The Farm to Work program is a modified community-supported agriculture model at worksites in Texas.The objective of the Farm to Work program is to increase fruit and vegetable intake among employees and their households by decreasing cost, improving convenience, and increasing access while also creating a new market for local farmers at worksites. The objectives of this article were to describe the development, implementation, and outcome of a 5-year participation trend analysis and to describe the community relationships that were formed to enable the successful implementation of the program.The Farm to Work program began in November 2007 as a collaborative effort between the nonprofit Sustainable Food Center, the Texas Department of State Health Services, the Web development company WebChronic Consulting LLC, and Naegelin Farm. The program provides a weekly or biweekly opportunity for employees to order a basket of produce online to be delivered to the worksite by a local farmer. A 5-year participation trend analysis, including seasonal variation and sales trends, was conducted using sales data from November 2007 through December 2012.The total number of baskets delivered from November 2007 through December 2012 was 38,343; of these, 37,466 were sold and 877 were complimentary. The total value of sold and complimentary baskets was $851,035 and $21,925, respectively. Participation in the program increased over time and was highest in 2012.The Farm to Work program increased access to locally grown fruits and vegetables for employees and created a new market for farmers. Increased program participation indicates that Farm to Work can increase employees’ fruit and vegetable consumption and thus help prevent chronic diseases in this population Consumption of fruits and vegetables in the United States is lower than recommended, and several government health goals and initiatives focus on increasing it –4. A dieAn effective way to increase fruit and vegetable consumption is through community-supported agriculture (CSA) programs. These programs consist of individuals who purchase farm shares, thereby distributing the farm’s risks and benefits, and regularly receive a portion of crops during the growing season . There aThe Farm to Work program is a modified CSA model designed to increase fruit and vegetable consumption by providing access to fresh produce at worksites. This program does not require participants to purchase a share but instead provides a weekly or biweekly opportunity to order a basket of produce online to be delivered to the worksite by a local farmer. The basket consists of 12 to 15 pounds of fresh produce, including mostly vegetables and some fruits and herbs; a trade basket is available for participants to trade produce items. This modified CSA model supports local farmers and has the added convenience of delivery to the worksite. The objectives of this article are to describe the development and implementation of the Farm to Work program, to outline community engagement efforts and community relationships that were formed, and to present outcomes of a 5-year participation trend analysis.Similar to national consumption, consumption of fruits and vegetables is low in Texas; in 2011, the median reported daily consumption rate among Texas adults was 1.0 time per day for vegetables and 1.6 times per day for fruits ,13. The Development of the Farm to Work program required new partnerships that would be mutually beneficial to all organizations. The community engagement effort created a relationship between worksites and farmers. Outcomes of interest for this partnership were increased fruit and vegetable consumption among employees and their households, development of a new market for farmers, relationship formation between farmers and consumers through worksites, increased engagement of consumers and farmers in the local food system, increased access to fruits and vegetables from small farms, and increased knowledge among Farm to Work participants of the local food system related to the seasonality and source of local produce.The Farm to Work program began in November 2007 as a collaborative effort between the nonprofit Sustainable Food Center (SFC), the Texas Department of State Health Services (DSHS), the Web development company WebChronic Consulting LLC (WebChronic), and Naegelin Farm. SFC, a nonprofit organization with a mission to “cultivate a healthy community by strengthening the local food system and improving access to nutritious, affordable food,” operates in central Texas and was identified as a potential partner because of its established relationships and reputation with local farmers and its work in the local food system, including other “farm to institution” endeavors . DSHS waIn developing a method to distribute produce, the partners first considered conventional models, such as CSAs and farmers markets, to increase the availability and intake of locally grown fruits and vegetables at worksites. In most CSAs, members must purchase a basket at consistent intervals  for an entire growing season. CSAs do not allow flexibility for times when the member is unable to pick up or use the produce. The standard CSA model was modified by replacing the weekly or biweekly commitment with a weekly or biweekly opportunity to order a basket, which was made possible by the collective purchasing power at worksites. Farm to Work was intended to reach employees who did not already engage in the local food system and needed to overcome a cost and convenience barrier. The program also provided an additional way of purchasing local food to those employees who already participated in the local food system, such as those who had developed relationships with CSAs and farmers markets. As a state agency worksite, DSHS represented a mixture of employees with various levels of socioeconomic status. This program reached the entire worksite, providing flexibility for the employees and an additional source of income for the farmer.The partners collaboratively implemented the program. A coordinator employed at each worksite volunteered to oversee internal operations, including produce delivery and pickup, program promotion, and direct customer service for program participants. Volunteer coordinators were usually self-selected; they spent a minimum of 2 hours per delivery week on distributing produce, providing customer service, and promoting the program. SFC initially ran the production side of Farm to Work operations by recruiting and training farmers, matching worksites to farmers, and providing ongoing technical support to farmers. The DSHS Nutrition, Physical Activity, and Obesity Prevention Program developed a protocol to implement Farm to Work through worksites and operated the consumer side of Farm to Work by training and providing ongoing support to coordinators. Over time, the responsibility of training and providing ongoing support to coordinators transferred to SFC.SFC contracted with WebChronic to create and maintain the online system. To date, the cost of developing the online order site and administrative system, including initial development and upgrades, is approximately $29,000, and 3% of the purchase price covers monthly maintenance costs. Each worksite had a unique Web address for their ordering website, and the data were linked to an administrative website.The Farm to Work program was launched in November 2007 at the DSHS main campus in Austin and expanded to its second worksite, Austin State Hospital, in December 2007. The program launch was funded by an obesity prevention grant from CDC, which was used to organize a communications plan and purchase promotional materials. The DSHS Communications Unit developed a logo and artwork for the program. DSHS, SFC, and WebChronic created a promotional video and placed it on the Farm to Work website to encourage employees to participate. Communications and promotional materials were developed for dissemination through other worksites to promote the program. For example, logo and artwork files were sent to coordinators when the program was launched at their worksite. These worksites then personalized the marketing materials to meet their own needs. Initially, volunteer coordinators also received a complimentary basket, but this practice was discontinued in the second year of the program due to rules at some worksites related to receiving gifts.Partner communication was essential to promotion of the program. Partners communicated with one another via email and in-person meetings. Farm to Work was promoted to employees through wellness fairs, posters, emails, and a link placed on organizations’ wellness websites. DSHS and SFC met with interested worksite staff to manage expectations related to the content of the basket, online system, and responsibilities. Communication to the public was achieved through the Farm to Work website and the Farm to Work webpage on the SFC and DSHS sites.The Farm to Work program was evaluated using mixed methods in 2007, 2008, 2010, and 2011 . All evaParticipant and partner feedback were used to further refine the program to increase satisfaction for participants and farmers. Results from participant satisfaction surveys conducted in 2010 informed best practices for farmers, which included providing high-quality, fresh produce, adding variety to increase value, ensuring accurate information about the produce list, having a trade box regardless of the number of customers, using creative marketing strategies to inform participants, and making recommendations to improve the website. Results from the 2010 participant satisfaction survey informed the start of a promotion that rewarded participants with a complimentary basket for every 10 baskets ordered during a 1-year period. Participant concerns with the volume and variety of produce offered were addressed by farmers rotating produce in the baskets, providing a trade basket, and ensuring at least 12 to 15 pounds of produce per basket. In 2012, WebChronic contracted with a website usability expert who gathered insights from SFC, DSHS, worksite coordinators, and participants. The findings from the usability testing and participant satisfaction surveys conducted in 2010 informed updates to the ordering and administrative websites in spring 