Interventions based on meditation and mindfulness techniques have been shown to reduce stress and increase psychological well-being in a wide variety of populations. Self-administrated Internet-based mindfulness training programs have the potential to be a convenient, cost-effective, easily disseminated, and accessible alternative to group-based programs.This randomized controlled pilot trial with 90 university students in Stockholm, Sweden, explored the feasibility, usability, acceptability, and outcomes of an 8-week Internet-based mindfulness training program.Participants were randomly assigned to either an intervention (n=46) or an active control condition (n=44). Intervention participants were invited to an Internet-based 8-week mindfulness program, and control participants were invited to an Internet-based 4-week expressive writing program. The programs were automated apart from weekly reminders via email. Main outcomes in pre- and postassessments were psychological well-being and depression symptoms. To assess the participant’s experiences, those completing the full programs were asked to fill out an assessment questionnaire and 8 of the participants were interviewed using a semistructured interview guide. Descriptive and inferential statistics, as well as content analysis, were performed.In the mindfulness program, 28 out of 46 students (60%) completed the first week and 18 out of 46 (39%) completed the full program. In the expressive writing program, 35 out of 44 students (80%) completed the first week and 31 out of 44 (70%) completed the full program. There was no statistically significantly stronger intervention effect for the mindfulness intervention compared to the active control intervention. Those completing the mindfulness group reported high satisfaction with the program. Most of those interviewed were satisfied with the layout and technique and with the support provided by the study coordinators. More frequent contact with study coordinators was suggested as a way to improve program adherence and completion. Most participants considered the program to be meaningful and helpful but also challenging. The flexibility in performing the exercises at a suitable time and place was appreciated. A major difficulty was, however, finding enough time to practice.The program was usable, acceptable, and showed potential for increasing psychological well-being for those completing it. However, additional modification of the program might be needed to increase retention and compliance.ClinicalTrials.gov NCT02062762; https://clinicaltrials.gov/ct2/show/NCT0206276 (Archived by WebCite at http://www.webcitation.org/6j9I5SGJ4) Structured group-based meditation interventions, such as the Mindfulness-Based Stress Reduction (MBSR) program , have inThe Internet provides an opportunity to deliver evidence-based psychosocial programs to a broader range of individuals and a possibility to disseminate interventions targeting stress and stress-related problems to large groups -8. An inSeveral studies have explored the experiences of Internet-based interventions among users, although few of them have investigated participant perceptions of specific mindfulness-based programs. In one randomized controlled trial (RCT) assessing the feasibility of an Internet-based mindfulness program for stress management in the Unites States, participants were asked to complete a questionnaire about overall feedback on the intervention and reasons for early study or program termination . About 2This randomized controlled pilot trial examined the feasibility, usability, acceptability, and outcomes of a newly developed 8-week Internet-based mindfulness training program among Swedish students. Feasibility was examined by determining the degree to which participants were engaged in and completed the program. Usability and acceptability were assessed using postintervention questionnaires and semistructured interviews of experiences at completion of the program. Outcomes were examined by comparing pre- and postassessments of psychological well-being and depression symptoms both within the intervention group and between those participating in the mindfulness training program and those randomized to an active control condition. This broad approach of evaluation aims to expand the knowledge about the potential of Internet-based self-administrated mindfulness-based programs to improve mental health status.Study participants were recruited between December 2013 and March 2014 by advertising at different university campuses in Stockholm, Sweden. The study was open to students aged 18 years and older with access to a computer and an email address. Students interested in participation phoned or sent an email to the study coordinators to receive additional information about the study design. Participants were randomized to either the intervention group (Internet-based mindfulness training program) or an active control group (Internet-based expressive writing program) on a rolling basis using a random sequence of numbers. One of the authors generated the sequence of numbers using SPSS statistical analysis software (IBM Corp) and another author enrolled and assigned participants in the order they were recruited. All participants in both groups were asked to fill out a questionnaire before and after the program and complete weekly assessments. Participants who did not respond to the weekly assessments were reminded by email. The completion of a week’s training was not time-limited, but the next set of program material was only made available after the participant completed the previous training and assessment. Those who did not respond to the reminder or did not fill out the weekly assessments marking continued participation were not asked to give a reason for discontinuation or noncompliance. All participants completing the Internet-based programs were compensated in an amount of SEK 500 (about $54).The mindfulness training program developed for this study was a modified version of the group-based mindfulness program developed by Jon Kabat-Zinn ,26. The The main departures in the content of our self-administrated program from MBSR as described in the standards of practice from the University of Massachusetts Medical School  were (1)Participants in the Internet-based expressive writing program were asked to write about stressor-related emotions and thoughts for 20 minutes on 4 occasions spread out over approximately 4 weeks. This procedure is drawn from work by Pennebaker and colleagues and has been tested across dozens of RCTs . In thisParticipants were asked to complete a baseline questionnaire which included questions on age, gender, level of education, and living situation. This was done in connection to the obtaining of baseline measures of the outcome variables.Psychological Well-Being is a questionnaire measuring 6 dimensions: environmental mastery, self-acceptance, positive relations with others, purpose in life, personal growth, and autonomy. It has been extensively used and has shown acceptable factor structure and validity . In thisThe Center for Epidemiologic Studies Depression Scale is a 20-item scale measuring depression symptoms in nonpsychiatric populations . The alpAfter each week, the participants in the mindfulness intervention group were asked to answer questions about how much time they had spent on exercises during the previous week. Participants in both groups were also asked to respond to a number of questions assessing potential mediators of intervention effect: mindfulness skills after weeks 2, 4, 6, and 8 and positive/negative affect after weeks 1, 3, 5, and 7. For the analyses in this paper, the time and frequency of practice is reported, but no analyses of the mediation was performed.At the postassessment follow-up, respondents were asked to answer 7 questions on a scale of 1 to 9, where 1 indicates “not at all” and 9 indicates “very,” to evaluate their overall experiences of the programs. The questions were based on research into factors considered to be important for participation in Internet-based programs  ,29,31 ant tests. The most specific test of the hypothesis as a whole was the difference between groups on the contrast between baseline and follow-up. This was tested using multivariate repeated-measures analyses of variance (MANOVA) with baseline and follow-up scores as dependent variables. Time and group (mindfulness vs expressive writing) were entered as factors in the analyses. In addition to the MANOVA, inferential analyses were conducted to examine pre- and postintervention change for each dependent variable, stratified by randomization condition, using independent sample t tests. Cohen's d effect size for within and between group differences was calculated based on the difference between group means on baseline and follow-up change scores. The denominator was based on the pooled standard deviation (SD) at baseline and follow-up adjusted for different sample sizes  there were unfinished sentences that were difficult to understand.Woman, 26 yearsThe organization of audio files in the weekly modules was perceived as confusing by one of the respondents. In addition, some participants had complaints about the questionnaires. Most of these were about repetitive questions and difficulties in finding a suitable answer.This category comprises explicit proposals for improvements of the program mentioned by the interviewees. Some participants suggested improvements regarding the interaction with study coordinators and technical and layout issues. One of the respondents said that more emails reminding participants to exercise might facilitate completion of the program. Another suggestion was to arrange a meeting with the study coordinators and other participants at the beginning of the program in order to facilitate participation in and completion of the program. It was also suggested that a phone call from the study coordinators at the beginning of the program would increase the completion rate. Other suggestions were related to technical improvements, such as providing access to a special smartphone app where the participants could log their training. A reorganization of the audio files was proposed as was the provision of some kind of bank with questions from other participants, with related answers from the study coordinators.The topics included in this subcategory are about circumstances connected to the participants’ personal situations that contributed to facilitating implementation of the program. Some of them were related to attitudes or motivation, like curiosity and personal interest, and others to more practical or technical conditions, like having the opportunity to download files onto a phone and listen to them on the way to work.Well, I have a positive attitude towards it because I have practiced mindfulness before, privately on my own, in different ways [. . .] I am very curious and interested.Woman, 32 yearsThe topics in this subcategory are about circumstances connected to the participants’ personal situations that impeded implementation of the program. The absolutely dominant topic was that participants had difficulties in getting the training to fit into their daily lives and in finding the time to practice.During that time, I was preparing for an exam and it was a bit hard and challenging to find the time to perform these exercises, and it was a little more stressful than I thought. I needed time, and more time, and everything.Woman, 28 yearsAt the beginning I was more careful to ensure that it was 45 minutes every day, but then sometimes it became only 30 minutes. Then there were some days when my schedule didn’t work out, and I didn’t have time for anything at all.Woman, 25 yearsA couple of other issues were also mentioned as impeding the training. One of the participants had technical problems with the computer at home, and another lived together with a partner in a small flat and therefore had difficulties finding an undisturbed environment to practice.Statements reflecting satisfaction that are not closely related to the technical and pedagogic functioning of the program were categorized as positive experiences. A prominent topic in this subcategory is appreciation of the opportunity to choose between exercises and time to practice.The advantage is that it has been great to be able to do it just when you feel like it, that you don’t need to fit in with a time.Woman, 23 yearsA number of participants also mentioned positive experiences from the training itself, like getting help to relax and calm down. The facts that participation was anonymous and that the exercises were performed at home were also mentioned as positive, as well as the experience of being in a permissive condition.Statements reflecting dissatisfaction not closely related to the technical and pedagogic functioning of the program were categorized as negative experiences. The negative experiences reported were to a large extent the stress the participants felt when they tried to find time to practice with the intended duration and frequency.What I do think is that I have felt a little stress that there have been so many times when we've had, so to speak, . . . when it has been expected that you