An increasing number of methods are being developed for the early detection of infectious disease outbreaks which could be naturally occurring or as a result of bioterrorism; however, no standardised framework for examining the usefulness of various outbreak detection methods exists. To promote comparability between studies, it is essential that standardised methods are developed for the evaluation of outbreak detection methods.This analysis aims to review approaches used to evaluate outbreak detection methods and provide a conceptual framework upon which recommendations for standardised evaluation methods can be based. We reviewed the recently published literature for reports which evaluated methods for the detection of infectious disease outbreaks in public health surveillance data. Evaluation methods identified in the recent literature were categorised according to the presence of common features to provide a conceptual basis within which to understand current approaches to evaluation.There was considerable variation in the approaches used for the evaluation of methods for the detection of outbreaks in public health surveillance data, and appeared to be no single approach of choice. Four main approaches were used to evaluate performance, and these were labelled the Descriptive, Derived, Epidemiological and Simulation approaches. Based on the approaches identified, we propose a basic framework for evaluation and recommend the use of multiple approaches to evaluation to enable a comprehensive and contextualised description of outbreak detection performance.The varied nature of performance evaluation demonstrated in this review supports the need for further development of evaluation methods to improve comparability between studies. Our findings indicate that no single approach can fulfil all evaluation requirements. We propose that the cornerstone approaches to evaluation identified provide key contributions to support internal and external validity and comparability of study findings, and suggest these be incorporated into future recommendations for performance assessment. The use of automated methods in public health surveillance for the early detection of naturally occurring or bioterrorism-related outbreaks aims to reduce the time between when an outbreak starts and when it is detected, allowing additional time for investigation and intervention for disease control. An increasing number of methods are being developed to detect outbreaks of infectious disease using routinely collected data, however, which automated surveillance method is best for detecting outbreaks is not easily determined.A fundamental difficulty in the evaluation of outbreak detection methods involves specification of the aberration of interest . Data abThe lack of standardised methods for the assessment of usefulness, including outbreak detection successes and failures, as well as the diversity of factors that influence performance, makes the comparison of methods and accumulation of knowledge in this area problematic . This laThere is a need for a standardised evaluation approach to allow the identification of methods which most successfully identify outbreaks under different conditions. Reviews published to date have examined whether outbreak detection methods have been evaluated, and which aspects have been evaluated ,6, but nWe reviewed reports in the recently published literature which document the evaluation of outbreak detection methods. We searched the Entrez PubMed electronic database using various combinations of the following search terms  in September 2004 to identify relevant papers published since 1999. Several additional relevant papers were also obtained from a review of the reference lists of the publications retrieved. A second search was performed in October 2004 using the Web of Science search engine to locate papers published between 1999 and October 2004 that cited one of 18 key references  was published which included reports from a national syndromic surveillance conference. This volume was also reviewed for relevant papers.The titles, abstracts and where appropriate the full text version of located publications were examined to determine inclusion in this review. Papers were excluded if they did not evaluate automated methods for the detection of outbreaks of infectious disease, did not provide information on the evaluation of outbreak detection methods described, included limited detail on the fields of interest (e.g. letters), were based on non-human data, were not published in English, contained data and evaluation methods very similar to those in a paper already reviewed, or presented forecasting or other statistical methods which were not evaluated in the context of the detection of outbreaks or bioterrorism-related events.Papers documenting the evaluation of methods for the detection of outbreaks were reviewed, and characteristics of the evaluation approach used were recorded in an electronic database. Information recorded included the purpose of the surveillance, type of surveillance data analysed, data source, evaluation design (retrospective/prospective), and evaluation methods including the use of a criterion, criterion description, and whether different detection methods were compared. This abstracted information was reviewed and evaluation methods were classified according to the type of approach used. The classification developed is described and discussed.The adequacy and comprehensiveness of the framework developed was subsequently investigated by assessing its ability to describe the methods used to evaluate outbreak detection methods reported in the recently-published literature. The Pubmed database was again searched for relevant papers published between January 2005 and July 2006, and the same inclusion criteria and review methods that were used for the original search were applied.A total of 1418 unique references were obtained from the original PubMed search using 14 combinations of the selected search terms. Searches based on citations of the 18 key references  of the disease-specific surveillance methods analysed disease notification data.As illustrated in the framework developed for classifying approaches to evaluation Figure , papers Syndromic or bioterrorism-related surveillance methods were also most commonly evaluated using authentic data (62%), with these studies being approximately equally likely to use a prospective or retrospective design. Of the 38% of syndromic or bioterrorism-related methods evaluated using synthetic data, 8 of these 10 studies used synthetic outbreak signals combined with authentic baseline data.Approaches to evaluation can be further classified based on the use or non-use of a gold-standard criterion to define the occurrence of outbreaks, or events of interest Figure . The majA number of papers that used criterion-related approaches to evaluation emphasised the difficulty involved in selecting a suitable criterion. Difficulties associated with the use of criterion-related approaches with authentic outbreak data include identifying the occurrence and exact timing of true outbreaks within the data, whereas difficulties associated with the use of criterion-related approaches with synthetic data include the specification of outbreak and baseline parameters to be used for evaluation. Retrospective evaluation using authentic data particularly highlights difficulties with the application of criterion-related methods, as available historical data may not consistently or comprehensively identify all outbreaks that occurred during the period of interest.Methods used to evaluate outbreak detection performance can be further classified by the specific approach used to determine the occurrence of events of interest within the dataset. Four main methods were identified among the 63 papers reviewed, and these were labelled the Descriptive, Derived, Epidemiological and Simulation approaches. No single approach of choice was apparent among the papers reviewed, and 14% of studies used multiple approaches to evaluation. The prevalence and main features of the four specific approaches identified are summarised in Table The Descriptive approach is characterised by the description of outbreak detection method performance, including the nature of events detected and the conditions under which alarms occur. The Descriptive approach differs from the other approaches identified in that indicators of performance are not based on a nominated outbreak criterion. This approach may be based on the assertion that it is not possible to accurately define the occurrence of all outbreaks in authentic data, or confirm changes detected as epidemiologically significant.Descriptive indicators may incorporate qualitative and quantitative descriptors of both the data analysed and events detected, including incidence; seasonality; type of aberration detected; the frequency, timing and duration of alarms; the time between alarm and peak number of cases; and the magnitude of rise or proportion of cases before alarms. Although a limited amount of descriptive information on outbreak detection performance was often reported when other evaluation approaches were used, the Descriptive approach was the least commonly used approach in isolation, being most frequently applied in the early stages of performance evaluation.The analysis by Hutwagner et al.  providesDescriptive evaluations can be difficult to compare between studies due to the large amount of information that may be relevant to the occurrence of outbreaks and their detection, and the often limited amount of data analysed. However, a specific strength of the Descriptive approach is that it can be effectively used to directly compare the performance of multiple outbreak detection methods using common data, where no single method is designated as the gold standard. Most (83%) of the studies reviewed that predominantly used a Descriptive approach compared different outbreak detection methods using common data.A Descriptive approach can also be used to evaluate outbreak detection methods in relation to criteria other than outbreaks. Signals generated can be descriptively evaluated with reference to broad public health goals of surveillance based on existing understandings of disease and intervention capacity. For example, Teklehaimanot and co-workers  evaluateThe Derived approach is distinguished by the use of a standard indicator of outbreaks to derive performance measures from the data being analysed. Outbreak indicators are derived through the application of simple or complex data-derived models. The simplest examples of this approach involve the use of an absolute number of cases or statistically derived thresholds (for example based on standard deviations) to indicate the occurrence of an outbreak, which may be associated with a requirement to exceed a threshold for a minimum period of time. Complex models may incorporate multiple variables or methods to account for fluctuations in the surveillance data such as seasonal effects which result in varying outbreak criteria over time or space.The study by Lewis et al  used theThe Derived approach was most frequently used for the evaluation of disease-specific surveillance methods