2013. Website features added as a response to user needs included a recipe section and an encyclopedia of produce called the Vegipedia. The interface and design of both websites supported ease of use and consistency in program branding. Employees could ask questions and provide feedback at distribution, use the feedback feature on the order website, or respond to order reminder emails; online questions and feedback were routed to the respective worksite coordinator to reply to the employee.Success of community engagement efforts was assessed with process-related data collected through the online system. The ability to track participation by the number of baskets and sales by worksite was built into the Farm to Work administrative site. SFC, WebChronic, and DSHS used the data for quarterly reports, invoices, and evaluation of participation and sales, respectively. SAS 9.2  was used to analyze the participation and sales data. Analysis of variance (ANOVA) was used to determine if there was a significant difference in participation by season and by month. Because there were significant differences in participation by season and by month, a Student-Newman-Keuls post-hoc test was used to determine which seasons and months were statistically different from the others.t = 2.96, P = .004) and every 7 months . The trend line increased by a slope of 2.947 baskets per month. However, participation decreased from 2009 to 2010 ; however, results of the Student–Newman–Keuls post-hoc test indicated there was no significant difference when comparing the other 4 growing seasons . Basket deliveries were highest in early summer  and lowest in fall . Average basket sales for the remaining 3 growing seasons ranged from 896.8 (late summer: August and September) to 1,302.6 (spring: March and April).From November 2007 through December 2012, the total number of baskets delivered was 38,343; of these, 37,466 were sold and 877 were complimentary. Over the 5-year period, the total value of sold baskets was $851,035, and the total value of complimentary baskets was $21,925. Price per basket differed by worksite and changed over time, ranging from $10 (2 baskets) to $20  and $25 . Participation in the program was highest in 2012, which was likely due to continued growth in the number of participating worksites. A 1-way repeated measures ANOVA indicated that a significantly higher number of basket deliveries occurred in early summer  compared with the other growing seasons   .To build trust with the first farmer to commit to a new program, SFC recruited Naegelin Farm, which had communicated a need for help in increasing sales. SFC trained farmers on how to use the administrative site and on the production needs of the program. On the consumer side, the support from the worksite itself and worksite coordinators created the trust necessary for employees to purchase the produce. DSHS and SFC trained coordinators on how to order a basket, what their involvement entailed, and expectations related to basket contents. To address participant perceptions of the produce being more expensive than grocery store produce, coordinators conducted price comparisons with prices of comparable produce from conventional grocery stores and shared findings with participants.Unexpected successes included the amount of profit generated for the farmers and a waitlist of worksites. There also has been both state and national recognition and interest in replicating the program at other sites. Farm to Work was recognized as an innovative program by national organizations such as CDC’s Center for Training and Research Translation, Association of State and Territorial Health Officials, and the National Association of County and City Health Officials.The Farm to Work program created a new access point for locally grown fruits and vegetables and created a new market for farmers at worksites. The program expanded to 35 active worksites in 2012 and generated $851,035 in sales over a 5-year period from November 2007 through December 2012. Other communities interested in setting up a Farm to Work program can download the Farm to Work Toolkit or consider attending SFC’s Program Replication training to receive hands-on training and a program replication guide ,17. The The Farm to Work program has increased access to locally grown fruits and vegetables for consumers and created a new market for local farmers; increasing participation levels in the program suggest that it has the potential to increase fruit and vegetable consumption and prevent diet-related chronic diseases.


Especially, gapmers modified with locked nucleic acid (LNA) shows potent knockdown activity; however, they also cause hepatotoxic side effects. For developing safe and effective gapmer drugs, a deeper understanding of the mechanisms of hepatotoxicity is required. Here, we investigated the cause of hepatotoxicity derived from LNA-modified gapmers. Chemical modification of gapmer’s gap region completely suppressed both knockdown activity and hepatotoxicity, indicating that the root cause of hepatotoxicity is related to intracellular gapmer activity. Gene silencing of hepatic ribonuclease H1 (RNaseH1), which catalyses gapmer-mediated RNA knockdown, strongly supressed hepatotoxic effects. Small interfering RNA (siRNA)-mediated knockdown of a target mRNA did not result in any hepatotoxic effects, while the gapmer targeting the same position on mRNA as does the siRNA showed acute toxicity. Microarray analysis revealed that several pre-mRNAs containing a sequence similar to the gapmer target were also knocked down. These results suggest that hepatotoxicity of LNA gapmer is caused by RNAseH1 activity, presumably because of off-target cleavage of RNAs inside nuclei.Gapmer antisense oligonucleotides cleave target RNA effectively  RNAseH1 is ubiquitously expressed and localized in the nucleus and mitochondria. It recognizes RNA–DNA duplexes and catalyses non-specific cleavage of RNA strand. It is considered to play a pivotal role for DNA replication and repair by hydrolysing phosphodiester bond between DNA-RNA hybridized sections89et al. suggested that the hepatotoxicity would be mediated by promiscuous knockdownRecently, Food and Drug Administration in United States approved a first gapmer drug, mipomersen, for the treatment of familial homozygous hyperchoresterolemia. Mipomersen is MOE-modified gapmer targeting apolipoprotein B-100 mRNA in human liver12137171920212224et al., the off-target effect would be an important factor; however there is a possibility that the other factors are involved in gapmer’s hepatotoxicity.The following four hypotheses can be considered in regard to the mechanism of hepatotoxicity caused by gapmers: 1. biochemical/biophysical toxicity derived from non-natural oligonucleotide(s); 2. innate immune responses caused by toll-like receptors (TLRs); 3. on-target knockdown-related dysfunction; and 4. off-target knockdown of essential RNAs. Considering recent findings by Burel The aim of our study was to address the major mechanism(s) of the liver toxicity of gapmers. We herein show that chemical modification of the gap region of these LNA gapmers critically suppresses hepatotoxic effect. Furthermore, small interfering RNA (siRNA)-mediated silencing of RNaseH1 successfully reduces gapmer hepatotoxicity, while the knockdown of RNaseH2a shows no significant effects. Gapmer-mediated knockdown results in severe hepatotoxicity, but siRNA targeting the same position on the target mRNA does not. Microarray analysis reveals that several pre-mRNAs, which has a sequence similar to that of the gapmer target, are knocked down after gapmer administration. We also find that these pre-mRNAs contain presumptive target sequence in their introns, which have 5 or fewer mismatches to the parental target sequence. This unintended knockdown is not occurred by gap-modified LNA gapmers, as well as siRNA. Moreover, silencing of RNaseH1 in liver critically suppressed the reduction of those pre-mRNAs. Our results suggest that the hepatotoxicity is derived from the knockdown activity, and arises because of off-target RNA cleavage by the low-specificity of LNA gapmer.in vivo, with a dramatic increase in plasma ALT/AST levelsWe examined the mechanisms of hepatotoxicity caused by gapmers, largely utilizing two LNA gapmers. One targets the glucocorticoid receptor . GR is ubiquitously expressed and regulates various cellular activities in response to ligand bindingAcsl1. In this case, the plasma ALT/AST level of gapmer-recipient mice were significantly increased, and remained so until day 10, while those of non-gapmer recipients remained at background levels  was also used; because RNaseH2 is a member of the RNase H enzymes that hydrolyse the RNA strand of an RNA/DNA duplex, it might be related to gapmer knockdown/hepatotoxic activity3335Rnase H1 and RnaseH2a mRNA expression was efficiently regulated at 37% and 26% of levels in saline-injected mice, respectively . This subtle increase at mRNA level was considered to be tolerable to perform knockdown experiments -conjugated, fully chemically modified siRNA is known to effectively reduce target RNA expression in liver39Triantennary Acsl1 pre-mRNA was reduced to approximately 40% of the saline control level at every site, indicating that the gapmer digests Acsl1 pre-mRNA inside the nucleus. Administration of GalNAc3-siRNA did not change the expression level of introns, presumably because Ago2, an endogenous nuclease that functions with siRNAs, localizes only in the cytoplasm , indicating that the target recognition of LNA gapmer would not be highly specific. It implies that more RNAs—those containing 6 or more mismatches—might also be digested by RNaseH1. In line with recent findings, the data shown here offer deep insights that gapmers cleave mismatch-containing pre-mRNA in vivo; this is considered to be a fundamental cause of the hepatotoxicity. Additionally, comparative analyses between GalNAc3-siRNA and gapmers imply that siRNAs might be safer than gapmers for the knockdown of cytosolic mRNAs.A recent publication by Burel in silico analysis and chemical biology will open up new possibilities for using gapmer ASOs as safe and effective therapeutics.There are two approaches that could help avoid off-target knockdown. One is in