should do these exercises. It's been something that I thought, what can I say, was a bit stressful.Woman, 26 yearsSome participants found it stressful to plan for the training on their own. Somewhat related to the issue of planning was a statement regarding difficulties in choosing between different exercises in the program. Lack of contact with other participants was also brought up as a dissatisfying, in contrast to the expressed view that anonymity was a good thing.This study gave support for the usability and acceptability of our self-administered Internet-based mindfulness training program among those who completed it. Although less than two-fifth of the participants completed the full program and participants practiced less than recommended, a significant increase in psychological well-being was observed. There were, however, no statistically significant differences between the intervention and control group. Most of those completing the program expressed that the program was meaningful and helpful in improving their way of being. The flexibility to perform exercises where and when it was convenient for them was appreciated and overall the program layout was perceived as satisfactory. More frequent contact with the study coordinators and reminders were suggested as ways to help participants to complete the daily exercises and to increase the likelihood of successful completion of the program. A major difficulty for several of the participants was to find enough time to practice. In addition, the majority of the participants perceived the program as challenging.The fact that no statistically significant differences in outcomes between the mindfulness and expressive writing group was detected could be due to the active condition in the control group and the large drop-out rate in the mindfulness group. A large drop-out rate is often associated with an underestimation of the intervention effect in intention-to-treat analysis using last-observation-carried-forward approach -43. The The flexibility regarding location and time for training was perceived as positive by participants, in line with earlier research ,7,8,25. Choosing between different exercises and having to plan one’s own training were considered demanding by some of those interviewed. Perhaps some participants might have felt the need for clearer guidance and support in the latter part of the program. Earlier research has shown that participants need support, for example in managing time challenges, when taking part in Internet-based programs ,30.The participants did not spend the intended amount of time practicing mindfulness in this training program. It is possible that greater improvements in well-being and depression symptoms could have been reached with a higher level of compliance. However, a previous 14-day Internet-based mindfulness-based program encouraging students to practice mindfulness meditation 10 minutes each day resulted in a significant group × time interaction for anxiety/depression symptoms, suggesting that it is possible to achieve improvements in mental states with a rather limited effort. In summary, results from this study suggest that students can benefit from an Internet-based mindfulness training program.Our study highlights the challenge of developing health-related Internet-based interventions, including mindfulness-based programs, that are sufficiently easy to complete for an intended target group. A way to enhance completion of Internet-based programs might be to use more reminders and make personal contact by phone before program start. Less time-consuming exercises and a shorter program period might also be considered in order to raise the completion rates in these interventions. Acquiring further knowledge about how to develop and deliver such programs is warranted in order to make use of the potential of the Internet in health care and other relevant settings.Although this study is of great interest because it is one of the first to explore the feasibility and effect of an Internet-based mindfulness intervention, it has several limitations. First, the participants were not required to have a certain level of stress or other psychological symptoms to be included in the study, which may have reduced the ability to detect changes in the outcome measures. A possible absence of stress or distress may also have influenced participant perceptions of the program and their motivation to practice. Perhaps they would had given the program a higher priority in their daily lives if they had felt that they really needed the training. Second, our study did not systematically investigate if the students experienced some negative effects from the mindfulness training. A literature review from 2008 concluded that no negative effects from mindfulness-based interventions have been documented . HoweverOur findings support the usability and acceptability of a self-administered Internet-based mindfulness training program for several participants. The program showed potential for increasing psychological well-being. However, additional modification to the target group might be needed to increase retention and compliance.


There are errors in the Funding section. The correct funding information is as follows: This work was funded by the Muscular Dystrophy Association of USA (MDA), the Fight-MG grant of the FP7 EC program, the Association Francaise contre les Myopathies (AFM), the European Commission (Contract No 242210), the Greek GSRT (program “Aristeia”), FP-7 Research potential Program/Regpot SEEDRUG of University of Patras (Grant number: EU FP7 REGPOT CT-2011-285950) and by the Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF) Research Funding Program: THALES. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


Although many behavioral interventions have proven to be efficacious, new methodologies are required beyond efficacy trials to understand how to adopt, implement with fidelity, and sustain behavioral interventions in community settings. In this paper, we present a new approach, based on systems engineering concepts and methods, for characterizing implementation strategies that are used to deliver evidence-based behavioral interventions in health and social service settings. We demonstrate the use of this approach with implementation strategies, used or being used for broader dissemination of 10 evidence-based prevention program projects focused on the prevention of drug or HIV sex risk behaviors.The results indicate that there are wide variations in intervention approaches and that there are challenges in program implementation including maintaining program fidelity, serving community needs, and adequate resources. The results also indicate that implementation requires a committed partnership between the program developers, implementation researchers, and community partners. In addition, there is a need for adaptability within programs to meet community needs, resources, and priorities while maintaining program fidelity.Our methodological approach enabled us to highlight challenges associated with the community implementation of health risk prevention interventions. We also demonstrate how comprehensive descriptions of interventions facilitate understanding of the requirements of program implementation and decisions about the feasibility of implementing a program in community settings. Drug use and sexually transmitted infections remain significant public health problems in the USA. In 2011, an estimated 8.7 % of the population had used or abused an illicit drug or a psychotherapeutic medication; of these 24 % were 18–20 year olds  did what we did was based on… these people [community partners] telling us what it is that we would need to do in order to make this [research] work, and we listened to them… you [researcher] have to be inclusive and you have to find ways to make people feel that you’re there not just to get from them but to provide as well.”Second, partner agencies need to have a strong commitment to the program. Most of the interviewees felt strongly that if their partner agencies were not committed to the program and did not remain committed, implementation would fail. This commitment entails several elements. One essential element is that the agency has to have a complete understanding of the program’s characteristics and requirements. A second component is the agency’s readiness to implement the program and a third is having the staff, resources, and support necessary for a program. Another essential element is agency “buy-in”; the degree to which the agency is willing to expend the effort needed to take ownership of the program. This might include, for example, reducing the workload of case workers so that they have sufficient time to deliver the program or adapting the number of sessions to accommodate families. One interviewee discussed a reason for lack of receptivity among parents for a family-based program was the lengthy duration of the program. “Unable to commit to a 7-week program because of their time schedules or they had children in developmental situations … working swing shift jobs, those kinds of things.” Another key element of “buy-in” is having staff engaged in and able to deliver the program. The skill level of the staff is also critical to program success. In addition, if a program includes group activities the cohesiveness of the group is important. Many of the interviewees also mentioned the importance of flexibility. Successful implementation often depended on research staff being able to modify and adapt the program to local needs and exigencies. This might include adapting the language and exemplars used in a program or adapting a program to be delivered in a particular setting such as a church as opposed to a clinic or to the structure or personnel within an organization. For example, as one interviewee responded: “I think we are going to have to be more flexible in terms of fidelity because of skill level… let’s say there’s one principal for three middle schools and the person who has the most contact with the parents by default is the secretary in the front office … because of her skill set … we have to take out or redo some of the demands of our program.”One major challenge identified by most of the interviewees is having strategies to assess and manage treatment fidelity. In some cases assessment of intervention fidelity is resource intensive and time-consuming. Not surprisingly it is also difficult to maintain fidelity over time. Most of the respondents also indicated the need for strategies for mechanisms to implement “corrective action” if required. As expected, there is tension between program fidelity and flexibility. As noted, flexibility or the ability to adapt a program to cultural or contextual nuances is often a key to successful implementation yet this adaption also raises concerns that core elements of the program might be omitted or changed in ways that reduce the effectiveness of an intervention.An additional challenge to implementation for many programs is scheduling and logistics. Most of the interviewees stated that they faced challenges scheduling program sessions or lesson delivery. Collaborating agencies often have many demands that outweigh the desire to implement an intervention program. Scheduling and logistics challenges can be exacerbated by staff turnover and/or promotion both within the program development team and within partner CBOs is a critical challenge. Furthermore, the logistics associated with training staff when the program is being implemented at multiple locations—including international settings—is also a challenge and often resource demanding. Overall, the interviewees were conscious of the challenge of coordinating these activities and of attending to the many logistical challenges sustainable programs require.In sum, adequate resources within CBOs and allocating these resources to program implementation are a major concern and represent a continued challenge to the implementation of intervention programs. Another major challenge is securing a commitment on the part of the organization to implement the program in a way that is consistent with program requirements.The goal of this paper was to demonstrate how a systems engineering approach could be used to identify the requirements for implementing prevention programs, focused on the prevention of drug or HIV sex risk behaviors, in a community setting. The study was also designed to identify factors important to and potential barriers to implementation success. We provide data from a survey and interview with 10 evidence-based prevention programs that were in various states of program implementation.In general, the programs were quite varied in terms of their characteristics and implementation requirements and strategies. Several important themes emerged that cut across all programs with respect to successful implementation, however. First, the tension between fidelity and adaptability is high. All of the programs were scripted and contained core elements, yet adaptation of a program is generally required to meet community needs and shifting resources and priorities. In addressing this tension, the community-research partnerships arrived