Architecture for Knowledge-Based and Federated Search of Online Clinical Evidence Background It is increasingly difficult for clinicians to keep up-to-date with the rapidly growing biomedical literature . Online evidence retrieval methods are now seen as a core tool to support evidence-based health practice . However , standard search engine technology is not designed to manage the many different types of evidence sources that are available or to handle the very different information needs of various clinical groups , who often work in widely different settings . Introduction Clinicians need to keep up-to-date with the biomedical literature in order to practice according to the best available evidence . However , this has become increasingly difficult as the amount of medical literature a clinician needs to consider grows exponentially -LSB- 1,2 -RSB- . As a result , the effort required to find a specific piece of evidence increases year after year -LSB- 3 -RSB- . Clinicians typically work under time pressure , which compounds the problem . The need to develop robust methods and tools to support evidence access is now widely recognized . Online evidence retrieval methods are increasingly seen as a core tool in support of evidence-based health care -LSB- 4 -RSB- . In the traditional model of online evidence services , clinicians have access to a number of online information sources , such as journals , databases , and Medline , each with its own idiosyncrasies and search interfaces . This means users need to know which resources are most suitable for their current question and how the search query must be formulated for a given resource . Interoperability standards for the efficient dissemination of content are being developed -LRB- eg , the Open Archive Initiative -LSB- 5 -RSB- -RRB- , but until the majority of content adheres to such standards , there is still a need to search through heterogenous data sources . The meta-search engine approach -LSB- 6,7 -RSB- addresses many of the limitations of these models by providing a mechanism to search all the available resources at one time and by translating user queries into the respective query languages of each resource . This typically uses a least-common-denominator approach , directly passing on user keywords to different information sources without regard for the specific capabilities or limitations of these resources . For example , a meta-search engine often disregards the rich query language available with some resources in order to simplify the overall meta-search process . Consequently , while the user expects the meta-search to return an integrated set of search results , the reality is that some resources would have been able to perform much better had they been queried individually ; the user is unaware of the variations in search quality across the different resources that have been queried for them . Variants of the standard meta-search engine approach have been shown -LSB- 8 -RSB- to provide search capabilities beyond the least common denominator but still require users to select the resources they wish to search . One solution to this problem is to `` federate '' the different resources so that they more genuinely behave as one uniform data source . A federated search system may perform a syntactic reformulation of a user query , translating it into queries that have been optimized for the native query language of individual evidence sources . Semantic reformulation is also possible -LSB- 9 -RSB- . For example , user keywords may be translated into equivalent keywords or phrases using a terminological system . However , a federated search can still produce an excessive number of candidate documents , or hits , many of them failing reasonable tests of relevance . One way to improve the chance of retrieving clinically relevant information is to pre-program a search system with specialist bibliographic knowledge using search filters . Search filters capture expert strategies for searching that are known to improve the precision of searches . For example , Medline offers a small set of `` clinical queries , '' which are pre-defined and validated search filters optimized to retrieve documents that are most likely to be clinically relevant , emphasizing disease etiology , diagnosis , therapy , or prognosis -LSB- 10,11 -RSB- . Such search filters are necessarily highly customized to the capabilities of individual information sources and their native search engines . For a federated search system to consistently use search filters , it would need to develop a generalized approach to search filters , or meta-search filters . Quick Clinical -LRB- QC -RRB- -LSB- 4 -RSB- is a federated evidence retrieval system designed to meet the specific needs of clinicians . Its design incorporates the novel use of meta-search filters to optimize search strategies , and it is based upon a wrapper-mediator architecture built around a universal query language . This paper describes the system architecture of QC and the technical challenges to the design of online evidence retrieval systems , and it reports on the technical performance of the system from a clinical trial with primary care physicians . Methods The Quick Clinical System User Interface In the QC user model , a user is presented with a single query interface , which connects to an arbitrarily large number of federated knowledge sources and incorporates query specific meta-search filters called `` profiles . '' QC guides users to first consider the purpose of their search through selection of a profile , and it then asks them to provide specific keywords related to that search task . As a consequence , users are guided through a process that structures their query for them and improves the chances that they will ask a well-formed query and receive an appropriate answer . Figure 1 depicts the QC search interface . On the left hand is a list of search filters that describe typical search tasks and that are customized to the specific information needs of different user groups . Figure 1 shows filters specifically designed for use by primary care physicians . Figure 1 The QC search query user interface In QC , individual profiles are able to define different keyword types , such as `` disease , '' which describe the keyword classes typically associated with that profile . Thus , on the right of the interface are four fields where