silico analysis to predict putative off-target cleavageC57BL6/j male mice  were purchased and maintained according to the instruction of Association for Assessment and Accreditation of Laboratory Animal Care International. All experimental protocol were approved by the Institutional Animal Care and Use Committee of Shionogi Co., Ltd., and all experiments were performed in accordance with the Committee’s guidelines. Anaesthesia was induced by intraperitoneal administration of approximately 20 μg of sodium pentobarbital, and then the liver was isolated. For western blot analysis, approximately 100 mg liver was immediately frozen in liquid nitrogen and stored at −80 °C. Approximately 40 mg of liver sample was stored in RNA Later  at 4 °C for overnight and then at −80 °C for quantitative reverse-transcription PCR (qRT-PCR) and microarray analysis. The rest was fixed in 4% paraformaldehyde and embedded in Optimal Cutting Temperature compound  for histological observation.s.c. injection of ASOs. We designed a fully chemically modified, triantennary N-acetylgalactosamine -conjugated siRNA, which targets the same position of the target mRNA as does the gapmer . Detailed sequence information is shown in e gapmer . Both chMouse plasma was collected from the tail vein routinely, and from the vena cava at the end point. ALT and AST were measured using Transaminase CII-test Wako , according to the manufacture’s instruction for 96-well format. Plasma ALT and AST levels are shown in international unit.Gapdh and are presented relative to a saline or untreated control. Primers for conventional qRT-PCR are listed in Total RNA was purified from the RNAlater-treated frozen liver samples using an RNeasy 96 Universal kit (Qiagen) according to the manufacturer’s instructions. In brief, liver tissue was homogenized in 750 μl Qiazol reagent. The homogenate was mixed with 150 μl chloroform and the supernatant, containing the RNA, was applied to an RNeasy 96 well plate. cDNA was synthesized from 1 μg total RNA using a Superscript III First Strand Synthesis kit (Life Technologies). qRT-PCR was conducted using SYBR Premix Ex Taq II  according to the manufacturer’s instructions on an ABI7900HT Real Time PCR system . Quantified mRNA levels were normalized to Liver tissues were homogenized in a 5× volume of radio-immunoprecipitation assay buffer  using a Tissue Lyzer with 7-mm stainless steel beads (Qiagen). The protein concentration of the homogenate was measured using a BCA Assay kit . Homogenate containing 12.5 μg protein was subjected to SDS-PAGE, electrically transferred to polyvinylidene difluoride membrane, and immunoblotted using primary antibodies for RNaseH1 , Acsl1 , or β-actin , followed by horseradish peroxidase-conjugated secondary antibodies . The blots were visualized utilizing chemiluminescence with ECL Prime .In Situ Cell Death Detection kit, Fluorescein , according to the manufacture’s instruction. In brief, 10 μm-thick cryosections were prepared from mouse liver, then the sections were incubated in 0.1% citric acid containing 0.1% Triton-X 100 on ice for 2 min, washed twice in PBS, and then immersed in TUNEL reaction solution at 37 °C for 60 min. After washing three times in PBS, sections were observed under confocal microscope FV500 .Apoptotic cells in the liver tissue were detected by TUNEL assay, using an http://gggenome.dbcls.jp/en/).Total RNA isolated from mouse liver was analysed using a whole mouse genome (4 × 44 K) oligo microarray kit  according to the manufacturer’s instructions. RNA transcripts containing a sequence similar to the target sequence of the Acsl1 gapmer (two or fewer mismatches) were screened using the ultrafast sequence searching database gggenome .


Unplugged to improve the drug use prevention efforts of Brazilian public schools. The aim of this study was to evaluate the process of program implementation in three Brazilian cities among middle school students between 6th and 9th grade (11 to 14 years old).Most Brazilian schools do not have a continuous program for drug use prevention. To address this gap, the Ministry of Health adapted the European evidence-based program Mixed methods were used in this process evaluation study, including focus groups, fidelity forms, and satisfaction questionnaires. Study participants included 36 teachers, 11 school administrators, 6 coaches, 16 stakeholders, and 1267 students from 62 classes in 8 schools.Unplugged lessons were all implemented in 94 % of the classes. However, only 57 % of the classes were completed as described in the program's manual. The decision to exclude activities because of time constraints was made without a common rationale. Teachers reported difficulties due to the amount of time necessary to plan the lessons and implement the activities. In addition, they mentioned that the lack of support from school administrators was an obstacle to proper program implementation. The majority of students and teachers responded positively to the program, reporting changes in the classroom environment and in personal skills or knowledge.The 12 Unplugged program can be feasibly implemented in Brazilian public schools. However, it is necessary to reduce the number of activities per class and to restructure the format of the standard teaching schedule to ensure that the normal academic content is still taught while Unplugged is being implemented.The  Universal prevention in the school environment is a necessary strategy to control substance use among teenagers, particularly because the incidence of initiation of alcohol and other drug use increases significantly between the beginning and the end of adolescence . In BrazUnplugged Program for drug prevention in the school environment  “What am I going to leave out?” This 10-minute opening will last 2 minutes. The energizer [group dynamics to stimulate interaction among students in the classroom] is out. This here, out… That's what I did!” (Teacher)Many of the activities in the program were not used or were only briefly performed with the students, indicating that the objectives of the lessons and the program may not have been reached.Unplugged lessons was perhaps due to the Brazilian culture and the learning conditions of several students, which affected the program activities. This finding indicates a need for the program to be better adapted to the Brazilian school setting.“T1- [50 minutes] is how long students in Europe take to complete the activity. Here, maybe because of our culture, until we arrive, until we organize the classroom, until students are seated…T2- (…) Here, a 50-minute lesson ends up taking an hour and a half, an hour and forty minutes.” (School administrators)“Then, there is also our students' difficulties in writing. Our students cannot write. In the 6thgrade there are students who are almost illiterate. There are questions that they need to answer, and if you let them do it at their own pace, it would take a long time for them to answer.” (Stakeholder)School administrators and teachers thought that the increased time necessary to cover the The main difficulties and successes of the program according to the teachers, school administrators, and coaches were identified through the focus groups.Most of the difficulties experienced in the program implementation process were described by the teachers, who identified 3 main obstacles that affected the feasibility of the implementation: time spent planning lessons, lack of material resources, and the undermining of the students’ standard curriculum content.“[Unplugged] is not something that you can start applying right away. The teacher needs to study these lessons, to prepare them. For certain lessons, they need materials, even some of the energizers need it, so they need preparation. In this sense, I notice that [the teachers] are a bit overloaded because in addition to Unplugged they need to cover the curriculum, and their time is limited.” (School Administrator)The lack of time dedicated to preparing the program activities and to appropriately implement them was strongly highlighted by the teachers because they added a classroom activity to their previous ones, and there was no reduction in their other responsibilities.This moment of having a meeting with everyone is impossible because at this time of the year we don't have the time to do that. Sometimes someone in the school asks 'can you talk to me now?', [and I say] 'no, I can't'! It’s impossible.” (Teacher)“The analysis of the coaches’ responses clearly showed that the teachers were overwhelmed with the excessive amount of program protocols required. The teachers themselves also mentioned this issue:There was a discrepancy between the teachers and the school administrators regarding the support provided by the school. School administrators highlighted more than once that they offered full support in terms of pedagogical materials for the development of the program, whereas the teachers mentioned that a lack of pedagogical materials and resources to make copies of the material was a barrier to the feasibility of the program. According to the teachers, not all the school administrators offered support for the implementation of the program.Unplugged because the teachers had to replace the curriculum lessons with the Unplugged lessons. Teachers unanimously felt that their academic curriculum was not fully covered, with parts of it being only superficially taught to the students during the semester; this may have led to gaps in the students’ education. Teachers feared being blamed by the students for these gaps.“Another important aspect is that they [teachers] had to stop teaching the content of their subjects, and that is it. If something is added, something else has to be removed, and that is what happened.” (Coach)The content of the normal academic curriculum delivered was also affected in the students whose teachers taught Unplugged into the regular classroom curriculum.