fruitful: clinicians are well informed about histoplasmosis and are quite aggressive in looking for the infection, while the mycology laboratory has the capacity to appropriately process and identify Histoplasma coinfections on the South American continent is not a trivial problem. The scarcity of the published research on this topic reflects the tragic fact that this problem is evolving under the radar of health care systems and is truly a neglected disease. Generations of young doctors will learn to look for tuberculosis, pneumocystosis, and bacterial pneumonia when confronted with a febrile patient with respiratory signs, but not for histoplasmosis. Similarly, important clinical clues, such as cytopenia (ascribed to bone marrow involvement with or without haemophagocytic syndrome) and liver enzyme abnormalities will often not lead to the suspicion of disseminated histoplasmosis. A big danger is that a smear negative, treatment resistant, “tuberculosis-like” syndrome may often be labelled drug-resistant tuberculosis, when it was never tuberculosis in the first place. It is thus of paramount importance to fill this knowledge gap and revise the diagnostic and therapeutic algorithms in the region. The “Know your epidemic, know your response” UNAIDS slogan should also be applied to histoplasmosis.The high prevalence of HIV–The HIV/AIDS epidemic is still active in countries in the Amazon basin. Guyana, Suriname, French Guiana, and the Brazilian state of Amapa all have HIV prevalence rates over 1% of the population. Although the AIDS incidence has steadily declined in the southern states of Brazil, the situation in the northern  and the northeastern states of Brazil is still concerning. A very coarse calculation based on 600,000 HIV patients and an annual histoplasmosis incidence rate of 1.5% would estimate the annual number of cases to be in the thousands. Unfortunately, histoplasmosis thus still has a future in HIV patients. Although there is a need for epidemiologic research to measure the true burden of disease in various regions of South America, actions can, and should, be taken to diagnose and treat patients now. We need to develop standard mycological practices in the area that emphasize early and aggressive clinical diagnosis, and we need to develop new rapid diagnostic tools and advocate for affordable treatment. New affordable diagnostic assays  are presently being tested in Brazil, French Guiana, Suriname, and Colombia. We hope they will allow us to improve our knowledge of local epidemiologies and reduce patient mortality through early diagnosis and increased awareness. Although amphotericin B is available, it has potential significant renal side effects. Liposomal amphotericin B is the treatment of choice of the most severe cases of HIV-associated histoplasmosis, but its cost exceeds 800 US dollars per day. Gilead Sciences, Inc. has committed to the procurement of HIV drugs at affordable prices. Extending this policy to the problem of treating HIV-associated histoplasmosis, a neglected disease, would be an important step in improving the health of HIV/AIDS patients in the region. In the near future, DNDi (Drugs for Neglected Diseases initiative) should provide a low-cost, heat-stable alternative to liposomal amphotericin B that could be valuable for histoplasmosis treatment. Our focus has been HIV-associated disseminated histoplasmosis; however, it should be emphasized that the problem of missing the diagnosis of histoplasmosis in South America also extends to some immunocompetent patients or patients with causes of immunodepression other than HIV We need tests; we need treatments; but first of all, we physicians need to integrate our South American epidemiology in our diagnostic algorithms. Looking for malaria in febrile patients in malaria-endemic areas is automatic; looking for histoplasmosis in febrile, immunosuppressed, HIV-infected patients in South America, Central America, and perhaps way beyond


The aim of this study is to describe the magnitude of educational inequalities in utilisation of general practitioner (GP) and specialist services in 9 European countries. In addition to West European countries, we have included 3 Eastern European countries: Hungary, Estonia and Latvia. To cover the gap in knowledge we pay a special attention to the magnitude of inequalities among patients with chronic conditions.Data on the use of GP and specialist services were derived from national health surveys of Belgium, Estonia, France, Germany, Hungary, Ireland, Latvia, the Netherlands and Norway. For each country and education level we calculated the absolute prevalence and relative inequalities in utilisation of GP and specialist services. In order to account for the need for care, the results were adjusted by the measure of self-assessed health.People with lower education used GP services equally often in most countries (except Belgium and Germany) compared with those with a higher level of education. At the same time people with a higher education used specialist care services significantly more often in all countries, except in the Netherlands. The general pattern of educational inequalities in utilisation of specialist care was similar for both men and women. Inequalities in utilisation of specialist care were equally large in Eastern European and in Western European countries, except for Latvia where the inequalities were somewhat larger. Similarly, large inequalities were found in the utilisation of specialist care among patients with chronic diseases, diabetes, and hypertension.We found large inequalities in the utilisation of specialist care. These inequalities were not compensated by utilisation of GP services. Of particular concern is the presence of inequalities among patients with a high need for specialist care, such as those with chronic diseases. Access to health care for all in need is a basic social right. At first sight, all European countries have