users can provide keywords describing the specific attributes of their search . Selection of a different profile may thus alter the keyword types requested from the user for a given search . QC then translates and submits search queries to the sources specified in the chosen profile , collects and processes the results , and presents them to the user as a list of documents -LRB- Figure 2 -RRB- . The title of a document is followed by the link and a short abstract of the content . A user can drill-down into a specific group of results by source type -LRB- eg , journal articles or guidelines -RRB- . Figure 2 Screenshot of a QC results page Quick Clinical System Architecture Overview Most information sources such as websites , online texts , and databases have their own proprietary search interface , including query language and format for the display of results . Therefore , a federated meta-search engine that wishes to query a number of different information sources needs to first represent a user query using some internal query language -LSB- 13 -RSB- and then translate that internal query into the specific query languages of the relevant data sources . A well-documented -LSB- 12 -RSB- approach to this problem is to use a `` wrapper '' -LRB- Figure 3 -RRB- , which acts as an adapter between the proprietary language of individual information sources and the internal language used within a meta-search system . In QC , the internal query language is called the unified query language -LRB- UQL -RRB- . Each information source known to QC has its own wrapper that translates queries from UQL into the native language of the source . As a result , internal components of QC only need to know UQL and not the individual query languages of the data sources . System maintenance is also simplified since the introduction of a new data source to the system only requires one new wrapper component to be generated . Once the results of a search are returned by an information source , the information must again be translated into a standard output format for presentation to the user , which , in QC , is called the unified response language -LRB- UReL -RRB- . UReL also allows other components in the system to modify the presentation of search results without needing to understand the presentation format of individual sources -LRB- eg , to remove duplicate documents -RRB- . In Figure 3 , a search is initiated from the user interface , which forwards a query -LRB- in XML -RRB- to the mediator . The mediator splits the query into several subqueries and sends these to the appropriate wrapper -LRB- via a capability manager if required -RRB- . Finally , the wrapper translates the query into the native query language of the data source -LRB- eg , in HTML for Web data sources -RRB- . Similarly , the result from the data source gets translated back into the system 's XML representation and sent back to the user interface . Figure 3 Architecture overview of Quick Clinical Unified Query Language UQL is used to represent queries obtained from users in a consistent internal way , and UQL statements identify query elements such as the external information sources to be searched and a set of search attributes used to delimit the search . For example , UQL expressions can store date range delimiters for a search . UQL also contains statements that indicate whether or not QC needs to process the query further . For example , we may wish to remove duplicate items obtained from different sources . In our current implementation , UQL is implemented using XML . To define the structure of the data within the XML document we use a data type definition -LRB- DTD -RRB- , which allows various internal components of QC to validate the XML data received in the UQL query . The following example illustrates how a UQL query might look in XML . < QUERY keyword = `` iron AND deficiency '' profile = `` treatment '' duplicateRemoval = `` yes '' sortBy = `` rank '' useLexicalVariants = `` yes '' timeout = `` 20 '' dateRangeBeginDay = `` 1 '' dateRangeBeginMonth = `` 1 '' dateRangeBeginYear = `` 1999 '' > <SOURCE name = "PubMed" /> <SOURCE name = "Harrison’s online" /> <SOURCE name = "Merck" /> <SOURCE name = "MIMS" /> </QUERY> Unified Response Language Similarly to the UQL , the unified response language -LRB- UReL -RRB- is used internally to guide display of information to users , also represented using XML . Each separate result , or `` article , '' from a source can be broken up into smaller chunks and given meta-data labels to represent the different sections of the data -LRB- eg , abstracts from journal articles -RRB- . Since the majority of sources accessed by QC are journals , the data that are retrieved typically contain document elements such as Title , Author -LRB- s -RRB- , Journal Name , Date of Publication , and the URL where the electronic version of the paper is accessed . Other sources , such as drug descriptions from pharmaceutical compendia , have sections such as Drug Name and Manufacturer . These different document elements , based upon the typical sources QC expects to find , are defined as specific fields in the UReL definition . The following example illustrates how a set of documents retrieved by QC might be represented in UReL . <RESULT> <ARTICLE> <LINK> <HREF> http://www.ncbi.nlm.nih.gov:80 / entrez/query . fcgi?cmd = Retrieve & db = PubMed & list_uids = 12198020 & dopt = Abstract </HREF> <LINKNAME> Abstract </LINKNAME> </LINK> <AUTHORLIST> Heath AL , Skeaff CM , Gibson RS . </AUTHORLIST> <TITLE> Dietary treatment of iron deficiency </TITLE> <DATE> <YEAR> 2002 </YEAR> <MONTH> 9 </MONTH> </DATE> <SOURCE> PubMed </SOURCE> </ARTICLE> <ARTICLE> <LINK> <HREF> http://mims.hcn.net.au / ifmx-nsapi/mims-data / ? MIval = 2MIMS_abbr_pi & product_code = 288 & product_name = Ferrum + H+I njection </HREF> <LINKNAME> More Information </LINKNAME> </LINK> <AUTHORLIST> Sigma Pharmaceuticals Pty Ltd. . </AUTHORLIST> <TITLE> Ferrum H Injection </TITLE> <SOURCE> MIMS </SOURCE> </ARTICLE> </RESULT> Wrappers For every information source known to QC , there is a specific wrapper that translates a UQL query into the native query language and format of the source . The wrapper also extracts the relevant information from the HTML result pages returned by the search engine and re-expresses it in UReL . Figure 4 shows the basic architecture of wrappers in our current system . Each