“Usually the school project always includes prevention actions (…) in this sense, I think that somehow (…) we can think of structuring [Unplugged] to be a part of the regular classroom curriculum.” (Stakeholder)However, the stakeholders did not mention the pressing need to adapt the logistics of the program for it to be sustained in the schools, demonstrating a clear discrepancy between the practical perceptions of the implementation by the stakeholders, school administrators, and teachers. Nevertheless, the stakeholders did highlight the need to incorporate Unplugged.Teachers highlighted the need to make basic adaptations to the program for it to become part of the school curriculum. According to them, the training they received, the support by the school administration, and the presence of coaches were the main factors that facilitated the implementation of p value indicates that for all the questions, both teachers and students tended to choose the positive answer option.The results obtained in this study showed a satisfactory acceptability of the program based on the triangulation of data from the focus groups, fidelity forms, and satisfaction questionnaires, although there were some discrepancies between the data from the students and from the teachers. For 69.4 % of the students, the program helped them answer personal questions. Of the teachers, 88.9 % said that it improved their knowledge and skills on drugs and prevention. The program satisfaction in the school setting was clearly observed, as shown in Table One of the study’s notable findings was the improvement in the relationship both between teachers and students and between students in the classroom. This result was identified from qualitative and quantitative data, namely teachers’ and students’ focus groups discussions and satisfaction forms Table .Unplugged lessons in the 62 classes was, on average, very high or high in 48.2 % of the lessons (n = 316), moderate in 46.5 % (n = 304), and absent/very low in 5.2 % (n = 34).According to the teachers' opinions in the fidelity forms, the level of students' interest in the 12 n = 334). In 45 % (n = 295) of the cases, there was a moderate level of comfort, and no comfort was reported in 4 % of the cases (n = 26).An indirect assessment of the acceptability of the program by the teachers was obtained from their reported level of comfort in teaching the lessons. Teachers provided this information at the end of each lesson on the fidelity form. Based on the data from these forms, most of the teachers described, on average, a high to very high comfort level  said that they were “satisfied or very satisfied” with the program. Students had a similar positive perspective, although a smaller proportion of them were “satisfied or very satisfied” (77.9 %).“I liked the one [lesson] in which we either followed a group's decision or not because you don't have to do what the group does to join it, to be like them.” (6th and 7th grade students)“I liked the exercise where there were two groups and there were also judges. One was about defending alcohol and tobacco and what alcohol and tobacco did.” (6th and 7th grade students)When asked which lessons they liked the most, the students said that their interest in the lessons depended on the topic discussed. Although their interest was usually high, their responses showed that the lessons with information on drugs and making choices in groups were the ones that generated the most interest.Unplugged activities, they suggested that there should be a specific class for the program with more time allocated to it than what was planned in the pilot phase. They also supported the continuation of the program in the following year.“I think that there should be more time for the lessons; there was a lesson we started and then the bell rang, and we had to finish it in the following class. We should have a specific class for Unplugged.” (8th and 9th grade students)Because the students enjoyed the Unplugged in the following school years.Finally, 76.5 %  of the students reported that they would like to have a program similar to This study presents the process evaluation of a European evidence-based drug use prevention program that was created in developed countries and implemented in Brazil, a Latin American, middle-income, developing country. The process evaluation results of this study, in addition to the outcome results, will inform stakeholders’ decisions regarding the program’s maintenance and expansion in Brazilian public schools by providing data on the program’s feasibility and acceptability as well as possible adaptations to increase its fidelity.Unplugged was essential for its appropriate implementation in schools, as a better understanding of the acceptability is an important tool in the development of management strategies to expand drug prevention interventions. User satisfaction is a component of social acceptability and is necessary for a program to be successful [Unplugged was evident in the findings of this process evaluation.Researching the acceptability of the program in the different groups involved in ccessful . AcceptaThe assessment of the feasibility of the program indicated that its implementation was possible despite the difficulties highlighted by the teachers. The teachers emphasized that the program required time to plan the activities and to prepare the classroom, which was not incorporated into the schools' regular curriculum. This affected the teachers' regular curricular activities and overburdened them with new activities. The data showed that the time per lesson and, consequently, the total time needed to apply the program in a school year were elements that had to be factored into the regular classroom schedule as only 57 % of the lessons were effectively taught within the expected time. We found that the teachers randomly excluded activities when they realized that they would not able to teach the complete lesson, which suggests that it would be useful for the program developers to identify the core elements of a lesson that should be taught by the teacher even when time is constrained.Unplugged [Unplugged in European countries, almost half of the classes were not delivered to the experimental group, and despite this fact, the program revealed effectiveness in reducing alcohol and tobacco consumption among students [The fidelity evaluation conducted in this study, as proposed by the developers of nplugged , 27, focnplugged . Howeverstudents . Althougstudents , in our The only way to guarantee the sustainability of the program would be to incorporate it into the school curriculum; this would ensure that the program activities would not interrupt the time allocated for teachers' regular subjects. However, it is important to note that the lack of time reported by the teachers to implement the normal school program is not unique to this setting. A study evaluating the process of implementation of a depression prevention program for teenagers in classrooms showed similar conflicting demands of teachers' time between the program and the regular curriculum. In addition, it revealed a culture in which exclusively academic activities were more important than the personal, social, and health-related activities of the students, which negatively affected the implementation of the program in schools in England .Unplugged was adopted to fill this organizational gap as it also aligned with the guidelines described in the “Integrated Policy of Attention toward Alcohol and Drug Users" written by the Brazilian Ministry of Health [According to Sloboda et al. , when thf Health . These gf Health , for a pUnplugged has proved to be an intervention that is well accepted among the participants directly involved (students and teachers) in addition to being effective in European countries. Furthermore, the program is structured using interactive techniques, which allows for the development of life skills. In a meta-analysis that evaluated school prevention programs, Tobler et al. [r et al.  found thr et al. , informar et al. .Unplugged provided a distinct form of intervention in the school environment. It also influenced the perceived relationship between the teachers and the students as well as between students in the same classroom, independent of the results on drug use prevalence (which were not the focus of this article). These results suggest that it would be important to include classroom environment outcomes as secondary outcomes in the next randomized controlled trial of Unplugged.Unplugged program that focuses on the implementation process and not on the program’s effectiveness results. This research expands the program’s literature on transcultural adaptation as Unplugged was designed for developed European communities and not for developing countries. Considering the unique nature of the public schools in one of the most unequal countries in the world, the absence of acceptance among stakeholders, school directors, teachers and students would have resulted in the quick termination of the program in schools despite the federal government’s support for its implementation.This is the first study of the Although the study presents relevant data, there are inherent limitations of the methods that should be considered. One of these limitations was that the participating schools were not randomized; they were nominated by the department of education in each of the participating cities. In addition, the school staff selected the students who participated in the focus groups, and this could have prevented the representation of the general student body in the study. Finally, the high burden of demands on the teachers may have reduced their willingness to complete the satisfaction questionnaire that was collected in the last school week of 2013.There is no way to conclude whether the schools included in this study differed from those not included. What we can confirm is that the schools included had a similar drug use pattern to the ones described in the last national survey on drug use by middle and high school students in Brazilian capitals , 23, whiUnplugged in schools in developing countries.The relevance of this study is that it deepened the available scientific knowledge on drug use prevention programs in the school environment; in particular, it generated results that can inform decision-making regarding the implementation of Unplugged that was offered in the classrooms was satisfactory as almost all the classrooms received 12 lessons. However, the number of activities completed in each class was inadequate; almost half of the lessons were not completed during the 45- to 50-min class period. All the studied groups described positive perceived results on school environment, and teachers and students mentioned an improvement in their relationships. However, a significant challenge reported by the study participants was the inability of the teacher to provide the same quality teaching of their normal curricula; teachers had to deliver the Unplugged lessons during their regular class time and did not have additional hours to teach the subjects that were replaced by the Unplugged activities.The dose of Unplugged program to avoid using the regularly scheduled class time for the Unplugged activities. Finally, a randomized controlled trial that includes school environment outcomes in the analysis, such as the relationship between teachers and students, is recommended.Based on the analyzed results, we suggest three adaptations that could improve the implementation of the program. The first recommendation is to adapt the number of activities per class with the support of the developers to allow each class to be fully executed and to prevent teachers from having to randomly exclude activities. Second, we recommend restructuring the general workload of the teachers who implement the