at different decisions regarding adaptation, with respect to what aspects of the protocol can be adapted, to what extent and by whom. We recommend that during the design and evaluation of interventions researchers pay special attention to what aspects of an intervention can be adapted and provide general guidelines or protocols for implementing and documenting adaptations both during research trials and in practice settings. Adaptation issues should also be addressed in CONSORT-type checklists for randomized intervention and implementation trials.Also, all of the study participants recognized the need to maintain program fidelity but struggled with ways to measure and maintain this fidelity given community constraints. From a systems perspective, simply monitoring for fidelity is not sufficient to maintain standards; mechanisms for feedback and accountability also need to be in place . It is iAll of the study participants also emphasized the need for a strong and committed partnership between the program developers, implementation researchers, and the community partners who will be involved in implementing the program. In this respect, many of the programs included in this study relied on a community partner such as a school, church, coalition, or other agency to help with access to clients and communities; and to help with program delivery. In all cases, the commitment of these partners is considered essential to program success. Also, having a strong partnership is critical to ensuring effective communication between researchers and organizational staff. Determining the optimal structures and functioning of community coalitions is an active area of research , 45, andouter context  and the inner context . Like Aarons and colleagues [The factors identified through the interview and survey presented above are also supported by the dissemination and implementation conceptual model put forth by Aarons and colleagues , which dlleagues  suggest,This paper has identified a number of implementation challenges. However, these implementation challenges can also be considered opportunities for implementation science. For example, they imply that better tracking and coordination systems could help reduce the costs and barriers to successful implementation. The identified challenges also indicate that a process to help determine how to implement a program to achieve the optimal balance of maintaining program fidelity and adaptability to meet contextual demands would be a useful next step for implementation science. The use of technology systems to facilitate staff training especially staff in remote locations could also prove to be useful.The systems perspective has enabled us to highlight these challenges and demonstrate how comprehensive descriptions of interventions facilitate understanding the requirements of program implementation and decisions about the feasibility of implementing a program in community settings. Intervention researchers in collaboration with community service providers can determine if they have adequate staff and resources to successfully replicate the essential elements of a program and if the program is sensitive to and meets the “culture” of the community. Indeed, a “cost calculator” tool already exists in child welfare that helps organizations and communities budget and plan for how a specific program can be implemented in their settings . This syHowever, it should be noted that the usefulness of this approach depends on having a common language/taxonomy for describing programs and implementation strategies. This is a challenge within implementation science. Currently, despite some attempts, there is as yet no fully accepted standard language/taxonomy for describing the components and processes of prevention delivery systems across diverse fields , 48–50 oAnother challenge for implementation science is to identify strategies that can address implementation challenges so that program implementation proceeds more efficiently. This will almost certainly involve innovative uses of mixed methods  and techThis survey and interview were tested together on 10 prevention programs for drug abuse and/or HIV sex risk behavior prevention, and thus we are not able at this time to generalize to their value in other settings, including treatment in contrast to prevention, where randomized implementation trials are being designed. However, the breadth of these 10 programs, and the deliberate choice of having the interviews conducted by a researcher who was unfamiliar with these particular programs and this particular scientific field, suggests optimism that this approach could be valuable for not only specifying differences in a wide variety of randomized implementation trials but also for purposes of training new investigators and providing useful feedback to the researchers and community leaders themselves. Other researchers conducting intervention trials can use this approach to help determine the essential requirements of their intervention, which will provide information about requirements for broad scale implementation.However, this study has some limitations. As noted, it was restricted to trials concerned with prevention of substance abuse and sexual risky behaviors. Thus, it needs to be replicated with other types of intervention programs. In addition, we only examined limited components of the “intervention system” from the perspective of the researcher. To fully gain benefits from this approach, a more detailed analysis of the characteristics of the target population and other individuals involved in implementing the intervention should be conducted. If for example, the intervention is being delivered in a school setting and involves parents and students, an analysis of the characteristics of the students, parents, and teachers would be helpful to understand their preferences, skills, attitudes, and needs. Additionally, an analysis of the context should be conducted including the organization (e.g. school) as well as the neighborhood and larger social and political context. Finally, other aspects of the intervention should be included in the analysis such as the usability, perceived value, work flow, and communication patterns. The ultimate goal of the systems approach is to identify potential mismatches or degree of fit between the elements and requirements of an intervention; the needs, preferences, and characteristics of the target population; and the characteristics and resources/constraints of the implementation setting.


To examine factors influencing the choice of psychiatry as a career between residency program application and ranking decision making.Using an online questionnaire, applicants to the largest Canadian psychiatry residency program were surveyed about the impact of various factors on their ultimate decision to enter psychiatry residency training.Applicants reported that patient-related stigma was a motivator in considering psychiatry as a career, but that negative comments from colleagues, friends, and family about choosing psychiatry was a deterrent. Training program length, limited treatments, and insufficient clerkship exposure were noted as deterrents to choosing psychiatry, though future job prospects, the growing role of neuroscience, and diagnostic complexity positively influenced choosing psychiatry as a specialty. Research and elective time away opportunities were deemed relatively unimportant to ranking decisions, compared with more highly weighted factors, such as program flexibility, emphasis on psychotherapy, service– training balance, and training program location. Most applicants also reported continuing to fine tune ranking decisions between the application and ranking submission deadline.Stigma, exposure to psychiatry, diagnostic complexity, and an encouraging job market were highlighted as positive influences on the choice to enter psychiatry residency. Interview and information days represent opportunities for continued targeted recruitment activity for psychiatry residency programs. Recruitment to psychiatry residency positions remains a challenge across Canada,8To enhance the understanding of career decision-making processes and contribute to a comprehensive recruitment strategy, we surveyed applicants to the University of Toronto Psychiatry Residency Program who participated in the 2012/2013 CaRMS Residency Program Orientation and Interview activities. Applicants were surveyed immediately following the residency program ranking submission deadline, to probe a cross-section of perspectives immediately proximal to the decision-making window for trainees. Given that applicants to psychiatry residency programs do not ultimately exclusively rank psychiatry programs, the goal was to better understand the influences on final ranking decisions.n = 111) University of Toronto Psychiatry Residency Program applicants applying through CaRMS. Applicants were surveyed shortly after the ranking preference submission deadline for applicants and programs but prior to the match date or announcement of residency position assignments by CaRMS. This post-ranking submission and pre-match results day survey window was explicitly chosen to minimize undue concern about participation impacting program ranking decisions, elicit feedback proximal to the medical students’ reflective process regarding ranking choices, and eliminate potential bias related to the psychological impact of the actual match result. Participation was voluntary and anonymous. The University of Toronto PGME Office provided research design support and the University of Toronto Research Ethics Board provided research ethics approval.In March 2013, an online self-report survey was sent to all  respondents participated in the survey (54% response rate), with 97% (n = 58) of respondents completing all questions. Descriptive statistics and narratives were used to interpret the responses.Sixty  of applicants described themselves as having been firmly decided on both psychiatry and a particular program as their top choice when they applied 5 months pre-match. Twenty-eight per cent of applicants (n = 16) stated that they had decided on psychiatry as a career choice but were undecided about the specific training program they would ultimately rank or select prior to entering the tour of programs. And 36% (n = 21) reported at the time of applying that they had been strongly considering psychiatry while also strongly considering other disciplines and were thus still refining their career decisions during the CaRMS interviews and program visits.Students were asked to retrospectively report on the degree to which they felt firmly decided on psychiatry as a career at the time of applying, which, in the Canadian matching process, is about 3 months before program and student selections and rank lists are due. Thirty-three per cent  a marginalized professional identity or discipline.Complementing existing knowledge and scholarship,Responses regarding the timing of residency program ranking decision making indicate that applicants are genuinely considering their options about program and discipline choice during their interview tours of schools and programs. With only a minority of respondents certain of their likely rankings at the time of application, we hypothesize that there are considerable opportunities for post-graduate training programs to further enhance recruitment in their approach to the residency program application process, particularly given unmatched and unfilled spots. Thus, during the interview and program-showcasing processes, psychiatry program directors may wish to ensure that their messaging highlights program features that serve as key motivators, while directly addressing potential deterrents. Societal need, the job market, and the growing interface between psychiatry and neuroscience should be highlighted as positive features of our discipline. While the job market consideration may have geographic variation, barriers to entry remain relatively low for graduating psychiatrists in comparison with procedural specialties requiring substantial infrastructure.Our survey and synthesis advances our understanding of some important factors that impact recruitment to psychiatry by illustrating perspectives of applicants at the time of high-stakes career decision making. These findings have the potential to guide undergraduate and post-graduate mental health capacity building by identifying strategic foci to optimize recruitment activities at various points of opting in or out of considering psychiatry. While the deterrent of program length may not seem overtly modifiable by residency training programs, the evolving competency-based framework for residency education may offer some opportunities for change. Further scholarship is needed in complementary areas, most notably the optimization of medical school selection of psychiatry-inclined trainees to expand the pool of interested and skilled applicants to psychiatry. Finally, as is apparent from a broad mental health stigma literature, our findings underscore the importance of patient and discipline antistigma efforts as a critical component of capacity building for the mental health service needs of today and the future.