wrapper has three main components : a feeder , extraction rules , and a sieve . The feeder converts the user query into the native query language of the data source . The data source responds to the query and returns HTML raw data . The feeder passes the raw data to the sieve , which converts it to UReL in XML format by using the extraction rules for the data source . The UReL is then sent back via other components to the user interface , which can interpret the XML and display the results . Figure 4 Wrapper components Mediator A key requirement of a multisource information retrieval system is the ability to perform concurrent searches on multiple sources with a single query -LSB- 6,7 -RSB- . The mediator addresses this requirement . The mediator first analyzes a query and determines how many sources are to be searched . It then creates a separate search job for each of these sources and forwards the search job to other system components . Additionally , the mediator collects individual results as they arrive and amalgamates them for the user into a single result . By introducing parallelism , the time to perform a search across a number of resources should be reduced to the duration of the slowest source . However , the potential drawback of parallel processing is the increased administration overhead of running multiple parallel processes within a system . As a rule of thumb , we would expect the benefits of parallel execution should increase with the number of sources queried , as response times for Web resources can be many seconds long , and computational execution of processes to manage parallel search are typically much less than one second . Connection speed and latency of response time from sources are , for practical purposes , nondeterministic in an Internet environment , and a meta-search engine can therefore experience large fluctuations in responses from the same source under different circumstances . Latency is subject to network traffic conditions , making it impossible to guarantee that all resources that are queried at a particular time will respond predictably and equally . To counter this , the mediator has a time-out feature . If a response is not received within the time-out specified by a profile , the mediator will cancel a subsearch and forward all the results currently available from other sources to the user interface . This effectively guarantees a defined response time irrespective of the state of the individual data sources and provides some control over the speed/accuracy trade-off . Capability Manager Search capabilities vary considerably between the search engines that QC might wish to interrogate , and some sources will have limitations in their ability to process search queries . One approach to this problem is to try to raise all sources to as high a level of common performance as possible by emulating missing capabilities locally , usually by modifying the query and/or search result -LSB- 13 -RSB- . A trivial example is mimicking the ability to perform a Boolean search when a data source does not have this capability . To emulate a Boolean AND , a meta-search engine would perform two parallel individual searches on the source and then itself perform the Boolean operation on the two results . In QC , a capability manager -LRB- CM -RRB- is responsible for mimicking a range of search capabilities and is located between the mediator and wrapper . The CM may modify a query and/or the result depending on the capabilities of the sources about to be queried . Capabilities of the CM within the QC system included the following : Date-CM : search within a date range Duplicate-CM : remove document duplicates Sort-CM : sort results by title , author , document rank , or date Lexical-CM : expand a search term with lexical variants of the term . A lexical variant is a synonym , pluralization , hyphenation , or other modification that changes the text but not its meaning . Lexical variants are particularly important in the medical domain -LSB- 14 -RSB- because many concepts can be expressed in Latin or English -LRB- eg , cardio vs heart -RRB- . Moreover , there is a common confusion between terms in American English versus British English -LRB- eg , hemoglobin vs haemoglobin , epinephrine vs adrenaline -RRB- . QC uses a stacking mechanism to insert individual CMs into the processing of queries for wrappers and the processing of results from a source . A component called the search planner , containing simple rules , is responsible for stacking the CMs . This means that the sequence of CMs can be ordered to ensure the correct outcome of query or result translations . Theoretically , this corresponds to a composition of operations . A lexical variant CM , for example , has to replace the search terms in the query before the wrapper executes the search . The Date-CM , on the other hand , can only perform its job after the successful execution of the wrapper . Search Filters Expert searchers typically will use search strategies that are more likely to accurately locate information , based upon an understanding of the specific capabilities of an evidence source . There is an increasing interest in the writing of search filters which capture such strategies , usually focusing on the major evidence repositories like Medline -LSB- 10,11 -RSB- . Search filters are designed for typical clinical queries such as `` diagnosis '' or `` prescribing , '' and they are crafted to find evidence most likely to satisfy the query by first selectively searching resources identified to be of high quality and , second , by automatically adding specialist keywords to the general question posed by a user . Within QC , search filters are stored in the profiles function . For example , if a clinician selects the `` diagnosis '' filter and enters the search term `` asthma , '' QC can add in the additional terms when it queries Medline -LSB- 10 -RSB- : sensitivity and specificity -LSB- MESH -RSB- OR sensitivity -LSB- WORD -RSB- OR diagnosis -LSB- SH -RSB- OR diagnostic use -LSB- SH -RSB- OR specificity -LSB- WORD -RSB- These terms have been shown to significantly enhance the quality of Medline results , but they are unlikely to be known to a typical clinical user . Unlike standard search filters , QC profiles are meta-search filters because they encode search filters for multiple different sources . Profiles thus encode expert search