for the detection of large well-defined seasonal outbreaks. The models used reflect characteristics of the conditions under surveillance and the context of surveillance, for example, the rarity of the condition and the extent of background variability in the data. The evaluation of timeliness among studies using this approach was most commonly performed comparatively, based on the time of outbreak detection for several different detection methods, or the time to the epidemic peak. The Derived approach was typically associated with the use of a small number of variables to define the occurrence of an outbreak, which may provide a limited indicator of the occurrence of outbreaks within the data. For example, smaller outbreaks may be missed.The definition of outbreaks used in the Derived approach combines elements of both the Descriptive and Epidemiological approaches as it is based on agreement with an alternative data model or algorithm which has some epidemiologic credibility. The Derived approach differs from the Descriptive approach in the specification of a gold standard criterion, and differs from the Epidemiological approach in the limited account of complexity considered in the specification of the criterion. Although this approach provides an operational definition of outbreaks, difficulties remain in the definition of properties of outbreaks, including the time of commencement. For these reasons the Derived approach is not considered entirely independent of the other approaches identified.This approach is most closely linked with traditional surveillance methods in the determination of the occurrence of an outbreak relative to some loosely-defined measure of expectation, and was the most commonly used approach to evaluation among the literature reviewed. Expert judgement is used to determine the occurrence of events of public health importance, often using traditional epidemiological investigation techniques. Expert judgement may be based on a variety of available information, including surveillance data and information from epidemiological investigations, and may vary in the extensiveness of investigation methods or data utilised to determine if a data aberration represents an outbreak. Typically judgements were based on multiple factors using flexible methods.Terry and Huang's  analysisAn advantage of the Epidemiological approach is that it allows complexities associated with the determination of occurrence of events of public health importance to be considered for each potential outbreak. However, epidemiological investigations can be resource intensive, and detailed descriptions of the investigations performed and the decision-making processes used are required to fully understand the basis of the outbreak definition applied. There is also evidence of variability in opinion among experts, and there has been little evaluation of the factors associated with this variability, or how it is best managed. Consensus among multiple raters has been used in a number of studies to control for individual variability.A range of factors may influence expert opinion and decision-making relating to the occurrence of outbreaks, including specialist knowledge, previous experience and contextual information. Expert figures commonly used in the papers reviewed include epidemiologists, public health practitioners, public health physicians and infection control practitioners.Approximately 40% of papers reviewed which used an Epidemiological approach used a prospective study design. Prospective surveillance of more than one data source can be used to promote a more comprehensive indicator of events of interest occurring by allowing the investigation of failures to signal as well as reasons for signalling. The use of official public health records or other published reports to identify known outbreaks was common among retrospective studies, and represents the application of traditional epidemiological methods for outbreak detection. Retrospective methods may suffer from incomplete ascertainment due to reliance on conventional methods and historical information, and inconsistencies in the methods used to identify outbreaks.Evaluation using a Simulation approach is based on criterion-related evaluation methods and requires that the definition of an outbreak be considered in the generation of data for evaluation. Studies that use synthetic data for evaluation using criterion-based methods are unique in that the number and timing of cases added to the baseline are known. Using synthetic data for evaluation addresses a number of problematic issues associated with the use of authentic data, including precisely determining the existence and timing of outbreaks within the data, and addressing a lack of data for evaluation and development. The Simulation approach is unique in enabling quantitative replicable evaluation of performance indicators including sensitivity and specificity with large sample sizes.Reis and Mandl  used theSynthetic data can facilitate the comparison of multiple methods based on a standard dataset with specified outbreak and baseline characteristics. Approximately half of all studies which used synthetic data to evaluate performance used authentic baseline data with outbreak cases added. A comprehensive description of the simulated outbreaks and baseline data used in these evaluations is essential to allow their findings to be interpreted and integrated with those of other studies. The usefulness of synthetic data for evaluation is linked to the assumptions used to construct the data, which influences the ability to generalise evaluation findings to the authentic context. Both simple and complex outbreak simulation methods have been used to assess outbreak detection performance. Parameters that have been considered in the generation of synthetic data include outbreak size, outbreak shape, baseline rate and characteristics, and spatial distribution. Simulation methods also have the potential to influence the evaluation outcomes via effects produced by the simulation process which may not reflect the system or process being modelled.Studies that used a Simulation approach for evaluation predominantly described the evaluation of syndromic surveillance methods or proposed new analysis methods for outbreak detection. This reflects the lack of authentic data available for evaluation of syndromic surveillance methods and the ability of synthetic datasets to allow comprehensive description of the performance of outbreak detection methods across a variety of scenarios.Our search of the literature published since 2005 located a total of 42 papers that were considered to be highly relevant to the current study. These papers were reviewed in detail to investigate the adequacy of the conceptual framework developed and describe current trends in the evaluation of outbreak detection methods.The evaluation methods used by all papers reviewed were able to be described by the conceptual framework developed. The 42 studies located included 9 studies (21%) which were primarily descriptions or evaluations of new analysis methods that were not specific to outbreak detection or infectious disease surveillance, but were suitable for use in syndromic or disease-specific surveillance systems. Seven of these 9 studies described purely spatial analysis techniques. Of these 9 studies, 8 (89%) used a simulation approach to evaluate the performance of the algorithms, and 4 (44%) used a descriptive-comparative approach to illustrate and compare algorithm performance based on authentic data. Three studies used both a simulation and a descriptive-comparative approach to evaluation.The remaining 33 papers described specific studies of surveillance systems and outbreak detection methods, and the approaches to evaluation used are summarised in Table The primary goal of evaluating outbreak detection methods is to make inferences about their effectiveness. An unbiased assessment of performance is critical for identifying the most appropriate methods to use in specific monitoring applications. However, conclusions reached can be dependent upon the specific evaluation methods used, and consideration of the design of evaluation studies is essential in the interpretation of study findings.Our review of a large sample of relevant published literature highlights the highly specific and varied nature of performance evaluation. Recent guidelines have been drafted for evaluating outbreak detection systems generally; however there are not yet any guidelines specific to performance assessment. As a result, a variety of criteria have been used to assess outbreak detection performance, and the majority of studies in the area do not provide comprehensive assessment of performance of the methods tested. These factors introduce barriers to the accumulation of knowledge in the field, as well as the wider application of the research to practice.We describe a simple framework for the classification of approaches to the evaluation of outbreak detection methods. This framework identifies four specific approaches which are applied in the reviewed literature, and provides a logical structure within which to understand methods currently used for evaluation. The framework developed was found to be sufficient to describe the approaches used to evaluate outbreak detection methods in an independent sample of recently published studies. Based on the papers reviewed there does not appear to be any single approach of choice for the evaluation of methods for outbreak detection in public health surveillance data. A number of studies used multiple approaches to evaluation, indicating that any one approach may not satisfy all evaluation requirements, and highlighting the complementary nature of the approaches identified. The review of studies published since 2005 suggests the criterion-based simulation and epidemiological approaches to evaluation are the current approaches of choice, with the simulation approach becoming more commonly used. The recent development of tools which help to identify and simplify the technical demands of creating simulated data for evaluation -15 may pMultiple approaches to evaluation, including the use of authentic and synthetic data, allow the exploration of both applied and theoretical aspects of outbreak detection performance. Synthetic data are considered to allow more comprehensive characterisation of detection properties  and provAs recently highlighted by Sokolow et al. , authentApproaches to defining outbreaks in authentic data for use in evaluation appear to vary according to the specific purpose and context of surveillance. The range of applied definitions of outbreaks reflect both practical constraints including the availability of sufficient data for evaluation, as well as the range of factors relevant to the determination of whether an outbreak has occurred for different surveillance purposes. For example, the specific methods used to distinguish outbreaks from background variation may include consideration of variables associated with potential causative factors, which may not be able to be specified in advance.For public health surveillance purposes, the adequate definition of outbreaks is often problematic in the