Polygonum minus (Huds) using in vitro and in vivo approaches.The study was aimed to evaluate the anti-inflammatory activity of ethanolic and aqueous extracts of The in vitro tests used to evaluate ethanolic extract are cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), lipooxygenase (5-LOX), secretory phospholipase-A2 (sPLA2) inhibition assay whilst the in-vivo effect was measured by the ability of aqueous extracts to reduce paw edema induced by λ-carrageenan, in rats.Polygonum minus to inhibit both 5-LOX and COX, prompted a study to evaluate the effects of using an aqueous extract of Polygonum minus(LineminusTM); as this would be more suitable for future clinical testing. The anti-inhibitory activity of the aqueous extract from this plant was evaluated using a rat model where inflammation was induced in the paws by injection of λ-carrageenan. The aqueous extracts from Polygonum minus administered at doses of 100 and 300 mg/kg body weight (b.w.), significantly (p < 0.01) reduced paw edema induced by λ-carrageenan in the experimental model, at 4 h compared to the vehicle control. Furthermore, administration of 100 mg/kg b.w. or 300 mg/kg b.w. completely reduced inflammation of the paw 4 h after injection.The ethanolic extract inhibited the activities of 5-LOX and COX-1(p < 0.05) whilst the inhibitory effect on COX-2 was only moderate. A marked inhibition of 5-LOX was observed at 30 μg/ ml. The extract did not inhibit the activity of sPLA2. The ability of the ethanolic extracts of Polygonum minus possesses potent anti-inflammatory activities.These findings suggest that aqueous extract of  Inflammatory reaction, typically characterized by redness, swelling, heat, and pain is one of the most important host defense mechanisms against invading pathogens. However, persistent or over-inflammation can result in tissue damage and possibly failure of vital organs. In a number of pathological conditions, acute and/or chronic inflammation can lead to acute or chronic inflammatory diseases such as septic shock, rheumatoid arthritis, gastritis, and atherosclerosis , 2. OverIn the past few years, there has been concerted research focusing on the LOX pathway as controlling this pathway can play an important role in the relief of joint pain. The LOX pathway is a parallel inflammatory pathway to the COX pathway, where the AA produced is converted to LT, one of the strongest chemotactic agent produced in the body , 7. If lIn the recent years, the use of herbal remedies for the treatment of inflammatory disease has been gaining momentum . There hPolygonum minus [(Huds) (Polygonaceae)] is a small herbaceous plant commonly known in Malaysia as Kesum . The study was conducted in accordance with the recommendation of the IAEC as well as the “Purpose of Control and Supervision of Experiments on Animals (CPCSEA)” guidelines for laboratory animal facility published in the Gazette of India, December 15Polygonum minus aqueous extract (100 mg/kg) and (iv) Polygonum minus aqueous extract (300 mg/kg); respectively. The paw volume of each rat was measured at different time intervals  after carrageenan injection using this instrument. The percentage inhibition was calculated using the formula 100 (1-Vt/Vc), where Vc was the mean edema volume observed in the control group whilst Vt was the edema volume measured in the test groups [The test was conducted according to method based on previous published study . Brieflyt groups . All datPolygonum minus ethanolic extract showed dose-dependent inhibition of COX-1 and COX-2 with 100 and 25% inhibition respectively at 100 μg/ml (Table Polygonum minus did not show any inhibitory activity on the sPLA2 enzyme at both the concentrations (30 and 100 μg/ml) tested. The ethanolic extract from Polygonum minus inhibited COX-1, COX-2 and 5-LOX enzymatic activities.Polygonum minus (100 and 300 mg/kg b.w.) after 4 h compared to the rats that were fed with the vehicle control (Table Polygonum minus posses potent anti-inflammatory properties. These findings show that the aqueous extracts (100 and 300 mg/kg b.w.) of Polygonum minus inhibited the inflammatory processes induced by the injection of λ-carrageenan in the paw of rats after 4 h of oral administration.Injection of λ-carrageenan into the sub-plantar region of the left hind-paw rapidly induced paw edema. A significant (p < 0.01) reduction of paw edema volume was observed in the rats that were fed with the aqueous extract from ol Table . These fDual 5-LOX/COX inhibitors are potential new drugs to treat inflammation. These agents act by blocking the formation of both PG and LT but appear to have no measurable effects on the formation of lipoxin. These types of inhibitors of inflammation with dual functions help to avoid some of the disadvantages of selective COX-2 inhibitors .Polygonum minus extract has anti-inflammatory effects that can inhibit both the COX-2 and 5-LOX enzymes. The Polygonum minus has been reported to be rich with flavonoids [Polygonum minus aqueous extract used in this study was reported to possess high antioxidant content demonstrated by the ORAC score of between 16,000 to 35,000 μmol TE/g [Leukeotrienes (LTs) also play a major part in the inflammatory process . These cavonoids , 35. Flaavonoids . Based oavonoids  it was fmol TE/g , 38. Othmol TE/g . Hence, Polygonum minus, the current study that evaluated its anti-inflammatory activity and when comparing to the closely related Polygonum hydropiper, also known as laksa leaf in Singapore. Anti-inflammatory effects in vitro and in vivo for Polygonum hydropiper were reported, demonstrated by the inhibition of mRNA expression of pro-inflammatory genes such as COX-2, TNF-α, nuclear factor (NF)-κB and PG [Polygonum minus was drawn due to molecular systematic studies of the two showing 100% similarity using molecular genetic marker derived from four accessions of Polygonum minus[Polygonum minus extract may have also inhibited formation of LTs from 5-LOX and may prevent accumulation of these key inflammatory factors, which contribute to tissue damage through a putative 5-LOX shunt seen with NSAIDs. The current experiments demonstrate that, unlike NSAIDs, Polygonum minus extract does not only inhibit COX metabolism of AA to PGs rather it acts via inhibition of both COX and 5-LOX enzyme activity. Other well researched flavonoids, such as green tea catechins and quercitin have been shown to inhibit sPLA2 thus modulating the generation of AA from membrane phospholipids [Polygonum minus extract in the tested doses did not inhibit PLA2 activity in this study. The result suggests that Polygonum minus extract does not have the ability to modulate the generation of AA from membrane phospholipids produced by the destruction of tissue. Instead, it appears that Polygonum minus extract might possess potent active principles, which inhibits 5-LOX enzyme. With this point of view, the anti-inflammatory activity of Polygonum minus extract was evaluated using an established rat model to study inflammation. This rat model is widely used to screen the ability of new anti-inflammatory agents to reduce local edema induced in the rat paw by injection of an irritant agent [Polygonum minus aqueous extract showed significant anti-inflammatory effect in λ-carrageenan-induced rat paw edema around 4 hours after administration of carrageenan. The maximum inhibition takes place around 4 hours during which these anti-inflammatory mediators are expected to be released. An anti-inflammatory effect was also observed in vivo in another closely related plant species, Polygonum hydropiper, which is also known as Kesum in Malay [In the present study the expression of reactive oxygen species (ROS), TNF-α and nuclear factor (NF)-κBprotein were not evaluated but could be expected by the well-established antioxidant property of B and PG . A paralum minus. These rholipids , 43. Thent agent . Carragent agent . Flavonont agent . The secnt agent , 47. Thein Malay .Polygonum minus exert an anti-inflammatory effect by inhibiting both COX and 5-LOX activity, which was studied using an in-vitro model and further qualified in vivo.These studies provide evidence to show that the


Although program evaluation is a core requirement of Internal Medicine residencies, little is reported in the literature regarding resident satisfaction with training. Most program evaluation consists of numerical rating scales from which it is often difficult to pinpoint exact sources of dissatisfaction.nd and 3rd year internal medicine residents enrolled in the IM residency training program. Five chief residents were trained to conduct 5 focus groups with 8 residents in each group. The focus groups examined possible issues contributing to the deterioration of morale noted in the quantitative survey.Our goal in this work is to evaluate the utility of focus group methodology to uncover in detail the reasons for residents’ deteriorating morale in an IM residency program, as well as to solicit suggestions for correction. This study employed focus groups (FG) in a qualitative research design, in which descriptive statistics from a resident program evaluation survey served to guide an intensive focus group process. Participants were 40 of 45 2Many unexpected themes were uncovered by the FGs. Residents identified the following factors as the major contributors to deteriorating morale: 1) Pace of change 2) Process of change 3) The role of chief residents in change 4) Fear of intimidation and retaliation. Groups also suggested practical recommendations for improving the culture of the residency.Introducing change in residency training is a challenging process. Respectful attention to resident frustrations and solution-focused discussions are necessary to understand and improve morale. Focus groups proved to be a useful tool in revealing the precise source of pervasive resident concerns as well as providing potential solutions. In addition, FGs methodology can be adapted in a practical manner to residency evaluation. Program evaluation is a core requirement of residency training programs. Most prThe study was triggered by an annual written resident survey that uncovered new resident dissatisfaction and a lower overall level of morale compared to prior years. Specifically, resident evaluations of program leadership, fairness of evaluations, and educational quality declined compared to the two previous years, as did resident personal and professional morale  developed a preliminary version of the FG questions based on data from the year-end survey. The 5 chief residents and a psychologist with many years’ experience designing FG protocols and facilitating focus groups reviewed and modified this question protocol. The questions were open-ended to allow diverse opinions to emerge. The protocol included probes and follow-up questions.We employed a modified FG methodology, following adjustments recommended for conducting focus groups in small communities with a high degree of social familiarity. As in aWe recruited 5 separate groups of residents with 8 members in each group. Each group held two sessions with a team of two program chief residents, one of whom served as facilitator, the other as note-taker.The 5 chiefs were trained as moderators in a sesAn audit trail of transcriptions, field notes, focus group summaries and interpretations was established,21. A quThis research project was reviewed and approved by the University of California Irvine Office of Research institutional review board (HS#2011-8427). Because information was collected in a manner such that no identifiers were used and participants could not be linked to the data, the study was approved as exempt research and written consent was not required. All potential participants were given information about the goals and methods of the study. They were informed that they