universal insurance coverage and, thus, it is often assumed that these countries also enjoy universal and equitable access to health care services. However, a number of studies indicate that that is not the case-7. AlthoAlthough a number of international studies have documented inequalities in utilisation of health care services in European countries, this information remains incomplete. Previously only income inequalities in utilisation were studied internationally, thus information is lacking regarding educational inequalities in the use of health services. A theoretical argument in favour of also using education is its growing importance in relation to the relative position of the individual in the distribution of other important assets such as paid labour, occupational status and income level. Additionally, previous studies largely focused on West European countries, missing the growing "new" European populations for which the magnitude of socioeconomic inequalities has hardly been studied. InequalThe aim of the present study is to describe the magnitude of educational inequalities in utilisation of GP and specialist services in 9 European countries. In addition to West European countries, we have included 3 Eastern European countries: Hungary, Estonia and Latvia. Special attention is also paid to the magnitude of inequalities among patients with chronic conditions.Data on utilisation of GP and specialist services were derived from micro-level data of national health surveys in 9 European countries . Most surveys were conducted in or after the year 2000, except for the German survey which was conducted in 1998 : primary or no education and lower secondary education; higher secondary education; tertiary education.First, we assessed educational inequalities in utilisation of GP and specialist services using prevalence rates of having made at least one visit to a GP or specialist. Prevalence rates were calculated for each type of service by education group and participating country. The prevalence rates were standardized by 5-year age groups and gender to the total survey population, as a representative sample for the standard European population. We use prevalence rates to judge about the absolute differences of GP or specialist services use between different educational groups.Second, we estimated relative inequalities in utilisation of GP and specialist services among higher and lower educational groups of the general population using the relative index of inequality (RII). The RII is a regression-based index used to measure socioeconomic inequalities in health in a comparable way in different countries,12. The Third, we estimated relative inequalities by education in utilisation of GP and specialist services among persons with chronic diseases, hypertension and diabetes.All calculations were done using log-binomial regression analysis in SAS statistical package (version 8.02). We included categorical variables in the regression models, representing 5-year age groups and gender, to control for demographic confounders. To take the need for care into account, we adjusted our results by the ranked measure of self-assessed health, which quantifies the relative position of each group of people in one answer category in the hierarchy of all answer categories. Ranked measure of self-assessed health was calculated on the basis of the cumulative relative frequencies of the valid cases and allows for better comparison between countries.The study populations in the different European countries did not differ greatly regarding age and gender distribution Table , except Only in Belgium and Germany were lower educated people significantly more likely to report a visit to a GP . At the same time, higher educated people used specialist care services significantly more often in all countries (except for the Netherlands). Educational inequalities in utilisation of specialist care among women were slightly larger than among men in some countries, although the general pattern of use was similar for both men and women. Inequalities in utilisation of specialist care were equally large in Eastern European and in Western European countries, except for Latvia where the level of inequalities was somewhat larger. Similarly large was the level of inequalities in utilisation of specialist care among patients with chronic diseases, diabetes, and hypertension.The high percentage of non-response in some countries could have biased our results if both the educational level and the reported utilisation of services had been unequally distributed among respondents and non-respondents. Although some studies reported that non-response is related to socioeconomic status-15, prevWe used education as an indicator of socioeconomic position. Education allows the classification of individuals who do not work, prevents reverse causation, and facilitates international comparisons due to its relative ease of measurement. In addition, recent studies suggest that in some countries education has an independent effect and is more strongly related to the likelihood of health services utilisation than income and employment status,19. On tThere were large differences between countries in the educational distribution. These differences reflect, in part, the real situation of educational attainment in different countries of Europe. HoweverThe recall period for use of GP and specialist services was shorter in the Netherlands and Belgium than in the other countries. A longer recall period would have influenced the overall utilisation rates for the total population. It is, however, unlikely that it would have a differential effect on utilisation of services by different educational groups.Self-assessed health was used in order to control for the health care needs of the population. Although the measure of self-assessed health is often used in health care research due to its wide availability and good comparability, it does not completely