absence of sufficient epidemiological knowledge. This requirement for epidemiological knowledge is linked to the frequent use of an Epidemiological approach to evaluation, which allows consideration of complexity and causation in the evaluation of outbreak detection performance. Epidemiological indicators of outbreaks are not absolute due to their reliance on individual judgement; however, they provide the closest approximation to current practice, and are able to accommodate changing standards, expectations, response capacities, interventions and contextual factors more readily than methods using purely data-derived models. Furthermore, the use of prospective methods for the comprehensive investigation of alarms following their occurrence to determine their public health significance as well as the investigation of detection failures has specific advantages over retrospective methods. Retrospective methods do not allow evaluation of the extra sensitivity or specificity of outbreak detection methods, as signals from historical data which have not been detected by conventional means are classified as false positives .Rare or highly variable events pose a specific challenge for evaluation. Although not commonly used among the studies reviewed, sensitivity analyses can be used for criterion-related approaches to address consequences of uncertainty or variation in detection goals. Criterion-related approaches have advantages over descriptive methods when the detection goal can be adequately defined, however their validity is dependent upon the assumptions used to construct outbreaks, as well as the comprehensiveness of the evaluation. The Descriptive approach provides an alternative approach to evaluation, particularly when there is no adequate definition of events of interest within a dataset, or when comparing outbreak detection methods.The advantage of the Descriptive approach lies in the potential for systematic description of the key features of the aberrations detected and the data examined, and the comparison of multiple detection methods using common data. As the validity of outbreak detection methods may vary according to the outbreak scenario as well as surveillance system factors, different methods need to be evaluated under the same conditions to determine their relative value . AlthougThe Descriptive approach requires further development to facilitate comparisons between outbreak detection methods through promoting more standardised, systematic and comprehensive descriptions of basic dataset features and measures of performance. Due to the potentially large reporting burden, further work is required to identify the attributes which would be most useful in standardised descriptions . HoweverOur review provides information on type and prevalence of approaches currently used to assess outbreak detection performance, and their strengths and limitations. We propose a basic framework to represent approaches currently used which provides a foundation for promoting increased comparability among studies and synthesis of knowledge in the field. This framework should offer assistance for both developers and consumers of outbreak detection research. Although there was considerable heterogeneity of study design within the approaches identified in this review, the type of approach used provides a reasonable guide to the strengths and limitations most relevant to specific studies.None of the approaches identified is alone sufficient to provide a comprehensive assessment of outbreak detection performance. In light of the complementary nature of their strengths and limitations, the use of multiple approaches to evaluation where possible is recommended, as has been highlighted previously . AlthougA major finding of this review is the identification of three of the four approaches described as 'cornerstone' approaches to evaluation, as they each use specific methods to address major requirements of the evaluation process. The key requirements of outbreak detection performance evaluations can be characterised by three main properties, being internal validity, external validity and comparability. These requirements can be related to the corresponding strengths of the three cornerstone approaches identified, being the Simulation, Epidemiological and Descriptive approaches respectively. As such, the use of multiple approaches to evaluation can provide the basis for a comprehensive and contextualised assessment of outbreak detection performance.Evaluation of the performance characteristics of outbreak detection methods is essential to allow an understanding of the type of outbreaks that can be identified, and how early these outbreaks can be identified . The curOur findings indicate that no single approach can fulfil all evaluation requirements. The varied nature of performance evaluation demonstrated in this review supports the need for further development of evaluation methods as has been identified previously ,6,25, toThe author(s) declare that they have no competing interests.AJP and REW conceived and designed the study, REW conducted the literature review and content analysis and, REW, SE, RGH, LD and AJP were involved in finalizing the results, and drafting and critically revising the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:This file includes a list of all studies reviewed.Click here for file


The effects of cimetidine and indomethacin on the growth of dimethylhydrazine induced or transplanted intestinal tumours in the rat have been studied. Cimetidine is a histamine type 2 receptor antagonist and indomethacin is an inhibitor of prostaglandin synthesis. Two models of rat intestinal tumours were used: a colon carcinoma line transplantable in syngeneic animals and intestinal tumours induced by dimethylhydrazine treatment of Sprague-Dawley rats. Cimetidine and indomethacin were given in drinking water, alone or in combination. Cimetidine had no effect on the growth of transplanted colon cancer but significantly increased the incidence of chemically-induced tumours, with a tendency toward more invasive and metastatic tumours than in the control animals. Indomethacin did not significantly modify the incidence or other characteristics of the tumours in any of the models. This result is at variance with a protective effect of indomethacin on chemically-induced rat colon cancer previously reported by others.


Xenopus oocytes to identify plant transporter function. We utilized the full-length cDNA databases to generate a normalized library consisting of 239 full-length Arabidopsis thaliana transporter cDNAs. The genes were arranged into a 96-well format and optimized for expression in Xenopus oocytes by cloning each coding sequence into a Xenopus expression vector.We have developed a functional genomics approach based on expression cloning in in vitro transcribed cRNAs from the library in pools of columns and rows into oocytes and subsequent screening for glucose uptake activity identified three glucose transporters. One of these, AtSTP13, had not previously been experimentally characterized.Injection of 96 Xenopus oocytes, combined with uptake assays, has great potential in assignment of plant transporter function and for identifying membrane transporters for the many plant metabolites where a transporter has not yet been identified.Expression of the library in  The final concentration of glucose and sucrose was adjusted to 15 μM by addition of unlabelled glucose or sucrose. Oocytes were pre-incubated in Kulori for 5 min to ensure intracellular steady state pH [Uptake assays were performed in the saline buffer, Kulori  declare that they have no competing interests.Xenopus oocyte expression vector and participated in the screening of the library and drafted the manuscript. MHHN participated in the design of the study, participated in the screening of the library and provided several of the constructs for testing the influence of plant UTRs on expression and helped to draft the manuscript, BAH participated in the design and coordination of the study and helped to draft the manuscript. All authors read and approved the final manuscript.HHN carried out the construction of the transporter database and generation of full-length cDNA library, performed the cloning of the CDSs into the AGI code for the 239 genes in constructed full-length transporter library. This table provides a list of the genes included in the library. Predicted functions are stated.Click here for fileUSER cloning primers. This table provides a list of the primers used to amplify the individual CDS'es from each full length cDNA.Click here for file


In order to carry out a methodological research survey of systematic reviews of adverse effects we needed to retrieve a sample of systematic reviews in which the primary outcome is an adverse effect or effects.We carried out searches of the Database of Abstracts of Reviews of Effects (DARE) and the Cochrane Database of Systematic Reviews (CDSR) for systematic reviews of adverse effects published between 1994 to 2005. The search strategies used a combination of text words in the title and abstract, Medical Subject Headings (MeSH) and subheadings/qualifiers. In addition, DARE records in progress were hand searched. No language restrictions were placed on any of the searches. The performance, in terms of sensitivity and precision, of the search strategies and their combinations were tested in DARE and CDSR.In total 3635 records were screened of which 257 met our inclusion criteria. The precision of the searches in CDSR was low (0% to 3%), and no one search strategy could retrieve all the relevant records in either DARE or CDSR. Hand searching the records from DARE and CDSR not retrieved by our searches indicated that we had missed relevant systematic reviews in both DARE and CDSR. The sensitivities of many of the search combinations were comparable to those found when searching for primary studies in which adverse effects are secondary outcomes.Searching major databases of systematic reviews, for systematic reviews of adverse effects, proved more difficult than anticipated due to a lack of standard terminology used by the authors, inadequate indexing and the variations in the search interfaces of the databases. At present hand searching all records in DARE and CDSR seems to be the only way to ensure retrieval of all systematic reviews of adverse effects in these databases. Balanced decision making in health care requires evidence on the potential adverse effects of interventions as well as their beneficial effects. Although well-conducted systematic reviews of adverse effects are important sources of evidence such reviews are relatively rare in the literature  and it iIt should be easier to identify systematic reviews that were conducted with the express purpose of evaluating adverse effects. We might expect that study retrieval would be facilitated by some mention of adverse effects in the title, abstract or indexing terms. As part of a wider study of methods used in systematic reviews of adverse effects we decided to assess whether we could identify systematic reviews of adverse effects quickly and easily in two major databases of systematic reviews.We searched for systematic reviews