School dropout may have important negative consequences for the individual as well as for society. It is therefore important to help students stay in school. Group interventions have been developed to reduce dropout, but the theoretical underpinnings of such programs are not always obvious. This study focuses on the Norwegian dropout-prevention program named ‘Guttas Campus’ (The Boys’ Camp). We draw on published and unpublished research, other sources of written information, discussions with stakeholders, and direct observation of the intervention, to identify central theories that form the basis of the intervention. These theories are briefly presented, and the impact of the ideas on the intervention is analysed. School dropout represents a significant social problem within the OECD area due to its detrimental consequences . DroppinDuring the period 2013–2019, 74% of the male students and 82% of the female students completed upper secondary school in Norway, indicating that male students seem to have more problems completing than female students. Falch, Borge, Jujala, Nyhus and Strøm  speculatFurthermore, dropping out of school means an increased risk of incarceration , and intThe Norwegian educational system is organized into three levels: 1. Elementary school (ages 6–13); 2. Lower secondary school (ages 13–16); and 3. Upper secondary school (ages 16–19) . ElementA number of school dropout prevention interventions have been introduced in Norway. One relatively new is called ‘Guttas Campus’ (GC). GC is a group intervention aimed at giving 9th grade boys with a high risk of dropping out of upper secondary school the academic and social support needed to transition successfully into upper secondary school and eventually complete upper secondary school and find employment.The GC intervention was developed around the practical observations and academic understanding of a group of experienced educators and psychologists. They had spent decades interacting with children and adolescents in schools, kindergartens, home environments, and in therapy. They had experienced how many children were disappointed and frustrated when trying to fulfil the demands of the educational system while protecting their personal well-being. Therefore, they developed an educational intervention to inspire aspirations in young people at risk of school dropout and to teach them the necessary skills to fulfil these aspirations, so they can feel good about themselves. The Norwegian version described here was inspired by the Danish program called DrengeAkademiet . The NorThis model has been evaluated in Norway, finding substantial academic improvement and low dropout rates during lower secondary school and during the first two years of higher secondary school . In DenmWhile there has been some empirical research on the effects of GC, suggesting that this group intervention may contribute to the prevention of school dropout, there is a need to further explore the theoretical underpinnings of the program. Examining the theoretical basis of the program will help us gain more understanding of the pedagogical and psychological processes that are in effect in the program. This may be useful in the further improvement of the program and may also be relevant to researchers and other stakeholders designing group-based interventions for youth at risk of dropping out of school. Consequently, the purpose of this study is to examine the theoretical basis of the dropout-prevention program GC. We had the following research questions: (1) Which theories are central to the GC program?; (2) Which scientific literature underlies the theories? i.e., referred to in research question no. (1); and (3) How do these theories influence the GC program in practice?This qualitative study aimed to examine the theoretical underpinnings of the GC program. We followed a four-phase research process.In the first phase, we gathered data for the analysis from different sources, including written information, videos, informal meetings and discussions, and observations. The data were gathered in a three-step procedure: In the first step, we gathered all available written information, published and unpublished research, evaluation reports, briefs, publicly available videos from prior camps, information leaflets sent to participants and parents, etc., that included direct and indirect information about the theories and ideas that formed the basis of the program. The first author also attended a conference on dropout organized by GC. In the second step, the first author had several informal meetings with the program’s stakeholders, including its founders, its current management, and program instructors, and discussed central ideas and theories. In the third step, the first author observed preparations for the camp and parts of the camp itself as well as the graduation ceremony and made notes regarding possible theoretical influences.In the second phase, following the gathering of these different sources of data, we examined all the data, identified and named ideas and theories that appeared central to the program, and created a list of relevant theories. Furthermore, we sought to identify the most important theories; those that were given more emphasis in the data and that occurred in different sources of data were considered to be more central. For instance, theories that were mentioned in published research as well as in informal discussions with stakeholders were understood to be more central to the GC program. Following this procedure, we were able to create a short list of the four theories we found to be most influential to the program.In the third phase, we identified relevant literature underlying the four central theories and reviewed the literature with the purpose of giving a short description of the relevant theories, as presented in In the fourth phase, we analysed how these four core theories influenced the program in practice, by comparing the theories to the day-to-day teaching, routines, and events of GC. By following this procedure, we were able to substantiate our findings regarding which theories were most influential. Phase four resulted in a description of how the theoretical underpinnings of the GC program were implemented in actual practice in the program, as presented in We identified four main theoretical underpinnings of the GC program: positive psychology, positive education, character strengths, and visible learning.A main inspirational