encompass the full spectrum of need. A better control for need would likely result in greater inequalities in specialist visits, while inequalities in GP visits might have also emerged in some countries.Most European countries have achieved universal access to health care. However, the results of the present study show that universal access does not mean equal use. One might argue that differences in utilisation do not directly reflect inequalities in access to care. The decision to use health care services and the type of provider is, after all, a personal choice. Nevertheless, this personal choice is affected to a large extent by various enabling and predisposing factors. People from lower socioeconomic strata are likely to have fewer enabling factors and more barriers to use specialist care.European countries have very different health care systems. For example, some countries operate with GP gate keeping , others have more direct access to specialists and hospital care (France); some countries use only public insurance , others only private or a combination of the two ; some countries use co-payments, others do not; etc. Regardless of the way the system is organised, we find a generalised pattern of differential access to primary and secondary care for people with different socioeconomic positions. Such a universal pattern indicates that patients with a lower socioeconomic position encounter barriers that are common in all countries, and thus lie beyond the national structure and organisation of the health care system.Proper communication between the patient and health provider where the patient not only receives information about his disease, diagnostic procedures, and treatment, but also feels understood and helped is essential. Successful communication contributes to both patient outcomes,23 and gOne may suggest that a simple substitution of care occurs i.e. equal quality care for the same problem, which is performed by one type of provider instead of another without any consequences for the health outcomes of the patient. Our data, however, indicate that lower-educated people use GP services slightly less often compared to higher-educated people in most European countries, while inequalities in the use of specialists are large. A better control for need of care may even reveal pro-rich inequalities in the use of GP services. Thus, we do not find evidence for the substitution of care. Others also showed that the likelihood to consult a specialist increases given a consultation with the general practitioner.Another common feature of the health care system is its enormous complexity: whichever type of organisation exists in a country it is never easily understood, particularly by those with a lower socioeconomic position. This complexity is often coupled with constant changes in the way the system operates that may disorient even well-educated patients. Since primary care (GP practices) is the easiest, most accessible and least changeable type of care, people with a lower socioeconomic position may not feel inclined to go further up the hierarchy of the health care organization, in order to avoid this confusing complexity.Within the generalised pattern of differential utilisation of different types of services, there remain some variations that indicate that national health care systems may play an additional role in (dis-)motivating patients to use particular types of care. For example, compared to other countries, we observed larger inequalities in the use of specialist care in Latvia and smaller inequalities in the Netherlands. Similar differences were also observed in studies on income inequalities in utilisation of care. It is pWe hypothesized that inequalities in access to care in East European countries would be larger than in the West European countries due to disruption of the social protection and health care systems that occurred during the 1990s in many former Soviet countries. Our data do indicate larger inequalities in use of specialist care in Latvia. Compared to the neighbouring countries, Latvia has implemented a system with larger co-payment mechanisms for public health services. Thus, the financial barriers met by the population for the use of health services might have resulted in much lower utilisation rates and the highest level of inequalities observed in the present study. Also in Hungary, in addition to large inequalities in utilisation of specialist care, there were significant pro-rich inequalities in the use of GP services, indicating gross general inequalities in utilisation of health services. Our findings are supported by studies reporting larger inequalities in mortality amenable to medical care found in East European countries compared to West European countries -34. HoweThe present study paid particular attention to people with chronic diseases. The results show large inequalities in utilisation of specialist services in this vulnerable group. Hampered access to specialist care might have a more severe impact on the health status of patients with high need, such as the chronically diseased, compared to the general population. Thus, there is an urgent need to investigate and remove barriers to the use of specialist care among patients with chronic diseases.In summary, large inequalities were observed in the utilisation of specialist care that are not compensated for by the use of GP services. Of particular concern is the presence of inequalities among patients with a high need for specialist care, such as those with chronic diseases, which raises important issues regarding the access to care among vulnerable subgroups.The authors declare that they have no competing interests.IS designed the study, performed the statistical analysis and wrote the main draft of the manuscript. AK supervised the study and provided comments to all drafts of the manuscript. AM contributed to study design and provided comments to drafts of the paper. JM conceived the study and contributed to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/11/288/prepub