of adverse effects using the Database of Abstracts of Reviews of Effects (DARE) and the Cochrane Database of Systematic Reviews (CDSR). These databases were chosen because they are major collections of systematic reviews. No additional sources were searched as DARE is compiled through rigorous monthly searches of bibliographic databases (including MEDLINE and EMBASE) as well as hand searching key journals, grey literature, and regular searches of the web . No langThree approaches were used to identify records in DARE figure . FirstlyThe second approach was to use Medical Subject Headings (MeSH), such as DRUG TOXICITY, and subheadings/qualifiers unattached to any indexing terms ('floating' subheadings), such as 'adverse effects'. This was an essential part of the search strategy as many systematic reviews examine specific adverse effects, such as, headaches, so would not necessarily be identified by text words of synonyms of 'adverse effects' and searching for each named potential adverse effect individually would be impractical. Previous research has also indicated the usefulness of searching with 'floating' adverse effect subheadings -4.Finally, DARE records in the process of being written do not yet have an 'outcomes assessed in the review' field. The titles of all of these 'provisional' records were, therefore, hand searched by the researchers to identify additional relevant reviews.To enable all three approaches to be executed, three searches of DARE were conducted, two via the Centre for Reviews and Dissemination (CRD) website and one via The Cochrane Library website figure . The texSearches for Cochrane Reviews were conducted in the web version of The Cochrane Library Issue 1: 2005)  and DARE (n = 2646) were also scanned for relevant systematic reviews. All relevant records identified then formed our gold standard (GS) set of records.Once we had established our gold standard set of records we were able to test the performance of individual approaches in retrieving the gold standard records. The search terms used to identify the systematic reviews were assessed for their usefulness in retrieving relevant records by measuring their sensitivity and precision. Sensitivity is a measure of the search's ability to identify relevant papers, and a high value is important for searches for systematic reviews. Precision, on the other hand, is a measure of the proportion of relevant records identified by a search strategy expressed as a percentage of all articles (relevant and irrelevant) identified by that strategy. Highly sensitive strategies tend to have low levels of precision. Sensitivity and precision for each database were calculated as follows;In total 4262 records were retrieved from CDSR and DARE, of which 3635 were unique records. From the 3635 titles and abstracts screened, 298 full reports were retrieved and 256 reviews (257 publications) met our inclusion criteria. Of the 257 publications, 246 had DARE abstracts and 11 were Cochrane Reviews  which met our inclusion criteria. In total, therefore, 270 systematic reviews of adverse effects were identified; 256 from DARE and 14 from CDSR.The relevant records not retrieved by our search strategies were sifted for any potentially relevant generic adverse effect search terms. Only 2 of the 13 contained potentially useful terms. Both contained the MeSH indexing term RISK FACTORS and one had the term 'hazards' in the title. These search terms, in addition to the terms used in our search strategies, were tested to identify the most sensitive search strategy possible.The sensitivity and precision of the different search approaches are presented in table All the single search terms in CDSR yielded very low precision (0 to 3%). In DARE, however, some terms did provide high precision table . The sinThe most sensitive search strategy used 'floating' subheadings table . 'FloatiThe most sensitive search strategy in DARE, with the terms tested here, used a combination of text words in the title and abstract, a MeSH term and 'floating' subheadings (see figure In CDSR the most sensitive search strategy used the 'floating' subheading 'adverse effects' combined with searching for 'adverse near/20 objectives' in the abstract. This strategy retrieved 79% (11/14) of the relevant records. However, the precision of this search was low at 3% (11/338).This research highlights the advantages and disadvantages of searching databases through the CRD website and The Cochrane Library website. The CRD website offered the most current version of DARE and allowed searches to be limited to sections of the abstract, whereas The Cochrane Library version of DARE allowed searching using 'floating' subheadings. Even when conducting consecutive searches on DARE and CDSR in two different interfaces it is difficult to retrieve all systematic reviews of adverse effects on these databases. A sensitive search using text words in the title and abstract, indexing terms and 'floating' subheadings was unable to retrieve all the records of interest. An assessment of the missed systematic reviews indicated that most of these records could not have been retrieved without searching for specific adverse effects. Although adding these terms to our search strategy would have increased the sensitivity of the searches, adding the MeSH term RISK FACTORS, in particular, would have decreased the precision.Research has indicated that primary studies of adverse effects are difficult to locate -5. This Interestingly our searches shared similar sensitivities to those reported by Badgett et al's  and GoldDerry et al  found thThe variation in reported sensitivities from the different case studies may reflect their different inclusion criteria. Derry et al  limited Derry et al  and BadgOur searches were limited to CDSR and DARE. Although these are excellent sources of systematic reviews of adverse effects, not all reviews reported as being systematic are contained in these databases: DARE has a strict quality inclusion criterion and CDSR contains only Cochrane Reviews. These databases are sources of systematic reviews that tend to be of higher methodological quality, which may reflect better reporting and hence better indexing.The low number of systematic reviews of adverse effects on CDSR (14) precluded any useful analysis of the data, including comparisons to DARE and previous research. In addition, the usefulness of individual search terms was difficult to assess because of a low number of records.The search terms tested in this study were predefined from previous research and were not obtained by objective methods . HoweverSearching major systematic reviews databases for systematic reviews of adverse effects proved more difficult than anticipated due to a lack of standard terminology used by the authors of reviews, inadequate indexing and the variations in the search interfaces of these databases.Our research suggests that it will be even more difficult to conduct thorough searches for systematic reviews that report adverse effects as a secondary outcome even in resources devoted to systematic reviews such as DARE and CDSR. At present hand searching all records in DARE and CDSR seems to be the only way to ensure retrieval of all systematic reviews of adverse effects in these databases.Every systematic review with adverse effect(s) as a primary outcome should be indexed with appropriate term(s).Authors of systematic reviews should use standardised terminology to make it explicit that they are reviewing adverse effects.Database producers and indexers need to improve the consistency of their indexing of adverse effects.The publishers of The Cochrane Library and the producers of DARE could increase the utility of these databases to users – the former by allowing searches to be limited to sections of the structured abstracts in both DARE and CDSR records, and the latter by introducing the facility to search DARE with 'floating' subheadings.The author(s) declare that they have no competing interests.SG participated in the conception and design of the study, carried out the searches, sifted the records for relevant reviews and carried out an evaluation of the searches and helped draft the manuscript. YL carried out sifting of records for relevant reviews and helped draft the manuscript. HM conceived the study, sifted the records for relevant reviews, and helped draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


The Committee to Assess the Health Implications of Perchlorate Ingestion [National Academy of Sciences (NAS)] released its final report  in JanuaThe NAS committee was composed of 15 leading physicians and scientists with combined range of expertise to evaluate every scientific aspect of the perchlorate database and of the U.S. EPA’s assessment of that database. The makeup of this committee and its credentials are available on the NAS website . The NASseveral of the animal studies … to be flawed in their design and execution. Conclusions based on those studies, particularly the neurodevelopmental studies, were not supported by the results of the studies.Although if inhibition of iodide uptake by the thyroid is duration-dependent, the effect should decrease rather than increase with time, because compensation would increase the activity of the sodium-iodide symporter and therefore increase iodide transport into the thyroid.Evidence has subsequently shown this to be the case .The California EPA perchlorate risk assessment  relied oIn summary, the concerns presented by


Early interventions proved to be able to improve prognosis in acute stroke patients. Prompt identification of symptoms, organised timely and efficient transportation towards appropriate facilities, become essential part of effective treatment. The implementation of an evidence based pre-hospital stroke care pathway may be a method for achieving the organizational standards required to grant appropriate care. We performed a systematic search for studies evaluating the effect of pre-hospital and emergency interventions for suspected stroke patients and we found that there seems to be only a few studies on the emergency field and none about implementation of clinical pathways.We will test the hypothesis that the adoption of emergency clinical pathway improves early diagnosis and referral in suspected stroke patients. We designed a cluster randomised controlled trial (C-RCT), the most powerful study design to assess the impact of complex interventions. The study was registered in the Current Controlled Trials Register: ISRCTN41456865 – Implementation of pre-hospital emergency pathway for stroke – a cluster randomised trial.Two-arm cluster-randomised trial (C-RCT). 