were being asked to take part in research; what their participation would involve, including risks and benefits; and how their privacy and confidentiality would be protected. Because participants were residents in the program, we emphasized that participation was voluntary, and that participants could withdraw at any time or refuse to participate without any adverse consequences. Everyone who agreed to take part in the study consented verbally to their involvement.The reporting of this study conforms to RATS guidelines for qualitative research. In particular, it presents an argument for the relevance of the study question. It provides explanation and justification for the particular qualitative methodology selected. It demonstrates transparency in describing study procedures, including sampling methods and recruitment strategies, data collection and analysis, roles of researchers and ways in which possible conflicts of interest were addressed. It discusses informed consent and efforts to guarantee anonymity and confidentiality to study participants. Finally, it attempted to draw conclusions based in the literature that did not overreach and that honestly recognized study limitations.There was widespread agreement across all groups that morale had declined. Researchers identified 4 main themes contributing to this demoralization: the pace of change; the process by which change was introduced; alteration in the role of chiefs from resident advocates to agents of change; and fear of retaliation. Each theme contained a number of "surprises" that had not been expected by the PD or the residency program, and could not have been deduced from the survey questionnaire results.Program changes included a shift away from float night coverage to overnight call; the introduction of a new morning conference; and the implementation of a weekly protected half-day of focused educational experience (the Academy). FG participants attributed some of the deterioration of morale to the many changes that had occurred over a short period of time, leaving them feeling helpless and out of control. In the words of one resident, "It has been this culture over the last twelve months of constant change… it felt like a completely different residency program" (Group 4). In itself, this theme was self-evident, as multiple, simultaneous changes are obviously stressful. However, a revelation to administration was that residents found even positive changes such as new educational conferences to be nerve-racking, principally because of the time commitments involved. "Even some of the things which I think are good, adding the academy, morning report, caused some stress last year because they were new and they changed the routine" (Group 3). A minority of residents disagreed: "Bringing morning reports, introducing the academy-where you get to see your colleagues – these were great changes-everyone likes that. It’s better having it than not" (Group 4).The depth and strength of resident feelings was also surprising. As one resident put it, "We feel like we’re guinea pigs. That we’re being experimented on, especially the call schedule" (Group 3). Many residents described intense frustration and disorientation in response to perceived loss of structure, instability, and uncertainty. "This program has changed completely… to deal with the stress of all of these changes kind of brings us down" (Group 1). "The whole experience was awful, incredibly awful, the team was completely fragmented" (Group 5). All groups reported an unexpected level of anxiety and distress. However, a few residents were more philosophical: "Big changes take awhile for people to adjust to; people aren’t going to like it in the beginning" (Group 5). Another disputed the negative effects entirely: "The environment is excellent overall, I don’t feel overworked, and there is agood balance of teaching and time off" (Group 4).According to participants, the process by which change was introduced was more stressful than the changes. This too was an unanticipated outcome for the residency program which, in its own eyes, had made every effort to take account of resident perspectives and include residents in all decision making processes. Still, many residents did not feel that they had a say in the call schedule change – to them, it seemed superimposed from above. "It seemed like there was some sort of charade to make it look like this was what residents wanted" (Group 2). In their view, resident feedback sessions were not really relevant to the actual change process. "Whether or not the vote actually counted for anything I’m not sure and I actually doubt it" (Group 1). The process "seems like it was a farce" (Group 4). "People ended up being insulted by the whole process. Why bother telling us you want our opinion when you’re just going to do it anyway?" (Group 4).Much of the responsibility for morale decline was placed at the feet of the prior year chiefs, yet another unanticipated finding. Because of their competence and the respect in which they were held by both the residency director and their fellow residents, these chiefs were given the task of presiding over the transition. Yet, confronted with changes that were dramatic and in some cases unpopular, residents largely misconstrued this liaison role and tended to blame the chiefs for their difficulties with the new system. For example, some residents described them as agents of the administration who "…didn’t care…were more of a watchdog than helpful" (Group 1). One resident summed up the sense of vulnerability: "There was a pervasive feeling that you don’t have somebody you can tell things to, or air your complaints to, and not feel that there may be some type or retributions or that it’s not going to stay confidential" (Group 4). However, the anger at the previous chief was not universal. As one resident pointed out, "The chiefs drop in occasionally, heck to see how the teams are doing: ‘Hey guys, how’s it going?’ They bring candy. The chiefs help with how to put in orders or deal with systemic problems" (Group 2). Another liked that a chief was present at the sign-out process, "…not for sake of correcting people, but to make sure things are okay-giving specific feedback verbally, what to do if patient has this…" (Group 4).The process of change, in turn, was affected by perceptions about the culture of the residency. A minority of residents considered the atmosphere of the program to be fairly positive, which corresponded to the perceptions of the administration. "[The PD] is receptive to hearing feedback… he’s pretty responsive" (Group 5). Others considered the program to be "somewhere in between" openness and retaliation (Group 2). A resident from a different group protested, "I do not consider the atmosphere to be at all intimidating. It’s always hard to receive feedback, and in this program people try to give feedback in a helpful manner" (Group 1).However, the majority was more negative, stating that the program culture often was actively hostile, defensive, and resistant to feedback. Again, the intensity of resident feelings was startling to the residency program. "At residency meetings, the administration is antagonistic and intimidating to the residents" (Group 2). Residents reported feelings of being ignored, discounted, or not legitimized. They expressed concern that speaking out might jeopardize their landing future fellowships. "People are afraid for their fellowships; they’re afraid for their futures, you piss off the wrong person…" (Group 3). They appeared afraid of upsetting people in power. "When you’ve been open and been attacked, it makes you not speak up anymore" (Group 3).Fear of retaliation existed in part because of the perceived lack of anonymity in registering complaints. Many residents were not aware that anonymous reporting mechanisms existed. It was pointed out that evaluations could easily be traced back to particular persons. "End-of-block evals are not anonymous… I made a comment about the call system. I wrote some very strong comments and I was called in for that" (Group 5). A pervasive sense of evaluations being misused in a punitive way was also uncovered. Some residents reported examples of "quid pro quo" evaluations – situations where they felt faculty retaliated against an honest evaluation with a negative evaluation of their own. "… Most people felt like they couldn’t give an honest eval because what happens is the attendings will wait and look for it" (Group 4). In a minority view, one resident offered the alternative suggestion that "Maybe chiefs reported things out of concern for the person. And you could think about being called in to the PD’s office as a way to offer help and show concern" (Group 2).Overall, however, across all five focus groups, in the opinion of the research team analyzing the transcripts, the intensity of the language used conveyed a sense of moral outrage and bitterness that could not have been predicted from the survey results alone. Moral outrage is defined in the social sciences as a response to transgressions by others based on individuals’ expectations of perceived rights and privileges. Moral outrage is an outgrowth of moral distress, and occurs when distress cannot be relieved. The resAs a result of the FG process, we developed crucial insights into what had gone wrong with a process of change that the administration believed to be inclusive and transparent. While cautious of generalizing from the experience of a single program, we believe there are relevant conclusions other training programs should consider.First, because residents are stressed and often overwhelmed, the proFurther, change creates stress, and more change creates more stress. Residents perceived some changes as adverse while others were in concept positive and productive. However, the sheer volume of near-simultaneous changes created undue stress and affected morale. This was especially true because even changes that were perceived as positive required increased time commitment from the residents. The FG process uncovered dissatisfaction with increased educational time and resources, a surprising phenomenon which was not at all evident in the paper survey where these new conferences were given high marks.As well, residents can feel intimidated, powerless, and vulnerable to abuse. The PD,Many medicine residents plan to go on to additional fellowship training. Success in obtaining fellowships is highly dependent upon the recommendations of faculty. Residents seemed especially reluctant to openly express their views for fear of not being able to obtain fellowship positions. To counteract such deep-seated fears, extra care must be taken to guarantee resident safety in dialoguing openly about problems. Chief residents play a crucial mediating role between faculty and residents. Chiefs are among the best of the program’s house officers, and for this reason are asked to stay on as faculty for an extra year to teach and supervise. Both the program administration and residents regarded the chiefs who guided the change process as capable, hardworking, and respected. They were viewed as excellent teachers and innovators. For these reasons, the administration felt that they would be key persons to explain and promote change. However, while program administration felt that giving chief residents an important role in the change process would be beneficial, in fact placing the chiefs in that position led to loss of their credibility as resident advocates, a crucial aspect of the chief resident role. In the eyes of their fellow residents, once they were required to become "agents of change" for the administration, they were perceived as unsafe. Therefore, they had diminished capacity to function as effective problem-solvers and as liaison to the administration.Although