The authors sought to identify variables associated with MD–PhD program graduates’ academic medicine careers.We analyzed data for a national cohort of MD–PhD program graduates from 2000 to 2005, using multivariable logistic regression to identify independent predictors of full-time academic medicine faculty appointment through 2013.Of 1,860 MD–PhD program graduates in 2000–2005, we included 1,846 (99.2%) who had completed residency training before 2014. Of these 1,846 graduates, 968 (52.4%) held full-time faculty appointments. Graduates who attended schools with Medical Scientist Training Program (MSTP) funding  and participated in ≥1 year of research during residency  were more likely to have held full-time faculty appointments. Asian/Pacific Islander  and under-represented minority  graduates (each vs. white graduates), graduates who reported total debt of ≥$100,000 (vs. no debt) at graduation , and graduates in surgical practice  and other practice  specialties  were less likely to have held full-time faculty appointments. Gender was not independently associated with likelihood of full-time faculty appointment.Over half of all MD–PhD program graduates in our study had full-time faculty appointments. Our findings regarding variables independently associated with full-time faculty appointments can inform the design of strategies to promote academic medicine career choice among MD–PhD program graduates. Further research is warranted to identify other factors amenable to intervention, in addition to those included in our study, which will foster the further development of a diverse academic medicine physician–scientist workforce nationally. Enrollment in MD–PhD joint-degree programs at Liaison Committee for Medical Education (LCME)-accredited US medical schools experienced a period of substantial growth over the past 20 years. From 1993 to 2013, the total number of students who entered medical schools increased by 17%, while the number of students who were enrolled in MD–PhD programs increased by over 100% , and 45 Historically, MD–PhD program graduates, particularly those of MSTP-funded programs, predominantly pursued careers in academic medicine , 11. HowMedical students who are enrolled in MD–PhD programs are eligible to apply for individual F30/F31 predoctoral awards , 15, butFollowing Institutional Review Board approval at Washington University School of Medicine, a database was constructed with individually linked, de-identified records for all 129,867 students who had matriculated at one of the 129 LCME-accredited medical schools in the United States from 1993 to 2000 and who graduated between 2000 and 2005. We restricted our study sample to graduates in 2000–2005 because MD–PhD program enrollees take 7–8 years, on average, to complete the program , and we SRS data included matriculation date, graduation date, students’ self-identified sex, and race/ethnicity as was reported from a list of options on the American Medical College Application Service questionnaire. We categorized race/ethnicity as Asian/Pacific Islander, URM , other/unknown , or white (reference group).We used GQ data to create a 5-category variable for total debt at graduation .The AAMC also provided data for medical schools’ MSTP-funding status based on rosters of MSTP-funded institutions updated annually by the NIGMS, as previously described ; of the We used GME Track data to distinguish between graduates who had completed ≥1 year of research during GME, as indicated by their program director on the GME Census, and graduates for whom there was no documentation of research during GME.We used AMA Physician Masterfile data for type of practice to exclude from analysis those MD–PhD program graduates still in GME at end of 2013, as trainees are ineligible for full-time faculty appointments, and to create a three-category variable for practice specialty, for graduates no longer in GME: ‘internal medicine, pediatrics, neurology or pathology’, the specialties historically chosen most frequently by MD–PhD program graduates , ‘surgerData for full-time faculty appointment at a US LCME-accredited medical school were obtained from AAMC Faculty Roster records . We creaP values <0.05 were considered significant.We used chi-square tests to describe associations between two categorical variables. We report adjusted odds ratios (aOR) and 95% confidence intervals (CI) from a multivariate logistic regression model to identify independent predictors of full-time faculty appointment among all MD–PhD program graduates in our study sample. All tests were performed using IBM SPSS Statistics, version 22 ; two-sided Of the 129,867 medical-school matriculants in our database, there were 3,420 MD–PhD program graduates, including 1,860 who had completed the dual-degree program in academic years 1999–2000 (2000) through 2004–2005 (2005). Of these 1,860 MD–PhD program graduates, we excluded 14 graduates who were still in GME at the end of 2013. Our final study sample of 1,846 MD–PhD program graduates (99.2%) included 968 (52.4%) MD–PhD program graduates who had held full-time faculty appointments by the end of 2013.Descriptive statistics for the 1,846 MD–PhD program graduates in our sample, grouped by full-time faculty appointment, are shown in As shown in Of all 1,846 MD–PhD program graduates in our cohort, 52.4% had been appointed to a full-time, academic medicine faculty position. This proportion was substantially greater than the proportion of MD graduates without PhD (18%) who had full-time faculty appointments in the larger cohort, as previously reported , 21. We Our observation that receipt of F30/F31 predoctoral fellowship awards was associated with greater likelihood of full-time faculty appointment among MD–PhD program graduates informs the evidence base for the role these predoctoral fellowship programs can play in the development of the physician–scientist workforce .Concerns have been raised that the increasing debt load among medical school graduates might negatively impact physician–scientists’ career paths; thus, the goal of the NIH Extramural Loan Repayment Program (LRP) is ‘to attract and retain early career health professionals in biomedical and behavioral research careers ’. Two naAfter controlling for total debt at graduation and other variables of interest, MD–PhD program graduates in the surgery and the other practice categories were less likely than graduates in the ‘internal medicine, pediatrics, neurology, and pathology’ practice category to have had faculty appointments. Lengthier GME requirements for general certification by member boards of the American Board of Medical Specialties might explain these observations in part for graduates in surgery . HoweverAbout 30% of all MD–PhD program graduates in our study were documented by their residency training program directors to have spent ≥1 year in research during GME; by comparison, only 9% of MD-degree graduates in this national cohort were documented to have spent ≥1 year in research during GME . OptionsThe proportion of female MD–PhD program graduates has more than doubled over the past 20 years; women comprised less than 20% of MD–PhD program graduates in 1995  and nearThe racial/ethnic diversity of MD–PhD program graduates also has increased over the past 20 years. In 1995, 75% 236/313) of MD–PhD program graduates were white; in academic year 2014–2015, this percentage declined to 61% (376/616) . URM gra3 of MD–Pcurricula vitae provided by graduates themselves (Our study had a number of strengths. We included information for several different variables that have been identified in the literature as possible predictors of MD–PhD program graduates’ career paths but have not previously been explored for their associations with academic medicine careers, and we had data for a national cohort of MD–PhD program graduates, all with a minimum follow-up of 8 years after graduation. Unlike previous studies of academic medicine faculty appointment among MD–PhD program graduates that utilized data obtained from emselves  or data emselves , we obtaOur study also has several limitations. Because we did not have programmatic information for the MD–PhD programs in which the graduates in our sample had been enrolled, it is possible that outcomes for graduates of specific MD–PhD programs may be different from the findings we report here. We did not have information about graduates’ PhD degree fields. MD–PhD programs offer PhD in a wide range of fields other than biomedical and physical sciences , 32, butDespite these limitations, our observations may be of interest to many agencies and organizations that provide funding to MD–PhD programs and those that provide financial support for LRPs in which MD–PhD program graduates may participate. Our findings regarding variables associated with initial full-time faculty appointment among MD–PhD program graduates also can inform the efforts of US medical schools seeking to recruit a diverse and highly qualified academic medicine physician–scientist workforce well-positioned to advance our national biomedical-research agenda.