source for GC is positive psychology. Psychology in general has successfully focused more on human shortcomings and illnesses than on virtues and achievable aspirations, according to Maslow , who firIn line with this thinking, a teenager who is taught interpersonal skills and an optimistic attitude and who is helped to find flow experiences in sports is less at risk of mental health problems and substance abuse . This meThe positive education movement advocates well-being programs in school because they believe that these programs, first, promote skills and strengths valued by most parents; second, improve well-being and behaviour; and finally, facilitate engagement in learning and achievement. According to Norrish, Williams, O’Conner, and Robinson , “positiAlthough the core message of positive psychology—to increase our attention to the relevance of positive emotional experiences in life and at school—does make immediate sense, this viewpoint has met with some valid criticism. According to Ciarrochi and colleagues , facing Second, Ciarrochi and colleagues  state thTo remediate such problems, Ciarrochi and colleagues  propose The DNA-V  model consists of six main recommendations. First, the model recommends empowering contexts for young people to help them clarify their values and act on them . Second,Summing up the contextual, positive psychology perspective, Ciarrochi and colleagues  state thOne concept associated with positive psychology attracted particular attention from the three educators while developing the theoretical basis of the GC intervention, namely their second inspiration: character strengths. Positive psychology had provided an overall perspective on how to build and maintain positive educational aspirations, but the perspective needed a description of how to realize and put into action this overall positive psychology.Context-focused psychology (CPP) concentrates, as described above, on the importance of context and situational factors in influencing youth behaviour and development . This peThe 24 character strengths are explained to be the processes or mechanisms that define the virtues: their trait-like manifestation . The chaNevertheless, 24 character strengths are a lot to work with when thinking in terms of interventions to improve youth development, school achievements, or adjustment. Thus, there was a call for a more manageable list of strengths . There hThe National Research Council (NRC) contributed to this search for a manageable list of character strengths by going through a large research database seeking to identify dimensions of “21st century skills”. In its final report, the NRC names three “competency clusters” that have increasing significance in modern society . First, Trying to answer the question of which competencies, other than cognitive competencies, to promote in school children, Park and colleagues  set out Finally, there was a fourth inspiration for the development of the GC intervention: visible learning. Visible learning is the name of a book by John Hattie , in whicHattie himself comments on some of the problems associated with the research reported in “visible learning;” for example, that he has given no attention to the effects of social background or context, because in his opinion these factors cannot be influenced in schools . HoweverThe GC intervention follows the basic principle of positive psychology by focusing on building strengths instead of fixing problems. By testing the boys’ competencies in math, reading, and writing before the camp, the teachers can start building on the students’ actual competencies from the first day of the camp and thus build extensive and authentic mastery experiences. The GC also includes the contextual positive psychology perspective by providing environments in which these young people can thrive and focus, thus teaching them to change their context to provide more vitality and meaning. Through a varied program and diverse activities, everybody is given a chance to excel. One example of acknowledgement and mastery-experiences is the assignment of the “Man of the Day” title. Every day, one of the boys is appointed “Man of the Day” for excelling in supporting his team or the entire group by contributing something special, like helping a teammate, volunteering for unpopular tasks, showing fairness, and so on. The chosen boy is called up in front of the entire group to receive the applause of all his teammates; he is given a diploma that is hung on the wall and handed to him at the graduation ceremony; and he also gets a selfie with the head of the camp and another staff member. This very simple acknowledgement of contributions to the group’s well-being is a very popular event in the day’s program and a much sought-after mastery experience among the boys. Many of these teenagers have learned little about their strengths in school and a lot about their shortcomings ,5. The fIntroducing the boys to a wide variety of activities like basketball, swimming, table tennis, canoe paddling, ziplining, climbing, and games, while including them in social situations with a group of new peers, aims to build mastery experiences outside the classroom too. The activities are organized so as to give all the boys a chance to feel good about themselves, find their competencies and strengths, and experience belonging or, as Seligman  said aboNevertheless, GC is a learning camp, implying that teaching the subjects of reading, writing, and math is a main priority. Inspired by “visible learning”, the boys are met by several posters on the walls of the classroom; the posters display the character strengths and the rules of the camp. In math, one of the posters is a learning ladder where each step defines a certain competence: I can add, I can calculate percentages, I can do algebra, I can do equations, and so on. The boys get a sheet of tasks to work on and a list describing the requirements for success at each step of the learning ladder. When they think they have mastered one competence level on the ladder, through working on their task sheet and getting help from the teachers, they receive a quick test; when the test is passed, they go up to the poster and write their name on the current step of the learning ladder. This visualization of learning and success is followed by applause from the teachers and the other boys in their group. Thus, the boys constantly support each other’s academic progress, and the learning of the