the large majority of the FGs expressed significant dissatisfaction, this was by no means a universal response. There were dissenting opinions which were more supportive of the residency, more sympathetic to the constraints on the PD, and more tolerant of the change process. Although the FG process itself did not provide specific insights regarding why certain residents seemed more positive and resilient, in discussions of the research team it appeared that these individuals seemed to have an unusually strong capacity to deal with adversity and unexpected situations. This reminds us that introducing change elicits a range of responses in residents, influenced in part by their attitudes toward their working conditions, and sugThis study was limited by a number of factors. The study was constrained by unavoidable modifications made in the FG methodology, especially the use of current chief residents as FG facilitators. However, these changes also made the FG process more realistic for other residency programs. The faculty researchers made every effort to ensure that the facilitators understood the importance of a neutral stance and did not have any "axe to grind" based on their own experiences in the residency. The team spent significant time in the training session practicing nonjudgmental questions and probes with the facilitators to reduce potential contamination of the findings.Another potential limitation is that, despite conscientious efforts to give residents a choice about participating in the study, residents may have felt pressured to attend the FGs; and the possibility of coercion in turn might have inhibited the honest expression of critical viewpoints. However, based on the content of the data, we believe that the FG participants felt safe enough to express authentic opinions that accurately reflected their concerns. It is at least equally if not more likely that the high participation rate reflected the strength of resident feelings.Finally, it is possible that our choice of methodology – focus groups rather than individual interviews – may have skewed the findings. In other words, there is a concern that a focus group, by voicing strong affect in a particular direction, may result in an overrepresentation of similar findings. An individual interview might produce more accurate feelings. The literature on focus groups addresses this point by emphasizing the importance of contrary opinions; and in its methodology, often explicitly requests opinions different from those being expressed. The eviMost qualitative researchers acknowledge that there are advantages and disadvantages to both focus groups and individual interviews. For example, focus groups are preferable in terms of obtaining a real-world response and avoiding tendency to please the interviewer. Focus groups are also considered superior when wishing to explore whether consensus or disagreement exists about an issue. On the other hand, individual interviews can better generate in-depth information about a single individual. They avoid the influence group dynamics may exert; and they are generally more useful when probing extremely sensitive subjects. On balaThe FG process helped this medicine residency program to uncover a depth of dissatisfaction not previously recognized, and furthermore, uncovered sources of dissatisfaction which were surprising and could not have been determined from the mostly Likert scale written survey. Researchers note that "critical events" in training can be a source of both distress and personal growth. We hopeThe authors state that they have no conflict of interest in conducting this research.LR originated the idea for the study and was responsible for its intellectual conceptualization. He also organized the research team. He was the primary developer of the question route used in the study. He played a major role in the interpretation of the data. He had a major role in conceptualizing and writing of the paper reporting study findings. JS provided expertise in focus group methodology. She provided two training sessions in FG methods for the research team; and continued to provide guidance throughout the study. She was responsible for troubleshooting problems in the design and implementation of the study and in data analysis and interpretation. She played a major role in data analysis and interpretation, as well as in preparing multiple drafts of the paper reporting study findings. HF, KH, SR, ZS, and KT participated in focus group methodology training sessions and made substantial contributions to the design and content of the question route. They all conducted focus groups and participated in the data analysis. They reviewed multiple drafts of the paper and contributed critical changes and suggestions. All authors have read and approved the final manuscript.LR was Program Director for the UCI-SOM Internal Medicine Residency Program at the time of the study. JS is Director of the Program in Medical Humanities & Arts, UCI-SOM. HF, KH, SR, ZS, and KT were Internal Medicine residency program chief residents at the time of the study.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6920/14/132/prepub


Conceivably, using expired  CO2 as the input signal of closed-loop ventilation (Intellivent-ASV®) should optimize CO2 control compared to manual ventilator setting changes based on PaCO2 measurements.Both hypo- and hypercapnia can be deleterious to brain injured patients. Due to the variability of CO2 evolution over time during standard controlled ventilation and during Intellivent-ASV®.The aim of this study was to compare PaCO2 evolution during two sequential 2-hour periods of ventilation (standard ventilation and Intellivent-ASV® version VUP02.11c in the “brain injury setting”), applied in random-order. A one-hour washout period was inserted between both periods. Arterial blood gas analysis was performed every 30 minutes. The number of manual settings adjustments made on the ventilator and actions performed to reduce intracranial pressure (ICP) were also recorded. Due to the small number of patients in this preliminary dataset, no statistical differences were tested.Prospective interventional randomized study with a crossover design. Comparison of PaCO2, GCS at admission: 6 [4-6.5]. SAPS 2 score: 42 [32-50]. PaCO2 was 36 [33-37] mmHg (range: 28 and 43 mmHg) during standard ventilation and 36 [34-37] (range: 30 and 43 mmHg) during Intellivent-ASV®. DeltaPaCO2 between two consecutive PaCO2 measurements are illustrated in Figure (medians [IQR]):11 patients were included . Age: 52 [42-54] years. Body mass index: 25.5 [24.7-27.0] kg/m®. Four  and 2 (increase in sedation) actions were performed in order to decrease ICP during standard ventilation and Intellivent-ASV® respectively.During standard ventilation, 22 settings adaptations were performed whereas only two manual adjustments were made during Intellivent-ASV® CO2-regulated closed-loop ventilation mode can be safely used to deliver automated ventilation in brain injured patients. PaCO2 never reached extreme values and delta PaCO2 were very low during Intellivent-ASV®. Accordingly, fewer ventilator settings adaptations were required during Intellivent-ASV®. These preliminary results are promising and more patients must be included to evaluate the potential advantage of using Intellivent-ASV® to optimize the control of capnia during neuro-resuscitation.The Intellivent-ASV


BCR-ABL. Based on this result, the patient was placed on dasatinib as a targeted therapy. In the era of molecular diagnostic medicine and targeted therapy, it is essential to have an understanding of the limitations of molecular assays and to follow a comprehensive diagnostic approach in order to detect common abnormalities and rare variants. Incorporating NGS methods in an algorithmic manner into the standard diagnostic PCR-based approach for BCR-ABL1 will aid in minimizing false negative results.Patients with BCR-ABL1 positive hematologic malignancies and Philadelphia-like B-lymphoblastic leukemia (B-ALL) are potential candidates for targeted therapy with tyrosine kinase inhibitors (TKI). Before TKIs, patients with B-ALL had a much worse prognosis and current treatments with targeted TKI therapy have improved outcomes. Thus, the detection of BCR-ABL1 is crucial and a false negative BCR-ABL1 result may adversely affect patient care. We report a case of a 76-year-old male with a new diagnosis of B-ALL who was initially found to be BCR-ABL1 negative by quantitative polymerase chain reaction (PCR). A concurrent qualitative PCR was performed which detected a positive BCR-ABL1 result that was confirmed by a next generation sequencing (NGS) based assay and identified as the rare fusion variant e1a3 of p190 BCR-ABL, encoded by the fusion transcript e1a2 in the minor breakpoint region (m-bcr) which is commonly associated with B-ALL in both adults and children. The 210-kDa protein known as p210BCR-ABL is most commonly seen in CML [The Philadelphia chromosome (Ph), t9;22)q34;q11.2), is consistently seen in chronic myelogenous leukemia (CML), 25% of adult B-acute lymphoblastic leukemia (B-ALL), 2–4% of childhood B-ALL, and rarely in acute myeloid leukemias [1.2, is c2q34;q11.BCR-ABL. Based on this positive result, the patient was ultimately placed on dasatinib as a targeted therapy.We report a case of a 76-year-old male with a new diagnosis of B-ALL that was initially found to be BCR-ABL1 negative by quantitative PCR. A concurrent qualitative PCR was also performed which was able to detect a low level positive BCR-ABL1 result which was subsequently confirmed by a next generation sequencing (NGS) based assay and identified as the rare BCR-ABL1 fusion variant e1a3 of p1903 . He was significantly fatigued and had a petechial rash. After transfusion of a unit of platelets, his complete blood count showed a white blood cell count (WBC) of 7.1 K/mm3 , hemoglobin 13.1 g/dL , platelets of 34 K/mm3, and a leukoerythroblastic peripheral blood smear showing 2% circulating blasts  with 95% of the cellularity involved by diffuse sheets of monotonous round to slightly irregular lymphoblasts . The bioBCR-ABL fusion. DNA was sequenced to a median coverage depth of 492x. No other fusion transcripts were identified including p210BCR-ABL or p230BCR-ABL. Previous validation experiments confirmed the sensitivity for detection of fusion events as >99% for tumor cell fractions between 20 and 50% and 97% for tumor cell fractions of 10%. High specificity was confirmed for all fusion events (PPV > 95%) [Molecular studies for the BCR-ABL1 mutation showed a low positive qualitative PCR result for the BCR-ABL1 fusion transcript . A repea3 with normal differential, hemoglobin was 10.9 g/dL, and platelets were 171 K/mm3) and he became transfusion independent. He tolerated the treatment well and by Day 98 of dasatinib treatment, the patient continued to be in complete hematologic remission. Monitoring for the BCR-ABL1 transcript will be performed with the qualitative PCR testing and if negative with the NGS assay.Due to the positive BCR-ABL1 result, the patient was started on induction therapy with dasatinib and steroids as per the protocol described by Foà et al. . One monThe qualitative BCR-ABL1 RNA test was performed at the University of California Davis Medical Center Molecular Pathology Laboratory . The Lightcycler assay detects the BCR-ABL1 fusion transcripts b3a2, b2a2, and e1a2, which covers more than 95% of the described t translocations [The quantitative BCR-ABL1 fusion tests were performed at ARUP Laboratories  utilizing reverse-transcriptase-quantitative PCR (RT-qPCR) for the detection of BCR-ABL1 transcripts e1a2 (or p190) and e13a2 and e14a2 (or p210). Total RNA is isolated and converted to cDNA. Fusion transcripts are quantitated by real time PCR amplification. The primers are designed to detect the major (p210) BCR-ABL1 breakpoint including fusions between BCR exon 13 and ABL1 exon 2 (e13a2) and BCR exon 14 and ABL1 exon 2 (e14a2) and the minor (p190) BCR-ABL1 breakpoint with a fusion between BCR exon 1 and ABL1 exon 2 (e1a2) . The tarn = 405); targeted RNA-seq for rearrangement analysis was performed for 265 genes that are frequently rearranged in cancer. Sequencing of captured libraries was performed using an Illumina HiSeq 2500 to a median exon coverage depth of >250x, and resultant sequences were analyzed for base substitutions, insertions, deletions, copy number alterations , and select gene fusions, as previously described. To maximize mutation-detection accuracy (sensitivity and specificity) in impure clinical specimens, the test was previously optimized and validated to detect base substitutions at a ≥5% mutant allele frequency (MAF) and indels with a ≥10% MAF with ≥99% accuracy [FoundationOne Heme Assay  uses hybridization capture applied to ≥50 nanograms of extracted DNA or RNA for 405 cancer related genes and select intronic regions from 31 genes  domain. The domain is required for full leukemogenic potential in vivo and its absence has been proposed to be associated with a more benign clinical course [p190 need to be identified as high-risk patients and monitored closely for efficacy during TKI therapy [We report a 76-year-old male with a recent diagnosis of B-ALL with the rare fusion variant e1a3 of p190l course . Accordil course . Verma eBCR-ABL variant.Rare BCR-ABL1 fusion transcript variants can potentially go undetected with the use of limited molecular assays such as the quantitative RT-PCR method that targets specific fusion sequences with limited primers. For example, primers are selected specifically for e1a2 (for p190) and e13a2 and e14a2 (for p210) . TherefoUltimately, a qualitative BCR-ABL1 test can aid in the detection of a rare BCR-ABL1 fusion variant when confirmed with a next generation sequencing based assay that is designed to provide a high throughput assessment on clinically relevant mutations that influence therapeutic decisions. Furthermore, this case illustrates that NGS based assays are more sensitive than the traditional PCR approach and may be very useful in the workup of suspected BCR-ABL1 neoplasms in certain circumstances. In addition, NGS would also be able detect Ph-like B-ALL cases, which are BCR-ABL1 negative and characterized by a gene-expression profile similar to that of BCR-ABL1 positive B-ALL with genetic alterations that are also responsive for TKIs .We propose the following approach for molecular testing for BCR-ABL1 for the detection of BCR-ABL1 at the time of diagnosis to optimize the detection of rare fusion variants which could enhance patient care. First, perform qualitative PCR with cytogenetics and/or FISH testing. If positive, perform quantitative PCR p190/p210 to determine the BCR-ABL1 transcript. If negative for quantitative PCR/cytogenetics testing or equivocal for qualitative PCR testing, proceed to next generation sequencing to detect possible rare variant transcripts and/or Ph-like ALL disease. This will allow the capture of all clinically significant molecular mutations that could potentially guide therapy and management.One limitation in detecting rare variant transcripts solely via NGS is the inability to use standard PCR, in some cases, for residual disease monitoring and follow-up. Therefore, NGS may be the only alternative for determining the presence or absence of residual disease.p190 may not actually be as infrequent as previously thought. The actual clinical significance of these rare variants is not yet fully understood and their role in clinical management with targeted therapy needs to be further elucidated with the aid of detecting variants and molecular profiles by newer molecular methods such as next generation sequencing.In the era of molecular diagnostic medicine and a repertoire of potential targeted therapy options, it is essential to have a thorough understanding of the limitations of the individual molecular assays and to follow a sound yet comprehensive diagnostic approach that would not only detect the common abnormalities but rather be able to find the rare variants as well. Incorporating next generation sequencing methods into our current standard diagnostic PCR approach for BCR-ABL1 and BCR-ABL1 negative Ph-like B-ALL will aid in minimizing false negative results and may ultimately enhance patient care. In addition, with the higher specificity of testing at the sequencing level, the rare e1a3 variant of BCR-ABL1


Although several face-to-face programs are dedicated to informal caregivers of persons with dementia, they are not always accessible to overburdened or isolated caregivers. Based on a face-to-face intervention program, we adapted and designed a Web-based fully automated psychoeducational program  inspired by a cognitive approach.This study aimed to evaluate through a pilot unblinded randomized controlled trial the efficacy and acceptability of a Web-based psychoeducational program for informal caregivers of persons with Alzheimer’s disease (PWAD) based on a mixed methods research design.We recruited and randomized offline 49 informal caregivers of a PWAD in a day care center in Paris, France. They either received the Web-based intervention and usual care for 3 months  or only usual care . Caregivers’ perceived stress , self-efficacy, burden, perceived health status, and depression (secondary outcomes) were measured during 3 face-to-face on-site visits: at baseline, at the end of the program (month 3), and after follow-up (month 6). Additionally, semistructured interviews were conducted with experimental group caregivers at month 6 and examined with thematic analysis.P=.98). The experimental group significantly improved their knowledge of the illness  from baseline to month 3. Of the 25 participants allocated to the experimental group, 17 (71%) finished the protocol and entirely viewed at least 10 of 12 online sessions. On average, participants used the website 19.72 times (SD 12.88) and were connected for 262.20 minutes (SD 270.74). The results of the satisfaction questionnaire showed that most participants considered the program to be useful , clear , and comprehensive . Significant correlations were found between relationship and caregivers’ program opinion (P=.01). Thus, positive opinions were provided by husbands and sons (3/3), whereas qualified opinions were primarily reported by daughters (8/11). Female spouses expressed negative (2/3) or neutral opinions (1/3). Caregivers expected more dynamic content and further interaction with staff and peers.Intention-to-treat analysis did not show significant differences in self-perceived stress between the experimental and control groups . Due to the worldwide aging population, the number of persons with dementia (35.6 million currently) is expected to double by 2030. The socioeconomic consequences of this rapid rise and the absence of an effective pharmacotherapy have positioned dementia as a major public health concern in recent years . The AlzVarious nonpharmacological intervention programs for caregivers are available on-site ie, ,10). Nev. Nev10])Based on a face-to-face psychoeducational program , we adapThe main aim of this pilot RCT was to evaluate the impact of the Diapason program on caregivers’ perceived stress. We hypothesized that this program offering information, skills training, and a forum for caregivers would significantly reduce their perceived stress and burden, and enhance caregivers’ self-efficacy, self-perceived health, and self-perceived knowledge about the disease. Qualitative analyses would facilitate the identification of subgroups benefiting from the program and would guide us to improve content and methods to evaluate this type of intervention.We carried out an unblinded monocentric pilot RCT (NCT01430286) between 2011 and 2014 in a day care center geriatric unit . Informed consent was obtained before participation. French ethical CPP approved this protocol in July 2011. The in-depth description of the protocol study has been reported elsewhere .The recruitment strategy included flyers and posters placed in the hospital. During the consultations, geriatricians proposed this protocol to caregivers of PWAD. The caregivers interested in the study filled out a contact form. Then a psychologist provided them with the information form, confirmed inclusion criteria, and collected the signed informed consent.Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [Eligible participants were required to be French-speaking caregivers of community-dwelling PWAD who met the criteria of the  Edition . CaregivBased on the literature, a 6-point difference on PSS-14 was expected between the experimental and control groups at 3 months . With anThe Diapason program  was deliEach session included theoretical and practical information, videos of health professionals, and a practice guide for applying the session’s content in real life. The length of the intervention was 3 months, with each weekly session lasting 15 to 30 minutes on average, but there was no time limit and the participants could access different website sections  for as long as they wished at any time. The program content is summarized in Weekly SessionsOne session per week had to be entirely viewed at least once to unblock the next sessionSession 1. Caregiver stress: this session presents a definition of stress, its causes and consequences on caregivers, the risk factors for chronic stress, and the mechanisms and effects of relaxation (includes a link to the relaxation training in the Diapason website), as well as strategies for managing stress underlining the importance of looking for respite.Session 2. Understanding the disease: in this session, the Alzheimer’s disease diagnosis procedure, the symptoms, the progression of the illness, and the consequences on daily life activities for persons with Alzheimer’s disease (PWAD) are explained.Session 3. Maintaining the loved ones’ autonomy: this session presents the reasons and strategies to involve loved ones in the process of care in order to stimulate the preserved functions and compensate for the lost ones. The session underlines the importance of maintaining the self-esteem of PWAD.Session 4. Understanding their reactions: in this session, the most frequent behavioral and psychological symptoms of dementia (BPSD) and their characteristics are succinctly described and illustrated by examples from daily life. The contextual and intrinsic factors that might be associated with them are also described.Session 5. Coping with behavioral and emotional troubles: this session presents practical advice on how to cope vis-à-vis the BPSD described in the previous session.Session 6. Communicating with loved ones: this session includes the description of the most frequent language troubles and the strategies to modulate and adapt communication to the preserved skills of PWAD.Session 7. Improving their daily lives: this session presents strategies to facilitate the performance of activities that become difficult or impossible to execute due to apraxia, illustrating them with examples adapted to daily life.Session 8. Avoiding falls: the session includes practical advice for maintaining and stimulating the relative’s balance and actions to adopt in the event of a fall. In addition, various actions are described to adapt the relative’s home.Session 9. Pharmacological and nonpharmacological interventions: this session includes a brief presentation of different interventions available for caregivers in France with pharmacological treatment as well as cognitive and psychological support.Session 10. Social and financial support: this session presents the different stakeholders and services that may help caregivers in their daily life. The financial and social support provided by the French government is also overviewed.Session 11. About the future: this session provides caregivers with information about the role of disease progression anticipation, inviting them to try and foresee solutions keeping a prospective vision, encouraging them to look for further sources of information, and social support to reduce the uncertainty of caregiving situations.Session 12. In a nutshell: the last session encompasses a summary of the Diapason program, emphasizing the acceptance of support and help and the importance of obtaining more information to anticipate and avoid stressful circumstances.Additionally the website contains other sections that can be consulted at any time.Relaxation training: guidelines for learning relaxation as well as 2 videos for the modeling of Schultz’s Autogenic Training and Jacobson’s method.Life Stories: stories about 4 couples, based on testimonials of caregivers, in which difficult situations are illustrated and possible solutions to manage them are discussed .Glossary: a glossary for technical words Stimulation: practical activities to stimulate autonomy and share pleasant activities with the relatives in daily life.Forum: a private and anonymous forum to interact with peers, to express their concerns, discuss solutions to daily problems, and share their feelings and experiences. The participants use nicknames to protect their privacy. A clinical psychologist participates in the discussions if necessary .Participants were recruited and randomized offline in 2 parallel groups based on a computer-generated randomization list using blocking and stratification by sex and relationship (spouses vs nonspouses).The experimental group participants received at baseline a 10-minute training session on how to use the website, a log-in and password, a printed version of the user’s manual, and a notebook to write personal ideas about their application of the program’s content. Each week, participants had to read through an entire thematic session and fill out a printed satisfaction questionnaire. Other website sections  were available but not mandatory to complete the program. No modification regarding methodology, program content (except for forum discussions), or the website was done during the course of the study.The control and experimental group participants received usual care, in which they were provided with information about the illness during their semiannual follow-up with their geriatrician. The control group participants were given access to the Diapason program at the end of their participation. All participants were advised to look for additional help if necessary and were asked to inform the researcher about it.An individual face-to-face assessment was conducted at the Broca hospital by research psychologists (VCL or JW) at baseline, at the end of the program (at month 3), and after 3 months of follow-up (at month 6). Each 90-minute assessment visit consisted of a structured interview, standardized questionnaires, and visual analog scales (VAS). Additionally, experimental group volunteers participated in an optional one-to-one semistructured interview at the 3-month follow-up.Based on a cognitive approach inspired by Lazarus and Folkman’s  stress aTo evaluate the perceived stress of caregivers (primary outcome), we used the 14-item Perceived Stress Scale (PSS-14) . The totThe secondary outcomes were:Self-efficacy measured by the Revised Scale for Caregiving Self-Efficacy (RSCS) , which dPerception and reaction to cognitive or behavioral symptoms of PWAD were evaluated with the Revised Memory and Behavior Problems Checklist (RMBPC) . This inSubjective burden was evaluated with the French version of the Zarit Burden Interview . The totDepressive symptoms were measured with the second version of the Beck Depression Inventory (BDI-II)  includinSelf-perceived health was measured with the French version of the Nottingham Health Profile (NHP) . We analAt each visit, we collected information on caregiving variables (structured questionnaire). On the 4 VAS, caregivers evaluated their current levels (from 0=low to 100=high) of (1) knowledge about Alzheimer’s disease, (2) overall stress, (3) self-efficacy for coping with the illness, and (4) the caregivers-PWAD relationship quality.Web metrics (session length and rate of visits) were collected for each experimental group participant automatically and anonymously. Participants completed a weekly satisfaction questionnaire focused on utility, clarity, and comprehensiveness . They rated from 0 to 100 the applicability and positive emotional impact of each session and reported their opinion of the program (open-ended question). At the end of their participation, we proposed a semistructured interview exploring their opinion of the program.Concerning the PWAD, we collected at baseline the Mini-Mental State Examination (MMSE)  from thet tests (or Mann-Whitney tests) and Spearman or polyserial correlations were used to assess associations between variables. The missing data within each scale were treated according to the recommendations of the literature when available. Otherwise, simple mean imputation was used. The last observation carried forward method was used for participants who dropped out. After checking normality and homoscedasticity of primary outcome (PSS-14), we conducted an analysis of covariance (ANCOVA), controlling for regression to mean phenomenon and effects of potential confounders at baseline on primary outcome. All analyses were conducted using R Software for Windows (version 3.0.0).All available data at baseline were analyzed by intention-to-treat analysis. Descriptive statistics (means and percentages) were calculated for caregivers’ and PWAD’s characteristics. Moreover, Interviews and open-ended questions were concurrently analyzed by two trained psychologists (JW and VCL) following the thematic analysis method, using a semantic approach, driven by analytic interests and an essentialist/realist approach .As summarized in the flowchart , of the We randomized 49 participants. Of the 25 participants allocated to the experimental group, 17 (71%) finished the protocol and validated at least 10 of 12 online sessions. Four participants ended their participation in the study without withdrawing consent.Demographics and other characteristics of participants are summarized in P<.001) and weekly help received (P=.01) were significantly associated with PSS-14 at month 3. Thus, no significant relationship was found with the intervention (P=.34). ANCOVA showed similar results when stratification factors were not included.Mann-Whitney tests did not show significant differences between the experimental and control groups over time . We condd=.79, P=.008). Indeed, the experimental group scores increased by 13.8 points (SD 15.1), whereas the control group scores decreased by 0.04 points (SD 17.4)  . HoweverOnly one user reported problems watching the videos  and another with little experience using the Internet could not use it unaided. The high scores on the weekly satisfaction questionnaire showed that nearly all participants considered Diapason topics to be useful , clear , and comprehensive . Topics describing strategies to maintain relatives’ autonomy and coping skills with the PWAD’s behavioral troubles fostered higher levels of positive emotional impact . The most applicable session was focused on coping skills of the PWAD’s behavioral troubles . In contrast, the session describing caregiving stress factors and protectors received the lowest scores for positive emotional impact  and applicability .On average, participants used the website 19.72 times (SD 12.88) and for 262.20 minutes (SD 270.74) during the first 3 months. The most frequently visited section was the forum , whereas only 10 messages and 10 answers were posted. Four spouses (45%) and 4 daughters (33%) visited the website 26 times or more (third quartile). No significant correlation was found between the PSS-14 score (M3–M0) and frequency (ρ=–.15) or duration (ρ=–.05) using the website. After month 3, connection times were near zero.P=.01). Thus, most wives had a negative opinion, whereas daughters primarily expressed a qualified opinion about the program. Only male caregivers expressed a positive opinion  and those with a clearly positive , qualified  or negative  opinion. These trends were significantly associated to the relationship  stages of the disease than their relatives. Most children thought the overall “message” was more adapted for spouses rather than for them. The contrary was not stated.“I expected something else.” Some participants found the content was not in-depth enough. They expected more specific and individualized advice, and more “human interaction” with professionals or peers.“This is not for me.” Other participants preferred another kind of intervention  or reported not feeling a need for help. Others considered the program had come too late or did not believe that someone/something could help them. Most of them ended their participation.Additionally, many experimental and control group participants reported having used other resources to better understand the disease and adapt their behavior .Statistical analysis did not show significant differences in self-perceived stress (PSS-14) between the groups over time. This result is most likely due to low statistical power. Perceived stress levels remained stable over time in PSS-14 scores although the disease progressed. This stabilization has been observed in control groups from similar studies, suggesting that caregiving stress rarely increases over a period of 3 months . After 6As in other studies , the expDuring the first 3 months, the program was highly used, in contrast with other studies , most liOur qualitative findings are comparable to previous works. Caregivers considered the program could be useful for people other than themselves . They wiTo our knowledge, this is the first pilot RCT based on a mixed methods research design evaluating an online program for caregivers of PWAD. By using a mixed method research design, this program follows current methodological trends  using quIn spite of using different strategies, the recruitment for this study was difficult; only 38.0% 49/129) of prescreened caregivers were actually enrolled. These difficulties occur in Internet-based intervention studies , suggest/129 of pAlthough face-to-face trials allowed the control of bias, isolated caregivers and those living in remote regions could participate more easily if the trials were conducted online only. In any case, replication with larger samples is necessary to complement our results. In addition, due to the heterogeneity of caregiver populations, we advise limiting the number of inclusion criteria  and the This pilot study evaluated the first online version of the Diapason program. Qualitative results revealed little acceptance of the program and high expectations from caregivers. The Diapason program needs to evolve toward dynamic, flexible, and more customizable content based on a structure that favors interaction with professionals and peers, such as online community support .Although a lack of statistical power prevents any definitive conclusions being reached about the efficacy of this program, the mixed research analysis provided us with valuable information for improving content and methods. Caregivers outlined high expectations about the program’s functionalities and showed little acceptance of our program. Dynamism, flexibility, personalization, and socialization appeared as key characteristics expected by caregivers. Overall, further studies about caregivers’ help-seeking behaviors and readiness facilitators or predictors are warranted.