A process evaluation of a participatory supportive return to work program, aimed at workers without a (permanent) employment contract who are sick-listed due to a common mental disorder, revealed that this program was executed less successfully than similar programs evaluated in earlier studies. The program consisted of a participatory approach, integrated care and direct placement in competitive employment. Aim of this study was to get a better understanding of the execution of the program by evaluating stakeholders’ perceptions. In the absence of an employer, the program was applied by the Dutch Social Security Agency, in collaboration with vocational rehabilitation agencies. Together with the sick-listed workers, these were the main stakeholders. Our research questions involved stakeholders’ perceptions of the function(s) of the program, and their perceptions of barriers and facilitators for a successful execution of the program within the Dutch social security sector.Semi-structured interviews were held with five sick-listed workers, eight professionals of the Social Security Agency, and two case managers of vocational rehabilitation agencies. Interview topics were related to experiences with different components of the program. Selection of respondents was based on purposive sampling and continued until data saturation was reached. Content analysis was applied to identify patterns in the data. Two researchers developed a coding system, based on predefined topics and themes emerging from the data.Although perceived functions of some components of the program were as intended, all stakeholders stressed that the program often had not resulted in return to work. Perceived barriers for a successful execution were related to a poor collaboration between the Dutch Social Security Agency, vocational rehabilitation agencies and healthcare providers, the type of experienced  problems, time constraints, and limited job opportunities.For future implementation of the program, it will be important to consider how a better integration of services by the Dutch Social Security Agency, vocational rehabilitation agencies and the mental healthcare sector can be improved in order to address treatment and vocational needs simultaneously, and to better match the sick-listed worker with the limited opportunities in the Dutch labor market.NTR3563The online version of this article (doi:10.1186/s12889-016-2997-x) contains supplementary material, which is available to authorized users. Complex interventions consist of multiple interacting components , 2. WhenIn an earlier study we conducted a process evaluation of a participatory supportive return to work (RTW) program, alongside a RCT, using quantitative research methods . Aim of Findings of our process evaluation revealed that the participatory supportive RTW program was executed less successfully compared to similar programs evaluated in earlier studies . A smallThe aim of this present study was to get a better understanding of the execution of the participatory supportive RTW program, by evaluating the execution of the intervention in relation to its setting. Several authors state that to account for the complexity of an intervention, it is not only important to quantify what happened in practice, but also to identify  factors that could have influenced the execution of an intervention –10, and Qualitative study methods are considered useful for unravelling processes of change, exploring responses to the intervention and describing the intervention as executed in practice . For thaThe study design consisted of a qualitative study that was conducted alongside a RCT, titled ‘the Co-WORK study’. The aim of the Co-WORK study was to investigate the (cost-)effectiveness of the participatory supportive RTW program in comparison with usual OHC by the Dutch SSA. The Medical Ethics Committee of the VU University Medical Center  gave Ethical approval for the study. The same committee declared that no comprehensive ethical review was needed for this qualitative study. The trial was registered at the Dutch Trial Register  on August 7, 2012 (NTR3563). All participants signed informed consent. More information about the trial can be found in the study protocol .The participatory supportive RTW program was aimed at unemployed workers, temporary agency workers and fixed-term contract workers who had filed a sickness benefit claim at the Dutch SSA, with mental health problems as main reason for their sickness benefit claim. Other stakeholders in the intervention were insurance physicians, labor experts and RTW coordinators of the Dutch SSA, and case managers of contracted vocational rehabilitation agencies. Seven SSA front offices participated in the program, located in the western, central and eastern region of the Netherlands, and three vocational rehabilitation agencies, operating on a national level.To get a broad understanding of perceived functions of the program and perceived barriers and facilitators for a successful execution, we wanted to identify all different perceptions of stakeholders in our study. We used purposive sampling to select stakeholders with various characteristics, as we expected that their perceptions of the execution of the program could differ. In the remaining of this article sick-listed workers who participated in the participatory supportive RTW program are referred to as ‘clients’, as at least some of them were no longer sick-listed at the timing of the interviews.Clients were selected on the basis of a variation in gender, educational level, age, duration of last employment, region and date of enrolment in the Co-WORK study. This information was collected during the baseline measurement of the Co-WORK study. Clients were matched to a SSA front office for RTW guidance, based on their zip code. By selecting clients from different regions they automatically belonged to different SSA front offices. We only selected clients that had actually participated in the participatory supportive RTW program. We also selected insurance physicians, labor experts and RTW coordinators from different participating SSA front offices. Moreover, these professionals had to have applied the participatory supportive RTW program at least twice, so that perceptions were not based on only a single case. As at each SSA office a maximum of two professionals of each profession participated in the program, further selection based on other characteristics was not possible. This was also the case for the vocational rehabilitation agencies. Of the three participating agencies, one case manager was selected for an interview.For the recruitment of respondents we used communication methods that had been used before for contacting the different stakeholders during the Co-WORK study. Clients were invited for an interview by telephone. During this telephone conversation, they were informed about the purpose of the interviews, the content and duration of the interviews, and other study procedures. In case someone was willing to participate, an appointment for an interview was made directly. A confirmation of this appointment was sent to the client by postal mail, including a summary of the study procedures and an informed consent form. By signing informed consent, the client agreed with his participation in the study and with the recording of the interview. Professionals were invited for participation by e-mail. In this e-mail all study procedures were explained. By responding to the e-mail and expressing their willingness to participate, professionals consented to their participation in the study.Three clients that were approached for participation in an interview declined. Further, one insurance physician and one case manager did not respond to the invitation. Selection and recruitment of respondents for the interviews was continued, until data saturation was reached. Data saturation was considered to be reached when a new interviewee within a stakeholder group described to a large extent the same functions of the participatory supportive RTW program and/or the same barriers and facilitators for a successful execution of the program, compared to earlier interviewees within the same stakeholder group.In total, 15 respondents were included in this study. Interviews were held with two insurance physicians, three labor experts, three RTW coordinators, two case managers of vocational rehabilitation agencies and five clients. Professionals were from four different SSA front offices and two vocational rehabilitation agencies. Clients belonged to four different SSA front offices. More background information on the clients can be found in Table See Additional file 1) gives an overview of the topics that were discussed during the interviews. Each interview was recorded and fully transcribed (verbatim).The interviews were conducted by telephone by L.L., the first author of this study. The semi-structured interviews took 20–45 min, dependent on the number of topics discussed. Prior to the interviews a topic-list was created for each group of respondents or stakeholders. This topic list contained both general topics and more specific questions about experiences with different components of the participatory supportive RTW program. Examples of general topics were ideas about the program’s effectiveness and points of improvement. The more specific topics were related to the specific role of the respondent in the program, and differed between stakeholders. Insurance physicians were asked about contra-indications for participation in the program and about their experiences with the application of an integrated care approach. Labor experts and RTW coordinators were asked to evaluate the use of a participatory approach. Specific topics for the case managers of the contracted vocational rehabilitation agencies included ways in which was searched for suitable competitive jobs and their effectiveness. Clients were asked to evaluate all different components of the program, i.e., integrated care, a participatory approach and direct placement in a competitive job. Table A1  codes. In this way, both researchers created an extended code list. During the phase of axial coding, the code lists were discussed by both researchers in order to reach consensus about a provisional list of codes and the interpretation of these codes. During this consensus meeting, it was carefully assessed whether the created codes were appropriate to describe the data and whether the text parts were given the most suitable code. The relation between main and sub codes was discussed, codes describing the same themes were clustered, and codes describing multiple themes were split into different codes. After consensus was reached, all transcripts were (again) analyzed by L.L, using the provisional code list. When necessary, new codes were created. Finally, patterns in the data were identified by looking for returning themes and by making connections between these themes. During this phase, we identified perceived functions of the participatory supportive RTW program and of its separate components, and perceived barriers and facilitators for a successful execution if the program. Codes describing the functions of the program were mostly directed by the predefined topic list. Barriers and facilitators mostly emerged from the data. All authors were involved in this phase of selective coding.We used quotes originating from the interviews to illustrate our findings. Cited professionals were described by the job title of their profession. For clients, we used numbers 1–5), corresponding to the numbers used in Table –5, correWe present stakeholders’ perceptions of (1) functions of the participatory supportive RTW program, (2) barriers for a successful execution of the program, and (3) facilitators for a successful execution of the program. We distinguished between perceived functions of the program’s separate components, i.e., integrated care, a participatory approach and direct placement in a competitive job. Subsequently, frequently mentioned barriers and facilitators for a successful execution of the program were summarized. We distinguished between perceptions by different stakeholders, when they had different points of view.Insurance physician 1: “I believe that working together for a client can have a positive effect, because it leads to respect for each other’s discipline.”Insurance physician 2: “It leads to interaction, while normally you ask for information and that’s it.”The insurance physicians thought that the communication and cooperation between them and the clients’ healthcare provider(s) had improved after they had contacted the healthcare provider(s).Insurance physician: “My experiences were positive, because the healthcare providers became aware of the clients’ participation in the program and also responded positive to the focus on work resumption. So, this had opened the healthcare providers’ eyes and they were no longer solely focused on the health complaints of their clients.”Another perceived function of this component of the participatory supportive RTW program was a shift in paradigm by the healthcare providers from a disability-oriented approach to an approach in which work became more central.However, the insurance physicians not always thought it was necessary to contact the clients’ healthcare provider(s). One of the insurance physicians stressed that only sick-listed workers with mild  problems participated in the participatory supportive RTW program. Therefore, no conflicting advice could be expected. In case of more severe problems, the insurance physician would not have the client start with the program.Client 4: “Of course he understood my situation. He told me: ‘You’re not fit. You’re not at your best. You should realize that your chances of getting hired are extremely small.”The clients indicated that work resumption was barely discussed with their healthcare providers. They also had not received any conflicting advice from their healthcare providers regarding their possibilities for RTW.Labor expert: “Normally we ask clients about their background and we discuss some obstacles, but then we mainly speak about limitations that were noticed by the physician. Now, clients had to come up with their own ideas about obstacles and suggestions to overcome these obstacles. This self-reflection was hard, but it helped to get them in another mindset.”The RTW coordinators and labor experts thought that it was important to actively involve the client in the creation of a RTW action plan and also believed that this participatory approach had actually led to a more active participation in vocational rehabilitation by the client.According to the labor experts and RTW coordinators, many clients were strongly involved in the identification of obstacles and finding solutions and suitable work. However, they also thought that the input of the clients varied.Labor expert: “I found it very surprising how clients already had made some important steps in the time between the meeting I had with them for the identification of RTW obstacles and subsequently the brainstorm session in which they discussed solutions to overcome these obstacles with the RTW coordinator, because it was clear for them what was the core of their problems and which of their problems they could influence.”Another function of the participatory approach, perceived by these stakeholders, was that it had helped clients to get a better understanding of their barriers and possibilities for RTW.Client 2: “They assessed my capabilities and such. They also contacted the vocational rehabilitation agency. Then that part of the program started. And if there were any questions, I could contact them. But these did not really occur. We simply proceeded with the program and I did not receive any further support.”The clients did not mention these functions when they reflected on the counselling they had received by the SSA. From their perception, obstacles for RTW and solutions to overcome these obstacles had barely been discussed. They thought that they had received not enough counselling by the SSA, as was explained by one of the clients:All clients indicated that their participation in the participatory supportive RTW program did not result in RTW in a competitive job. Also the other stakeholders confirmed that the program in many cases did not have the intended result, as many of their clients were not placed in competitive employment.When the case managers of the vocational rehabilitation agencies were asked what actually had been done after referral of the client to their agency, they explained that they had put in a lot of effort to place the clients in a suitable job. They stressed that they did more than solely job hunting, e.g., helping the client with the writing of their CV and preparation for a job interview.Client 1: “I had one meeting with her and she would set to work. Finally she called me and said: ‘I never hear anything from you’. I asked her: ‘But shouldn’t I hear something from you?’ Actually, I did not understand anything of it.”When describing the support they had received from the vocational rehabilitation agencies, some clients told that the case manager had not taken their job preferences into account and they had been treated like numbers. Others indicated that they had been in regular contact with the case manager who had helped them with their CV and application letters. Some mentioned that the case manager also had contacted companies to look for job opportunities. As a result, some clients were more positive than others. Still, most of them emphasized that they had received too little support from the case managers.The RTW coordinators of the SSA were responsible for monitoring the implementation of the RTW action plan. They also thought that the quality of the contracted vocational rehabilitation agencies differed a lot. They were dissatisfied with one agency, because of poor communication and involvement of this agency, but satisfied with another agency, because this agency started their job search very early after referral of a new client to their agency.When clients were asked about their own participation in the program, they often indicated that they had been looking for job opportunities by themselves and had applied for several vacancies. They all wished to return to work. Some had found a voluntary job.The case managers were quite positive about the cooperation by the clients in the search for a suitable job. However, in some cases they thought that the client could have participated more actively.The professionals of the SSA mentioned several barriers that were related to a poor collaboration between their service and the contracted vocational rehabilitation agencies and/or the mental healthcare sector.Insurance physician: “That could be very time consuming. Some of the healthcare providers I could not reach by telephone. I even did not get their numbers. Once, the assistant of a general practitioner did not want to give me the number of a healthcare provider, because she was not sure that I was who I said that I was.”One of the insurance physicians explained that, because of segregation of services by the SSA and the healthcare sector, it was sometimes difficult to get in touch with the clients’ healthcare providers.Case manager of a vocational rehabilitation agency: “We talked with our client about what was discussed with the SSA, to see if this was still applicable. That was often the case. Sometimes we also considered other possibilities than the ones discussed by the SSA, so that we could use a broader perspective for our search. This was sometimes necessary, because we had to take the limited opportunities in the labor market into account.”Another example of a poor collaboration mentioned by the SSA professionals was that the vocational rehabilitation agencies often analysed obstacles and solutions for RTW, while this was already done by the SSA. During the application of a participatory approach at the SSA, an action plan for RTW was made. From the perspective of the SSA professionals, the RTW action plans were useful in the search for a competitive job, as these summarized the most important obstacles for RTW, preconditions for RTW and suitable work. However, they thought that the agencies made only little use of the information in these action plans. This was confirmed by the case manager of one of the contracted vocational rehabilitation agencies, who explained that it could sometimes be necessary to use a broader perspective:The RTW coordinators of the SSA also admitted that, mainly due to time constraints, after referral of the client to the vocational rehabilitation agency they often had only limited contact with the client and barely monitored the actual implementation of the RTW action plans.According to all stakeholders the type of  complaints experienced by the clients sometimes hampered a successful execution of the participatory supportive RTW program. In other words, the participatory supportive RTW program was not always considered suitable. In case the program was not seen as appropriate, this was often related to the perceived severity of the client’s  problems.Insurance physician: “Often it concerned more complex cases, clients who needed attention on multiple aspects to improve functioning. In those cases, the program would have counteracted its purpose, because having to visit different professionals who ask different things would have been too demanding and intensive. It seems easy, but for some this is a huge task.”The insurance physicians indicated that for clients with severe  health problems, participation in the program early after sick-listing could be too demanding, because of its intensity and early focus on work, and they were afraid that it would worsen their complaints.RTW coordinator: “I believe that when you have serious mental health complaints, you can’t think clearly anymore. You don’t know exactly what has caused your complaints and what your capabilities are.”One of the RTW coordinators emphasized that for clients who participated in the participatory supportive RTW program it could be very difficult to point out obstacles for RTW, as a consequence of their mental health problems:Labor expert: “When someone has psychological problems it is more difficult to find a solution, then when someone faces a more concrete return to work obstacle”Mentioned by both labor experts and RTW coordinators was the difficulty to come up with solutions for obstacles for RTW, when these obstacles were related to the experienced mental health problems.Client 4: “You have to compete with the rest of the world, while your own perception is that you’re not capable enough. That’s like being placed inside a boxing ring, together with professional boxers, while you’re still nothing.”Case manager of a vocational rehabilitation agency: “…not searching for vacancies, because they were so insecure about their own capabilities that it complicated their job search. Every time they asked themselves: ‘Am I capable enough?’.”Also the placement in a competitive job was according to many stakeholders sometimes hampered by characteristics of the clients, such as an older age, a large distance to the labor market, a lack of application skills, passivity and mental health problems. According to some, this could lead to feelings of uncertainty, which formed another major obstacle for RTW.One of the case managers believed that the presence of mental health problems sometimes resulted in passivity and a lack of motivation. According to this case manager some clients also placed great demands on a vacancy, which made it difficult to find a suitable job.RTW coordinator: “To be able to return to work, sometimes an increase of their mental resilience was necessary.”Some of the professionals doubted if the client was ready for RTW, given his or her mental health problems. They thought that these clients needed more training prior to placement in a competitive job, such as training in empowerment or application skills, to increase their confidence, skills and motivation.All stakeholders indicated that a lack of time was an important barrier for a successful execution of the program.The labor experts and RTW coordinators stressed that the application of a participatory approach was very intensive. On the one hand this gave them the opportunity to get a full understanding of the client at an early stage and to gain the client’s confidence in their counselling. On the other hand, it was time consuming and asked a lot from both professionals and clients.RTW coordinator: “The workload at our department was high and we had to achieve several targets. Because there were no performance indicators for our participation in the Co-WORK study, often this work was done after other work was finished.”An important obstacle mentioned by all stakeholders was a lack of capacity at the SSA or vocational rehabilitation agency, often resulting in limited time to execute the program.Labor expert: “In this way, every team member has to be available all the time. The workload was very high.”As was illustrated in this last quote, the limited capacity was partly related to the study setting. The participatory supportive RTW program was not part of the daily practice of the professionals and there were often other competing priorities. Moreover, only a few professionals in the organizations were trained in the program. In this way, it was not always possible to schedule all steps of the program in accordance with the prescribed time frame, as was explained by one of the labor experts:Case manager of a vocational rehabilitation agency: “Given the problems of some people, or actually the majority of the people, a time-frame of 2 to 3 months appeared to be rather short sometimes. You want to get someone back on track very quickly, while sometimes there are serious complaints that get in the way and that need more attention.”The case managers found that the period of 2 to 3 months in which they had to place the client in a suitable competitive job was too short, especially when the client was still facing mental health problems.Also many clients stressed that the received support for their job search was too short in time.A frequently mentioned barrier was the limited availability of suitable paid jobs in the Dutch labor market during the execution of the program, caused by the economic recession at the time.RTW coordinator: “You can wish to work on your own, because you can’t work together, or to get only one task at a time, or to have a break every ten minutes. Then you have figured out how you could function, but when you present these wishes to an employer, it is not realistic to think that they will offer you a job. Sometimes these work solutions may have been helpful, but they were not realistic to present to an employer.”The labor experts and RTW coordinators thought that in this situation it was difficult to think of suitable work. A RTW coordinator explained that it was often difficult to convert the preconditions for RTW into a concrete job:Many stakeholders acknowledged that the clients often had to compete with a large number of other job seekers and many of them believed that an employer was not willing to hire an employee who is not fully employable.A facilitating factor mentioned by the labor experts was diminishing the number of professionals involved in the program, for example by letting the RTW coordinator perform all steps of the participatory approach. According to them, in this ways the capacity problem could be tackled.One of the RTW coordinators and one of the case managers thought that involvement of the vocational rehabilitation agency in the development of the RTW action plan could have facilitated the search for a suitable job. Because of their knowledge of the labor market, the case managers could have helped matching the clients’ wishes and preconditions for RTW with opportunities in the labor market.Some clients, and also a few professionals, indicated that it would also have helped if the vocational rehabilitation agencies had already made some work arrangements with employers, including arrangements regarding therapeutic or sheltered workplaces. They stressed the importance of work and also of voluntary work, which could serve as a stepping-stone to more sustainable employment and help clients to become more self-confident.The aim of this study was to gain insight into the execution of the participatory supportive RTW program within the Dutch social security sector, by evaluating stakeholders’ perceptions of the function(s) of the program, and their perceptions of barriers and facilitators for a successful execution. The findings of our study reveal that according to the professionals of the Dutch SSA, the functions of two components of this program – integrated care and a participatory approach – were as intended. These functions were respectively improving the communication and cooperation with the clients’ healthcare provider(s) to avoid conflicting advice about the clients’ possibilities for RTW, and making a consensus-based RTW action plan. However, the clients did not mention these functions. Instead, most of them stressed that they had received too little support from the SSA. Furthermore, both professionals and clients indicated that the job search based on the RTW action plan often did not result in placement of the client in a suitable competitive job. The execution of the program in the study’s practice appeared to be often not proceeded as intended. Several barriers for a successful execution of the full program were mentioned by the stakeholders. These barriers were related to a poor collaboration between the SSA, the vocational rehabilitation agencies and the mental healthcare sector, the type of  problems experienced by the clients, time constraints for the professionals, and limited opportunities at the Dutch labor market. Perceived facilitators for a successful execution of the program were: diminishing the number of SSA professionals involved, earlier involvement of the vocational rehabilitation agency, and making work arrangements with employers.The use of a participatory approach had been positively evaluated in the previous process evaluation . This coAn important barrier, mentioned by many stakeholders, was the limited availability of suitable jobs in the labor market. This barrier was seen before in studies evaluating the feasibility and effectiveness of supported employment in the Netherlands and other European countries , 19. RelThe perceived barriers related to the type of  complaints, illustrate that there is still a very cautious approach regarding an early RTW of persons with a CMD. Although ‘place-and-train’ interventions such as supported employment have received growing attention in the last few years –20, in EThe difficulties in the collaboration between the SSA, vocational rehabilitation agencies and the mental healthcare sector mentioned by professionals in our study illustrate how, despite attempts made for a better integration, this remained limited. This limited integration of services can be explained by comparing the participatory supportive RTW program with other RTW interventions. When we look at RTW interventions in which an integrated care approach was applied successfully , 20, 21,The different perceptions of functions of the participatory supportive RTW program by clients and professionals of the SSA was in line with previous research. The study of Maiwald et al.  revealedAn important strength of this study is that members of all stakeholder groups were interviewed. This made it possible to look for differences and similarities between perceptions of these different stakeholders of the execution of the participatory supportive RTW program in practice. This helped to get a full understanding of functions of the program according to these different stakeholders, and their perceptions of barriers and facilitators for a successful execution.Another strength of this study is that the coding system was developed by two researchers, which increases the credibility of the analysis. However, the co-authors of this paper were only involved in the last phase of coding, i.e., selective coding. This can be seen as an important limitation of this study.Another limitation of this study was that all interviews were held by telephone. This method was chosen, because we expected that both clients and professionals were more eager to participate and to talk freely when they could participate via a telephone conversation. However, non-verbal communication was not visible for both the interviewer and the interviewee, which is an important limitation of this method.The non-response among some clients could be seen as another limitation. This could have biased our findings, as clients that agreed to participate might differ in perceptions from the ones who did not agree. However, the application of purposive sampling helped us to include clients with various characteristics.N = 36) [Non-response among professionals was low. Nevertheless, input of one contracted vocational rehabilitation agency was missing, as its case manager was no longer working for this agency and we were not able to contact him. Furthermore, professionals of only four SSA offices participated in the present study, whereas in total seven SSA offices had participated in the Co-WORK study. This was caused by the very low number of cases in which the participatory supportive RTW program had been applied at the remaining offices. By selecting professionals that applied the program at least twice, we may have selected professionals who were more willing to implement the program. Still, also the selected professionals had applied the program only a few times. The number of clients that had actually participated in the intervention was very low (N = 36) . This meThe timing of the interviews can be seen as another cause of possible bias and forms another limitation of this study. All clients had started with the program more than 1 year before the interview. This might have resulted in recall bias.Our findings emphasize the need for a better integration of services from the Dutch SSA, vocational rehabilitation agencies and from the mental healthcare sector, in order to respond to the  needs of workers without a (permanent) employment contract, sick-listed due to a CMD. An important point of improvement mentioned by the respondents in this study, is an earlier involvement of vocational rehabilitation agencies in RTW counselling.Furthermore, lessons may be learned from supported employment . In thisTo stimulate a successful integration of mental healthcare in vocational rehabilitation of workers without a (permanent) employment contract who are sick-listed due to a CMD, it seems important that employment problems and outcomes become central in the treatment of mental health problems . In thisWe recommend to evaluate in future research whether more intensive and earlier involvement of vocational rehabilitation agencies and mental healthcare providers would help to identify barriers for RTW in an early phase, and to better match the sick-listed worker with (the limited) opportunities in the labor market.The results of this study indicate that, despite the quite positive evaluation of the functions of integrated care and a participatory approach, there were multiple barriers for a successful execution of the full participatory supportive RTW program. Execution of the program seemed to be highly influenced by the limited availability of suitable jobs in the Dutch labor market, the belief of some professionals that an early RTW of sick-listed workers with mental health problems should be avoided, the segregation of services within the Dutch social security sector, and by time constraints for professionals. For future implementation of the program in the Dutch social security sector, it will be important to consider how integration of services by the Dutch SSA, vocational rehabilitation agencies and the mental healthcare sector can be improved in order to respond to the  needs of sick-listed workers with a CMD.Data and materials for this study are available through communication with the corresponding author of this manuscript, F.G. Schaafsma.