individual student becomes clear to the teacher and to the student through constant feedback to the teacher and the student about how the teaching and the learning are progressing. This can be understood as an implementation of Hattie’s  overall In reading classes, this need for visibility is also achieved by poster registration: Poster 1. Now I am reading…; Poster 2. So far, I have read…; and Poster 3. Small book reviews. Again, the point is to make it immediately visible to the individual boy what he has achieved and how far he has come in his reading efforts. This visualization has relevance because several of them have not read many books in their lives. Some boys finish reading their first book at the camp; therefore, every chapter matters. Books are chosen for their relevance in the boys’ lives and include themes boys are interested in like heroism, bullying, sports, love, friendship, discrimination, gaming, crime mysteries, growing up in minority groups, or fantasy novels.There is hardly any group teaching using the blackboard with the whole group, just individual teacher–student contact and sometimes boys working together in a group and helping each other out. There are 3 teachers present in a group of about 15 boys. The teachers can always be called on, so that nobody will be stuck for long periods with problems they cannot solve. Such close individual follow-up and focus on the dialog between the teacher and the individual student also adheres to one of Hattie’s  core ideFinally, the GC has implemented Hattie’s ideas  regardinHowever, the character strengths are not only meant to help participants develop meta-strategies for learning in the classroom. The GC program also emphasizes social competence and the ability to navigate life in general. Therefore, upon arrival, the boys are assigned to one of three teams named Alfa, Bravo, and Charlie. The teams stay together all through camp and continue as mentor groups. Participants go to class with their team, they do activities with their team, and they help and support each other in sports and various tasks to develop a solidarity and empathy with their team members under the motto “best together”. Many of the participants have reported during evaluation that these new acquaintances were among the most valuable elements of the camp. Character strengths are also applied in building team spirit and positive relationships by learning how gratitude promotes bonding and how optimism, grit, and zest will get you through team challenges. The social competence promoted is also about adapting to each other and everyday life, which means, for example, having table manners, taking turns, structuring time and tasks, concentrating by putting away your mobile phone, taking care of yourself by eating healthy, and getting enough sleep. Consequently, the participants learn how various character strengths influence and stimulate each other so that improving their relationships evokes individual mastery experiences and how building character strengths like optimism, self-control, and curiosity can help them develop more giving relationships.After the camp, the boys meet up with their teammates and teachers from the camp twice a month for one and a half years at what are called mentoring centres. The purpose of these meetings is to keep track of the boys’ academic and social development. The boys will get help with their homework, they can share problems concerning their classroom behaviour or their academic challenges, and they can plan strategies for coping with school problems and social relations. However, the social aspect of meeting up with their teammates from the camp, eating pizza, playing table tennis or basketball, and having fun together is always an important element in these meetings.New and efficient ways of helping demotivated secondary school students complete high school are in high demand. Providing interventions that can prevent high school dropout and the risk of subsequent marginalization is a prioritized task in EU2020 strategy . In NorwA main finding in this study is that the central theoretical basis of GC has been positive psychology’s focus on human strengths and positive attributes or, put in different words, what makes life worth living ,30. SecoIn addition to these four theoretical pillars, there are other theoretical frames that might have been included in our overview of theories that have influenced the shaping of the GC model. For example, the social emotional learning (SEL) framework, with its focus on learning how to integrate your feelings, thinking, and behaviour in successful realization of important life tasks ,60, may We believe that the purpose of the GC program must be taken into consideration when discussing the programme’s theoretical basis. In addition to helping individual students achieving their goals—an important contribution of GC as we see it—is to create a laboratory for researching teaching and learning outside the school system, because changing large systems is challenging. Testing well-founded ideas by means of an intensive learning camp might be an efficient way of studying and leaning about what to change in school teaching and how. In the context of such an intensive learning camp, it may be impossible and even unnecessary to simultaneously explore all relevant theoretical frameworks and concepts involved in promoting learning. Identifying a few central theoretical pillars and then gradually including other influential factors based on experiences with the camps might be a sensible way to progress. In this manner, the GC intervention might lead to insights that can be adopted by other interventions or even by the general school system.Considering future research, it is crucial to understand what the intervention is and how it is expected to work. Greenhalgh et al.  point toSo far, the evaluations made after each camp and a study investigating the Danish version of this intervention  give somIn this study, we have examined the theoretical basis of the GC dropout-prevention program. We have identified and discussed the four main theoretical pillars on which the program builds: positive psychology, positive education, character strengths, and visible learning. In addition, we have demonstrated how these theories are applied in practice in the group intervention. More research is needed to examine the effects of the program and to form the basis of future adjustments and improvements to the program.