The term “tactical medicine” can be defined in more than one way, but in the nonmilitary setting the term tactical emergency medical services (TEMS) is often used to denote medical support operations for law enforcement. In supporting operations involving groups such as special weapons and tactics (SWAT) teams, TEMS entail executing triage, diagnosis, stabilization, and evacuation decision-making in challenging settings. Ultrasound, now well entrenched as a part of trauma evaluation in the hospital setting, has been investigated in the prehospital arena and may have utility in TEMS. This paper addresses potential use of US in the tactical environment, with emphasis on the lessons of recent years' literature. Possible uses of US are discussed, in terms of both specific clinical applications and also with respect to informing triage and related decision making. The use of ultrasound (US) outside the radiology suite has grown markedly over the past few decades . With inOver a decade ago, investigators began assessing deployment of US for use even before patients arrived at the hospital . First fUses of US in the hospital and ambulance EMS settings have been well reviewed elsewhere , 4, 5. T The goal of this paper is to overview the potential uses of US for trauma evaluation and care in the TEMS environment. The paper includes performance of US by physicians and nonphysicians and addresses specific clinical situations in which US could potentially be helpful in tactical medicine. The paper's intent is not to be comprehensively inclusive of all relevant literature; the aim is rather to address specific clinical situations and provide illustrative references from the past five years' literature.Many uses of US have been investigated and reported in the prehospital setting. Some of these, such as cardiac output estimation or differentiation of chronic obstructive pulmonary disease (COPD) from congestive heart failure (CHF), are promising but not likely to be applicable in most tactical settings –8. TheseWith the understanding that there may be other situations in which US could be of aid, this paper includes discussions of US use for triage, for trauma diagnostic applications , and as an aid for evacuation decision-making in TEMS. The discussion does not extend to scientific or technical information about US, available machines, or how to obtain or interpret images. Readers are referred to standard texts and related sources, for this information.The first applications covered are for cardiac imaging or echocardiography. Lung-related US is discussed next, followed by inferior vena cava (IVC) and abdominal imaging. Extremity applications, including both fracture and vascular assessment, are covered next. The final clinical situation considered is retinal scanning to detect increased intracranial pressure (ICP). The paper's final sections address triage, feasibility, and areas for further research in TEMS application of US. It is hoped that the information in the paper can be of utility to TEMS programs considering US investigations, deployment, and/or educational efforts. Echocardiography is one of the oldest and best-characterized uses of US in the hospital, with many anatomical and functional applications . On a muIn the Emergency Department (ED) or even in routine EMS settings, the timely identification of patients in whom resuscitation should be halted is usually not considered a major challenge. There is little risk to inadvertently prolonging resuscitation efforts. In tactical medical situations, though, extraction and evacuation can occasionally pose significant risk to law enforcement members (operators) and/or medical team members. Furthermore, if there are multiple casualties, early determination of which patients are nonsalvageable can help focus resources—resources that are much more seriously limited in TEMS settings than in the ED. For the reasons just iterated, the use of tactical medicine echocardiography for assessment for cardiac motion is attractive. For those patients who can be clearly identified to have cardiac standstill after trauma, US can allow for conservation of air or ground evacuation resources and eliminate risks attendant to extracting and transferring patients with no chance of survival. Prehospital physicians have been shown to be able to reliably identify cases of cardiac standstill (and thus predict who will fail to survive if transported to the ED) , 11. Whe Most TEMS injuries are penetrating, and therefore traumatic pericardial effusion is a possible diagnostic entity in cases of chest injury. It is well known that US can diagnose traumatic pericardial effusion when deployed in the prehospital (standard EMS) setting . On occaOne of the most important uses of US for trauma is in the rapid identification of pneumothorax . Since pcaveats regarding application of US  [Pneumothorax is a major, yet treatable, cause of death in penetrating trauma. Prehospital identification of pneumothorax with US has already been successfully taught, in a French system that emphasized the importance of identifying pneumothorax in the field to enable immediately life-saving interventions . There aagnosis) , but exiagnosis) .In the TEMS situation, unnecessary needle thoracostomy can remove a needed law enforcement officer from tactical utility, and also may necessitate both evacuation and invasive follow-up procedures. Thus, in tactical medicine one of the most important uses of US for evaluation of the pleural space is the potential ability of the imaging to rule out pneumothorax and thus avoid nonindicated interventions. Prehospital US has been identified as an important tool to prevent placement of unnecessary needle thoracostomies and also reduce requirements for resource-intensive evacuation .When needle thoracostomy has been performed, US can be used to assess the