16 emergency services and 14 emergency rooms were randomised either to arm 1 (comprising a training module and administration of the guideline), or to arm 2 . Arm 1 participants  attended an interactive two sessions course with continuous medical education CME credits on the contents of the clinical pathway. We estimated that around 750 patients will be met by the services in the 6 months of observation. This duration allows recruiting a sample of patients sufficient to observe a 30% improvement in the proportion of appropriate diagnoses.Data collection will be performed using current information systems. Process outcomes will be measured at the cluster level six months after the intervention. We will assess the guideline recommendations for emergency and pre-hospital stroke management relative to: 1) promptness of interventions for hyperacute ischaemic stroke; 2) promptness of interventions for hyperacute haemorrhagic stroke 3) appropriate diagnosis. Outcomes will be expressed as proportions of patients with a positive CT for ischaemic stroke and symptoms onset <= 6 hour admitted to the stroke unit.The fields in which this trial will play are usually neglected by Randomised Controlled Trial (RCT). We have chosen the Cluster-randomised Controlled Trial (C-RCT) to address the issues of contamination, adherence to real practice, and community dimension of the intervention, with a complex definition of clusters and an extensive use of routine data to collect the outcomes. Stroke is the third most common cause of death in developed countries . In 80% Around 10% of all people with acute ischaemic stroke will die within 30 days of stroke onset, while 50% of the survivors will experience some level of disability after 6 months [As early effective interventions proved to be able to improve prognosis , implemeA systematic review on the adoption of in-hospital clinical pathways suggested that the currently available evidence is insufficient to support routine implementation of care pathways for the hospital management of acute stroke or stroke rehabilitation . TherefoWithin Lazio, the region with 5,302,302 inhabitants in which the capital city of Rome is located, the emergency medical services (ES) are accessible by dialling "118" with automatic connection to the nearest dispatch facility. The emergency network is organised in three levels of complexity. The basic level involves emergency rooms for first aid; the first level is equipped for mild-severe diagnosis and the second level for the most severe urgency. These services are in a number and a geographical disposition to grant the required assistance in emergency  who should be trained to recognize early symptoms and should be empowered to contact ES in order to identify the appropriate level of care required, and to transport patients directly to stroke units.An evidence-based clinical pathway was developed with the methods adopted by the most qualified guidelines development agencies  with the involvement of the emergency health workers in the expert panel, and we decided to evaluate its effectiveness in standardising and improving the procedures in pre-hospital (ES) and emergency (ER) setting, before considering its widespread adoption in our region.The cluster randomised trial design is indicated in assessing the effectiveness of complex interventions  and it aWe present the protocol of study that compares the adoption of an evidence-based prehospital pathway versus current practice.It is our intention to describe the methodology of the study in the present publication in order to ensure independence of the results and to stimulate criticism and suggestions from the journal readers. The protocol has been presented in several international conferences to share our initiative with the scientific community and to collect their comments and ideas.As we are aware of the many limits and peculiarity of this study design we believe that lessons on how to deal with complex intervention in the difficult environment will be the added value of the present study.We identified all the emergency services referring to the two stroke units presently available in Rome figure . There wParticipants are all the workers belonging to the services enclosed in the study (enclosing the ambulances' drivers).About 152 physicians, 280 nurses, 50 drivers will be trained on the contents of the clinical pathway. We estimated that around 750 patients will be met by the services in the 6 months of observation.Participants in the intervention arm will be trained on the content of the clinical pathway and will be given the clinical pathway itself for consultation and discussion in groups.The clinical pathway is based on available evidence based pre-hospital and emergency interventions for suspected stroke patients.It consists of the following main points:- ES dispatcher uses a short form of Cincinnati pre-Hospital Stroke Scale (CHSS) to identify suspected stroke patients during the telephone call;- ES health workers confirm diagnosis by CHSS on the scene;- patients are provided CT and referred to appropriate care.A group of trainers from the expert panel that developed the clinical pathway, and composed of:- an ES medical doctor- anaesthesiologist working on helicopter emergency unit- two neurologists working in stroke unit- a physician working in an emergency department- a neurosurgeon- two epidemiologist and evidence-based medicine experttrained a group of health workers selected from all the entities participating in the intervention arm study to act as "facilitators" for peer education. The facilitators trained their colleagues in the workplace with the help of audiovisual materials produced by the teachers themselves.At least one representative of the teachers' group took part in the meetings on the workplace to support groups' discussion and to answer possible questions. As a result of the training sessions every person working in any entity participating in the intervention arm of the trial have been trained on the content of the pathway.No interventions will be implemented in the control group.The objective of this cluster randomised controlled trial is to evaluate the effectiveness of pre-hospital and emergency clinical pathway for patients with suspected stroke in: improving early identification of stroke, promoting appropriate triage coding, achieving coherence between diagnosis, interventions and referral.The outcomes relate to organizational aspects  and will be measured as:- proportion of patients with a positive CT for ischaemic stroke and symptoms onset <= 6 hour admitted to the stroke unit- proportion of patients with a positive CT for hemorrhagic stroke and symptoms onset <= 6 hour admitted to a neurosurgical ward- proportion of patients with a positive CT for hemorrhagic or ischaemic stroke or symptoms onset >6 hour admitted to the nearest hospital- proportion of ICD9CM code for stroke in emergency setting confirmed in the hospital discharge data- proportion of patients with stroke confirmed by CT results- proportion of patients with ischaemic stroke receiving treatment within 6 hour of symptoms onsetAll the outcomes will be reported at cluster level and will be cross-checked by the integration of data from the available information systems.We calculated the sample size, i.e. the duration of recruitment, keeping into account the number of emergency calls and the number of emergency room admissions for suspect stroke.For the ES the mean number of patients per 19 clusters was about 50  (n°10)• Groups of emergency services (n°6)• Only emergency rooms (n°4).Clusters were attributed sequential numbers and sample function of STATA 7 (StataCorp LP 2005) was used to generate random numbers. We utilized the Italian lottery extracted number of 6th November 2004 in Rome as seeds number for generating the random sequences.To assess the impact of the adoption of the clinical pathway over the current practice, we will analyse the data currently available from the actual information systems and no additional information will be collected.In this way, emergency health workers will not be charged with extra work deriving from registration of ad-hoc information, and they will be completely devoted to the implementation of the pathway itself.The Agency of Public Health created and maintains the Information System of Emergency Rooms (ISER), the Stroke Surveillance System (SSS) and the Hospital Information System (HIS) sufficient to obtain data for measuring the outcomes. Moreover the Agency for Public Health has access to the Information System of ES 118 (IS118).• Baseline characteristics of the entities will be compared to ensure randomisation success;• Analysis will be performed in an Intention to treat basis;• Other analysis by protocol will be performed as a sensitivity analysis;• Preliminary analysis will be performed after three month of the beginning of the observation.All the analysis will be processed with SAS (version 8) and STATA 7 (StataCorp LP 2005).The present protocol was designed following the indication of Helsinki adopted by the 18th World Medical Association General Assembly in June 1964 and following amended in 1975–2002 and clarified respectively for paragraph 29–30 in 2002 and 2004. The ethical committee of the Agency for Public Health approved the protocol with the document n.124 of 15 June 2004. The ethical committee was created according to Helsinki indications including, among others, a member of a patients' rights organization.An informed consensus was signed by the responsible of each entity participating in the study who received a document containing all the relevant information and copies of the clinical pathway and the study protocol. No informed consensus will be requested to patients .The nature of the intervention to be experimented prevented us from identifying specific stopping rules and we could only commit ourselves to submitting any possible problems to the ethical committee. The core of the pathway consists of transferring patients likely to benefit from complex interventions to specialized structures, rather than providing them with minimal assistance in the nearest hospital. This means that health workers belonging to experimental clusters may need to transfer patients for longer distance than they used to do. The risks we can foresee are unexpected events during transportation and troubles deriving from the unavailability of ambulances. Health workers have been warned to promptly report any kind of problems to the study coordinator.The emergency and pre-hospital field has not been studied sufficiently in randomised controlled trials, likely reasons are organizational difficulties, critical conditions of patients and the related ethical problems .We are therefore pioneering this kind of study in a difficult environment and we are prepared to face many obstacles. First, there are the changes in the network of the emergency services. During the last twelve months many new entities were created and others were suppressed generating problems in the identification of clusters. Lack of personnel and high turnover increase risk of contamination due to personnel sharing during the summer and the holydays.Other problems have to do with the local law imposing that patients taken from the scene should be brought to the nearest hospital where the emergency physicians will determine the need (opportunity) to transfer elsewhere for appropriate cure. This procedure delay interventions and determines a very low percentage of cases directly admitted to the stroke unit: 14% of the ambulances transport , and 47% of the emergency room admissions. However health workers participating in the experimentation expressed their worry about possible legal consequences of their decisions caused by the implementation of the protocol study, and this may represent an important obstacle to adherence.Accuracy of data registration is crucial for process evaluation but our quality control system revealed that, even though a priori criteria for data collection are homogeneous, results are sometimes heterogeneous. Nevertheless, as misreporting is non differential the deriving underestimation may not severely affect results.CME = continuous medical educationCT = computer tomographyES = Emergency ServiceER = Emergency RoomALS = Advanced Life SupportBLS = Basic Life SupportCHSS = Cincinnati pre-Hospital Stroke Scaleth revision Clinical ModificationICD9CM = International Classification Diseases 9ICC = intra cluster correlationISER = Information System of Emergency RoomsSSS = Stroke Surveillance SystemHIS = Hospital Information SystemIS118 = Information System of ES 118The author(s) declare they have no competing interests.MF wrote the manuscript and assisted in the design of the study;ADL contributed to the manuscript, ideated and coordinated the study;PGR assisted in the cluster creation, sequence generation and allocation and analysis planning and contributed to the manuscript;GL provided data analysis from the information systems and planning of information retrieval for the assessment of outcomes;GG gave the input of the project, provided overview of all the steps of the study, and contributed to the manuscript final review.All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