Identification of diagnostic error is complex and mostly relies on expert ratings, a severely limited procedure. We developed a system that allows to automatically identify diagnostic labelling error from diagnoses coded according to the international classification of diseases (ICD), often available as routine health care data.The system developed (index test) was validated against rater based classifications taken from three previous studies of diagnostic labeling error (reference standard). The system compares pairs of diagnoses through calculation of their distance within the ICD taxonomy. Calculation is based on four different algorithms. To assess the concordance between index test and reference standard, we calculated the area under the receiver operating characteristics curve (AUROC) and corresponding confidence intervals. Analysis were conducted overall and separately per algorithm and type of available dataset.Diagnoses of 1,127 cases were analyzed. Raters previously classified 24.58% of cases as diagnostic labelling errors (ranging from 12.3 to 87.2% in the three datasets). AUROC ranged between 0.821 and 0.837 overall, depending on the algorithm used to calculate the index test (95% CIs ranging from 0.8 to 0.86). Analyzed per type of dataset separately, the highest AUROC was 0.924 (95% CI 0.887–0.962).The trigger system to automatically identify diagnostic labeling error from routine health care data performs excellent, and is unaffected by the reference standards’ limitations. It is however only applicable to cases with pairs of diagnoses, of which one must be more accurate or otherwise superior than the other, reflecting a prevalent definition of a diagnostic labeling error. Diagnostic error is a frequent health care problem , 2], ,  with majprocesses and often aims to identify missed opportunities ) aTo address the shortcomings of rater based identification of diagnostic labelling errors, we developed an automated scoring system. The system (i) compares pairs of diagnoses, (ii) quantifies their degree of discrepancy and (iii) allows classifying them as either similar or discrepant, based on pre-specified values for either sensitivity or specificity of such classifications. Here, we describe and validate this automated scoring system.We developed a web based computer program that compares pairs of diagnoses coded according to WHOs international classification of diseases (ICD). The similarity between two given ICD-codes is determined in four different ways, described in the following.steps in the following) to determine the similarity of two given diseases is to count the edges on the shortest path connecting them , subdivided into 261 disease groups (e.g. E10 to 14: diabetes mellitus). These are further subdivided into 2,037 categories (e.g. E 10.-: primary insulin dependent diabetes mellitus), finally classifying each disease by one of 12,161 specific four-digit codes (e.g. E10.1: primary insulin dependent diabetes mellitus with ketoacidosis). The whole classification system can be depicted as a graph . A simplweights below).A slightly more complex approach allows adjusting for medical similarity by assigning different weights for each type of edge  accounts for the position of two given concepts in the classification hierarchy relative to the position of their least common subsumer (i.e. their most specific common ancestor) ). “a diagnosis that was unintentionally delayed […], wrong […], or missed […], as judged from the eventual appreciation of more definitive information”, [Because of the wide spread use of Grabers’ definition of a diagnostic error as mation”,  diagnostOur approach complements existing methods used in research into diagnostic error. The limitations of rater based assessments of diagnostic error, including hindsight-, and outcome bias , limitedIn general, electronic trigger tools watch out for predefined signals in electronic health records, indicative of diagnostic error or of suboptimal diagnostic performance . Triggerhttps://simple.right-icd.de, they can not only calculate the AUC the different algorithms achieve for their validation datasets, but can also determine cutoff values to achieve a given sensitivity (or specificity) for their specific classification task. Publication of their findings can help to empirically determine the use cases for which the suggested approach and program is suitable and where reasonable borders of its applicability are. In addition, such revalidation attempts may help to identify differences between the four different algorithms evaluated here and implemented on the project website. In the three datasets used in the current study, all four algorithms performed remarkably similar. We do not see any operational advantage of one over the other, but would recommend to use the steps algorithm as a default, simply because it is the least complicated and most comprehensible approach.Researchers and quality managers who consider to use the approach and/or program presented here can easily validate it for their specific purpose, provided they do possess a dataset for validation, i.e. containing a reference classification against which to evaluate the approach and program. By running their datasets of pairs of ICD coded