effectiveness of the procedure. US has been recommended as a screening tool for patients who are status post needle thoracostomy, to determine if they really need tube thoracostomy in the ED , 19. TheThe placement of an ETT is a relatively infrequent occurrence in TEMS, but the confirmation of intratracheal placement is of course a priority in those cases where intubation is performed. Similarly, rescue airways such as laryngeal mask airways also need to be evaluated for their functionality in ventilating patients. Traditional mechanisms for ongoing evaluation of ETT placement  may be scarce or difficult to deploy in the TEMS setting.Fortunately, some of the standard imaging techniques that can be used to assess for pneumothorax are also useful for indirect confirmation of bilateral ventilation. Specifically, if the SLS is visualized on both sides of the thorax concomitant with inspiration there is a strong suggestion that both lungs are being ventilated; US can both detect endotracheal positioning and also mainstem intubation . This haThe assessment of volume status for CHF identification has been demonstrated to be useful, even in challenging environments . Acute C While pulmonary US can demonstrate volume overload by demonstrating the presence of congestion and vascular overload, imaging of the IVC can be very useful at the other (low) end of the volume status spectrum. The technique has been rarely used in the out-of-hospital setting, but ED practitioners and others have reported utility to IVC imaging  as a reliable indicator of volume status, and therefore as a guide to fluid resuscitation , 22. ForIdentification of free fluid in the peritoneal space is a well-demonstrated use of trauma US, including in the prehospital setting where its application can lead to up-triaging patients and arrangements for expedited transport to the operating suite , 24. Stucaveat that  further data are needed before final adoption of a protocol.The primary utility in field US assessment for intraabdominal fluid appears to be triage and evacuation prioritization. Hypotension in the setting of free fluid on US could also guide administration of field resources such as tranexaminic acid. Given the state of the evidence, it is reasonable to include search for peritoneal fluid in the protocol for special operations sonography training, with the Detection of fractures in the special operations setting is quite important. The identification of a fracture (or confirmation of its absence) can guide important triage and evacuation decisions. Thus, US results can potentially inform decisions such as whether to plan on returning a team member back to mission or order evacuation using scarce vehicular resources. Overall accuracy of US for fracture determination in austere (military) environments has been found to be very high . Other sJust as US can be useful to diagnose fractures, postreduction images can be used to assess bony alignment before splinting or evacuation. Furthermore, US can be used to assess arterial pulses distal to an injury site, both before and after any reduction or splinting see . When decisions about evacuation are on the line, the capability to assess vascular function distal to an extremity injury can be critical. Fractures that are stabilized and splinted do not necessarily warrant emergent evacuation, but such evacuation is indeed necessary if there is distal lack of perfusion. Doppler US can also be used to assess functionality of tourniquets, and this has been shown effective as a measuring tool in multiple studies , 29. Documentation of a pulse in the radial or femoral region is useful as a gross estimation of blood pressure . Since pRetinal US is a useful tool for detection of elevated ICP in the setting of trauma , 31. WhiWhile many TEMS operations occur in urban settings in which evacuation is not problematic, there are also cases in which evacuation of casualties is logistically challenging, dangerous, or both. In these situations, the ability to accurately triage patients and allocate scarce resources is not just a matter of overloading the regional trauma center—it is potentially a matter of life and death for the injured patients or for others who would either participate in extraction or potentially need resources that should not be wasted on trivially injured cases. US has been demonstrated to be occasionally useful in triage, both in the trauma arrest situation and also as a part of the overall evaluation of injured patients , 3. As previously noted, identification of cardiac standstill and lack of valvular motion is a reliable mechanism to demonstrate death in the field. This end of the triage scale is important as a possible area for US contributions to decision-making algorithms involving evacuation in austere and potentially dangerous settings.In the “survivable injury” end of the spectrum, US application can differentiate patients who need immediate evacuation for life- or limb-saving care, from those who can be evacuated by ground or even be cleared for return to mission. US has been explicitly considered as a mechanism to improve trauma triage for those intermediate-acuity patients who may need helicopter transport . In addiIf US is insufficiently rugged or otherwise unsuited for use in the out-of-hospital setting, the preceding sections' potential utilities for the technology are moot. The question is relevant, given results from some early studies of US in the prehospital setting. A 2001 publication, for instance, reported that FAST exams could not be performed in nearly half of patients due to time or patient access or equipment restrictions; those air medical researchers understandably concluded that US had a long way to go before it was feasible for field use . At thatMore recent evidence strongly supports the notion that US has overcome its initial deployment difficulties. As US engineering has evolved, it has been demonstrated that US can be performed