Most analyses of spatial clustering of disease have been based on either residence at the time of diagnosis or current residence. An underlying assumption in these analyses is that residence can be used as a proxy for environmental exposure. However, exposures earlier in life and not just those in the most recent period may be of significance. In breast cancer, there is accumulating evidence that early life exposures may contribute to risk. We explored spatio-temporal patterns of risk surfaces using data on lifetime residential history in a case control study of breast cancer, and identified elevated areas of risk and areas potentially having more exposure opportunities, defined as risk surfaces in this study. This approach may be more relevant in understanding the environmental etiology of breast cancer, since lifetime cumulative exposures or exposures at critical times may be more strongly associated with risk for breast cancer than exposures from the recent period.p-values. These surfaces were compared for premenopausal and postmenopausal women, and were obtained for each decade, from the 1940s to 1990s. We found strong evidence of clustering of lifetime residence for premenopausal women (for cases relative to controls), and a less strong suggestion of such clustering for postmenopausal women, and identified a substantial degree of temporal variability of the risk surfaces.A GIS-based exploratory spatial analysis was applied, and spatio-temporal variability of those risk surfaces was evaluated using the standardized difference in density surfaces between cases and controls. The significance of the resulting risk surfaces was tested and reported as We were able to pinpoint geographic areas with higher risk through exploratory spatial analyses, and to assess temporal variability of the risk surfaces, thus providing a working hypothesis on breast cancer and environmental exposures. Geographic areas with higher case densities need further epidemiologic investigation for potential relationships between lifetime environmental exposures and breast cancer risk. Examination of lifetime residential history provided additional information on geographic areas associated with higher risk; limiting exploration of chronic disease clustering to current residence may neglect important relationships between location and disease. In a recent analysis of breast cancer by New York State's Department of Health, a breast cancer cluster in the Western New York area was identified . One of in utero exposures may affect risk [Previous studies using exploratory spatial analyses, however, have been based on either residence at the time of diagnosis or current residence, and only a few recent studies have examined disease risk using information on lifetime residence ,12. For ect risk . To examIn this study, we explored spatio-temporal patterns of risk surfaces using data on lifetime residential history in a case control study of breast cancer. We had previously identified geographic clustering of residence at critical points in early life in relation to breast cancer risk . Here weDescriptive characteristics of study participants by menopausal status are presented in Table We constructed lifetime cumulative risk surfaces to represent exposure opportunities in lifetime because cumulative exposures may be a more accurate indicator of potential environmental exposures related to breast cancer risk. Figure p-values. Those areas with standardized difference greater than 2 SD were quite different between pre- and postmenopausal breast cancer, although ranges of standardized the difference were similar; -6.37 to 4.43 for pre-menopausal, and -6.57 to 3.39 for postmenopausal breast cancer, respectively. There were about 29 rectangular grids in those areas greater than 2 SD for premenopausal, while about 59 grids for postmenopausal breast cancer. Further, the statistical significance of areas must be assessed in light of the fact that multiple areas are tested; these are statistically significant if the difference in density exceeds the critical value of 3.56 at α = 0.05 . There is one small geographic area of special interest for pre-menopausal residences in the central and upper region of the city. When these are compared with the geographic location of clusters of birth and menarche residences identified previously [We evaluated spatial patterns of risk surfaces based on the geographic distribution of lifetime residences in Figure eviously , we founNext, we evaluated effects of other risk factors on the risk surfaces. To create age-adjusted risk surfaces, the standardized difference between case and control densities stratified by menopausal status and age groups was examined. Table Lastly, we were interested in evaluating temporal variability of risk surfaces; the standardized difference was obtained for each decade, for both pre- and post-menopausal residences, from the 1940s to 1990s  that can be used to create risk surfaces, because it is more easily able to handle the difficulties that arise with small densities. Unsmoothed risk surfaces are relatively easy to manipulate, but they are sensitive to geographic scales, while the ratio of case to control density results in unstable risk surfaces due to small number problems. We were able to reduce this problem in creating risk surfaces based on a standardized difference approach. The selection of optimal bandwidths in the application of kernel methods to cluster detection, and comparison of different types of bandwidths, such as adaptive kernel, will be a subject of future study .It is important to note that current approaches to obtaining density surfaces of lifetime breast cancer risk are limited in several ways. First, we are using residential locations of breast cancer cases and controls; we obtained the difference in densities (risk surfaces) based on their residential location to identify areas with relatively higher case density. We do not know actual exposures and breast cancer risk associated with residential locations. However, this study provides evidence of differential exposure opportunities among cases and controls for further epidemiologic assessment, since spatio-temporal clustering of residential locations in a life course may be an indicator of differential exposure opportunities and the subsequent risk of breast cancer. Another limitation of this analysis is that we were unable to incorporate length of residence into the model. We were able to visualize risk surfaces with different weights based on the actual length of residence of each individual, but there were difficulties in incorporating this information into risk surfaces due to a substantial degree of variability in the length of residence. However, we observed spatial patterns consistent with those in Figure There is also need for cautious interpretation of these results due to the potential for selection bias inherent in the study design, including factors such as non-participation, and missing and excluded residential location. Although we had a relatively stable population and about 40% of study participants were lifetime residents in the study area, there may be different geographic patterns among those included and excluded groups. We excluded missing residential information and residential locations outside of the study area. In addition, we had a rate of non-participation of about 30% in the survey. However, in our earlier study , we founThis study has significant implications for further studies on environmental exposure and breast cancer. We had previously found strong evidence of clustering of residence in early life, especially residence at birth and menarche . In thesTo provide more accurate measures of personal cumulative exposures based on complete lifetime residential history, further studies should take into account the different effects of time periods or timing of exposures; construction of lifetime cumulative risk surfaces with different weights for exposure sensitivity at different points in time is a potential improvement and explanation of the methods employed to date. This approach may help to provide an answer to the question of where, when, and what kinds of exposures have influenced individuals' risk for a particular disease. Further, there has been recent development of a GIS-based framework to examine spatio-temporal patterns of lifetime residential history; the geospatial lifeline concept and space-time information system (STIS) approach is a good example of this -27. We aIn summary, we found evidence of clustering of lifetime residence for premenopausal cases relative to controls, and a substantial degree of spatio-temporal variability in the risk surfaces, thus providing a working hypothesis on breast cancer and environmental exposures. Geographic areas with higher case densities need further epidemiologic investigation for potential relationships between lifetime environmental exposures and breast cancer risk. Examination of lifetime residential history provided additional information on geographic areas associated with higher risk; limiting exploration of chronic disease clustering to current residence may neglect important relationships between location and disease. Further studies on the relationship between disease risk and environmental exposures associated with lifetime residential history should be replicated in other settings.Data from a population-based case-control study of breast cancer in western New York (the WEB Study) were used for our analyses. Participants were women, age 35–79 who were residents of Erie and Niagara counties, with no history of cancer other than non-melanoma skin cancer; cases were women with incident, primary, pathologically confirmed breast cancer, diagnosed during the period 1996–2001, and controls were randomly selected and frequency matched to cases on age, race, and county of current residence. Details of the WEB study, including selection, ascertainment, in-depth interview processes, have been described previously . We collx and y coordinates to be used in further spatial analyses. Address geocoding is a process that creates a theme based on the address data in a tabular form (event theme) and a reference feature theme (street map) to add point locations defined by the street address to the map. Matching depends not only on the quality of the reference theme, but also on the quality of the tabular data to be mapped. We used GDT/Dynamap 2000, an enhanced version of Topographically Integrated Geographic Encoding and Referencing system (TIGER), as a reference theme. In a study validating the positional accuracy of TIGER for the use in epidemiologic study [Geocoding of residential locations enables us to record each individual's locational information as ic study , we founThe overall matching rate for the 15,487 Erie and Niagara County residential locations was 82% ; 91% of the matches were matched with complete information (good match), while about 9% of were estimated with partial information (interactive match) as detailed below. Geocoding success rates were lower for earlier residences, mainly due to more missing and partial information of earlier residences and changes in streets names and zip codes. However, it is important to note that there were few changes in street structure for this region during the time period of interest. There was, of course, addition of new streets, but existing streets were unchanged for the most part, and thus we found that the process of geocoding using current information was not inappropriate. We utilized various resources, including historic city directories with address information for residents, historical maps, and commercial address databases, to find missing residence information, and we developed several strategies to improve matching rates . In addik is defined as, , and by averaging over these individual kernel functions, we obtain the kernel density estimator,  ;Kernel density estimation methods have been used for disease mapping and for the detection of geographical location of clusters in epidemiologic settings ,12,29. Ax is the location for density estimation, xi is the observed point location, n is the number of points, and h is a smoothing parameter that regulates the degree of smoothness. Kernel functions are symmetric around zero and integrate to one. Both kernel and kernel density estimator are density functions; thus ∫kx (x)dx = 1 and ∫fh(x)dx = 1. For the two-dimensional kernel density estimator:where  is used, where  and  are estimates of the intensity for cases and controls, respectively. Smoothed risk surfaces using the ratio or log ratio of case to control density can be less effective with small sample sizes; it is possible to have spurious, high risk areas in the application of the ratio of densities when the value of the control density is too small.While the estimation of intensity for one point pattern may show patterns of high and low risk areas, this is of limited utility in epidemiologic applications because it may largely reflect the pattern of population distribution . The ratThe relative difference between two densities provides an alternative way to assess the spatial variability of risk surfaces. Using the square root variance stabilizing transformation and the standardized difference, this measure allows us to identify areas with differences between case and control density exceeding two standard deviations . The stawhere The first step in creating smoothed risk surfaces using kernel methods was to create reference grids and overlay the study area with them. We obtained the smoothed intensity for both cases and controls by calculating the distance between each point on the reference grid and the locations of breast cancer cases and controls. We used the quartic kernel to estimate the intensity of points at each grid point, although the choice of kernel type is not crucial as long as the kernel is symmetrical . We applThe above analyses were repeated with varying bandwidths because the choice of appropriate bandwidth is one of the primary concerns of the kernel method. Although a subjective choice made from a range of values is commonly used , selectiRisk surfaces based on the ratio and difference in density surfaces between cases and controls were implemented in a GIS and S-Plus environment . In addiAll authors have participated fully in the conduct of this study, the acquisition of data, the analysis and/or the preparation of the manuscript in a substantial manner. DH performed the statistical analysis and drafted the manuscript; PAR and JLF provided critical review and input. JLF, JEV, MAB, JN, PM and MT participated in the design of the study, participated in interpretation, as well as in data acquisition efforts. All authors read and approved this manuscript.


Earlier studies have successfully demonstrated that medical students can achieve success in core clinical rotations with long term attachments in small groups to rural general / family practices.In this study, three students from a class of 226 volunteered for this 1-year pilot program, conducted by the University of Queensland in 2004, for medical students in the 3rd year of a 4-year graduate entry medical course. Each student was based with a private solo general practitioner in a different rural town between 170 and 270 km from the nearest teaching hospital. Each was in a relatively isolated rural setting, rated 5 or 6 on the RRMA scale . The rural towns had populations respectively of 500, 2000 and 10,000. One practice also had a General Practice registrar. Only one of the locations had doctors in the same town but outside the teaching practice, while all had other doctors within the same area. All 3 supervisors had hospital admitting rights to a hospital within their town. The core clinical rotations of medicine, surgery, mental health, general practice and rural health were primarily conducted within these rural communities, with the student based in their own consulting room at the general practitioner (GP) supervisor's surgery. The primary teacher was the GP supervisor, with additional learning opportunities provided by visiting specialists, teleconferences and university websites. At times, especially during medicine and surgery terms, each student would return to the teaching hospital for additional learning opportunities.All students successfully completed the year. There were no statistical differences in marks at summative assessment in each of the five core rotations between the students in this pilot and their peers at the metropolitan or rural hospital based clinical schools.The results suggest that isolated rural general practice could provide a more substantial role in medical student education. The last ten years have seen a global change in the methods used for the education and training of medical students -3. In paOne result of these changes has been a large scale move towards increasing community based medical education within the medical schools' curriculum, with students attached to a community based general / family practice ,6-8. AltAn additional benefit of placement in the community is the increased exposure to general / family practice. When the community is in a rural area, this has a positive influence on choice of rural practice as a career choice, an area of significant shortage in many countries ,12-14. TInitial concerns of both students and teachers experiencing long term placements in the community focused on the potential disadvantage to students because of the uncertainty of whether they would see a broad spectrum of clinical conditions through the community patient base to achieve their learning objectives ,10. HoweRecent studies examining assessment results indicated that students in longitudinal community placement performed as well, if not better than their hospital-based counterparts in acquisition of clinical skills, including those associated with specialist disciplines ,11. AldeHence, earlier studies have successfully demonstrated that medical students can achieve success in core clinical rotations with long term attachments in small groups to rural general / family practices. The aim of this pilot study was to assess the feasibility of successfully completing the five third year core clinical rotations while based alone without their peers in a relatively isolated rural community general / family practice, with success measured though academic achievement.The University of Queensland medical course is a four-year graduate entry program culminating in a Bachelor of Medicine and Bachelor of Surgery. The overall course plan is detailed in table Problem Based Learning (PBL) is a key component of the program at all levels. Using a series of carefully planned patient-centered exercises, the students work cooperatively with their tutors to examine core issues of health and disease. In years three and four, students examine a new PBL case each week. The remainder of their clinical time is focused on supervised learning from their patients, supplemented by clinical teaching, tutorials, case demonstrations and lectures. Adult learning processes are encouraged with students' teaching and learning driven by their own learning objectives and goals. Key features of the program include life long learning skills including an ability to search and critically analyze information.All students are learning under the same curriculum and participate in the same assessment process, regardless of the geographical location of their clinical experience. A summative mark is generated for each core clinical rotation in third year from an end-of-term test with or without an in-course assessment. From the rotation marks, an average score for the year is produced.The concept was initially developed at a stakeholder meeting of clinical and academic staff of the Central Queensland Rural Clinical Division held in early 2003. Several rural general practitioners (GP) who were clinical teaching staff at this Division expressed interest in developing and participating in the program. By late 2003, three rural GPs had agreed to participate.In August / September 2003, the second year student body was approached at a series of public meetings and offered participation in the new program. Those students who were interested were asked to provide a confidential written expression of interest, explaining their motivation to participate, although there were no formal criteria to evaluate this process. The three students who expressed interest attended a weekend orientation program visiting all three prospective locations, meeting with their prospective GP supervisors, as well as the rural teaching hospital. All three subsequently agreed to volunteer for the program and self selected their site for attachment for 2004.Program coordination was by a dedicated team based at the Division's rural teaching hospital. The attached academic staff also provided support both by telephone and regular visits.Each student was attached to a different private solo rural general practitioner / family doctor for one academic year. Each student's home base was their own consulting room located within the community based General Practice. The practices are located in relatively isolated and geographically separated communities, all a considerable distance from each other. They are between 170 and 270 km from the Rural Clinical Division teaching hospital. The demographics of these locations are detailed in table The educational process was similar to that of the teaching hospital, being based on supervised learning from patients, clinical teaching, tutorials and case demonstrations. In common with their peers at other geographical sites within the School of Medicine, the program was based on the adult learning model, requiring participating students to exercise a significant degree of self reliance and initiative. Although not essential, being a graduate rather than undergraduate program combined with an extensive use of the PBL mode of learning would have assisted this process.A notable difference was that only 25% of the clinical material was seen at the hospital interface. Each student participated in the care of a large variety of patients, experiencing in any given week problems covering all five core clinical rotations. They were also able to follow their patients over time, creating a longitudinal experience. However, for administrative reasons, the students operated within the five-term structure, with separate 8-week blocks for each of the five core rotations. Hence, the weekly PBL tutorials, activities and assessment tasks were aligned with the designated term, an essential process to keep the curriculum and assessment process uniform across all geographical locations within the School of Medicine.Although the GP principal in each of the practices was the primary teacher / mentor, the student's learning environment was enhanced by interactions with other locally based doctors, visiting specialists and allied health professionals. PBL tutorials were conducted by teleconference between the pilot study students and the designated tutor . A separate teleconference between the three students, but without supervision by the academic, teaching or administrative staff was conducted weekly to encourage peer-to-peer discussion and support. Each student also rotated to the Division's main teaching hospital or a second teaching hospital of the Division for 3–5 days per month to participate in either scheduled teaching activities with other students or one to one teaching with the hospital based specialists. This arrangement was flexible dependent on the needs of the students, in keeping with the philosophy of self-directed learning.Each student was provided with high-speed Internet access. This gave them the same access as students elsewhere to the Internet based resources of the university, where the PBL and other learning resources are located. Each student was issued with a hand held computer and associated software, providing access to information within the consultation process and for diarizing their learning experience. This personal learning tool, akin to a learning journal was for personal self learning and development, rather than program evaluation. At no time did academic staff have access to this information. This learning tool was not provided at other geographical locations.In order to ensure the comparability of the pilot study students' marks with their rural and metropolitan counterparts, the assessment process was uniform across the school regardless of geographical location. Although the pilot study students were in essence in a longitudinal rather than term based program, their assessment followed the term process. In-course assessment was completed on a nominal term basis, in the sequence rural, general practice, mental health, surgery and medicine. In contrast, end of course assessment could be attempted in any order chosen by the student, as long as they completed the process on the same day as their peers elsewhere and completed exactly the same assessment. All students chose to sit the surgery assessment at the end of term 4, the medicine assessment at the end of term 5, but varied in their timing of the other 3 assessments.The summative assessment process was essentially similar across the third year curriculum, combining a series of in-course assessments with a final written test in each of the 5 terms. Learning and assessment programs included knowledge, skills and attributes in four broad areas titled 'Domains': (1) basic and clinical sciences, (2) interpersonal and clinical skills, clinical reasoning and practice, (3) population and preventive health, and (4) ethics, personal and professional development. Hence over the course of the year, each student was extensively and repeatedly assessed in a variety of formats and settings, looking at a broad range of learning issues beyond merely acquisition of knowledge.The entire program was funded under the Rural Clinical School initiative of the Australian Government Department of Health and Ageing  and manaThe major concern during planning was to find appropriate preceptors as this program was heavily dependent on the active and dedicated participation of the preceptor in an intensive, one to one teaching and mentoring relationship. However, in the planning stages, supervisors who were essentially self-selected came forward and after the academic credentialing processes were appointed. Each supervisor was a dedicated rural doctor with greater than ten year's continuous service in that particular location. They all had extensive procedural experience although they utilized these skills to varying degrees. Each had been a supervisor of General practice trainees over many years, had supervised medical students in the past and were known to be effective teachers.Orientation and ongoing oversight of the supervisors was performed by the program's dedicated part time academic supervisor who made frequent contact with both the students and their preceptors, both by telephone and regular face to face meetings. He was supported by part time administrative support from the student affairs officer, finance officer and regional school manager.In order to physically accommodate students in the rural preceptors' practice, structural changes were required. These were jointly funded by the University and the preceptors. Unfortunately, the building / renovation program was not completed until after the academic year began. Student accommodation was sourced from the local real estate agents and funded by the University.The Statistical Package for the Social Sciences was used for analysing the results . Each stAll three students in this pilot study completed the full year.The marks for each rotation are detailed in table There were no statistically significant differences in marks in any of the between the three students in this pilot study and those students in the rural teaching hospitals or metropolitan hospitals.Student evaluation data showed no variation by geographic location in satisfaction with the course. However, there were differences in experiences between the pilot study students and their hospital based counterparts. Discussions with the students and their supervisors suggested that while the overall range of clinical conditions seen was essentially similar to their hospital based counterparts, there was a distinct frequency bias towards community based chronic disease. Pilot study students had the opportunity to participate in continuity of care, following the progress of individual patients over a considerable period of time. They were also able to follow their patient across multi-professional boundaries, from the community to the local hospital and in some cases accompany them to the regional hospital and participate in the surgical care they received there.On completion of the year, all 3 (100%) students remained in the same geographical region and attended the rural clinical school. In comparison, only 7 of the 22 (32%) students attending the rural clinical school in this region in year 3, continued to stay for year 4.This pilot study has demonstrated that it is possible for medical students to successfully complete the five core clinical rotations in an isolated rural general / family practice environment. However, addressing a number of apparent issues would assist further development of the program.The design of this pilot study exposed participating students to unusual levels of isolation, especially from their peers. Research into peer support has demonstrated that peer support helps to reduce student anxiety and stress and may improve students' confidence ,21 and tUnlike traditional teaching environments where a variety of clinical teachers contribute to teaching in any given subject, in this program a single general / family practitioner was given the onerous duty of providing the vast majority of the teaching. This was performed on a one to one basis in the context of isolated and usually very busy rural practice. Solo rural doctors could find the extra work associated with teaching to be unsustainable. However, unlike a traditional 4–6 week placement, the longitudinal nature of the program can deliver benefits to the practitioner's medical practice. Over time, the supervising GP develops a clear understanding of the strengths and weaknesses of the student and is able to allocate tasks for the student to perform under supervision that while facilitating learning are also service tasks. This can temper the workload of the supervisor, similar to the balance between service and teaching commonly seen in the post registration medical education environment.As one person provides most of the teaching in an environment with few if any other doctors, there is no real provision for backup if the primary teacher is incapacitated or absent. Although a temporary doctor may be found at short notice to provide patient services, it is unlikely this person would be equipped to seamlessly continue the teaching program. Utilizing group practices may be one solution to this dilemma, although these were generally unavailable in the pilot study region.Although the course was offered to 226 students, there were only three volunteers, a number quite acceptable for a pilot study of this nature. However, in a long term sustainable program of this nature, larger student numbers would be required to ensure a steady supply of students to interested practices, as there is the potential to gain or lose students at different points during the clinical years due to other factors, e.g. sickness, failure, changed family circumstances, etc. There may be economies of scale to be considered, considering the substantial infrastructure support required for the program, as well as enhanced opportunities for peer to peer interaction by distance with a larger cohort.This study has demonstrated the feasibility of teaching core clinical rotations in isolated rural areas. To maintain confidentiality, participant characteristics could not be described. Nonetheless, program effectiveness may be related to the characteristics of the self-selected participants such as gender and previous experience living and working in rural areas. Further studies, therefore, should be designed so that information about participant characteristics can be collected, reported and examined. These could also address the issues of student acceptance, teacher burnout and cost structure to assess the viability of expanding this program to a wider audience.The author(s) declare that they have no competing interests.SM shared executive responsibility for managing the project, analysed the results, prepared and reviewed the manuscript.LD was a clinical tutor, participated in the conception, shared executive responsibility for managing the project, prepared and reviewed the manuscript.VY analysed the results, prepared and reviewed the manuscript.The pre-publication history for this paper can be accessed here:


The incidence of hip fracture is expected to increase during the coming years, demanding greater resources and improved effectiveness on this group of patients. The aim of the present study was to evaluate the effectiveness of an integrated care pathway (ICP) in patients with an acute fracture of the hip.A nonrandomized prospective study comparing a consecutive series of patients treated by the conventional pathway to a newer intervention. 112 independently living patients aged 65 years or older admitted to the hospital with a hip fracture were consecutively selected. Exclusion criteria were pathological fracture and severe cognitive impairment. An ICP was developed with the intention of creating a care path with rapid pre-operative attention, increased continuity and an accelerated training programme based on the individual patient's prerequisites and was used as a guidance for each patient's tailored care in the intervention group (N = 56) The main outcome measure was the length of hospital stay. Secondary outcomes were the amount of time from the emergency room to the ward, to surgery and to first ambulation, as well as in-hospital complications and 30-day readmission rate.The intervention group had a significantly shorter length of hospital stay , a shorter time to first ambulation , fewer pressure wounds  and medical complications  than the comparison group. No readmissions occurred within 30 days post-intervention in either group.Implementing an ICP for patients with a hip fracture was found to significantly reduce the length of hospital stay and improve the quality of care. Hip fractures represent an increasing health problem in the Western world, mainly because the aging world's population. For instance, in the USA 350,000 incidents per year occur  and in tet al. [Changes in health status involve a process of transition . Recoveret al.  found thWe have recently shown that despite age and health status, patients with a hip fracture had a strong will to recover, although they used different strategies to engage in the rehabilitation process . These sThe aim of the present study was to evaluate the effectiveness of an ICP in patients with an acute fracture of the hip. The main outcome measure was the length of hospital stay; secondary outcomes were time from admission to the ward, operation, first ambulation, in-hospital complications and 30-day readmission. It was hypothesised that by coordinating and individualising the care path from admission to first ambulation and implementing a structured controlled training program it would be possible to reduce length of hospital stay and to decrease the number of medical complications.A nonrandomized prospective study was conducted comparing an intervention group, guided by an ICP, with a comparison group, representing standard care . The comA previously conducted audit of hospital records of patients with a hip fracture indicated that the mean length of hospital stay was 31 days (SD 14.5) . We estiIndependently living ambulatory patients (with or without assistive devices) 65 years or older admitted to the hospital with an acute hip fracture were consecutively selected. Exclusion criteria were pathological fracture and severe cognitive impairment as assessed by the Short Portable Mental Status Questionnaire (SPMSQ) . ApproxiAll patients were interviewed by a nurse and demographic information was gathered on age, social status, type of living and degree of independence before the fracture using the Functional Recovery Scale (FRS) ,22. The The intervention was developed with the intention of creating a care path with rapid pre-operative attention, increased continuity and an accelerated training programme without disturbing the flow of patients with other diagnoses. ICP documentation was developed in the form of a check list that displayed what to do and when to do it. Furthermore, the ICP covered all the critical elements of care and rehabilitation. The discharge plan, based on the patients' pre-fracture functioning, was developed within the first 48 h after admission. Long-term goals and intermediate goals were discussed with the patients' and their relatives in order to obtain a spirit of understanding. The nurses collaborated with the patients and their families throughout the hospital stay and were responsible in arranging contact with the communities' help service to secure the necessary training and support. As a part of the intervention, patients in the intervention group were transferred for medical reasons only and remained on the orthopaedic ward until they had attained an ADL level equivalent to their pre-fracture level, or until they did not progress further in their rehabilitation. No patient in the intervention group was transferred to other wards.Before the start of the intervention, staff in the emergency room and radiology department was encouraged to attend and treat these patients rapidly so they could be admitted to the ward and prepared for surgery as soon as possible. Post-operatively, the earliest first ambulation was encouraged . The training was then increased in accordance with the individual patient's prerequisites, although balancing between training and rest. Common rehabilitation interventions include providing advice, training, encouragement and listening to patients' concerns as well as drug treatment, physiotherapy, occupational therapy and help with use of appliances, equipment and daily living aids Figures  and 2.Parametric data were analysed with Student's t-test for independent groups while non-parametric data were analysed using Fisher's exact test and Chi-Square. Statistical significance was set to p < 0.05The two study groups did not differ in any of the pre-fracture demographic variables Table . The meaTime spent at the different pre-operative ICP steps was measured and compared. The intervention group spent less time waiting at the emergency room before receiving care on the ward as compared with the control group  and less time waiting for surgery The intervention group spent significantly less time between surgery to first ambulation , as well as from arrival to hospital to first ambulation .Contrary to the comparison group, significantly fewer patients in the intervention group developed complications: pressure wounds  and medical complications Data on physical functioning, ambulatory capacity and dependency on walking aids at discharge are shown in Tables The present study showed that our ICP was associated with a significantly shorter hospital stay, i.e. the number of care days was reduced by half compared with the comparison group. Despite a shorter hospital stay, the intervention group had better physical functioning and a higher ADL level. In the intervention group 25% more patients reached or approached their pre-fracture ADL level. Moreover, the intervention group was less dependent on walking aids, equal in gait capacity and more of the intervention patients returned to their former residence Figures  and 2. TThe randomised controlled trial design is considered the gold standard for evaluating interventions; however, its use in studies of this kind is somewhat problematic because such a design involves interactions between the patients and nurses. If two wards are used, it is difficult to know whether it was the change of actions or the interactions between the nurses and patients that contributed to any differences. In most studies a before-and-after design is preferred. The present study was carried out using a nonrandomized prospective design in which an intervention group was compared with a standard care group . A disadet al. [et al. [et al. [et al. [The results of the present study are largely consistent with those reported in similar studies of ICPs in patients with a hip fracture ,14,16,23et al.  found th [et al.  found thICPs, which are designed to streamline and standardise various aspects of patient care, are structured multidisciplinary care protocols defining and specifying critical steps and progress in the care of various patient groups . In implWhen the ICP protocol in the present study was developed, it was decided to build on the patients' engagement from an earlier study . The hosThe ICP in the present study was effective. Although a significant reduction of time to first ambulation was achieved, the greatest effect was due to the care and attention given to the patients. Further investigation is needed to illuminate what components of the ICP are responsible for this reduction in care days and to determine whether there is an effect on one-year survival.The author(s) declare that they have no competing interests.LEO, JK, IE contributed to the development of the study protocol, design, data collection, statistical analysis, interpretation of data and preparation of the manuscript. All authors read and approved the final manuscript.


In Ecuador, the prevalence of HIV in the general population is approximately 0.3%. However, up to 17% prevalence has been reported among specific groups of homosexual and bisexual men. The objective of this study is to explore correlates of condom use among men who have sex with men (MSM) across eight cities in Ecuador.A cross-sectional survey design was used. A questionnaire including variables on sexual behaviour, demographics, and socio-economic characteristics was distributed to a sample of MSM in eight Ecuadorian cities.Information was obtained for 2,594 MSM across the eight cities. The largest subcategory of self-identification was active bisexuals (35%), followed by those who described themselves as "hombrados" . The mean age was 25 years, and the majority were unmarried (78%), with a median of 10 years of schooling (IQR 7 – 12). Regarding condom use, 55% of those interviewed had unprotected penetrative sex with each of their last three partners, and almost 25% had never used a condom. The most important correlates of condom use were single status, high life-skills rating, and high socio-economic status .Our data illustrate the urgent need for targeted HIV-prevention programs for MSM populations in Ecuador. MSM have the highest HIV prevalence in the country, and condom use is extremely low. It is imperative that prevention strategies be re-evaluated and re-prioritized to more effectively respond to the Ecuadorian epidemic. In Latin America, the predominant group of individuals with HIV/AIDS is men who have sex with men (MSM). Despite the feminization of this epidemic in several Latin American countries in recent years, the highest infection rates remain among MSM, both in the gay community as well as among men who do not self-identify as homosexual or bisexual, but engage in penetrative sex with male partners .Currently, there is a dearth of information on risk behaviours among MSM in Ecuador, and few explanations of why the epidemic remains so confined to this population. Given the evidence of high prevalence of bisexual behaviour, authors have postulated that the bisexual population could function as a bridge to the heterosexual population -5. ComprThe available data point to high levels of HIV infection in MSM in Ecuador. A sero-survey performed between 1999 and 2002 with 632 MSM in Ecuador as part of a regional project revealed an HIV-1 seroprevalence of 17%, the fourth highest among the countries studied so far. A seroprevalence of 23% was observed for MSM aged 25 to 29 years. Factors associated with infection included more sexual partners and a history of sexually transmitted infections (STI) [To illustrate the lack of publications relating to MSM in Ecuador, searches for "Ecuador" and "MSM, homosexual, or gay", in the U.S. National Library of Medicine yielded only two references, which are both cited in this report, and 12 documents from AEGIS  , includiGiven the epidemiological situation and lack of data on sexual behaviour in this group, which plays such a central role in the dynamics of the regional epidemic, it is vital to obtain more population-specific information to inform decisions on policy, programming, and intervention design. Significant factors in the context of many developing countries include the relative lack of a gay identity, as well as antagonistic attitudes towards same-sex sexual practices. Therefore, successful prevention campaigns should consider particular strategies that will effectively target MSM in a context of discrimination and marginalization.The objective of this report is to present information from a survey of MSM behaviour in eight cities in Ecuador. The survey was implemented in the context of evaluating the Frontiers Prevention Project (FPP), an HIV prevention initiative focused on key populations that was designed with the active participation of the target populations.We performed a survey of MSM and SW in eight Ecuadorian cities . These cities were selected on the limited data available on STI and HIV prevalence as well as the views of Ecuadorian NGOs working with MSM and AIDS regarding the distribution/concentration of MSM risk behaviour among large and medium-sized cities.On one hand, the baseline survey aimed to inform the design and implementation plan for prevention activities within the FPP. On the other hand it established a point of comparison to allow the measurement of whether, and to what extent, the project has an impact, as compared to the changes that occur over the course of the project in the absence of FPP interventions. The overall framework of the evaluation is broader than the scope of this paper; the methodology described here will be limited to the aspects relevant to the analysis presented below.The study was approved by the Institutional Review Boards (IRB) of the National Institute for Public Health in Mexico (INSP), the National Health Council in Ecuador, and the International HIV/AIDS Alliance in the United Kingdom.The target population was defined as MSM within feasible reach of prevention activities. Feasibility was related to meeting place attendance. In order to estimate the size of the target populations, a mapping exercise was undertaken in each city. Members of the populations under survey visited the selected cities and, with the help of the local population and other key informants, mapped the sites where MSM were concentrated, while simultaneously providing numerical estimates of the populations in each of these areas.Total sample size was estimated, based on the expected differences in condom use rate at the end of the project, and adjusting for the design effect of cluster sampling, since the unit of randomization was cities.Results of the mapping were applied to assign sample size by city, although it should be highlighted that mapping data primarily disclosed numbers of easily accessible MSM, that is, individuals frequenting common meeting spots for these groups.The questionnaire was developed by an international multidisciplinary and inter-institutional team. The design process was coordinated by the lead researcher responsible for the FPP evaluation, and included an active collaboration of local researchers, as well as key local stakeholders, particularly members of the populations under survey.This questionnaire was designed to provide a comprehensive image of MSM and their contexts, including socio-demographic information , data on sexual behaviour , information on existing regular partners, knowledge about HIV/AIDS and STDs in general, and attitudes towards people living with HIV.To ensure suitability of language and context, a series of focus group discussions and in-depth interviews with MSM were performed. Data collection took place between July and September 2003. Anonymous face-to-face interviews were conducted with participants. Most interviews took place in locations frequented by MSM when away from work, while others were conducted in work places. Since names were not registered, data cannot be linked to specific individuals. Each hot-spot was visited once and before starting an interview, potential respondent was asked to confirm that he had not been interviewed before for this project.Before the commencement of each interview, the aim of the study was explained to potential candidates. Written informed consent was obtained from all participants. The participants were asked to sign or mark the consent form to indicate their consent. No attempt was made to validate the signature against any formal identification; the signature or mark was not scanned or otherwise captured in the electronic database; and the paper versions of the consent forms and questionnaires were secured in locked storage after data entry. A copy of the informed consent form was provided to each individual, which included contact information for the researchers.Data from the questionnaires were digitalized with a data entry interface using LSD software  previously used for complex surveys. As a way of guaranteeing data quality – specifically, conformity to information in the printed questionnaires – all surveys were entered twice, and inconsistencies in the first digitalization were revised against the printed forms and corrected. Variables included in the analysis were reviewed to eliminate outlier values. The resulting database was transferred to STATA 8.0 for analysis.Descriptive statistics were generated for the socio-demographic characteristics of MSM and reported rates of condom use. To examine associations between condom use with last each of the 3 partner and socio-demographic variables, logistic regression models were estimated, with condom use with each of the 3 last partners as a dependent variable, using an encounter panel allowing up to 3 observations per MSM. A significance level of 95% was applied for all analyses.For descriptive statistics as well as regression, the design effect of cluster sampling was taken into account to estimate robust errors. The multivariable model applied to identify association with condom use was estimated using town fixed effects and random effects by MSM.To facilitate inclusion in the multivariable model and interpretation of estimates, continuous variables were categorized into age, years of sexual life, years of schooling, and price paid for condoms. In each case, between three and four groups were created, according to the observed variable distribution. Additionally, three indices were generated and included in the model, specifically, socio-economic level, social capital, and life skills.A socio-economic index was created using a polyserial correlation model with net income, possessions, and level of education as principal components. The resulting scores obtained with the principal components methodology were categorized in quartiles.The social capital indicator was established using variables indicative of the MSM perception of the support they could receive in specific situations, while the life skills indicator was generated by taking into consideration variables focusing on self-perception of empowerment for condom use. The methods used for these two indices were analogous to those applied for a similar study in India .All variables were introduced simultaneously in the model. Interactions between variables were explored, in particular those between social capital and life-skill indexes, and socioeconomic level and condom price categories.Since it is argued that in the interpretation of odds ratios there is a tendency to over-estimate the risk (or protection) attributed to a variable , prevaleThe outcome variable for multivariate analysis was condom use, defined as whether condoms were used during intercourse with a given partner, that is condom use with each of the last 3 times he had penetrative sex .Overall, 2,594 MSM from eight cities were interviewed, representing about 63% of those reported in the mapping . Because the design of the evaluation, sampling in the larger cities (Quito & Guayaquil) was a lower proportion of the mapped MSM (29%), while in the other cities the number of MSM interviewed was larger than those identified by the mapping.Table Table Regarding education levels, in addition to a high level of literacy (94%), the average years of schooling  reveals a population with more than primary education, with a large proportion of individuals completing higher-level studies.Only 10% of the MSM interviewed were involved in sex work . The majority worked in other fields, lived with their families (consistent with the reported age), and did not engage in remunerated activities.In terms of openness about sexual preferences, the observed tendency was greater awareness in the community than family. Thus, while 87% reported that the community was aware of their sexual preferences, only 29% assumed that their family knew.Despite the reportedly high community awareness of sexual preferences, which may be interpreted as a sign of acceptance, 25% confirmed aggression from the police due to their sexual identity.Although the average number of partners per week is small (an average of 1), 25% of interviewees reported they had never used a condom. Only 16% were aware of where free condoms could be obtained.Taking into account the last three sexual partners of each man interviewed, only 25% used a condom consistently with all three partners, and 55% never used a condom. Finally, 30% of the most recent sexual partners were women.Bivariate and multivariate associations with condom use at each of last 3 partners are shown in Table The prevalence ratio for condom use among unmarried in relation to married subjects was 5.45 (95% CI 4.236–6.37), and 0.9 for a female partner (95% CI 0.81 – 0.99). Data on age and education obtained from multivariate or bivariate analyses were not statistically significant.The reported condom price was strongly correlated with condom use, suggesting that a higher cost significantly reduces use. It is important to highlight that this occurs in a model including the socio-economic level, and thus the issue is not the absolute cost of the condom, but rather its relative price.MSM who reported a higher number of partners in the preceding week (five or more) used a condom more often , although the effect was minor.Alcohol consumption was not associated with condom use, either positively or negatively, and neither was family awareness of sexual preference.MSM are more likely to use a condom with new partners than those they already know. Life skills also correlated strongly with condom use. However, the social capital indicator employed is not associated with the use of condoms.Finally, the socio-economic level plays an important role, and is directly proportional to the use of condoms. In this case, a dosage effect is not clear, but MSM belonging to the higher half of the socio-economic divide use condoms more often. Significantly, this result was obtained by controlling for education level and condom price.The results presented reveal a low proportion of protected sexual intercourse in a large sample of Ecuadorian MSM, confirming that these groups are highly vulnerable in terms of STI and HIV. In fact, almost one-quarter of the participants reported that they had never used a condom. More than half the participants had unprotected sex with their last 3 partners, while only a quarter used a condom with all 3 partners. These data are consistent with other studies on MSM in the region, which reveal low proportions of condom use.In terms of characteristics associated with condom use, a significant correlation was evident with the socioeconomic level, but not years of schooling. The data suggest that the effect of the socioeconomic level has more to do with wealth and less with education. This is reinforced by the observed association with condom price. Specifically, access to condoms is limited by economic capacity. While it is important to investigate why this happens even among higher socio-economic strata, an initial strategy should focus on increasing access to free condoms.Similarly, the relationship between socio-economic level and condom use indicates the need for more comprehensive prevention strategies. Other studies have established a correlation between economic limitations among MSM and HIV infection .We additionally observed a strong association between life skills  index and condom use. Life skills improvements require enhanced self-esteem, which is potentially one path for preventive interventions. Further research into the effects of social capital is required.Another important aspect is the potential bridge between MSM  and the general population by means of bisexual contact. Condom use is lower among those who report being married to a woman, and even more so when the sexual partner is a woman. Given the biological susceptibility of women to STDs, this behavior could spread infection outside MSM communities.The HIV/AIDS epidemic in Ecuador is largely confined to the MSM population, as is the case in most Latin American countries. Nevertheless, recent years have seen a trend towards feminization of the epidemic that may be related to a high prevalence of bisexual MSM in the region, as illustrated in the results of this survey .The population included in the MSM category is a very heterogeneous group. The width of the confidence intervals reflects important differences with regard to city, which need to be integrated in the design of interventions. For example, the percentage of MSM who had never used a condom varied from 4% to 38%, depending on the city.The participants of the survey turned out to be a young and reasonably well-educated population, with an average of almost 10 years of schooling. Consistent with the profile of the group in the region, bisexuality was very common. In fact, a fifth of participants were married, and almost a quarter were parents. This specific profile needs to be considered for prevention, since messages focusing on men having sex exclusively with other men may not be adequate to target this population. Importantly, meeting places identified in this survey provide an avenue for reaching a broad spectrum of MSM, who are important channels for communicating information. The fact that more than 90% of this heterogeneous population is literate also provides an opportunity to use more complex and targeted messages.While the interpretation of "community" is currently ambiguous, 87% of participants disclosed that their sexual preference was known in the community, while only 29% reported the same with respect to their family. This suggests a double life, which also has implications for prevention. It is important to distinguish prevention messages in environments where these individuals are in their MSM life from those in their heterosexual life. It also highlights the importance of providing information within the context of an environment that can be hostile to same-sex sexual behaviour.It is important to acknowledge the limitations of these results, which are due, in part, to the type of sample as well as the analysis performed. Firstly, although every effort was made to include a representative sample of all MSM in the cities, it was, at best, a model of the most accessible MSM at the moment of the survey. Since we performed a cross-sectional analysis, causality was not attributed to proposed independent variables. Although we believe it unlikely that some men were interviewed twice , no systematic effort was made to exclude repeat interviews.With any stigmatized population there are concerns about how potential stigma and discrimination may have introduced participation bias. Despite assurances of anonymity, potential respondents who are more worried about possible breaches of confidentiality may have been less likely to participate in the survey. It is difficult to speculate about the likely direction of such bias. On the one hand it may be that those most worried about disclosure are men who lead heterosexual lives and rarely venture into MSM venues. Or, one could argue that men at highest risk, those selling sex or using drugs, may be most wary of law enforcement and may be less likely to participate in the survey.The low levels of condom use in a high HIV-prevalence population necessitate urgent and immediate action. Preventive interventions, including revision of mechanisms to promote condom use that do not seem to be working, must be a priority in this population. MSM is the population group in Latin America most affected by this epidemic, and yet public health actions have been neither appropriate nor sufficient . The resThe author(s) declare that they have no competing interests.JPG conceived the idea of this report, contributed to the design of the study, designed and led the analysis and interpretation of data, and drafted the manuscript. DM, KM & FS contributed to the idea of the report and study design, and assisted in drafting of this manuscript. SMB led the study design, and contributed to the idea, as well as the design, interpretation and drafting of this report. All the above authors read, commented on, and approved the final version of the document.The pre-publication history for this paper can be accessed here:


It is generally believed that exhaustive searches of bibliographic databases are needed for systematic reviews of health care interventions. The CENTRAL database of controlled trials (RCTs) has been built up by exhaustive searching. The CONSORT statement aims to encourage better reporting, and hence indexing, of RCTs. Our aim was to assess whether developments in the CENTRAL database, and the CONSORT statement, mean that a simplified RCT search strategy for identifying RCTs now suffices for systematic reviews of health care interventions.RCTs used in the Cochrane reviews were identified. A brief RCT search strategy (BRSS), consisting of a search of CENTRAL, and then for variants of the word random across all fields (random$.af.) in MEDLINE and EMBASE, was devised and run. Any trials included in the meta-analyses, but missed by the BRSS, were identified. The meta-analyses were then re-run, with and without the missed RCTs, and the differences quantified. The proportion of trials with variants of the word random in the title or abstract was calculated for each year. The number of RCTs retrieved by searching with "random$.af." was compared to the highly sensitive search strategy (HSSS).The BRSS had a sensitivity of 94%. It found all journal RCTs in 47 of the 57 reviews. The missing RCTs made some significant differences to a small proportion of the total outcomes in only five reviews, but no important differences in conclusions resulted. In the post-CONSORT years, 1997–2003, the percentage of RCTs with random in the title or abstract was 85%, a mean increase of 17% compared to the seven years pre-CONSORT . The search using random$.af. reduced the MEDLINE retrieval by 84%, compared to the HSSS, thereby reducing the workload of checking retrievals.A brief RCT search strategy is now sufficient to locate RCTs for systematic reviews in most cases. Exhaustive searching is no longer cost-effective, because in effect it has already been done for CENTRAL. Literature searching for systematic reviews of interventions in health care has been largely based on finding all randomized controlled trials (RCTs), as this study design is considered the gold standard. However RCTs make up only a very small proportion of all the articles included in bibliographic databases, and so the problem for systematic reviewers has been to devise a search strategy which is sensitive enough to find all the RCTs, but specific enough not to bury them in a large number of other unwanted retrievals needing to be manually excluded.Two developments have facilitated searching for RCTs. The first is CENTRAL , the world's most comprehensive database consisting exclusively of controlled clinical trials. It currently contains over 425,000 citations. The majority of the trials in CENTRAL have been identified through systematic searches of MEDLINE and EMBASE. The first two phases of a three phase highly sensitive search strategy (HSSS) have been used to search MEDLINE . CENTRAL"it may still be worthwhile for reviewers to search MEDLINE using the Cochrane highly sensitive search strategy and to obtain and check the full reports of possibly relevant citations" [Because identification has relied solely on the titles and, where available, the abstracts, some relevant trials may not have been identified. Therefore, the Cochrane Handbook says tations" . HoweverThe second development is the CONSORT statement, introduced in 1996 , and sinItem 1 on the CONSORT checklist recommends that the method in which participants were allocated to interventions  is described in the title and abstract. This allows instant identification of RCTs, and should help ensure that a study is appropriately indexed as an RCT in bibliographic databases.As the Cochrane Collaboration has already done exhaustive work to ensure that CENTRAL is as complete as possible, we wanted to examine whether this eliminates the need for individual reviewers to run the HSSS, and the effectiveness of replacing this with a simplified search strategy.1. To determine the effect on the results of Cochrane reviews of using a brief RCT search strategy (BRSS).2. To examine the change in use of variants of the word random in the title or abstract of journal articles, pre- and post-CONSORT.All reviews new to the Cochrane Database of Systematic Reviews in the Cochrane Library 2004 issue 2 were selected. Those that stated that they were considering only RCTs, and which found at least one RCT, were selected.All trials included in each review were identified from the section 'References to studies included in this review'. Each trial was checked to determine whether it was indexed in CENTRAL , and then MEDLINE. If not in either of these databases, EMBASE was checked.The full bibliographic records of all trials that were in either MEDLINE or EMBASE (using the OVID interface) were examined to determine whether random$ was in any field. .The full papers of any trials that were: 1) not in CENTRAL, or 2) did not have random$ in any field in the bibliographic record, were obtained and checked to see whether they were actually RCTs. All non-English articles were translated, apart from those in Japanese and Chinese, as resources were not available.The impact of omitting the RCTs not found with the BRSS was quantified, using Review Manager 4.2.7. The forest plots for the meta-analyses were reproduced, both with and without data from the missing trials, and the results compared to see if omission would make any important difference. The differences could theoretically include;a) There might be less, or no data left, for some outcomes.b) There could be a different result; no benefit over comparator, or vice versa.c) There could be the same result, but with a different effect size.d) There could be the same result and effect size, but with a wider confidence interval, and possibly loss of statistical significance.In summary, the BRSS would involve: 1) searching CENTRAL, and 2) supplementing that with a search of MEDLINE and EMBASE, using a search of 'random$.af.' to pick up trials not in CENTRAL.There were 78 new reviews, of which 57 met the inclusion criteria. They cited a total of 920 trials; 79% (725) were journal articles. The remaining 21% were from the grey literature, 80% of these being conference abstracts).Twenty one reviews were excluded from our study; 14 because they did not find any RCTs that met their inclusion criteria, and seven because they included other study designs in addition to RCTs.It was found that 93.3% (677) of the 725 journal articles included in the systematic reviews were in CENTRAL. It was assumed that these were all RCTs, but this was not checked due to the large numbers involved (and it was not relevant to the aims of the study). This left 48 journal articles not indexed in CENTRAL.The full texts of all 48 of these articles (apart from the four in Japanese and five in Chinese) were translated and checked. It was found that 40 were RCTs, and the remaining eight used non-RCT study designs. (It was assumed that the untranslated articles were RCTs). Eleven of the 40 RCTs were found by searching MEDLINE or EMBASE with 'random$.af'. Therefore, 29 (4%) of RCTs would not have been found with the BRSS.The 29 trials were distributed over 12 reviews. Ten were in MEDLINE, 11 in EMBASE only. Twelve were non-English language.In two reviews ,7, each Therefore, this leaves 27 missing journal articles, in 10 separate reviews that contain at least one trial with data not found by the BRSS. Table Only one review did not do a meta-analysis The nineTwo consequences of missing data were found:1) In three reviews -15, the 2) In three reviews -17, the For the period 1966 to October, 2004, the HSSS search strategy retrieved 2,505,742 records in MEDLINE, compared to 'random$.af.', which retrieved 399,208 records. Therefore, only 16% of the number of records were found using 'random$.af.', compared to HSSS.Using the 725 journal articles in our sample, we compared the frequency of random$ in the title or abstract between pre-CONSORT (published up to 1996) and post-CONSORT trials (published from 1997 onwards). Figure In the post-CONSORT years, 1997–2003, the term appeared in 85% of the titles or abstracts, compared to 68% in the seven years before CONSORT (1990–96); mean difference was 17% . If a longer pre-CONSORT period is used, 1980 to 1996, the proportion is similar at 62%.Using the BRSS, rather than the much more exhaustive HSSS, to retrieve RCTs in journal articles for Cochrane reviews, affected only a very small percentage of total outcomes of a few reviews, and made no important difference to the conclusions of these reviews. The most affected review had four of the five included trials published in Chinese .The CONSORT statement appears to be associated with a significant increase in the frequency of random in the titles and abstracts of journal articles. Whether this is directly due to CONSORT, or whether CONSORT simply accelerated a pre-existing trend, and raised the general awareness amongst authors and editors for better reporting of RCTs, is uncertain. This improved description of RCTs by authors should mean that all RCTs are indexed with the appropriate publication type in MEDLINE, and also result in more sensitive retrieval of RCTs using the BRSS.The BRSS had a sensitivity of 96% for RCTs in journal articles. Compared to the HSSS, the BRSS reduced the MEDLINE retrieval by 84%. This would represent a major time and cost saving in manual screening.quantified the impact of omitting trials not found with the simplified search.The strengths of this study include firstly that we used Cochrane reviews, as they approximate the 'gold standard' in searching, due to the requirement for exhaustive searches. Hence we can be fairly certain that we were starting with as comprehensive set of included trials as possible. Secondly, we A weakness of this study was that we could not check whether the RCTs would have been in CENTRAL at the time the searchers did their searching, and hence eliminate the possibility that some RCTs were first identified by the reviewers, and then passed to CENTRAL. However, given the extensive searching routinely done for CENTRAL, it is highly likely most RCTs would be identified sooner or later, and therefore be included in a subsequent update of the review.A range of subject areas was included, which helps with generalisability, though it may decrease power in any one subject area. However, a recent study on identifying quality RCTs in pain relief gives general support to our findings . It inveThis study focused only on a simplified search strategy for retrieving RCTs in journal articles, since these made up the vast majority of the references used in Cochrane reviews, and are most important in terms of the quality and quantity of assessable data available. By contrast, most grey literature (the vast majority of which is meeting abstracts) gives very limited data. However, CENTRAL includes many grey literature trials, so these will be identified with the BRSS.There are currently over 2200 Cochrane reviews, and these will need maintaining in the future. Authors may be encouraged to update their reviews, if they can be confident they can identify RCTs comprehensively with a simple search. The simplified search may also be useful for those doing reviews in a tight timescale, or by clinicians who just want a rapid but reliable answer to a question. There is a case for the 'not quite perfect but rapid, easy and almost complete' search'.In practice, some of the few trials missed by the BRSS were small or of poor quality, and as Egger and colleagues have reported, the last few studies found by exhaustive searching could introduce bias, by being of poor quality .The issue is whether the marginal benefits of exhaustive searching justify the extra costs. When the inclusion criteria demand only RCTS, this study suggests that exhaustive searching is now, in the era of CENTRAL and CONSORT, no longer cost-effective.The author(s) declare that they have no competing interests.PR conceived and designed the study, and analysed the data. NW helped with interpretation and with drafting the paper. Both authors approved the final versionThe pre-publication history for this paper can be accessed here:


How nanotechnology can be harnessed to address some of the world's most critical development problems Nanotechnology can be harnessed to address some of the world's most critical development problems. However, to our knowledge, there has been no systematic prioritization of applications of nanotechnology targeted toward these challenges faced by the 5 billion people living in the developing world.In this article, we aim to convey three key messages. First, we show that developing countries are already harnessing nanotechnology to address some of their most pressing needs. Second, we identify and rank the ten applications of nanotechnology most likely to benefit developing countries, and demonstrate that these applications can contribute to the attainment of the United Nations Millennium Development Goals (MDGs). Third, we propose a way for the international community to accelerate the use of these top nanotechnologies by less industrialized countries to meet critical sustainable development challenges.http://www.panacea-biotec.com/products/products.htm)  is conducting novel drug delivery research using mucoadhesive nanoparticles, and Dabur Research Foundation  is participating in Phase-1 clinical trials of nanoparticle delivery of the anti-cancer drug paclitaxel [http://www.sani.org.za) is a national network of academic researchers involved in areas such as nanophase catalysts, nanofiltration, nanowires, nanotubes, and quantum dots . The final Delphi round was devoted to consolidating consensus by re-ranking the top ten of the 13 choices obtained in the previous round and to gathering concrete examples of each application from the panelists.Our results, shown in To further assess the impact of nanotechnology on sustainable development, we have compared the top ten applications with the UN Millennium Development Goals . The MDGWhat can the international community do to support the application of nanotechnology in developing countries? In 2002, the National Institutes of Health (NIH) conceptualized a roadmap for medical research to identify major opportunities and gaps in biomedical investigations. Nanomedicine is one of the areas of implementation that has been outlined to address this concern. Several of the applications of nanotechnology that we have identified in our study can aid the NIH in this process by targeting the areas of research that need to be addressed in order to combat some of the serious medical issues facing the developing world.To expand on this idea, we propose an initiative, called “Addressing Global Challenges Using Nanotechnology,” to accelerate the use of nanotechnology to address critical sustainable development challenges. We model this proposal on the Foundation for the NIH/Bill and Melinda Gates Foundation's Grand Challenges in Global Health , which iA grand challenge is meant to direct investigators to seek a specific scientific or technological breakthrough that would overcome one or more bottlenecks in an imagined path to solving a significant development problem  . A scienUnleashing Entrepreneurship: Making Business Work for the Poor [The funding to address global challenges using nanotechnology could come from various sources, including national and international foundations, and from collaboration among nanotechnology initiatives in industrialized and developing countries. These funds could be significantly increased if industrialized nations adopted the target set in February 2004 by Paul Martin, Prime Minister of Canada: that 5% of Canada's research and development investment be used to address developing world challenges . In parathe Poor  underscoPerhaps most importantly, our results can provide guidance to the developing countries themselves to help target their growing initiatives in nanotechnology . The goaTable S1(43 KB DOC).Click here for additional data file.−9 of a meter), that is, at the atomic and molecular levels, and the exploitation of novel phenomena and properties of matter at that scale.Nanotechnology is the study, design, creation, synthesis, manipulation, and application of functional materials, devices, and systems through control of matter at the nanometer scale (1–100 nanometers, one nanometer being equal to 1 × 10