diagnoses through the web based program provided at The approach presented in this paper and its validation have several limitations, which warrant consideration.First, the approach is limited to datasets of pairs of diagnoses, of which one should be more certain, of better quality or otherwise superior than the other is.Second, currently the program is limited to comparing pairs of single diagnoses. In theory, the approach can be applied to the comparison of two sets of one to many diagnoses each, and we are currently developing the program to account for that scenario. However, definition of a reference standard and thus validation become much more complex (and much less certain) in that scenario.Third, the program is currently limited to the comparison of pairs of diagnoses coded in any of the more recent versions of ICD, making it susceptible to all the limitations that are inherent to ICD coding, and requiring ICD coding of all diagnoses to start with.Last, we only validated our approach and program on medical cases. Weather our approach also works in e.g. neurological or paediatric cases remains to be tested. As pointed out above, researchers in possession of an ICD coded set of pair of diagnoses from any field can easily check the performance of our approach online.In comparison to the reference standard, the trigger system developed to automatically identify diagnostic labelling error from routine health care data performs excellent, and is unaffected by the reference standards’ limitations. It is however only applicable to cases with pairs of diagnoses, of which one must be better, more accurate or otherwise superior than the other, reflecting the prevalent definition of a diagnostic labeling errors in medicine.Supplementary Material DetailsClick here for additional data file.Supplementary Material DetailsClick here for additional data file.Supplementary Material DetailsClick here for additional data file.


Colorectal cancer is one of the most prevalent gastrointestinal cancers in Iran i.e., the fourth and the second prevalent cancer among Iranian males and females, respectively. A routine screening program is effective in the early detection of disease which can reduce the cancer burden both for individuals and society. In 2015, Iran’s Package of Essential Non- communicable Diseases program had been piloted in Shahreza city in Isfahan province. Colorectal cancer screening for the population aged 50–70 was a part of this program. So far, there was no study about the cost and outcomes of that program. Thus, this study aimed to analyze the costs and outcomes of colorectal cancer screening done from 2016 to 2019 in Shahreza.This cost-outcome description study used the data of 19,392 individuals who were 50–70 years old experienced a fecal immunochemical test (FIT) and had an electronic health record. All direct costs including personnel, building space, equipment, training, etc. were extracted from the financial documents existing in the Isfahan province Health Center. The outcome was defined as positive FIT, detection of adenoma or malignancy as recorded in the E-integrated health system.The results of this study indicated that the direct costs of the colorectal cancer screening program during the years 2016–2019 were 7,368,707,574 Rials  in Shahreza, Isfahan province. These costs resulted in identifying 821 people with a positive FIT test, of those 367 individuals were undergone colonoscopy. Of whom 8 cases of colorectal cancer, and 151 cases with polyps were diagnosed.This study showed that by paying a small amount of 320 thousand international dollars we could prevent 151 cases of polyps to be progressed to colorectal cancer,resulting in a significant reduction in colorectal cancer incidence. Cancer has caused 9.9 million deaths in the world in 2020 and it could be considered a significant public health problem . Coming Accordingly, the prevention and control of non-communicable diseases can reduce premature mortality and disability significantly. In order to realize this objective, the National Document on Prevention and Control of Non-Communicable Diseases and Related Risk Factors in the Islamic Republic of Iran was developed. The first phase of Iran’s Package of Essential Non- communicable Diseases (IraPEN) program that evaluated the risk of non-communicable diseases began in 2015 in the primary health center of four cities . In Shahreza, located in Isfahan province, IraPEN started in February 2015 [All people who are 50 to 70 years old were called to the primary health center where they were registered in the E-integrated health system (SIB (in Persian)) in terms of any cancer-related symptoms or familial history. Then, they were trained and asked to do a FIT test at home. Based on the FIT result, people were being followed. Those with negative FIT were asked to do a test every 2 years, and those with positive FIT were referred for colonoscopy .Since the implementation of the CRC screening program, as the first program in Iran, the cost and consequence of the program had not been studied yet. Thus, this study aimed to report and analyze the cost and consequence of the program since started. So, this study had been conducted to examine the costs and outcomes of the colorectal