The occurrence of pulmonary artery obstruction in the course of acute aortic dissection is an unusual complication. The mechanism implicated is the rupture of the outer layer of the aorta and the subsequent hemorrhage into the adventitia of the pulmonary artery that causes its wall thickening and, at times, produces extrinsic obstruction of the vessel. There are no reports of this complication in acute intramural hematoma.An 87-year-old woman was admitted to the hospital in shock after having had severe chest pain followed by syncope. An urgent transesophageal echocardiogram revealed the presence of acute intramural hematoma, no evidence of aortic dissection, severe pericardial effusion with cardiac tamponade, and periaortic hematoma that involved the pulmonary artery generating circumferential wall thickening of its trunk and right branch with no evidence of flow obstruction. Urgent surgery was performed but the patient died in the operating room. The post mortem examination, in the operating room, confirmed that there was an extensive hematoma around the aorta and beneath the adventitial layer of the pulmonary artery, with no evidence of flow obstruction.This is the first time that this rare complication is reported in the scenario of acute intramural hematoma and with the transesophageal echocardiogram as the diagnostic tool. Acute aortic dissection, acute intramural hematoma and aortic penetrating ulcer are entities with high mortality known as acute aortic syndromes. The usual fatal course of these conditions is closely related to their lethal complications . The mosAn 87-year-old woman with history of systemic hypertension and dyslipidemia was admitted to our hospital after having had severe chest pain of sudden onset radiating to the back and followed by syncope. She presented with marked hypotension 60/40), sinus tachycardia (130 beats per minute), and livid legs. She needed oral tracheal intubation, mechanical respiratory assistance, volume expansion and inotropic support. An urgent transesophageal echocardiogram revealed aortic intramural hematoma compromising the anterior wall of the ascending aorta Fig.  and righ0, sinus The post mortem examination, in the operating room, confirmed that there was an extensive hematoma around the aorta and beneath the adventitial layer of the pulmonary artery with no evidence of flow obstruction.This rare complication of the acute aortic syndromes has been carefully described by Buja et al. in a case of aortic dissection . Since tThere are few reports of this rare complication of acute aortic syndromes in the literature. Many of these reports are in patients who were initially thought to have pulmonary embolism. Indeed the ventilation-perfusion lung scan demonstrates mismatched absence of perfusion to the entire right lung in these cases ,5. FurthThe reason we thought of presenting this case is threefold – there are few reports of this uncommon complication of acute aortic syndromes in the literature; this is the first time that it is described in the scenario of acute intramural aortic hematoma; and it is the first time that transesophageal echocardiogram is used as the diagnostic tool -9.The transesophageal echocardiogram seems to be an accurate diagnostic tool not only to diagnose the aortic pathology but also to rule out this uncommon complication.The author(s) declare that they have no competing interests.MM carried out the transesophageal echocardiogram. MM and MSG performed review of the literature and wrote the paper. All authors read and approved of the final manuscript.Video of the transesophageal echocardiogram showing an intramural hematoma compromising the anterior aspect of the ascending aorta with no evidence of aortic dissection. A circumferential wall thickening of the pulmonary artery can also be seen both in short and long axis view. There is no evidence of pulmonary flow obstruction as shown by color and pulsed wave Doppler.Click here for file


Besides the color of the teeth the color of the alveolar gingiva plays a crucial role in esthetic rehabilitation in dento-alveolar treatment. Whereas nowadays the color of the teeth can be determined exactly and individually, the specific influence of the red color of the gingiva on treatment has not been assessed yet. The aim of this study was to evaluate the vascularization as the basis for gingival esthetics.Standardized photographs of defined areas of the alveolar gingiva in operated and non-operated patients were taken and assigned to groups with same characteristics after color comparisons. In addition, histologic and immunohistologic analyses of gingival specimens were performed for qualitative and quantitative assessment of vessels and vascularization. Finally, colors and number of vessels were correlated.Our results demonstrated three different constellations of colors of the alveolar gingiva in healthy patients. The operated patients could not be grouped because of disparate depiction. There was a clear correlation between color and vessel number in the alveolar gingiva.Our investigations revealed the connections between vascularization and gingival color. Recommendations for specific change or even selection of colors based on the results cannot be given, but the importance of vascularly based incision lines was demonstrated. Esthetic rehabilitation in dento-alveolar surgery was focused solely on reconstruction of position, shape and color of teeth for a long time. Significant improvement was achieved when reconstruction of form and volume of the peri- and paradental or periimplant soft tissue was added to the protocol. Esthetic impression depends on a coordinated interaction of red and white colors of dental and gingival structures. Nowadays the dental color is chosen in a very differentiated and individual way allowing the patient him/herself to select the color of the teeth to be replaced according to the neighbouring or missing teeth. In contrast the red color of the gingiva originates from acrylics, composite resins, silicones or porcelain-based materials which lack the range of differentiation of the white color. In cases without reestablishment of the red color the present red color is taken over regardless of color changes due to surgery. The role of the red color of the soft tissue is still unclear because of lack of complete fundamental knowledge, making definition of a starting point for a specific treatment of color changes impossible. The aim of this study was to evaluate the different mucosal and gingival colors and to classify them according to defined criteria. In addition, the vascular basis was analysed using histologic sections from the oral mucosa and compared with the colors.Standardized digital photographs of the maxillary and mandibular gingiva (#13 to 23 and #33 to 43) . By means of immunohistological staining of the vessels using CD31  distribution of the vessels inside the gingiva was evaluated qualitatively in each specimen. The number of vessels was counted in 5 randomly selected so-called hot spots [Analyses covered qualitative description of the distribution of the vessels in the different parts of the gingiva, quantitative assessment of the number of vessels in the keratinized and non-keratinized areas. Statistical analysis covered the comparison of distribution of vessels using t-test (significance level p < 0.05), and correlation between number of vessels and wave length/color of the different areas of the gingiva using a linear Spearman correlation analysis and calculation of coefficient of correlation.Standardized photographs from 54 healthy unoperated patients and 32 operated patients were analysed. For histological and immunohistological analyses 28 gingival specimens were available.In almost all patients characteristic formations of alveolar soft tissue was found which was divided into area of attached gingiva (gingiva propria), transition zone  and unattached area . This subdivision was not only because of mobility and surface structure but especially because of nuances of the red color. It was demonstrated that the muco-gingival line does not represent an independent anatomic structure with an own coloring but does appear as expression of the transition from attached to unattached gingiva, demonstrating the result of structural and color-coordinated changes.Qualitative evaluation of the photodocumentation according to the mentioned criteria resulted in three subgroups of the healthy unoperated patient cohort. These subgroups were again subdivided according to the intensity of the muco-gingival line Table . Group 1The natural structure of the gingiva was evaluated histologically including keratinized and non-keratinized areas. The vessels were clearly demonstrated in both areas and their distribution analyzed. There was a strongly vascularized area under the epithelium layers in the lamina propria of the mucosa Fig. .Using immunohistological staining the endothelial cells were marked specifically and the vessels analyzed quantitatively Fig. . The numTo date scientific evaluation of the gingival mucosa concentrated on two fields both disregarding the color. On the one hand, vascularization of oral mucosa was investigated using different techniques  declare that they have no competing interests.JK set up the design of the study, performed the surgical part, and helped to draft the manuscript. AB carried out the photographical analysis and performed the statistical analysis. TF carried out the histological and immunohistological studies and performed the statistical analysis. UJ participated in the design of the study, coordination of the patients and helped to draft the manuscript. All authors read and approved the final version of the manuscript. AB and TF contributed equally to this work.