in a variety of prehospital settings, including stationary and moving vehicles . FurtherFeasibility of TEMS US use is suggested by promising results from studies that concluded various sonographic signs can be easily taught to prehospital providers. For example, the SLS is demonstrated to be relatively simple to teach when the goals are limited to interpretation for the presence of pneumothorax or effective ventilation (as previously discussed) . PrehospAnother angle on US is the potential for data acquisition to occur “on-site” (at the patient) and then be transmitted for remote interpretation. One group has found that paramedics with minimal US training were able to obtain and transmit readable trauma US images; the image obtaining and interpretations were done by physicians in another room . Even mo The question of feasibility of US in TEMS has not been definitively demonstrated. Expert reviewers considering the paramedic application of US judged the literature has “demonstrated that with the right education and mentorship, some paramedic groups are able to obtain US images of sufficient quality to positively identify catastrophic pathologies.” The reviewers concluded that “more research is required to demonstrate that these findings are transferable” to EMS, and further study is also needed to determine how prehospital US can facilitate improved patient outcomes . Other rDespite the opinions of skeptics, the bulk of the evidence is, in the opinion of this discussion's authors, supportive of a move towards further assessment of the technology. In terms of both personnel  and machine , the foundation for further exploration of US in TEMS has been laid. Recent review articles have noted portable US use for prehospital trauma evaluation and triage, assessment for pneumothorax, and other applications, with a wide range of outcomes  . Promise for US in the TEMS environment also comes from a 2012 review of the evidence (consisting of five studies) addressing US use in the military special forces setting . These sImportant next steps for US research in TEMS include multiple areas for focus. Among the most important are (1) testing of the hypothesis that demonstrations of US feasibility in the “standard EMS” setting translate into TEMS functionality, (2) evaluation of which US clinical indications are most important and most viable for TEMS use, and (3) development and rigorous assessment of educational models for initial and ongoing training. The first of the three iterated areas for research deals with subjects ranging from image acquisition to transmission of US data for real-time assistance with interpretation. The second general area of investigation would include both assessment of the potential clinical uses already mentioned, and perhaps study of other areas for which TEMS US could be useful. These additional areas, including for instance skull fracture diagnosis , 45 and For most indications, data directly addressing US use in the TEMS setting are sparse, if present at all. Extrapolation of information from other settings, either from the ED or even the “standard” EMS arena, risks error. However, the existing evidence does support a potential role for US in TEMS. In terms of assisting diagnosis and medical management, as well as informing triage and resource utilization and personnel evacuation decision-making, US appears to have major potential. Due to the seemingly significant potential for US in TEMS, and the current lack of applicable data, focused research on clinical application of US in tactical medicine is warranted.


Although the association of alopecia areata (AA) and vitiligo occurring in the same patient has been frequently reported in the literature, the colocalization of AA and vitiligo is very rare. We report for the first time an adult patient with anatomic concurrence of AA and vitiligo on the scalp. Even though both AA and vitiligo are thought to have the same underlying pathophysiologic mechanisms, the striking rarity of their colocalization challenges this postulated common pathogenesis, and raises the question if autoimmunity is responsible for only a fraction of AA or vitiligo. Alopecia areata (AA) and vitiligo are common dermatological conditions reported to be frequently associated with other autoimmune conditions, particularly thyroiditis, pernicious anemia, and myasthenia gravis, and with each other.2 NeverthA 60-year-old woman presented to our clinic with a two-week history of a focal patch of alopecia on her scalp. She had a history of hypothyroidism and hypercholesterolemia, treated with eltroxin and simvastatin, correspondingly. The patient’s daughter was reported to suffer from vitiligo. On physical examination, she had a regularly shaped, well-defined alopecic patch involving the vertex of her scalp. In addition, a depigmented patch was localized almost exactly to the same area as the alopecia . She hadThe pathogenic basis for AA has been for long an enigma, and many theories regarding its elusive etiology have been introduced over time in the medical literature. These include, for example, the genetic, infectious, trophoneurotic, toxic, and endocrinologic hypotheses. However in recent years, the theory that autoimmunity stands at the basis of this disease has gained much support, and is currently considered the prevailing theory, on the basis of both direct and indirect evidence.–10 Furth12Considering the fact that it was suggested that AA and vitiligo share the same pathogenic pathway, it is surprising that colocalization of these two diseases is not observed more often. One explanation to this apparent infrequency might stem from the fact that antigenically different populations of melanocytes were reported to be present in the epidermis and hair follicle. In addit1318The previous few reports on colocalization of AA and vitiligo have highlighted in their discussion the common immunopathologic mechanisms of the two conditions.–6 In thi