cancer screening program during 2016–2019 in Shahreza, Isfahan province.This was a Cost-consequence analysis (CCA) that described the costs and outcomes of the CRC screening program in Shahreza in the period of 2016–2019. CCA is one type of economic evaluation study that compares the costs and outcomes of a program. Unlike other methods of economic evaluation, this method does not try to compare the cost and outcomes of a program with other alternatives. This method analyzes the costs and outcomes of a program simply by using descriptive tables to help the experts and policymakers to make a better decision regarding the question if the intervention or program is worthy or not .In the pilot CRC screening program run in Shahreza, Isfahan, a mix of active/ non-active inviting strategies was used. To invite eligible people, a public call was made through city-wide notification by using media, local radio, and television and distributing banners. In addition, people who had gone to the health center to receive other services were asked to participate in the program. In general, those eligible people who did not participate had been invited to be screened by a maximum of three phone calls.All registered people in the E-integrated health system (SIB (in Persian)) in Shahreza city who were 50–70 years old and have taken the FIT test entered into this study. The outcomes were identified as adherence rate , positive rate (the number of positive tests/ the number of FITs), colonoscopy adherence rate , polyp detection rate (the number of patients with polyp(s)/ all colonoscopy cases), and CRC detection rate .The required data such as the number of positive FITs, the number of colonoscopies in positive FITs, the number of detected people with polyps, and the number of detected cancer cases were collected from Isfahan province Health Center and Shahreza Health Center.Descriptive analysis such as frequency and mean was used to describe outcome data. Screening outcomes were described via frequency and rates, and data analysis was done in Excel for Windows.Direct costs of the CRC screening program included the costs of inviting the target group and the cost of implementing the program that was gathered based on the health care perspective. So, we categorized the costs of the colorectal cancer screening program into seven categories i.e., personnel; buildings and space; equipment; supplies, and pharmaceuticals; transportation; training; and social mobilization and publicity . Table 1The cost data were collected from the accounting department of the Isfahan province Health Center and Shahreza Health Center as well as the accounting department of Amir Al-Momenin Hospital. Staff involved in the program management were also interviewed when necessary. All calculated costs are reported as present value 2019) in Rials and also Dollars that are adjusted by the year-specific Purchasing Power Parity (PPP) conversion factor reported by the World Bank’s International Comparison Program indicators [ in RialsAbout 19,335 individuals were eligible for the program and about 28% of the target population were invited to the screening program annually. Finally, all the target population was invited for 4 years. The mean participation rate was 26% annually which ranged between 16 to 44%. This study included the result of the first screening round only. During the study period, a total of 19,392 people participated in the CRC screening program in Shahreza, of which about 53% were female. As depicted in Table From 2016 to 2019, overall, 19,392 FIT tests were performed. Of those 821 (4.2%) were positive. 367 (45%) individuals with the positive FIT test had been followed by colonoscopy, resulting in finding 8 cases of CRC as well as 151 cases of polyps. So, the average detection rates were 40 and 2% for polyp and CRC cases, respectively. As depicted in Table The total cost of the CRC screening program in Shahreza from 2016 to 2019 was about 7,368,707,574 Rials based on the Consumer price index (CPI) indicator in 2019 . More than half of all costs happened in the first year of the program by 4,342,202,632 Rials . As shown in Table The results showed that the total cost for each screened person in the CRC screening program in Shahreza was 379,987 IRR 16.6 PPP$). If the ultimate goal of the CRC screening program was to find any case of polyp or cancer, a cost of 46,344,073 IRR (2019 PPP$) had been paid for each detection of polyp or cancer case. Excluding the cost of colonoscopy and the cost of capital investment in the first year of the program, the FIT test process had 151,155 PPP$ costs that it means the health system faced 7.8 $ for every FIT test. Also, the health system costs an average of 462.9 $ for each colonoscopy performed. Figure 6.6 PPP$.This was a cost-outcome description study that aimed to describe and analyze the cost and outcomes of the CRC screening program which had been piloted in Shahreza city in Isfahan province from 2016 to 2019 as an integrated part of the IraPEN program. In this study, we looked at what was done in the CRC screening program, not what should have been done. The study found that of 19,392 individuals who had undertaken FIT, 821 individuals had a positive result. Of those, 367 were