The aim of this study was to compare the expressed levels of career satisfaction of three groups of comparable dental healthcare professionals, working in Trinidad, the United Kingdom and New Zealand.Three questionnaire surveys were carried out of comparable dental healthcare professionals. Dental nurses in Trinidad and dental therapists in the UK and New Zealand. Questionnaires were sent to all registered dental nurses or dental therapists.Career satisfaction was lowest amongst Dental Therapists working in Trinidad and Tobago. Approximately 59% of the Therapists working in New Zealand reported stated that they felt they were not a valued member of the dental team, the corresponding proportion in the United Kingdom was 32%, and for Trinidad 39%.Dental therapists working in different healthcare systems report different levels of satisfaction with their career. The career development and career satisfaction expressed by dental professionals is an area which has attracted much recent research -5. Most The expressed levels of job satisfaction among dental therapists working in the UK was described by Gibbons et al  who repoTrinidad & Tobago is a twin island state situated at the southern end of the Caribbean chain of islands. It is a democratic republic within the British Commonwealth having gained independence in 1962. The country's dental needs are currently served by dental professionals working in government health centres and in private practices. The Dental Council of Trinidad & Tobago presently only recognises two categories of dental professionals: dentists and dental nurses , with 216 and 50 registered and enrolled respectively . The DenCurrently, most dental therapists in New Zealand work within the School Dental Service treating children up to the age of 13 years. School dental services have provided free treatment since 1945 and it is estimated that more than 95% of New Zealand children are enrolled . A recenThe provision of dental services in New Zealand is undergoing a period of change, largely due to the implementation of the Health Practitioners Competence Assurance (HPCA) Act in September 2004. This act allows for an expansion of the scope of practice of dental therapists, and also enables these oral health providers to move into private practice for the first time, hitherto dental therapists in New Zealand have been restricted to working in the publicly funded health sector, where remuneration is low. It is not yet known how these changes will affect the dental therapy in New Zealand though it is anticipated that many therapists will choose to shift their practice to the private sector where their potential earnings are higher.Following the report of the Dental Auxiliary Review Group and the subsequent publication of a consultation document concerning professionals complementary to dentistry by the General Dental Council, recent legislation in the UK has allowed Dental Therapists to work in all sectors of oral healthcare. Prior to this dental therapists in the UK were limited to working in hospitals, community dental services or the armed forces where they were employed in salaried posts. This situation parallels that in New Zealand, and it is again anticipated that UK therapists will seek to enhance their income by working in the primary care sector where their earnings are likely to be paid on an item of service basis.Three issues arise from a review of the reported career satisfaction of dental professions. First, there are few data available on the perceptions of some groups. Second, different studies have used different measures, making comparisons both within and across professions difficult. Third, there are no studies which have compared similar professional groups across countries . The aim of the present study is to compare the expressed levels of career satisfaction of three groups of comparable dental healthcare professionals, working in Trinidad & Tobago, the UK and New Zealand.Three postal surveys were conducted. Parallel questionnaires, including a question about career satisfaction, were mailed to all dental therapists registered with the General Dental Council in the UK(n = 380), all dental nurses (n = 50) enrolled by the Trinidad & Tobago Dental Council and currently practising in Trinidad & Tobago, and all dental therapists on the Dental Council of New Zealand database (n = 716). Overall response rates for the surveys were: UK therapists 80%; Trinidad & Tobago nurses 76%; New Zealand 83%. Only dental therapists currently employed in that role were included in the analyses, reducing the sample size to: UK, 221 dental therapists; Trinidad & Tobago 38, New Zealand 502.Job satisfaction was determined by a single question. Participants were asked to rate their overall satisfaction with their career as a dental nurse or therapist (according to country) on a ten point scale with markers at each end where the value 1 was labelled "No satisfaction" and the value 10 labelled "Complete satisfaction".In addition information was collected on the following• Age of respondent• Whether the respondent had ever taken a break in their career• Whether the respondent felt a valued part of the dental teamUnivariate analyses were conducted to compare dental personnel across the three countries, on the variables identified. Mean and median scores on the satisfaction scale were calculated and compared using the Kruskal-Wallis test (a non-parametric version of the oneway ANOVA) since the satisfaction data had a skewed distribution (the standard error of the skewness statistic was greater than twice the skewness). Age was treated as a continuous variable and compared using a one-way analysis of variance, since the distribution of the data was approximately normal. The proportion of individuals who had ever taken a career break was compared across countries, and the respondents perception of whether they felt a valued part of the dental team was treated as a dichotomous variable  and compared using the Chi-square statistic.In order to examine the relative importance of each variable in predicting satisfaction, a logistic regression analysis was conducted. The outcome variable was satisfaction score dichotomised around the median value for the sample , whether the individual had taken a career break, place (entered as three separate dummy variables coding each of the three countries) and whether the individual felt a valued member of the dental team  were entered stepwise as predictor variables, in order of their simple correlation with the outcome variable. Additional variables were entered until there was no significant increase in the predictive utility of the variables. For each variable in the equation the following statistics were calculated: coefficient B, the standard error of B, significance, estimated odds ratio (exp [B]). For the final model the model chi-square and the log-likelihood statistic were calculated.Table The final logistic regression analysis model is summarised in Table The job satisfaction of three comparable groups of dental professionals working in different countries was compared, and found to be lowest in Trinidad & Tobago. These findings should be interpreted with some caution given the limitations of the study. This study adopted a single item measure of career satisfaction. Whilst this allows for comparison with other studies that have used similar single item measures for example ,4, singlThe extent to which an individual is satisfied with their job will be determined by many factors, including the pay and employment conditions. Country of work emerged as significant in the regression model, and is likely to act as a proxy measure for the working conditions, type of payment, healthcare system and experiences of the participants. However the present study did not investigate these explanatory variables in any depth. Surprisingly, whilst satisfaction was lowest amongst dental nurses in Trinidad & Tobago, this group had the highest proportion of members who felt a 'valued' member of the team. A feeling of being valued was lowest amongst dental therapists in New Zealand, suggesting that the satisfaction item was measuring something more than the perception of being valued in a team. The three countries in the present study place similar restrictions on the practice of dental therapy, and all three propose changes in the employment of this group of healthcare professionals but differ in the extent to which this change has been implemented. The UK system has taken the most steps towards changing the employment of dental therapists, followed by the New Zealand system. Career satisfaction was lowest amongst Dental Therapists in Trinidad and Tobago where the role is most restricted. Future research should address the extent to which the characteristics of the working environment impact upon job and career satisfaction. Research with dental practitioners has determined that system of remuneration, the characteristics of the working environment, and the type of service in which an individual works all exert an influence upon the practitioner's experience of their working life ,16,25.There is a need for further research addressing the impact of low career satisfaction on the dental workforce, including retention of workforce, the impact on the quality patient care and interactions with patients. It might be hypothesised that a dissatisfied workforce would be more likely to leave the career or be less motivated to deliver care of a high quality. Such associations have been found in studies of physicians  and rehaDental therapists working in different healthcare systems report different levels of satisfaction with their career, being lowest in Trinidad & Tobago. Career satisfaction in all three countries was related to feeling a valued member of the dental team.The author(s) declare that they have no competing interests.RN was responsible for the conduct of the survey in Trinidad & Tobago. JTN was responsible for the collection of data in the United Kingdom collated the data from the three countries and performed the statistical analysis. KA was responsible for the conduct of the survey in New Zealand. All authors contributed to the production of the manuscript.The pre-publication history for this paper can be accessed here:


A wide range of outcomes have been assessed in trials of interventions for carpal tunnel syndrome (CTS), however there appears to be little consensus on what constitutes the most relevant outcomes. The purpose of this systematic review was to identify the outcomes assessed in randomized clinical trials of surgical interventions for CTS and to compare these to the concepts contained in the International Classification of Functioning, Disability and Health (ICF).The bibliographic databases Medline, AMED and CINAHL were searched for randomized controlled trials of surgical treatment for CTS. The outcomes assessed in these trials were identified, classified and linked to the different domains of the ICF.Twenty-eight studies were retrieved which met the inclusion criteria. The most frequently assessed outcomes were self-reported symptom resolution, grip or pinch strength and return to work. The majority of outcome measures employed assessed impairment of body function and body structure and a small number of studies used measures of activity and participation.The ICF provides a useful framework for identifying the concepts contained in outcome measures employed to date in trials of surgical intervention for CTS and may help in the selection of the most appropriate domains to be assessed, especially where studies are designed to capture the impact of the intervention at individual and societal level. Comparison of results from different studies and meta-analysis would be facilitated through the use of a core set of standardised outcome measures which cross all domains of the ICF. Further work on developing consensus on such a core set is needed. Carpal tunnel syndrome is the most common peripheral entrapment neuropathy and a frequent cause of disability in the upper extremity. SurgicaThe evidence from trials evaluating the outcomes from surgical and non-surgical interventions is extensive,5, howevOutcome measures should not only capture the impact of the disorder on body structure (impairments) but also on activities and participation as defined in the International Classification of Functioning, Disability and Health (ICF). The ICFGiven the wide range of outcomes that have been employed in trials of surgical interventions for CTS and the lack of consensus among clinicians on what are considered the most relevant outcomes to assess it was hyA systematic review was performed to identify the outcomes assessed and concepts contained in the measures used in trials of interventions for CTS, and to relate these concepts to the ICF as a reference tool.Medline (January 1966 to July 2005), CINAHL (January 1982 to July 2005), AMED (January 1985 to July 2005) were searched using the following MeSH terms: randomized controlled trial, controlled clinical trial, carpal tunnel decompression, carpal tunnel release, carpal tunnel surgery. The titles and abstracts of articles retrieved through the search were checked applying the eligibility criteria as defined below. In order to crosscheck the sensitivity of the search strategy and identify any studies not retrieved through the search the bibliographies of a Cochrane review on surgical interventions for CTS were also examined[The bibliographic databases The review considered all published studies if they met the following eligibility criteria: randomized or quasi-randomized trials, the interventions were surgical, the patients had a diagnosis of CTS made through clinical symptoms with or without confirmatory electrodiagnostic testing, and the outcomes assessed were described. Studies designed solely for the purpose of evaluating the effectiveness of different local anaesthesia on pain during or within 48 hours of surgery were excluded.English language publications only were included and regardless of the time of the publication. The purpose of this review was not to assess the methodological quality of these trials as this has been done previously,11,12, b137 studies were identified through the initial search. After checking the abstracts and further review of the full-text article a total of 28 studies which met inclusion criteria were identified  A summarThe studies, conducted between 1985 and 2005, were all designed to evaluate the relative effectiveness of different surgical techniques such as endoscopic carpal tunnel release (ECTR) or open carpal tunnel release with or without epineurotomy. Standard open carpal tunnel release (OCTR) was the control intervention in 27 of the 28 trials. A total of 2558 hands in 2232 patients were studied in 28 studies. The length of follow-up after decompression varied greatly between the studies, ranging from 4 weeks to 2 years. The mean follow-up time was 37 weeks with 13 studies reporting follow-up at 1 year or longer. There was no apparent association between the type of outcomes assessed and other study characteristics such as the type of intervention studied, the length of follow-up or the country of the study.A wide range of outcomes were reported and these were classified according to the three ICF domains: i) measures of impairment of body function and body structure; ii) measurers of activity limitations and iii) measures of participation restriction . Measures of participation used in the trials were return to work which featured as a primary or secondary outcome measure in 15 studies and satisfaction (7 studies).The level of reporting on the actual methods of assessment varied between studies. In several studies standardised outcome measures were used but with none or minimal detail on the actual instrument used, method of administration or reference to literature on standardised protocols. For example, 11 studies assessed two-point discrimination with only 4 studies stating the instrument used and one study describing the method  employment status (self-employed versus employee) and variations in healthcare systems and how 'sick notes' are issued. The time taken to return to work also does not indicate whether someone is able to resume the activities without pain or discomfort and to the satisfaction of the individual and/or his employer. Furthermore, work as a measure of participation is not relevant to those patients who are not in employment or retired.Current understanding of the pathophysiology of CTS together with the clinical manifestation of signs and symptoms allows the specific body structures and functions to be identified which are implicated in this disease. Depending on the severity of their symptoms, patients are also affected in their ability to carry out activities (activity limitations) and participation in work or leisure (participation restrictions). These in turn are also influenced by personal and environmental factors .Using the ICF as a framework, firstly the codes and categories within health and health-related domains relevant to CTS were identified  and the he SF-36  which caWhilst it is important to obtain a comprehensive assessment of the impact of CTS on body function and structure as well as activity and participation, the use of a large battery of instruments also increases the burden on the patient and the tester. There was some overlap between the concepts assessed in trial outcomes. For example, in the domains body functioning, the functions of muscles were assessed by manual muscle testing of the abductor pollicis brevis muscle, dynamometry for pinch and power grip strength and degree of thenar wasting. In several trials two or more of these measures were used concurrently. A review of the evidence is needed on which of these methods and instruments is most valid, reliable and responsive which, in turn, reduces assessment burden and redundancy of similar outcome measures.The use of the disease-specific measure, the BCTQ is becoming more established in recent trials. A systematic review of the psychometric properties of the BCTQ indicated that it is valid for the population, has good reliability and is responsive  and shouThis review has some limitations: we considered RCTs only in this review, based on the assumption that in well-designed trials careful attention would be paid to the selection of outcome measures. There are however a number of large follow-up and cohort studies which also report outcomes from surgical decompression and inclusion of these studies may have highlighted additional outcome domains and instruments.The ICF provides a useful framework for identifying the concepts contained in outcome measures employed to date in trials of surgical intervention for CTS. It can help in the selection of the most appropriate domains to be assessed, especially where studies are designed to capture the impact of the intervention at individual and societal level. The findings of this review on surgical outcomes indicate that studies to date have focused primarily on assessment of impairment and less on the activity limitations and participation restrictions. It is important that consensus is achieved on which outcome measures should be used for which domains and on the standardisation of methods. A minimum set of outcome measures should include patient-reported scales of symptom severity and functional status such as the BCTQ, clinical measures of motor and sensory function and everyday performance in self-care, work and leisure as well as health-related quality of life. Further work is needed to review the psychometric properties of existing instruments in CTS populations and to develop consensus on a core set of outcome measures to be used in future clinical trials for CTS which crosses all three domains of the ICF.The author(s) declare that they have no competing interests.CJH conceived of the original idea, obtained funding and participated in the search, review and drafting of the manuscript. JCCL carried out the searching and reviewing of studies and helped draft the manuscript. FS provided expert advice on systematic reviewing and contributed to the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here: