The doubling of the number of people with dementia in the coming decades coupled with the rapid decline in the working population in our graying society is expected to result in a large decrease in the number of professionals available to provide care to people with dementia. As a result, care will be supplied increasingly by untrained informal caregivers and volunteers. To promote effective care and avoid overburdening of untrained and trained caregivers, they must become properly skilled. To this end, the European Skills Training and Reskilling (STAR) project, which comprised experts from the domains of education, technology, and dementia care from 6 countries , worked together to create and evaluate a multilingual e-learning tool. The STAR training portal provides dementia care training both for informal and formal caregivers.The objective of the current study was to evaluate the user friendliness, usefulness, and impact of STAR with informal caregivers, volunteers, and professional caregivers.For 2 to 4 months, the experimental group had access to the STAR training portal, a Web-based portal consisting of 8 modules, 2 of which had a basic level and 6 additional modules at intermediate and advanced levels. The experimental group also had access to online peer and expert communities for support and information exchange. The control group received free access to STAR after the research had ended. The STAR training portal was evaluated in a randomized controlled trial among informal caregivers and volunteers in addition to professional caregivers (N=142) in the Netherlands and the United Kingdom. Assessments were performed with self-assessed, online, standardized questionnaires at baseline and after 2 to 4 months. Primary outcome measures were user friendliness, usefulness, and impact of STAR on knowledge, attitudes, and approaches of caregivers regarding dementia. Secondary outcome measures were empathy, quality of life, burden, and caregivers’ sense of competence.STAR was rated positively by all user groups on both usefulness and user friendliness. Significant effects were found on a person-centered care approach and on the total score on positive attitudes to dementia; both the experimental and the control group increased in score. Regarding empathy, significant improvements were found in the STAR training group on distress, empathic concern, and taking the perspective of the person with dementia. In the experimental group, however, there was a significant reduction in self-reported sense of competence.The STAR training portal is a useful and user-friendly e-learning method, which has demonstrated its ability to provide significant positive effects on caregiver attitudes and empathy. The European Union (EU) is set to face major demographic challenges in the coming decades. Two main drivers for this are the (expected) doubling of the number of people with dementia and a rapid relative decline in the working population. In the Netherlands, for example, this is expected to change from a ratio of 1:42 for people with dementia to working people in 2010 to 1:16 in 2050 [In an attempt to address this, e-learning interventions could prove to be a useful tool to assist informal caregivers, untrained volunteers, and professionals by offering them relevant education, training, and support ,3 at a sPilot studies offering an Internet-based program of learning for dementia caregivers found that the caregivers who evaluated it reported it as useful, educational, and convenient  and founDiagnostic and Statistical Manual of Mental Disorders  [The European STAR project (2010-2014), funded by the European Commission in the Leonardo da Vinci Life Long Learning Programme, aimed to improve the knowledge about dementia for informal caregivers, volunteers, and professionals in dementia care by developing and evaluating an online training program in different languages and at different difficulty levels. The course content was developed from 3 theoretical perspectives: (1) the medical model of dementia, including information on types of dementia, symptoms, and diagnostics based on the evision) ; (2) theevision)  and how evision) . The conTo this end, the STAR training portal was designed and developed  to offerA collection of 8 modules on different topics in dementia care: 2 at a basic level and 6 at an intermediate and advanced level  and 3;A Learning Path Advisor through an online tool integrated in STAR that assesses baseline knowledge and confidence to help people decide at which point to start the course; andFacebook and LinkedIn communities to promote peer support and provide opportunities to contact other dementia care professionals.The developed course is currently available for a nominal fee. It is fully available in English and Dutch with translation into Swedish, Italian, and Romanian underway at the time of writing this paper.After development and testing of the training portal and e-learning course material during the first phase of the STAR project, the STAR training portal was evaluated in a randomized controlled trial (RCT) in the Netherlands and the United Kingdom from May 2013 to March 2014. The primary aim of this evaluation was to assess STAR’s usefulness, user friendliness, and impact on knowledge. Because the themes of the course, in addition to factual knowledge on the dementia syndrome, focus greatly on dealing with dementia and understanding dementia , the impact on empathy, attitudes, and sense of competence were studied as well. The aim of this paper is to describe the results of these different types of user evaluations.An RCT design was used to assess the effectiveness of STAR among Dutch and English users. Participants were randomly assigned to either a group that could participate directly in the STAR training or to a group that had to wait for 4 months before they could register (free of charge) for the STAR training. Participants followed the course at their own pace; however, within a specified period of 4 months. Pretest data were gathered and follow-up data were collected after 2 to 4 months of finalizing the course in the experimental condition and after the same period in the waiting list group (control condition).Participants were caring for someone with dementia as an informal caregiver, a volunteer in dementia care, or a professional caregiver, and were living in either the Netherlands or in the United Kingdom. Participants in the Netherlands were recruited through meeting centers for people with dementia and their caregivers, regional branches of the national Alzheimer’s organizations, case managers, care organizations, and via announcements through several informative websites targeted at informal caregivers, volunteers, and those with an interest in dementia. In the United Kingdom, participants were recruited through caregivers’ cafes, church groups, university service users and caregiver groups, and local dementia care and welfare organizations.Because STAR was developed both for informal caregivers (family caregivers and volunteers) as well as professional caregivers, participants who fulfilled the following criteria were recruited for the evaluation study: (1) were sufficiently computer literate to utilize the STAR website and (2) were currently an informal caregiver for someone with dementia living in the community, or a volunteer working with people with dementia with direct contact with community-dwelling people with dementia, or a professional caregiver for people with dementia with direct contact with community-dwelling people with dementia.The STAR platform was designed to be accessible through any Internet-enabled device so users could access the course at any time and place of their convenience. The STAR training portal consists of an online course with 8 modules relating to different topics. These topics were selected to cover a wide range of topics relating to dementia and dementia care. The modules consist of text, videos, interactive exercises, knowledge tests, and also include references to other websites, literature, and videos.The themes covered in the modules are as follows:What is dementia?Living with dementiaGetting a diagnosis and why it is importantPractical difficulties in daily life and how to help by best practiceThe emotional impact of dementia: how adaptation and coping influences behavior and moodSupport strategies to help people cope with consequences of dementiaPositive and empathic communicationEmotional impact and looking after yourselfBy answering questions from an interactive “learning advisor,” participants are provided with advice relating to which module and level to start with so they may follow what may be considered a personalized learning path through the modules. For example, professionals with earlier experience in dementia care could be directed to the advanced levels of the course , whereas informal caregivers who have never had to deal with dementia will be suggested to start their course with the basic modules on “What is dementia?” and “Living with dementia.” Caregivers can then follow their own learning path, either gradually working their way up to the more advanced levels or they can choose not to progress beyond the basic modules/knowledge.To ascertain what participants learn from the modules and to make the content more appealing, interactive exercises are included in the modules. These are used after each module at the basic and intermediate levels as quizzes to test level of knowledge. If an insufficient score is achieved in the quiz, participants are encouraged to reread the material and to try the quiz again following further learning.Participants randomly allocated to the STAR training group could follow all STAR modules and were invited to take part in their national community  on Facebook. They were explicitly asked to follow at least 4 modules, take part in the knowledge tests offered at the end of the modules, to complete the interactive exercises during the modules, and to watch a selection of videos that were offered in the modules.All questionnaires were offered online and were self-assessed in the participants’ own language. Background characteristics were inventoried for all participants. These were age, sex, relation to the person with dementia , time involved in care for the person with dementia, and prior experience with courses on dementia.For assessing usefulness and user friendliness, a questionnaire was composed specifically for this study, based on the Usefulness, Satisfaction, and Ease of use (USE) questionnaire  and onliThe primary outcome measures were knowledge on dementia and attitudes regarding dementia. Knowledge was measured with the Alzheimer’s Disease Knowledge Scale (ADKS)   . This quQuality of life was assessed with 2 distinct questions  and burden was assessed with 1 question. Finally, for sense of competence, the Short Sense of Competence Questionnaire   was usedParticipants, including informal caregivers , volunteers , and professional caregivers , in the Netherlands and United Kingdom were recruited through different partners (refer to Setting and Participants), both in person and through email. When people were interested in participating, a researcher provided them with additional written and oral information and a consent form. When a signed informed consent form was returned, the participants received a link to the online baseline questionnaire by email.After having filled in the questionnaires, participants in the Netherlands and the United Kingdom were randomized to either the experimental or the control group. Participants were randomized based on the following variables. In each country, strata for each participant group—informal caregiver, volunteer, and professional—and within these strata (1) for informal caregivers, spouse of a person with dementia or not and knowledge regarding dementia being low (ADKS score <19), average (ADKS 20-26), or high (ADKS >27), and (2) for volunteers, shorter or longer than half a year of work experience and, for professionals, education level high or low.Randomization software  was usedt tests).Descriptive analyses were performed to describe the baseline characteristics of the study population. Differences between the experimental group and the control group at baseline were analyzed with relevant difference tests  on the post-test data of the participants at 4 months, whereas pretest data were included as covariates. The background variables with baseline values that differed significantly between the experimental and control group and appeared to be related to one or more of the outcome measures  were also included in the analyses as covariates.In total, 142 persons participated in the STAR evaluation study. In the Netherlands, 85 people took part in the research. Of these, 50 persons were informal caregivers, 7 were volunteers in dementia care, and 28 were professional caregivers. In the United Kingdom, 57 people participated; 22 were informal caregivers, 17 were volunteers in dementia care, and 18 were professional caregivers. We grouped the informal caregivers and volunteers together as laypeople because of the relatively small number of volunteers. The background characteristics of the participants that completed both pretest and post-test measurements are detailed in During the pilot, 59 participants dropped out. The total response at post-test was 61%. Reasons for dropouts in the Netherlands (n=29) were no time (n=4) or unknown . Reasons for dropouts in the United Kingdom (n=30) were no time (n=1), no computer at home (n=1), or unknown . Due to a technical issue , one Dutch participant did not fill in the questions on usefulness and user friendliness, although he filled in all impact questions. Analyses to test differences in background characteristics between completers and dropouts indicated that for both formal and informal caregivers and volunteers there were no significant differences in age, gender, relationship, and duration of care/work between these groups. Furthermore, at baseline there were no statistically significant differences in background characteristics and primary outcome measures, such as knowledge, empathy, and approaches between the experimental and control group. For an overview of participants, refer to the flowchart in At post-test, participants from the experimental group (following the STAR training) were asked to indicate if they followed a particular module and, if so, to rate its usefulness on a scale from 0 to 10. These ratings are presented in The results on the opinions about usefulness of the different elements,  of the STAR training are shown in Analysis of logging files of the STAR training indicated that most of the STAR participants in the experimental group used the Learning Path Advisor. In the Netherlands, 73% of informal caregivers and 91% of professional caregivers used the Learning Path Advisor to obtain a personalized suggestion where to start in the course. In the United Kingdom, 9% of informal caregivers and 17% of professionals used the Learning Path Advisor.In 2) and on its subscale, person-centered care among laypeople , with a large effect size. For both cases, both the experimental group and the control group increased in score. Differences in baseline scores were accounted for by adding these as a covariate in the analyses. We did not find outliers at baseline that could explain this result. For the remaining primary outcomes (knowledge about and attitudes toward dementia), we did not find statistically significant differences in the experimental or control group among laypeople and professionals.For the primary outcome measures, we found a statistically significant effect on attitudes toward dementia  with a large effect size . At pretest, 31% of laypeople were most afraid of developing dementia; for professionals, this was 13%. At post-test, 46% of laypeople and 8% of professionals were most afraid of developing dementia. This indicates that after completing the course, laypersons were more afraid of developing dementia, whereas this fear decreased in professionals. The second question on attitudes toward dementia was “if you had a family member who was exhibiting confusion and memory loss, would you want the person to see a doctor to determine if the cause of the symptoms was Alzheimer’s disease or not?”. This was answered positively by all who completed the research, both at pretest and at post-test.r=–.34, P=.02).For the secondary outcome measures, we found statistically significant differences between the experimental and control group in the expected direction on several subscales of empathy: the distress subscale, empathy subscale, and perspective subscale. Although the scores on these scales remained largely the same in the control group at pretest and post-test, we witnessed a significant improvement in the experimental group, indicating that they felt less distressed in tense situations, had more empathy and concern for the well-being of other people, and were better able to understand situations and the actions of other people. On the other hand, we found a medium-sized, significant negative effect on sense of competence of informal caregivers, which declined in the experimental group compared to the control group, implying that participants in the course felt less competent to fulfill their care task after following the course. Post hoc analysis revealed that this decline in sense of competence was related to a higher age of the caregivers  and that they showed more sympathy and concern, which may help them to provide better care for people with dementia. No effects were found on knowledge about Alzheimer’s disease. This was likely because the selected instrument, the ADKS, mostly has factual questions on symptoms and prevalence, although the STAR course predominantly focused on informing caregivers how to deal and cope with the consequences of dementia. Therefore, positive outcomes related to dealing with dementia , rather than an increase in knowledge, were in-line with our expectations. On other outcome measures, such as quality of life and burden, no effects were found.These results are in-line with recent research, which has also found beneficial effects from Internet-based interventions , among oReview studies on the effectiveness of psychosocial and technology-driven interventions to support family caregivers show that interventions using a psychoeducational or psychotherapeutic approach appear to be among the most powerful psychosocial interventions to improve quality of life of persons with dementia and their caregivers, and delay patient institutionalization -28. NeveA strength of this study is that the STAR training portal was tested in an RCT design in 2 countries. A limitation of the study was the high number of dropouts in the RCT , especially in the experimental group; 43% (Netherlands) and 64% (United Kingdom) dropped out of the study. It seems likely that participants in the control group were more motivated to participate in the post-test because participating in the questionnaires would offer them free access to the course afterward. Furthermore, given that the STAR training portal was still in late development at the time of testing, some errors occurred when people followed the course. Another limitation was the fact that the online communities were not used often by participants, making them less informative and supportive than originally anticipated. The communities only contained a small number of participants because access was limited to only those in the experimental group of the research. However, they are expected to become more active and supportive in the future. This expectation is based on the fact that the STAR website has recently been updated to show links to the community websites more clearly. Additionally, when STAR gets more users, more users will potentially visit these communities, making them more lively and, therefore, more interesting to use for other visitors. We found little use for the Learning Path Advisor in the United Kingdom compared to use of it in the Netherlands. One explanation for this could be that the British group consisted of more volunteers with less experience in dementia care, who may have been more interested to follow the entire course, whereas the Dutch group consisted largely of informal caregivers and the majority (79%) had been caring for a person with dementia for 2 years or longer. It is likely that these experienced caregivers tended to use the Learning Path Advisor more frequently to find out which modules would provide them with new information, taking into account the knowledge they already had.In conclusion, based on the promising results of our study, especially the positive effects of the STAR training portal on empathy for both laypeople  and professionals, it is recommended to repeat the RCT on a larger scale and in more countries. STAR is currently available in Dutch and English; the basic and intermediate modules are available in Italian and Romanian, and some are available in Swedish as well.The positive effects of STAR on attitudes and empathy of caregivers may contribute to appropriate and high-quality dementia care in the community now and in the future. Therefore, an Internet-based intervention such as STAR can be a very useful alternative for face-to-face education and support for caregivers/informal caregivers and low-/unschooled professionals ,3 and at


Understanding how plants stabilize coastal dunes will be important for predicting effects of climate change along shorelines. This study used three years of data on plant communities and dune morphology on a barrier island to show how particular plant communities were associated with the disturbances that occur in coastal dunes. As expected, foredunes were very disturbed, with important effects on their vegetation. However, the much smaller disturbances that occurred in areas behind the foredunes had similar effects on the plant communities. These results will be important for modeling how increased storms and ocean level rise will affect sandy coasts. Uniola paniculata) in eroding areas. The significant effect of disturbance in the relatively stable interdunes was surprising, and may be due to the importance of flooding associated with small changes in elevation in these low-lying areas. Overall, this study documents changes in the plant community associated with elevation, and demonstrates that the foredune and interdune communities are also associated with the responses of specific species to local changes in elevation due to accretion or erosion.Coastal geomorphology and vegetation are expected to be particularly sensitive to climate change, because of disturbances caused by sea-level rise and increased storm frequency. Dunes have critical reciprocal interactions with vegetation; dunes create habitats for plants, while plants help to build dunes and promote geomorphological stability. These interactions are also greatly affected by disturbances associated with sand movement, either in accretion (dune building) or in erosion. The magnitude and intensity of disturbances are expected to vary with habitat, from the more exposed and less stable foredunes, to low-lying and flood-prone interdunes, to the protected and older backdunes. Permanent plots were established at three different spatial scales on St George Island, FL, USA, where the vegetation and dune elevation were quantified annually from 2011 to 2013. Change in elevation, either through accretion or erosion, was used as a measure of year-to-year disturbance over the 2 years of the study. At the scale of different dune habitats, foredunes were found to have the greatest disturbance, while interdunes had the least. Elevation and habitat  were significantly correlated with plant community composition. Generalized linear models conducted within each habitat show that the change in elevation (disturbance) is also significantly correlated with the plant community, but only within foredunes and interdunes. The importance of disturbance in exposed foredunes was expected and was found to be related to an increasing abundance of a dominant species ( Coastal sand dunes provide the first line of defense against storms and high water levels in many parts of the world  quantify the dynamic relationship between dune elevation and plant communities. The study also determines (ii) whether the nature of the relationships among elevation, change in elevation and the plant community changes with spatial location, as one moves from the newer and more disturbed foredunes to the low and wet interdunes, and finally to older, more protected backdunes.St George Island, FL, USA  is typical of barrier islands that form with low tidal ranges on wave-dominated coasts. It is ∼45 km long and 1 km wide, off the Florida panhandle in the northern Gulf of Mexico. Such islands worldwide share a number of habitats maintained by the wind and wave forces that created the islands themselves. At the ocean side of the island, foredunes are created and maintained by the sand blown from the beach plateau. They have high (3–5 m) and dynamic dune ridges subject to wind, spray and high tides. Foredunes are lower in overall plant diversity and are frequently quite dry . No elevation ‘standard’ is available in this area as past hurricanes have uprooted benchmarks. Because of the unstable nature of the landscape, an average elevation of 98 stakes in backdune areas thought to be stable were used as a standard elevation to compare across years. The topographic differences among the three habitats can be clearly seen by looking at these elevations , with the independent variables of (i) habitat, (ii) elevation in 2011 and (iii) change in elevation between 2011 and 2013. Replicate grid ID did not have a significant contribution from the model for any habitat and was not included in the results presented here. The change in elevation has a very awkward distribution, with both extreme high and low outliers that could not be easily transformed. To allow the data to be analysed, only the extreme outliers were transformed, by assuming that all values >0.2 m were equal to 0.2 m and all less than −0.2 m were equal to −0.2 m. Because there were strong interactions between the effects of some of the independent variables, separate GLM analysis were then conducted within each habitat, using just elevation and change in elevation as variables. The loadings of individual species in the NMDS were then used to determine which individual species were contributing the most to overall patterns in each habitat.The elevations in 2011 and 2013 were compared to get the change in elevation over the 2-year span  and replicate grid nested within habitat . As noted in Juncus spp., Phyla nodiflora and Paspalum distichum, while foredunes and backdunes have species associated with drier areas, such as Uniola paniculata, Schizachyrium maritima and Ipomoea imperata.Over 60 species have been documented across the three dune habitats, with species richness increasing from foredunes to interdunes to backdunes , with a The analysis of the full model predicting NMDS scores for 2013 based on habitat, elevation in 2011 and change in elevation from 2011 to 2013 suggested that there were significant effects of elevation, habitat and change in elevation, with elevation particularly loading on the first NMDS axis . The static patterns of dunes and vegetation have been well documented in a variety of coastal systems e.g. . HoweverAt the scale of the entire coastal ecosystem, elevation was the dominant factor correlated with vegetation patterns in 2013 Table . HoweverAt the scale of each dune habitat, the statistical models continue to show that elevation is the dominant factor correlated with vegetation patterns Table . HoweverU. paniculata is considered important for stabilizing dune ridges; it is interesting that this species has the same association across all three dune habitats. Schizachyrium maritima has also been found to be an important species for restoration after hurricanes  do affect the vegetation, but that these effects differ among foredunes, interdunes and backdunes. A particularly notable result is that, while interdunes are subject to only minor disturbances, these can have significant effects on the plant community, perhaps because of changes in the hydrology of this lower-lying habitat. Overall, this study provides a better view of the links between dynamic dune geomorphology and the plant community, which may be important for predicting future effects of climate change on coastal ecosystems.National Science Foundation (DEB 1050469) to T.E.M. and by funds from Florida State University.This work was funded in part by an award from the T.E.M. is responsible for all the organization of the fieldwork, data management, analyses and writing for this study.None declared.


Maternal mortality is higher and skilled attendance at delivery is lower in the slums of Nairobi (Kenya) compared to Ouagadougou (Burkina Faso). Lower numbers of public health facilities, greater distance to facilities, and higher costs of maternal health services in Nairobi could explain these differences.By comparing the use of maternal health care services among women with similar characteristics in the two cities, we will produce a more nuanced picture of the contextual factors at play.n=3,346 and 4,239 births). We compare the socioeconomic characteristics associated with antenatal care (ANC) use and deliveries at health facilities, controlling for demographic variables.We use birth statistics collected between 2009 and 2011 in all households living in several poor neighborhoods followed by the Nairobi and the Ouagadougou Health and Demographic Surveillances Systems (ANC use is greater in Nairobi than in Ouagadougou for every category of women. In Ouagadougou, there are few differentials in having at least one ANC visit and in delivering at a health facility; however, differences are observed for completing all four ANC visits. In Nairobi, less-educated, poorer, non-Kikuyu women, and women living in the neighborhood farther from public health services have poorer ANC and deliver more often outside of a health facility.These results suggest that women are more aware of the importance of ANC utilization in Nairobi compared to Ouagadougou. The presence of numerous for-profit health facilities within slums in Nairobi may also help women have all four ANC visits, although the services received may be of substandard quality. In Ouagadougou, the lack of socioeconomic differentials in having at least one ANC visit and in delivering at a health facility suggests that these practices stem from the application of well-enforced maternal health regulations; however, these regulations do not cover the entire set of four ANC visits. Maternal mortality remains high in sub-Saharan Africa as in other developing regions and its reduction is one of the indicators of individual countries’ progress toward the Millennium Development Goals , 2. PoorIn sub-Saharan Africa, health, including maternal health, in urban areas is better on average compared to rural areas. However, averages blur large subgroup disparities within cities: slum residents, who make up a sizeable share of urban dwellers in the developing world, can be heavily disadvantaged. A number of studies have shown that the residents of the slum areas of Nairobi   registerAfrican slum residents are not always at a disadvantage. In Ouagadougou for instance  , almost Women living in the slums of African cities encounter a number of obstacles in accessing maternal health services. The cost of health services remains an important impediment to health care utilization in low-income countries , and thiDistance to health services is another important obstacle to maternal health services utilization, combined with transportation . DistancFurthermore, quality of care is a key aspect of maternal service utilization . For exaThe current study focuses on the obstacles to maternal care utilization in the informal areas of the capital cities of two sub-Saharan African countries, Kenya and Burkina Faso. These sites were chosen because they are the home of the only two urban HDSS on the continent. To approach obstacles to maternal care utilization, the study will look at differences in ANC utilization  and place of delivery according to the sociodemographic characteristics of women giving birth in the two study areas. By comparing the practices of women with similar characteristics in the two cities, we will produce a more nuanced picture of the contextual factors, which promote (or hinder) ANC utilization and skilled delivery among the poor in urban sub-Saharan Africa. Our study aims to be a critical contribution in the search for successful pathways to reduce health inequities and improve maternal morbidity and mortality outcomes among vulnerable population in urban Eastern and Western Africa. The results are expected to reveal strides made in the right direction toward reducing maternal mortality and perhaps offer lessons for each country that can be adopted to improve the current status.We use data from ongoing HDSS of populations living in the two study sites in Nairobi and Ouagadougou for the period 2009 to 2011. The HDSS collect data on vital events  in all households living in the surveillance area. After an initial census, fieldworkers visit every household at regular intervals (every 4 months in Nairobi and 8 months in Ouagadougou) to record details on all vital events which occurred since the last visit. Details on data collection procedures for both sites are described elsewhere .In the NUHDSS, maternal and child health data were collected from all women who had a live birth since September 2006. Information was collected for each birth on antenatal clinic attendance, the place of delivery, and the type of professional attending to her during delivery, among other information. In the Ouagadougou HDSS, data on the place of birth and the type of attendant were collected for every live birth from 2008. Questions on ANC (number and dates of each visit) were introduced for births in 2010. The analysis is restricted to data collected between 2009 and 2011 to allow for comparison between the two sites. Altogether, 3,346 live births were recorded during that period in the Nairobi site and 4,239 in the Ouagadougou site. In Ouagadougou, the analysis uses all 4,239 births for the study on place at delivery, and 2,501 births for ANC use, questions which were added to the questionnaire only in mid-2010.Our variables of interest are: 1) the number of ANC visits and 2) place of delivery. We also performed the analysis for the type of birth attendant, but as it was almost identical to place of delivery, we dropped it in the analysis presented. In each site, we examine differences in ANC utilization and place of delivery by the following socioeconomic characteristics: household socioeconomic status (SES), mother's educational level, mother's ethnic group, and neighborhood of residence. We also control for several demographic variables, including mother's age, marital status, parity, and year of data collection. These variables have been found to be associated with maternal health service utilization in previous studies , 24–28.SES is computed as an index from 11 household goods in the Nairobi site . In the Ouagadougou site, SES status was calculated as an index from five household goods . Housing characteristics were not used because of the homogeneity in housing in informal areas in Nairobi and Ouagadougou. In both cities, principal components analysis (PCA) was used to generate a wealth index. Based on the scores of the first factor of the PCA (which accounts for 50% of the variance in the case of Ouagadougou and 24% in the case of Nairobi), households were classified as poor (those with larger loadings and above the median score) or non-poor .We examined the differences in women's number of antenatal visits and place of delivery by socioeconomic characteristics and demographic controls through a series of bivariate analyses, for each site. The chi-square test was used to identify significant associations. We then ran three multivariate logistic models to predict ANC use  and the place of delivery . As attending ANC is associated with skilled delivery , having In Nairobi,In Ouagadougou, as in Nairobi, few women did not have any ANC visit but the proportion of non-users was slightly higher (4.0% versus 2.1%). Moreover, only 22.0% of women had the recommended set of four or more visits . Like in Nairobi, women with no education, women from poorer households, and women in some neighborhoods (Nioko or Polesgo), and non-Mossi women reported fewer ANC visits. However, the differences were not significant at the bivariate level. Differences according to the control variables were also non-significant.Regarding the place where the delivery took place, 80.2% of the women in Nairobi delivered in a health facility while 18.9% delivered at their home or the home of the TBA. A lower proportion of women from poorer households delivered in health facilities. Significant differences were observed by ethnicity with a lower proportion of Luhya, Luo, and Kamba women delivering in health facilities, compared with Kikuyu women and women belonging to the ‘other ethnic group’ category. A lower proportion of women living in Viwandani than those in Korogocho delivered in health facilities. Women with a secondary education were the least likely to deliver at home, followed by women with no education or incomplete primary . RegardiA greater proportion of women in Ouagadougou (95%) than Nairobi (80%) delivered in a health facility and a substantial proportion of the few deliveries outside the health facility were reported as births that occurred on the way to the hospital. Like in Nairobi, women from poorer households, uneducated women, women from some neighborhoods (Nonghin and Nioko 2), and women from some ethnic groups (non-Mossi) were less likely to deliver in hospitals. However, these bivariate differences were small and non-significant . DiffereIn the multivariate models based on data from Nairobi, women with the least education and women from poorer households were significantly less likely to report ANC, everything else being constant . DiffereIn Ouagadougou, socioeconomic indicators were not significantly associated with women's likelihood of having at least one ANC visit . HoweverConcerning the place of delivery , a signiWhile no socioeconomic characteristics were related to hospital delivery in Ouagadougou in the bivariate analysis, having a secondary education and living in Polesgo was associated with higher odds of hospital delivery, when everything else was held constant . Ethnicity and SES were not associated with place of delivery in Ouagadougou in the multivariate analysis. Delivery in a health facility was not related to previous ANC use in Ouagadougou.anticipate delivering at home, and want to make sure their pregnancy offers no signs of complications. Prior studies on the barriers to access to formal obstetric care in the two slums of Nairobi found that women exhibited an entrenched distrust of health professionals in public health facilities; women were also found to believe that ANC was more important for a healthy outcome than delivering in a hospital  have differential maternal health utilization outcomes, with women in Nairobi having a much higher chance of completion of four ANC visits than in Ouagadougou. Women in Nairobi are surrounded by many more educated women, with higher levels of education in Nairobi overall; they may thus share norms more favorable to ANC utilization. Second, women in Nairobi may benefit from higher access to for-profit health facilities, which are more common in the Nairobi sites. The choice of different service providers, some more convenient and cheaper than others, could help more women meet the recommended ANC requirements in Nairobi than Ouagadougou. However, the question is then whether the quality of the ANC services is really up to standards for all these women. A prior study found that only about two-thirds of the births delivered in ‘health facilities’ received appropriate care, because many of the health facilities cited were substandard . The samhospital , 12. FinOur results also provide additional insights as to why women in Ouagadougou are more likely to deliver in hospitals compared with women in Nairobi, on top of the better-known factors . Our analysis revealed not only a high proportion of women delivering in hospitals in Ouagadougou, but also a virtual absence of socioeconomic differentials (and even demographic differences) for hospital delivery, as for the first ANC visit. These results may stem from the existence of a policy that prohibits TBAs from assisting with deliveries. Women in Ouagadougou have no choice between a home birth and a hospital birth, because they cannot rely on assistance were they to choose a home delivery. Altogether, women who do not benefit from any ANC or are unable to make it to the facility in time do not belong to specific sociodemographic groups in Ouagadougou, and these two variables are not linked there. However, these women might be worth targeting in maternal and child health program interventions.Our results also underscore the important role that distance may play in maternal health care utilization even in cities, as the neighborhood of residence was associated with skilled delivery in both sites. In Ouagadougou, one of the informal neighborhoods studied (Polesgo) is an ancient village and benefits from a dispensary located at its heart, as opposed to the two other areas. As expected, women in Polesgo were more likely to deliver in a health facility. In Nairobi, Viwandani is relatively underserved by health centers compared with Korogocho, and women deliver less often in a health facility there.One limitation should be recognized when interpreting these study results: despite our best efforts to standardize the measures, the variables of interest are not completely comparable across the two sites. In particular, poorer women in Nairobi live in households with more goods and amenities, but living costs are higher in that city. These women may also encounter other sources of uncertainties and challenges compared with women from poorer households in Ouagadougou. For example, households in Ouagadougou are more likely to own their home and live in settlements that are cleaner and safer than the Nairobi slums . In addiOverall study findings suggest that maternal health in urban Burkina Faso benefits from a set of relatively well-enforced regulations and policies, including subsidized low-cost delivery, free ANC, regulations stipulating that women need at least one ANC to deliver in a hospital, and the prohibition of TBAs from assisting deliveries. Such particular policies and level of enforcement was not evident in the Nairobi study sites. Reviews of national health systems have indeed concluded that the monitoring and the enforcement of regulations are stronger in Burkina Faso compared to Kenya . The priIn Nairobi, in contrast, where women have a choice of caregivers , a key issue might be the improvement of the quality of private facilities for ANC and deliveries. To give poor women better quality options at an affordable cost, a reproductive health voucher program has been tested in the slums of the NUHDSS between 2006 and 2012; 34.2% of all births registered during that period participated to the program . The exp


Brazil is well-known for its vigorous AIDS advocacy , 2. DuriIn recent years, AIDS groups have participated actively in pharmaceutical regulatory debates, closely informing decision makers about the highly technical aspects of IP. The Working Group on IP (GTPI), formed by a group of nongovernmental organizations (NGOs) interested in this issue and coordinated by the Brazilian Interdisciplinary AIDS Association (ABIA), has been the most active group within civil society in articulating the IP debates. A recent and important contribution of AIDS advocates is the regulation of Truvada (a combination of the ARVs tenofovir and emtricitabine) , which iAlthough tenofovir and emtricitabine are not protected by patents in Brazil, Gilead filed a patent request for Truvada in 2004, which was also strongly opposed by the GTPI. Truvada was approved by the Health Surveillance Agency in 2012 for clinical trials, and it is not yet authorized for commercialization in Brazil. These events highlight the capacity of activists to provide information on decisions that are highly technical and to collaborate with the INPI in the process of patent approval, rather than just using media exposure to express their criticism. Their intention was to clarify, based on sound evidence, why the INPI should not grant these patent applications.Another highly controversial issue has been the “pipeline patents” . An economic evaluation conducted by the GTPI compared the purchases of four drugs, which are included in a high-cost medicine programme and protected by the pipeline mechanism, with the lowest international price between 2009 and 2010. They found an excess cost of 55 million dollars for these products in Brazil . HoweverAdditionally, since 2007, the representatives of GPTI have been participating in public consultations at the Patent Office (INPI). At first, the INPI resisted this collaboration, arguing that these were technical meetings and thus excluding the participation of civil society on the grounds that it should include only pharmacists. There are two topics on the agenda: polymorphs, an important component of the active pharmaceutical ingredients that may affect the manufacturing process; and the “second medical use,” that is, the innovative therapeutic use of medicines already patented . AIDS activists support the fact that second medical use and polymorphs should not be granted patent protection. The former is due to its lack of novelty, given that what would be protected by a patent is the medical therapeutic indication, not the product. To them, polymorphism is a natural property (discovered via ordinary experimentation) and, thus, cannot be considered a human invention . The GTPFinally, regarding the discussions to end the prior consent mechanism  to review patent applications together with the INPI), the GTPI has petitioned in favour of this institutional arrangement several times. In 2013, Resolution 21/2013 established that prior consent would remain in operation and clarified under which circumstances ANVISA would be called into the patent application process. The GTPI contributed to this discussion in several ways. In November 2009, the GTPI was invited, together with other representatives of research-based pharmaceutical industries, for a public hearing in Congress to debate Bill Law 3709/2008, which discussed the role of prior consent. The GTPI strongly supported that prior consent should remain unaltered, as this is important to keep patent examination standards high and avoid underserved patents [In summation, contemporary AIDS activism in Brazil combines traditional strategies to voice the demands of activists for prevention and treatment with informational advocacy on regulatory policy. Most of these issues require a sophisticated understanding of pharmacology and law that is naturally well known to manufacturers of pharmaceutical products . However


Epigenetics plays an important role in regulating gene expression, and can be modified by environmental factors and physiological conditions. Studying epigenetics is a promising approach to potentially improving the diagnosis, prevention and treatment of human diseases, and to providing personalized medical care. However, the role of epigenetics in the development of diseases is not clear because epigenetic markers may be both mediators and outcomes of human diseases. It is particularly complicated to study pharmacoepigenetics, as medication use may modify the epigenetic profile. To address the challenges facing pharmacoepigenetic research of human diseases, we developed a novel design to rapidly identify, contact, and recruit participants and collect specimens for longitudinal studies of pharmacoepigenetics. Using data in real-time from electronic medical record systems, we can identify patients recently start on new medications and who also have a blood test. Prior to disposal of the leftover blood by the clinical laboratory, we are able to contact and recruit these patients, enabling us to use both their leftover baseline blood sample as well as leftover specimens at future tests. With treatment-naïve and follow-up specimens, this system is able to study both epigenetic markers associated with disease without treatment effect as well as treatment-related epigenetic changes. Epigenetic markers can be modified by environmental exposures , and areReports have suggested that epigenetic alteration is linked to the development of chronic inflammation ,8, whichet al. recently reviewed the PEGx research of ADME genes and other candidate genes [Pharmacoepigenetics (PEGx) is regarded as the study of epigenetic modifications, which may in turn affect or predict individual responses to therapies in terms of efficacy and adverse effects. Thus, the epigenetic profile may serve as an important biomarker representing the physiological responsiveness to the treatment, and may play a critical role in mediating the drug effect. Although the most promising PEGx studies have been demonstrated in the treatment of cancer, PEGx studies of therapies for other diseases may lead to a better understanding of inter-individual differences in drug response. In the past decade, researchers have investigated the epigenetic regulation of ADME genes , which play a critical role in the biological response to the drug targets. Ivanov te genes , which aUnlike the fixed genetic profile of an individual, epigenetic profiles can be modified by age  and enviEMR systems are able to capture and integrate data on most aspects of clinical care over time, with the data being represented in the form of standardized codes, controlled vocabularies and text-based clinical narratives. Nationwide initiatives in the US and European countries have promoted electronic data storage and sharing in health care systems to improve clinical care and decision-making. The availability of rich clinical phenotypes from the EMR databases has enabled genetic association studies using genome-wide association (GWA) designs ,20. ThesBecause epigenetic modifications can regulate gene expression levels, they may also play an important role in the molecular mechanism underlying the pathophysiology of the human diseases, as well as in the responsiveness and adverse effect of a certain medication. The epigenetic state of an individual may capture the cumulative environmental exposures in early life, and may serve as a biomarker of physiological plasticity in response to the medication. However, there are several major challenges facing epigenetic research in human populations ,25 centeIn a typical PGx study, participants are usually required to be free of medication for a period of time  before the trial starts. It is usually scheduled prior to initiation of the treatment and/or the placebo arms. This “washout period” is necessary to remove the residual effects of any previous medications to assess the actual change of clinical phenotypes for a given medication. The US Food and Drug Administration (USFDA) recommends to keep a minimal washout period of 5 half lives of the drug. In practice, many studies choose a sufficiently long period  for consistency and convenience between treatment arms and phases. Although this might be a valid approach to studying epigenetic predictors of drug response, such designs can be problematic if there are concerns about potential risks of disease progression during the washout period. In addition, clinical trials are typically associated with very high costs, which can limit the sample size for detecting the epigenetic association. Perhaps most importantly, though, is that the washout period may not be sufficient to recover the epigenetic changes caused by the medication. Thus, the epigenetic profile measured on the samples collected after a washout period can still remain partially modified by the medication, complicating interpretation of the results. To minimize the treatment effect on epigenetics, to reduce the potential risk due to the washout period, and to improve the efficiency of the sample collection for the PEGx research, we developed a novel approach for rapidly collecting leftover blood samples from routine laboratory tests by identifying and recruiting qualified patients using an automated search in the electronic medical record (EMR) system. We have developed a novel recruitment method that uses a real-time EMR database harboring the clinical, laboratory, demographic and pharmacy data. We propose the elimination of the washout period by identifying and recruiting treatment-naïve patients who are starting a targeted medication. At the same time point, we are able to collect leftover blood samples used for the routine laboratory test for PEGx research . The phenew prescription of the targeted medication . In other words, the identified prescription of drug X is the only observation of that specific drug for that specific person in the EMR dataset. Second, the participant must have a qualified blood test performed within the past N1  days, so as to allow the collection of leftover blood. It is important to note here that the clinical lab policies typically require that all lab samples be retained for seven days following a blood draw, thus allowing time for identification of new qualified patients (from Step 1) who have recently had a blood draw and have an available sample (from Step 2). Third, we require that the time between the prescription of drug X and the recent blood test is 2less than N  days. Since blood samples are usually collected right before the medication dispensings, and the epigenetic modification may take weeks to be modified, we use these baseline blood samples to measure the pre-medication epigenetics profile. Forth, we exclude individuals with previous diagnosis of disease Y, which drug X is used to treat. This restriction of disease Y-free status can exclude the potential modification of the epigenetic profile due to other treatment of disease Y. We use four key criteria to identify informative phenotypes based on EMR data in addition to typical inclusion criteria such as age, ethnicity and disease diagnosis. First, the participant must have a In practice, once qualified individuals are identified, we contact them via phone to obtain initial oral consent allowing us to keep their leftover blood specimens in the laboratory. We then follow up with a written consent through mail that allows for long-term storage of both the initial and specific  follow-up blood samples. During the phone call for the oral consent, we verify the key inclusion and exclusion criteria of the study. This is a critical step, as we have found that the disease-free status inferred from the EMR query may not always be definitive, because some new health plan members may, in fact, not have initiated care yet although they have a history of past disease. Therefore, having the disease or condition confirmed during the initial phone interview can help to identify the truly qualified participants. The Current Procedural Terminology (CPT) code is maintained by American Medical Association (AMA) to describe medical, surgical, and diagnostic services. The CPT code is designed to communicate uniformly about medical services and procedures among healthcare providers, patients and payers for administrative, financial, and analytical purposes. Similar to ICD-9 or ICD-10 coding for diagnosis, CPT coding identifies the provided services. The five-digit CPT codes between 80001 to 89999 are reserved for pathology and laboratory procedures. To collect specimens for DNA extraction, we focus on laboratory procedures using the blood samples (examples of CPT codes and descriptions were listed in We have found that lipid panels (80061) and basic metabolic panels (80048) are among the most commonly performed laboratory tests using blood samples, and are frequently obtained at the time that a new medication is initiated for a patient. After being used for the prescribed blood test and before being discarded, the leftover blood samples are stored in the laboratory for up to seven days . Assuming that the patients can be identified and contacted quickly after the test, and that the sample is stored under suitable conditions, the blood cells from these “leftover samples” are appropriate material for genetic or epigenetic research. Since these blood tests are routinely ordered and performed to assess the patients’ physiological condition, we can obtain the follow-up blood samples after the initial use of medication with the proper consent from the participants . As parti.e., reverse causation) or studying the longitudinal profile, results in inconclusive inference about the association between the epigenetic profile and the pharmacological outcomes. Our strategy of PEGx study using the EMR for sample identification, recruitment and blood collection has a number of advantages as described above. The applicability of this design in any particular EMR system, however, may be limited by the information captured and organized by the system. The strategy as described here requires frequent and routine monitoring of the EMR database to identify qualified participants, and requires quick action to obtain “opt-in” consent from the participants to bank the leftover specimen from the laboratory. Even with the automation of the database queries, a collaborative team needs to be assembled that is able to verify inclusion criteria, recruit participants, contact the laboratory, and to identify and bank relevant specimens. The requirement of the blood test in our design is not necessarily a limitation, because most disease diagnosis and new prescription of medication require some forms of blood test. The researchers can customize their algorithm to target the relevant blood tests accordingly to collect the specimen. PEGx is an emerging field. To our knowledge, well designed population studies of PEGx, particularly the epigenome-wide studies, are very few in numbers. In addition, using convenient samples from a cross-sectional design without taking into account of the treatment effect  for potential ethical concerns. While a more efficient approach to collecting biospecimens for PEGx study would be to establish a biobank with longitudinal samples, such an effort would require considerable more resources and funding than the approach we outlined here. If all leftover blood samples from participants are banked regardless of their medication use and the status of disease, the researchers may later conduct Although we present a general design of the PEGx study using EMR systems, researchers may want to pay special attention to the following issues when considering this approach. First, certain drugs have multiple indications beyond the primary disorder to treat. Because this may not be a common concern of most drugs of interest, the current algorithm does not directly address this issue. However, depending on the drug-disease pair of interest, the researchers should consider such drugs based on the domain knowledge, and exclude their influences on a specific PEGx project. Second, our design targets DNAm as a primary epigenetic mark in a population study. DNAm can be measured using genomic DNA extracted from leftover blood samples collected under the laboratory condition. However, we recognize that the stability of other types of epigenetic modification, such as histone modification and micro-RNA is not fully examined for the leftover blood. Further investigation of using leftover blood for other types of epigenetic marks is warranted. Third, a number of environmental factors are known modifiers of epigenetic profile. Measuring all, or even most of them, in single epidemiological study is a very challenging task. These environmental factors cannot be fully controlled for in a PEGx study. The recently proposed “exposome” research may greatly benefit the studies of epigenetic epidemiology, including PEGx. The exposome is a measure of the effects of life-long environmental exposures on health, and addresses the high-dimensional measure of environmental exposures. Certain -omics technologies, such as metabolomics, can measure thousands of chemicals as biomarkers of environmental exposures. With the availability of biospecimens , we are able to measure them quantitatively , and adjust for them to study the epigenetic association with medications. Last, the current pipeline is built based on the US system of EMR, including the clinical and pharmacy databases, as well as the CPT codes for the blood test. For the non-US system, our design is likely to be transferable. However, a thorough comparison is recommended to make necessary modifications of the US-based pipeline. Recent studies of chronic obstructive pulmonary disease (COPD) and rheumatoid arthritis (RA), which are related to local and systemic inflammation, identified and replicated a number of DNAm sites associated with disease outcomes using peripheral blood leukocytes (PBLs) ,27. The et al. [Epigenetic profiles are tissue and cell type-specific ,31. Our et al.  to projeet al. . Then we., whole blood, plasma and urine) to study metabolomic, proteomic and other -omic markers for pharmacological outcomes. Further understanding of the relationship between epigenetic variants and clinical outcomes from PEGx research has the potential to contribute to more effective, individualized approaches to evaluation, intervention, and prevention of human diseases, thereby, reduction of disability, death, and mounting health care costs.Although the design and approach described here focuses on PEGx study, this novel design can be applied to other studies of genetics and epigenetics. For example, this approach can be used in PGx studies that wish to identify informative patients who are initiating a specific medication, and would enable the collection of blood samples without extra effort on the part of the clinical team. This approach can reduce any additional risks for participants in clinical trials that otherwise might arise due to the need for drug-washout period. This design can also be used to study epigenetic changes related to other interventions, which may impact health outcomes via epigenetic mechanisms, such as radiation and chemotherapy for cancer. Both the baseline and the change of the epigenetic profile may predict the effectiveness and the potential side-effect of the treatment, thus providing insights in developing the individualized care to the patients. Finally, this strategy can be used to collect leftover biospecimens (e.g


Patient and public involvement (PPI) in studies carried out by the UK Medical Research Council Clinical Trials Unit (MRC CTU) at University College London varies by research type and setting. We developed a series of case studies of PPI to document and share good practice.We used purposive sampling to identify studies representing the scope of research at the MRC CTU and different approaches to PPI. We carried out semi-structured interviews with staff and patient representatives. Interview notes were analysed descriptively to categorise the main aims and motivations for involvement; activities undertaken; their impact on the studies and lessons learned.We conducted 19 interviews about ten case studies, comprising one systematic review, one observational study and 8 randomised controlled trials in HIV and cancer. Studies were either open or completed, with start dates between 2003 and 2011. Interviews took place between March and November 2014 and were updated in summer 2015 where there had been significant developments in the study (i.e. if the study had presented results subsequent to the interview taking place). A wide range of PPI models, including representation on trial committees or management groups, community engagement, one-off task-focused activities, patient research partners and participant involvement had been used. Overall, interviewees felt that PPI had a positive impact, leading to improvements, for example in the research question; study design; communication with potential participants; study recruitment; confidence to carry out or complete a study; interpretation and communication of results; and influence on future research.A range of models of PPI can benefit clinical studies. Researchers should consider different approaches to PPI, based on the desired impact and the people they want to involve. Use of multiple models may increase the potential impacts of PPI in clinical research.The online version of this article (doi:10.1186/s13063-016-1488-9) contains supplementary material, which is available to authorized users. There are a number of arguments to support PPI. In publicly funded research in particular, these revolve around accountability and democracy [Patient and public involvement (PPI) in research describes a variety of activities ensuring that research is carried out in collaboration with patients and/or members of the public [emocracy . On a moemocracy –5. Increhttp://www.ctu.mrc.ac.uk/resources/patient_involvement). This work is overseen by a PPI steering group, which is currently made up of eight members of staff from each of the major areas and types of clinical research carried out by the unit , two patient representatives (one involved in HIV research and one primarily in cancer) and two external PPI experts.The MRC Clinical Trials Unit (MRC CTU) at University College London (UCL) designs, conducts, analyses and reports high-quality randomised controlled trials (RCTs), meta-analyses and other clinical studies in a variety of health-care areas, primarily cancer, HIV and other infectious diseases. The unit is committed to active PPI in all its clinical research and has developed a policy and accompanying guidance to support this . We used purposive sampling to identify a cohort of studies representing the scope of our research and different approaches to PPI, and the geographical range of our studies. Our definition of PPI is based on that of INVOLVE (http://www.invo.org.uk/find-out-more/what-is-public-involvement-in-research/), and is the active involvement of patients, carers or family members, health service users, patient representatives or members of groups or organisations that represent those affected by the condition being researched as partners in the research process.The original idea for this work came from a participant at a workshop for involved patients and patient organisations hosted at the unit in June 2013  was invited to participate in semi-structured interviews around PPI within the study. We asked the researcher we interviewed from each study to nominate one or more patient, lay or community representatives who had been involved in the study to be interviewed also. None of the patient, lay or community representatives we interviewed were participants in our cohort of studies. We (BH) conducted these face to face wherever possible (otherwise over the telephone), following a topic guide designed to capture qualitative information on who was involved, the aims of involvement, the types of activities carried out by those involved, the support provided to those involved, the costs of PPI and its impact on the studies. It also included questions on motivation for involvement and lessons learned for the future. The full topic guide is provided in the http://www.hra-decisiontools.org.uk/ethics/) indicated that because our research was not a clinical trial of a medicinal product or device, no clinical data were collected and the interviewees were neither identified from or because of their past or present use of services, ethics approval was not necessary, and on this basis, was not sought. The UCL research ethics committee exempts ‘Research involving the use of non-sensitive, completely anonymous educational tests, survey and interview procedures when the participants are not defined as “vulnerable” and participation will not induce undue psychological stress or anxiety’ from the requirement to seek ethical approval from the committee. As our study met these criteria, as a service evaluation of PPI within our trials, ethical approval from the UCL research ethics committee was not sought. Interviewees gave verbal consent to being interviewed, and for the notes of these interviews to be analysed and published.Application of the National Health Service (NHS) research ethics committee Health Research Authority decision-making tool  then analysed the content of the summaries, following a process of familiarisation with the data, creating tables with data extracted from the written summaries organised by topic (based on the interview guide) to allow for comparison across the case studies, and identifying initial themes. The tables and initial themes were shared with the MRC CTU PPI steering group, who discussed and agreed the themes . The group also discussed and agreed the final interpretation . Responses from research staff and PPI contributors were considered separately where possible and appropriate.The unit currently has around 50 active clinical studies (predominantly RCTs). We identified 11 studies  that we wanted to do case studies on to represent the diversity of types of clinical studies  and approaches to PPI within the unit. We approached the lead researcher at the unit for each of these, of whom ten out of 11 agreed for a case study to be done on the PPI within their study. The reason given for not agreeing was that the researcher felt that there had not been much PPI in their study. We interviewed all patient representatives who the lead researcher identified and put us in touch with. We conducted 19 interviews with 13 researchers and seven patient representatives (one interview included two researchers from the same study), collecting information on eight individual RCTs –19 and oMost of the patient representatives interviewed were directly affected by the condition being studied in the trial, while one had been a carer for someone with the condition and two were employed by patient groups. The studies included six that were primarily carried out in the UK, two in sub-Saharan Africa and two across multiple continents. Table The main approach to recruiting patient and community representatives was via patient groups or by approaching people who were already involved in other research  Consumer Liaison Group (CLG)). Three studies , 13, 16 We categorised the findings into aims and motivations for PPI, models of involvement, impacts of involvement and lessons learnt. These findings are presented below.We found that the trial teams broadly agreed on their reasons for involvement. All researchers interviewed said that PPI gave them the opportunity to understand better the perspectives of the affected population. Some of the researchers interviewed were more specific, saying that PPI had provided help with issues around recruitment and/or retention, and, in the case of the two HIV prevention trials, to ensure acceptability of the study. Two trials also mentioned that PPI was a condition of their Health Technology Assessment (HTA) funding.There were also considerable similarities in the motivations patient representatives cited for being involved in the studies; for example, wanting to help with research that they felt was addressing an important question (8/11 patient representatives). While being affected by the condition (or caring for someone who was) was often a criterion for becoming a patient representative on these studies, it was not explicitly cited by the patient representatives as a motivating factor. Other reasons mentioned included interest in research, a desire to learn more about clinical trials, a desire to put forward a patient’s perspective, and a feeling that they had the time and skills needed to contribute.In this section we describe the models of involvement in terms of who was involved in the PPI, the types of activities included and the support offered. Table The most common models of PPI were having patient or community representatives on either the trial steering committee (five studies) or the trial management group (three studies), reflecting the typical management structures of the cancer and HIV trials within the unit. HIV trials . In our case studies, we had no examples of PPI impact on data collection or time and cost. Table All interviewees felt that PPI had impacted on the study, although the type of influence varied. Overall, the impacts were categorised into seven of the nine key areas of impact outlined in the public involvement impact assessment framework  an impact on recruitment to the study. Therefore, we look at these two areas of the PiiAF framework together. Eight studies reported improved communication with potential participants and/or impacts on recruitment as a benefit of PPI. For example, the patient representative on the QUARTZ trial management group gave talks about the trial at meetings that led to new clinicians signing up to the trial. Patient representatives on the SORCE and STAMPEDE trial management groups identified the need for clearer and simpler patient information sheets. Young people worked with a community organisation to design a logo and posters to promote the AALPHI study  and prodIn MDP301 , regularHIV trials in the UK often struggle to recruit participants of African origin. The PIVOT team  worked wTrials do not always go smoothly; for example, recruitment may be slower than anticipated and researchers then have to make the difficult decision on whether to continue the trial. In the case studies, researchers, including from the QUARTZ  and PROUResearchers on the STAMPEDE trial  highlighIn PIVOT , the patThere was considerable overlap in what interviewees reported in terms of the impact on analysis, writing-up and dissemination, therefore they are discussed together. Three studies reported that PPI had impacted on the interpretation and communication of the results. For example, when preliminary results of a PIVOT sub-study on cognitive impairment were presented at an investigators’ meeting, the patient representative on the trial steering committee was concerned about the language used and the appropriateness of the analysis, which had not taken socio-economic and cultural factors into account. This led the researchers to make appropriate adjustments to the analysis before the results were more widely disseminated. Similarly, the researchers involved in the PROUD trial  held a nThree of the patient research partners on the cervical cancer meta-analysis  wrote a The case studies also highlighted that where there is PPI in an ongoing or ending study, there is an opportunity for PPI input into future studies, which often follow on from existing studies, and may involve many of the same researchers and patient representatives. For example, the patient research partners on the cervical cancer meta-analysis raised concerns about the lack of information on the late side effects of cervical cancer treatment available from the meta-analysis. This led to researchers collaborating in a separate research project with a greater focus on late side effects.Another example is that the patient representative on the SORCE trial management group became involved in the trial development group, designing a follow-up study to SORCE on renal cancer.As recruitment to the PROUD pilot study came to an end, participants contributed to discussions about the future research priorities for HIV prevention among men who have sex with men in the UK through participant involvement meetings via a webinar and teleconference. These were advertised through the study website, study newsletter and in study clinics. Their discussions helped to directly inform the development of a funding application to the HTA programme.Researchers and patient representatives were asked what advice they would give to researchers looking to involve patients and the public, and shared their key lessons for future studies. These can be broadly grouped into three areas: who to involve, types of involvement and providing support. Advice on who to involve centred on the skills, characteristics or background required and on recruitment. Lessons around types of involvement tended to be reflections of what worked well in the study the interviewee was involved in. Discussion of support included the support that can be given by the research team, support available from existing community or patient groups, and the support other patient representatives can provide. Further details are presented in Box In our study, the case studies demonstrate that a range of models and approaches to PPI have led to numerous benefits across the key areas of impact, with examples from the design phase through to interpreting and communicating the results of studies. Motivations for involvement, both from the researchers and from the patient and public representatives who were interviewed were broadly similar with an overall aim of improving the study.http://piiaf.org.uk/). These covered each of the areas of agenda, research design and delivery, ethics, recruitment, analysis of data, writing-up and dissemination. Like the case studies evaluated by Evans et al. [These case studies follow on from a survey of PPI in MRC CTU studies, the results of which we reported previously . Clearlys et al. , 25, PPIThere is a growing body of literature around PPI; however, examination of the INVOLVE Evidence Bibliography reveals that most references that focus on PPI in clinical trials are case studies of individual trials , limitinOur analysis of the data is limited by the lack of audio-recording and verbatim transcriptions of the interviews. Relying on written summaries of the interviews may mean that we have missed key information. However, we are confident that the written summaries are accurate and contain the points considered important by interviewees, as all our interviewees were asked to read and correct or approve the written summaries prior to the start of analysis.Our findings have enabled us to describe better the wide variety of approaches being used to involve patients and the public in our research. In keeping with the findings of a previous survey of how consumers were involved in NHS research , most ofPerhaps the most novel finding of this study is the use of participant involvement by three of the HIV trials . This is distinct from usual PPI practice in clinical trials, where patient or community representatives who are not taking part in the trial are chosen for involvement roles. This approach is recommended as Good Participatory Practice in biomedical HIV prevention trials , but we There were no direct contradictions between the accounts of researchers vs patient representatives. There were some examples of an impact that were cited by one interviewee and not the others for a single study, perhaps because the other person interviewed may have been unaware of it. For example, the QUARTZ researcher said that PPI had given them the confidence to keep going with a trial that was struggling to recruit. The patient representatives did not mention this as an example of an impact, and subsequently told us he had been unaware of it until we fed the results of the case studies back to him.Most of the literature on PPI to date has focused on studies in high-income countries (particularly the UK). Our case studies include three trials where all (DART and MDP301) or a large proportion (BREATHER) of participants are from low-income countries (particularly sub-Saharan African countries). The PPI models used in these case studies all include community representation on the steering committee (as did the other HIV case studies), and participant meetings, with ongoing participant groups for DART and MDP301. Only one of our studies based in the UK (the PROUD HIV prevention study) involved participants. Although there were similarities in the models of PPI used in the three studies taking place in Africa, there does not seem to be an obvious pattern in the areas of impact described by interviewees, suggesting that the area of impact is not solely related to the model of involvement.Half the examined studies combined a mix of different PPI models, from long-term involvement in a formal steering committee through to one-off work to produce a video to promote the study. For example, in the PROUD study, there was long-term involvement of community representatives in the trial management group, trial steering committee and data monitoring committee, and in the community engagement group. There was also one-off involvement of participants in meetings to discuss specific questions . In the EPIC study, multiple approaches within a study were only identified in six out of 89 outline applications for HTA funding, so it seems that this is not widespread . In our We recognise that different approaches to PPI will have been adopted in other health-care areas and at other clinical trials units. Broader sharing of these experiences, their benefits and challenges may further benefit research practice.Our findings demonstrate that even within a single trials unit, a range of models of PPI are being employed to benefit clinical studies. Use of multiple models, possibly at different stages of the research process, may maximise the potential impacts of PPI in clinical research. Sharing experiences of the different approaches being used, across disease conditions and between clinical trials units, as well as an exploration of the impact and benefits of these approaches, is desirable. We recommend that researchers familiarise themselves with a range of methods. In partnership with patient representatives, they should consider which method(s) might be most appropriate, based on the desired impact, the people they want to involve and the time and resources available to support PPI.AALPHI, adolescents and adults living with perinatal HIV cohort (AALPHI is a cohort study of young people infected with HIV at birth and a HIV-negative comparison group); BREATHER, a trial of short-cycle therapy (5 days on/2 days off) in young people with chronic HIV infection; CLG, consumer liaison group; CSG, Clinical Studies Group; DART, Development of Antiretroviral Therapy in Africa ; HTA, Health Technology Assessment ; MDP301, a phase III trial to test the effectiveness of PRO2000/5 vaginal microbicide to prevent HIV infection; MRC CTU, Medical Research Council Clinical Trials Unit; NCIN, National Cancer Intelligence Network; NCRI, National Cancer Research Institute; NHS, National Health Service; PiiAF, public involvement impact assessment framework; PIVOT, protease inhibitor monotherapy versus ongoing triple-therapy in the long-term management of HIV infection; PPI, patient and public involvement; PROUD, pre-exposure option for reducing HIV in the UK (an open-label randomisation to immediate or deferred daily Truvada for HIV negative gay men); QUARTZ, quality of life after treatment of brain metastases ; RCT, randomised controlled trial; SORCE, a multi-centre phase III double-blind placebo-controlled study designed to examine the efficacy and tolerability of sorafenib (Nexavar) in patients with resected  primary renal cell carcinoma at high or intermediate risk of relapse; STAMPEDE, systemic therapy in advancing or metastatic prostate cancer ; UCL, University College London; UK, United Kingdom