strategies that are most likely to answer a certain class of query , and they encode , among other things , the most appropriate content sources to search -LRB- Table 1 -RRB- . For a primary care physician , these search profiles might be for diagnosis , prescription , review , and treatment -LSB- 4 -RSB- , but any set of profiles can be created within QC to meet the specific query types and search contexts of different users . In Table 1 , the Treatment profile describes a set of nine separate source-specific search filters , which collectively describe the search strategy believed most likely to retrieve an accurate search result from each resource . The # symbol delimits keyword variables that are to be instantiated with user keywords . For example , # 1 # represents the keyword type `` disease , '' and QC 's mediator component will substitute the user-provided keywords for `` disease '' throughout the profile , prior to sending the query to the individual wrappers for the different sources . More than one search string can be created for an individual source -LRB- eg , TGL 1 and TGL 2 -RRB- as a single strategy may not always retrieve all the relevant documents . Table 1 Quick Clinical meta-search filters Source Search String TGL1 -LRB- # 1 # AND # 2 # AND # 3 # AND # 4 # -RRB- AND + -LRB- `` treatment '' OR `` therapy '' OR `` therapeutic use '' -RRB- TGL2 -LRB- # 1 # AND # 3 # -RRB- AND + -LRB- `` treatment '' OR `` therapy '' OR `` therapeutic use '' -RRB- HealthInsite3 # 1 # AND # 2 # AND # 3 # AND # 4 # HealthInsite4 # 1 # AND # 3 # PubMed5 -LRB- # 1 # ATTR + -LSB- Title -RSB- AND # 3 # ATTR + -LSB- Title -RSB- AND # 4 # ATTR + -LSB- Title -RSB- ATTR + / ther -RRB- English 10 years Human PubMed6 # 1 # ATTR + -LSB- Title -RSB- AND -LRB- # 3 # ATTR + -LSB- Title -RSB- OR # 4 # ATTR + -LSB- Title -RSB- -RRB- ATTR + / drug ATTR + therEnglish 10 years Human Merck7 -LRB- -LRB- # 1 # AND # 3 # AND # 4 # -RRB- OR -LRB- # 1 # AND # 3 # -RRB- -RRB- AND + -LRB- `` treatment '' OR `` therapy '' -RRB- Harrison 's 8 Disconnected Harrison 's 9 Disconnected System Platform The system was constructed using Java , the Struts Web application framework , and a MySQL database and is deployed on a RedHat Linux platform . The user interface -LRB- JSP , servlet , and HTML pages -RRB- is deployed through an Apache Web server connected to a Tomcat servlet engine . The Apache-Tomcat platform incorporates load balancing and fail-over and is suitable for scalability and large-scale deployment . Technical Evaluation QC has undergone a series of clinical evaluations , which have been reported separately -LSB- 4,15,16 -RSB- . In total , 227 family physicians from across Australia participated in a trial of QC . Clinicians who had a computer with Internet access in their consulting rooms were recruited and asked to use QC for 4 weeks in routine care . Each participant was given a personal username and password to access the system . All clinicians completed an online pre-trial survey . QC was configured to search a set of eight sources , including remote sites such as PubMed , online journals such as BMJ and the Medical Journal of Australia -LRB- MJA -RRB- , and locally cached sources such as The Merck Manual and Therapeutic Guidelines Australia . For every search , the time from the request arriving at the system to the time when the results were sent back to the user was recorded -LRB- Figure 5 ; search time = system time + slowest source time -RRB- . Note that there is a cap on search time when the time-out cuts in . Time-outs are search-profile dependent and were set at either 15 or 30 s . The time it took to conduct the search on the individual sources was also recorded . The time taken to send data between QC and the user 's computer -LRB- user time -RRB- is not incorporated in these measurements . In the following section we report on the technical performance of the architecture and then reflect on its suitability for supporting evidence retrieval in clinical practice . Figure 5 Search time metrics Results In the pre-trial questionnaire , 40 % of the clinicians reported having a broadband -LRB- ADSL , cable , satellite -RRB- connection , while 43 % used a 56k or 64k modem connection . The remaining 17 % either did not know the type of connection used or had a slower connection . A total of 1662 searches were performed over the trial . Search Speed Under local network conditions -LRB- LAN , 100MBit -RRB- , the user time -LRB- from starting the search on a client computer to displaying the results -RRB- was approximately 1.5 s. However , since most users accessed the system through the Internet , latency was significantly longer and slowed down the overall search speed . The average search time was 4.9 s , with a standard deviation of 3.2 s -LRB- N = 1662 searches -RRB- . Figure 6 shows the distribution of all search times over the trial . There are four distinctive features in this chart . The first is a small peak at 1 s -LRB- ie , searches that took up to 1 s to complete -RRB- . The second feature is a peak around the mean value . Third , there is a small peak at 15 s , and , fourth , there is a small peak at 30 s. Figure 6 Distribution of search time for all 1662 searches System Time System time for a search was computed by subtracting the duration of the slowest source in every search from the search time -LRB- see Figure 5 -RRB- . From the system time histogram in Figure 7 , it can be seen that for the majority of the searches the system takes between 100 ms and 130 ms -LRB- mean = 117.9 ms ; SD = 68.4 ms ; N = 1614 -LSB- 48 searches had missing data , hence 1614 searches -RSB- -RRB- . Figure 7 Distribution of the system time for 1614 searches System Time Versus Number of Individual Sources Involved Depending on the search profile selected , the system will query a certain number of information sources and combine the results . To illustrate the dependency between system time and the number of sources queried , Table 2 shows average system time versus the number of sources queried in a search . The number of sources queried is predefined by the search profile , and none of the search profiles tested queried five , six , or eight sources . Table 2 System time vs number of sources queried Number of Sources Queried N Average System Time -LRB- ms -RRB- 1 48 18.1 2 9 31.8 3 15 73.3 4 7 59.7 5 0 - 6 0 - 7 1373 122.2 8 0 - 9 162 122.6 Speed and Reliability of Individual Data Sources In addition to the performance measurements of the whole searches , the speed and reliability of the individual data sources was measured . Reliability was measured as the number of error cases -LRB- ie , queries that were not answered due to an error condition , such as a network error , an HTTP error , or queries that timed out -RRB- . Reliability and speed figures are summarized in Table 3 . Table 3 Reliability and speed of data sources Source Type Number of Searches Number of Errors Error -LRB- % -RRB- Mean Speed -LRB- s -RRB- SD -LRB- s -RRB- Min -LRB- s -RRB- Max -LRB- s -RRB- Merck Local 2144 0 0.0 0.06 0.11 0.01 2.89 TGL Local 2193 0 0.0 0.05 0.12 0.01 2.85 BMJ Remote 73 1 1.4 4.55 3.92 0.99 17.5 HealthInsite Remote 2993 55 1.8 3.09 1.08 1.08 22.3 MedlinePlus Remote 653 0 0.0 1.87 1.36 1.09 12.5 MIMS Remote 650 3 0.5 0.98 1.14 0.28 8.30 MJA Remote 58 1 1.7 0.25 0.31 0.10 1.73 PubMed Remote 3288 39 1.2 3.76 1.69 1.87 15.0 Total 12052 99 Mean 0.8 1.83 0.63 * 0.68 10.4 * standard error of the mean The most reliable sources were the locally indexed sources Merck -LRB- The Merck Manual -RRB- and TGL -LRB- Therapeutic Guidelines Australia -RRB- , both which did not have any error cases . On the other end of the scale are HealthInsite -LRB- a national consumer site for health information -RRB- and MJA . The slowest source in the trial was BMJ , with an average of 4.55 s to process a query -LRB- SD = 3.92 s ; N = 73 -RRB- . This was followed by PubMed , which returned results at an average of 3.76 s -LRB- SD = 1.69 s ; N = 3288 -RRB- . The two locally indexed sources -LRB- Merck and TGL -RRB- returned search results within an average of 0.061 s and 0.047 s , respectively . However , the two local sources do have a relatively large standard deviation . Figure 8 shows the distribution of query times to the eight individual data sources . Figure 8 Histogram of search times for each of the eight data sources -LRB- x-axis is time taken for a search , in ms ; y-axis is number of searches -RRB- Discussion System Time From the results of the system time versus source time , we can observe that system-processing time is only a fraction of the total search time . However , there are exceptions , namely when local data sources are used exclusively . From a user 's perspective this still would not be an issue as the overall user time is greater by at least a factor of ten . It could , however , become a problem in a situation where many searches are dependant on the result of a previous search and have to be executed in series . System time has thus been kept relatively short , removing the initial reservation that too much parallelism could slow down the system excessively . From Table 3 it can be seen that the system time generally increases in line with the number of sources queried -LRB- with the exception of four sources queried -RRB- . However , the order of this increase does not appear to be squared or even exponential , but rather linear . Search Times The four distinct features in the histogram of search times described in Figure 6 are due to the nature of the data sources and the value of the time-outs . The first small peak at 1 s is from search profiles that use exclusively local data sources . The second feature is a peak around the mean value and is caused by the six Internet resources . The small peak at 15 s is due to the large number of search profiles that have this value as a time-out . And finally , the tiny peak at 30 s is where the remaining searches time out . It was to be expected that local sources would be more reliable and have a shorter latency in response time . This is due to the controlled environment , compared to the uncontrolled Internet environment of the external sources . It is interesting to note the difference between the six external data sources . While some sources are very popular -LRB- eg , PubMed -RRB- and therefore are expected to be busy , others might lack the resources to keep up with demand . The time-out value of individual data sources is a trade-off between speed and quality of results and is determined by the intended usage of the system . However , under certain circumstances there are optimizations that can be carried out without affecting quality of results . For example , the search duration histogram for HealthInsite -LRB- Figure 8 ; top right -RRB- reveals that if a search has not completed within 10 s it is highly unlikely it will complete within 15 s. Therefore , a time-out value of 15 s can safely be reduced to 10 s without significantly compromising search quality . Future Work The current QC architecture has demonstrated in trials that it meets the technical design goals set for it , and it provides good evidence that our general approach to federated searching is sustainable and maintainable . We intend to pursue research and development in areas of current interest to meta-search engines , information retrieval systems , and artificial intelligence . These include automatic wrapper generation -LSB- 17,18 -RSB- so that new data sources can be easily integrated into QC . Using this approach , a component could automatically generate a wrapper from knowledge of the data source query inputs and results . Another area of continued research will be automated data source consistency checking . Data sources often change in their formats , and this needs to be monitored with either automated or human intervention in order to modify wrappers accordingly . A third area will be intelligent search agents -LSB- 19 -RSB- . We envisage incorporating an intelligent agent that will guide users through the search process , using domain knowledge to help frame clinical questions and choose search parameters . This agent could learn to work with its user . An area of continued development will be semantic understanding of result sets . We would like QC to combine search results into a meaningful coherent story that presents a concise , relevant , and digestible response to the user -LSB- 20 -RSB- . These approaches , coupled with user support , will allow us to develop and improve the system with a view to it becoming an integral part of a clinician 's daily practice . Even without these enhancements , we have demonstrated that the QC framework is a functional and useful approach for the delivery of online , just-in-time clinical evidence .

O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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Acquiring

Tetanus

After

Hemorrhoid

Banding

and

Other

Gastrointestinal

Procedures

Tetanus

after

hemorrhoidal

banding

is

an

extremely

rare

but

serious

complication

of

the

procedure

We

describe

the

second

reported

case

of

this

complication

and

review

the

literature

concerning

tetanus

after

different

gastrointestinal

procedures

Although

a

rare

complication

practicing

physicians

need

to

be

aware

of

the

clinical

presentation

of

this

deadly

disease

when

encountered

in

at-risk

patient

populations

Such

cases

also

reemphasize

the

importance

of

primary

tetanus

immunization

and

follow-up

boosters

for

all

vulnerable

patients

Introduction

Tetanus

is

currently

a

rare

disease

in

the

United

States

and

other

developed

countries

where

active

immunization

programs

provide

a

considerable

degree

of

immunity

to

the

infection

in

the

general

population

The

incidence

of

tetanus

has

dropped

dramatically

in

the

United

States

and

other

developed

countries

due

to

a

successful

vaccination

program

instituted

in

the

During

the

period

from

to

the

Centers

for

Disease

Control

-LRB-

CDC

-RRB-

reported

the

average

annual

incidence

of

tetanus

to

be

new

cases

in

the

United

States

per

year

This

is

equivalent

to

cases/million

people

in

the

US

The

worldwide

incidence

of

tetanus

however

is

much

higher

and

estimated

to

be

around

to

million

per

year

In

developed

countries

tetanus

is

most

commonly

seen

in

immigrant

patients

who

have

never

received

a

complete

primary

immunization

series

Another

at-risk

group

is

the

elderly

people

who

have

not

received

recent

booster

doses

Such

cases

in

the

older

previously

vaccinated

adult

reflects

waning

immunity

if

a

booster

shot

is

not

received

every

years

Tetanus

is

caused

by

the

toxin-producing

anaerobic

bacterium

Closteridium

tetani

C.

tetani

is

a

spore-forming

bacteria

that

once

inside

the

body

of

susceptible

host

produces

a

potent

toxin

named

tetanospasmin

Tetanospasmin

binds

to

the

central

nervous

system

causing

diffuse

muscle

spasms

and

autonomic

instability

that

characterizes

tetanus

Tetanus

is

usually

seen

in

association

with

soil

contamination

of

a

cutaneous

wound

however

on

rare

occasions

it

may

occur

after

a

surgical

procedure

such

as

gastrointestinal

surgery

In

this

paper

we

describe

the

second

reported

case

of

tetanus

after

banding

ligation

of

internal

hemorrhoids

and

will

review

the

other

reported

cases

of

tetanus

after

gastrointestinal

procedures

Case

Report

A

female

with

no

significant

past

medical

history

presented

with

chief

complaint

of

days

of

anal

discomfort

due

to

hemorrhoids

Physical

exam

showed

a

cm

soft

and

inflamed

external

hemorrhoid

She

was

initially

treated

with

pramoxine

suppositories

and

a

week

later

was

scheduled

for

elective

hemorrhoid

banding

At

the

time

of

surgery

she

was

noted

to

have

a

small

noninflamed

external

hemorrhoid

as

well

as

a

grade

III

internal

hemorrhoid

at

the

eight

o'clock

position

there

was

no

evidence

of

infection

The

patient

underwent

rubber

band

ligation

of

the

internal

hemorrhoid

with

no

immediate

complications

After

the

procedure

the

patient

was

instructed

to

take

daily

Sitz

baths

and

given

a

prescription

for

docusate

-LRB-

oral

-RRB-

and

psyllium

to

prevent

constipation

Five

days

after

the

surgery

the

patient

returned

to

the

hospital

with

a

history

of

sore

throat

pain

upon

swallowing

headache

and

inability

to

open

her

mouth

She

was

noted

to

have

a

hoarse

voice

and

stated

that

she

had

difficulty

sticking

out

her

tongue

Initial

vital

signs

showed

blood

pressure

of

mmHg

pulse

of

temperature

of

°C

and

respiratory

rate

of

per

minute

Neurological

examination

was

remarkable

for

inability

to

completely

open

the

mouth

the

rest

of

the

neurological

examination

showed

normal

findings

including

muscle

tone

bulk

and

strength

A

neck

x-ray

was

obtained

and

it

was

normal

Patient

's

inability

to

open

mouth

prompted

further

evaluation

and

the

diagnosis

of

tetanus

was

entertained

Further

history

revealed

that

patient

had

never

been

immunized

against

tetanus

She

was

subsequently

admitted

to

the

intensive

care

unit

and

initially

treated

with

units

of

intervenous

-LRB-

IV

-RRB-

human

tetanus

immune

globulin

g

of

IV

ceftriaxone

every

h

IV

diazepam

and

methylprednisolone

On

the

next

day

the

patient

had

severe

pain

on

attempting

to

open

her

mouth

and

diffuse

muscular

spasms

of

jaw

neck

abdominal

musculature

consistent

with

trismus

and

generalized

tetanus

A

rectal

exam

at

the

time

showed

normal

postoperative

changes

there

were

no

masses

bleeding

signs

of

infection

or

hemmorhoids

She

subsequently

developed

respiratory

difficulties

due

to

laryngeal

spasms

and

required

intubation

and

paralysis

In

the

next

days

she

developed

a

number

of

complications

related

to

hospitalization

and

the

underlying

tetanus

The

patient

had

autonomic

lability

with

associated

hypertension

-LRB-

systolic

blood

pressure

up

to

mmHg

-RRB-

and

tachycardia

-LRB-

pulse

of

-RRB-

she

developed

an

episode

of

chest

paint

and

was

found

to

have

an

acute

anterior

wall

ST-elevation

myocardial

infarction

confirmed

with

EKG

abnormalities

and

elevated

troponins

Additional

complications

included

a

small

pneumothorax

after

placement

of

a

Swann

Ganz

catheter

left

lung

collapse

due

to

mucous

plugging

and

nosocomial

pneumonia

due

to

Acinetobacter

baumanii

Attempts

to

wean

her

during

endotracheal

intubation

were

unsuccessful

and

the

patient

required

a

tracheostomy

After

about

months

of

hospitalization

she

gradually

improved

and

was

weaned

from

the

respirator

She

had

upper

and

lower

muscle

atrophy

global

muscle

weakness

and

ankle

contractures

bilaterally

She

had

no

obvious

sensory

cognitive

or

language

deficits

She

was

able

to

roll

herself

in

bed

and

feed

herself

however

she

was

unable

to

stand

walk

or

place

herself

on

bedpan

She

was

subsequently

transferred

to

an

inpatient

rehabilitation

facility

for

intensive

physical

and

occupational

therapy

At

the

completion

of

a

month-long

inpatient

rehabilitation

program

she

showed

some

improvement

but

still

had

some

lower

extremity

weakness

-LRB-

grade

out

of

of

muscle

strength

bilaterally

-RRB-

and

residual

ankle

contractures

she

could

walk

with

assistance

using

a

forearm

crutch

The

patient

was

discharged

from

the

hospital

with

a

continuing

outpatient

rehabilitation

program

Review

of

Literature

Methods

We

searched

the

English

language

articles

from

to

January

in

the

MeSH

system

of

PubMed

for

relevant

case

reports

and

articles

MeSH

keywords

identified

included

tetanus

combined

with

digestive

system

surgical

procedures

surgery

surgical

procedures

operative

and

hemorrhoids

All

the

relevant

articles

were

reviewed

and

their

reference

list

examined

for

other

relevant

articles

Other

articles

were

obtained

and

reviewed

from

these

reference

lists

Postoperative

tetanus

cases

after

obstetric

gynecology

procedures

in

which

the

appendix

was

removed

were

not

included

one

such

paper

is

included

in

the

reference

list

however

Results

We

found

case

reports

of

tetanus

after

gastrointestinal

procedures

Findings

and

case

summaries

are

outlined

in

the

tables

below

-LRB-

see

Tables

and

-RRB-

Table

Cases

of

Gastrointestinal

Procedures

Complicated

by

TetanusCasesReferencesOpen

with

exploration

of

bile

for

a

gangrenous

perforated

small

Rubber

band

ligation

of

for

internal

of

anorectal

Billroth

II

and

transverse

colectomy

-LRB-

for

large

cell

lymphoma

-RRB-

laparotomy

-LRB-

for

carcinoma

in

omentum

and

liver

-RRB-

of

Presentations

for

the

Reported

CasesAuthorYearAge

-LRB-

Year

-RRB-

Gender

-LRB-

Male/Female

-RRB-

Time

to

Initial

Symptoms

-LRB-

Days

Postprocedure

-RRB-

Initial

SymptomsLater

SymptomsOnset

of

Later

Symptoms

-LRB-

Days

Postprocedure

-RRB-

Tetanus

ImmunizationOutcomeOpen

cholecystectomy

-LRB-

four

cases

-RRB-

Mandal

Mandal

gaitNo

mentionDeadO'Riordain

Buckley

Kirwan

spasm

pain

fever

mild

Glupczynski

Fastrez

Alle

Yourassowsky

and

face

pain

mentionNo

mentionCholecystectomy

with

exploration

of

bile

duct

-LRB-

two

cases

-RRB-

Gunn

Sellers

Stoddart

pain

abdominal

distentionOpisthotonusNo

mentionNoAliveLennard

et

al.

for

a

gangrenous

perforated

small

intestine

-LRB-

two

cases

-RRB-

Furui

et

al.

limb

Bolton

mentionAliveRubber

band

ligation

of

hemorrhoids

-LRB-

two

cases

-RRB-

neck

for

internal

hemorrhoids

-LRB-

one

case

-RRB-

Chhina

Kaul

of

anorectal

abscess

-LRB-

one

case

-RRB-

et

al.

limb

polypectomy

-LRB-

one

case

-RRB-

Shaff

Billroth

II

and

transverse

colectomy

for

large

cell

lymphoma

-LRB-

one

case

-RRB-

Hunter

Rudick

abdomen

back

pain

dysphagiaTrismus

and

laporatomy

-LRB-

for

carcinoma

in

omentum

and

liver

-RRB-

-LRB-

one

case

-RRB-

Mandal

mentionNo

Discussion

This

is

the

second

case

of

tetanus

after

hemorrhoid

banding

that

we

were

able

to

find

in

the

literature

As

noted

in

Table

tetanus

can

occur

after

a

wide

variety

of

gastrointestinal

surgical

procedures

including

major

intraabdominal

surgery

-LRB-

e.g.

cholecystectomy

for

cholecystitis

exploratory

laparotomy

for

intestinal

perforation

-RRB-

as

well

as

relatively

trivial

procedures

such

as

hemorrhoid

surgery

and

sigmoidoscopic

polypectomy

Tetanus

occurs

after

germination

of

the

spores

and

subsequent

production

of

toxin

by

the

organism

Clostridium

tetani

will

not

grow

in

healthy

tissue

therefore

a

number

of

factors

need

to

be

present

for

germination

to

occur

including

ischemia

devitalized

tissue

coinfection

and

injury

from

penetration

or

foreign

body

In

gastrointestinal

surgical

procedures

presence

of

ischemic

or

devitalized

tissues

permits

proliferation

of

C.

tetani

and

subsequent

toxin

production

In

our

case

the

devitalized

tissue

from

banded

hemorrhoid

was

the

likely

entry

point

for

the

organism

with

subclinical

C.

tetani

infection

occurring

at

the

site

C.

tetani

may

be

isolated

from

stool

flora

in

asymptomatic

individuals

in

farming

regions

where

individuals

are

in

constant

contact

with

soilor

domestic

animals

-LRB-

e.g.

horses

cattle

-RRB-

up

to

of

individuals

may

have

C.

tetani

in

their

stools

Given

standard

sterilization

procedures

tetanus

associated

with

infected

surgical

instruments

is

extremely

uncommon

in

industrialized

countries

our

patient

most

likely

developed

the

condition

after

contamination

of

the

wound

with

organisms

from

the

stool

or

external

environment

In

our

experience

with

patients

from

Latin

America

it

has

come

to

our

attention

that

some

of

them

use

herbal

products

such

as

out-door

plants

known

as

aloe

vera

-LRB-

buena

herba

in

Spanish

-RRB-

for

treatment

of

local

wounds

Although

we

are

not

aware

of

any

documented

case

report

of

this

practice

causing

transmission

of

tetanus

we

wonder

if

application

of

contaminated

outdoor

plants

might

play

a

role

in

some

of

the

postoperative

cases

Our

patient

did

not

provide

history

of

such

practice

and

the

exact

mode

of

contamination

will

not

change

the

clinical

presentation

or

management

Once

suspicion

arises

for

presence

of

tetanus

identification

depends

upon

recognition

of

the

characteristic

clinical

syndrome

Although

isolation

of

C.

tetani

from

a

wound

is

supportive

of

the

diagnosis

many

patients

have

negative

wound

cultures

and

presence

of

the

characteristic

clinical

syndrome

is

adequate

evidence

to

support

the

diagnosis

Although

rare

it

is

prudent

for

practitioners

to

be

mindful

of

signs

that

suggest

the

possibility

of

postoperative

tetanus

Patients

with

tetanus

usually

have

painful

spasms

and

contractions

of

their

skeletal

muscles

this

can

present

as

stiff

neck

trismus

or

opisthotonus

Lockjaw

also

known

as

trismus

leads

to

inability

to

open

the

mouth

and

the

characteristic

sardonic

smile

-LRB-

risus

sardonicus

-RRB-

it

is

a

sign

of

spasm

of

muscles

of

mastication

Trismus

along

with

back

pain

and

diffuse

muscle

spasms

is

one

of

the

most

frequent

findings

in

tetanus

Opisthotonus

is

a

sign

of

generalized

tetanus

and

is

characterized

by

painful

involuntary

bending

of

spine

and

extremities

It

leads

to

forward

convexity

of

the

body

with

patient

's

torso

arching

upward

and

body

supported

on

head

and

heels

There

can

also

be

periods

of

apnea

due

to

thoracic

glottal

pharyngeal

muscle

contractions

often

requiring

intubation

and

respiratory

support

Irritability

restlessness

sweating

labile

vitals

signs

or

even

a

myocardial

infarction

can

occur

due

to

autonomic

instability

Presence

of

these

signs

or

symptoms

could

be

due

to

underlying

tetanus

and

should

alert

the

practitioner

of

possibility

of

the

condition

Despite

the

case

reports

in

Table

it

should

be

emphasized

that

tetanus

is

a

highly

unusual

complication

of

gastrointestinal

surgical

procedures

Given

the

extremely

rare

incidence

of

this

complication

it

does

not

appear

to

be

practical

to

require

evidence

of

full

tetanus

immunization

before

a

procedure

Nevertheless

our

case

reemphasizes

the

importance

of

routine

tetanus

immunization

especially

in

patient

populations

that

were

not

immunized

in

childhood

or

failed

to

receive

a

complete

series

of

vaccinations

As

part

of

their

general

health

maintenance

adults

should

continue

to

receive

periodic

booster

shots

every

years

as

recommended

by

public

health

authorities

Furthermore

despite

its

rarity

practitioners

need

to

be

aware

of

the

clinical

presentation

of

tetanus

and

consider

the

diagnosis

in

at-risk

patients

who

present

with

characteristic

symptoms

such

as

trismus

and

muscle

rigidity

Conclusion

Postoperative

cases

of

tetanus

have

been

reported

after

a

number

of

different

gastrointestinal

procedures

Tetanus

can

occur

after

relatively

minor

procedures

such

as

hemorrhoidal

banding

Practicing

physicians

need

to

be

aware

of

the

clinical

presentation

of

this

deadly

disease

when

encountered

in

vulnerable

patient

populations

O B O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O B I I I O O O B I I O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

tetanus
hemorrhoids
surgical procedures operative
digestive system surgical procedures