followed by colonoscopy, resulting in finding 151 cases of polyp(s) and 8 cases of cancer. For every FIT test, an amount of 180,087 Rials (7.8 PPP$) had been paid by the health system. For every detected polyp or cancer case, the system incurred an amount of 46,344,073 Rials (2019 PPP$).To compare the results of this study with the previous studies, it should be noted that few studies have reported the direct costs of CRC screening programs in such detail as our study. Most related studies calculated the screening cost based on a model such as Csanádi, et al. (2020) , Lew. EtConcerning reported outcomes, we found that on average in the 4 years about 4.2% of screened individuals, in a range of 2.7 to 6.4% in different years, has positive FIT results. That it is lower than the reported positive in Tehran, Iran (9.2%) , UruguayRegarding the percentage of those followed by colonoscopy, on average, about 45% of those with positive FIT were undergone colonoscopy. However, it ranged from 24 to 88% in different years. The lowest rates were related to the first and last years of the program which can be explained by the lack of access to colonoscopy and not preparing the system in the first year and also decreasing the staff sensitization and complete follow-up in the last year. Studies reported lack of knowledge, fear of the result, procedure and pain, lack of awareness, high cost, and lack of gastrointestinal symptoms as common barriers .The polyp detection rate and CRC detection rate in the study among Iranian patients were 23.5 and 1.5%, respectively [To generalize the results to the province and the country, it should be considered that we do not have any evidence showing that the population of Shareza city is more willing to participate in the screening program. Thus, we can assume that this population is representative of the whole country. Even if it’s not the case, we do not have evidence that the detection rate is correlated with the participation rate, meaning that those who are more willing to participate are more susceptible to having polyp or cancer. Regarding the generalization of costs, because the personnel costs, which contain the largest share of whole costs, are valued almost the same throughout the country, there is less concern about the generalizability of costs. However, for those areas with lesser participation, it would be expected that the cost per person diagnosed with cancer or polyps to be a bit higher than those areas with more participation due to the effect of fixed costs.The reason that we could not conduct a full economic evaluation was the fact that we did not have any information on the effectiveness of the CRC program in Shahreza. Thus, this study was designed as a cost-consequence analysis. By using our findings in addition to effectiveness data, further research can be conducted to analyze the cost-effectiveness of the program.Due to data limitations, we faced some limitations. The way people had been invited was not recorded so the participation rate cannot be examined in different inviting strategies. Also, the data was recorded for only one round so it was not possible to compare the participation rate in different rounds. Another limitation was that we could not differentiate adenoma polyps from other polyps. Also, since this screening was done in the public sector, only public sector costs were included in the study.In this study, we use real financial data to provide a more precise estimation of the cost of the screening program which can be used in future model-based studies. This study showed that by paying a little amount of 321,029 $ we can prevent 151 cases of polyps to be progressed to CRC.


PRAME gene, and that PRAME loss is associated with poor outcomes and leads to cytotoxic T cell immune escape. The authors comment that “deletions...were located close to the Igλ gene.” I would like to bring to the attention of the authors and readers that the PRAME gene and neighboring ZNF280A, ZNF280B, and GGTLC2 genes are located between variable (V) subgenes for the immunoglobulin lambda (Igλ) light chain  rearranges the Igλ locus and utilizes one of the many V subgenes located more distantly from the J-C region. It is known that approximately 30% to 40% of B lymphocytes express Igλ . Therefore, it is not surprising that the loss of PRAME has been previously noted in multiple B cell malignancies, especially chronic lymphocytic leukemia (PRAME deletions more often have an Igλ rearrangement, but they also report cases of DLBCL with a PRAME deletion and rearranged Igκ. However, it is not clear if in such cases the Igκ rearrangement was productive and what the status of the Igλ locus was. A defective allelic exclusion process might lead to Igκ and Igλ expression in one B cell. PRAME deletion associates with prognosis in DLBCL (Takata et al.  reportedht chain . The PRAleukemia  observedin DLBCL , but it in DLBCL , and it in DLBCL .PRAME is an expected phenomena in a portion of normal or malignant B cells with Igλ rearrangement. It remains puzzling why in evolution PRAME has been placed between Igλ subgenes and why its expression is activated in DLBCL.In summary, loss of


BCR::ABL1 have a faster molecular response to therapy compared to patients expressing e13a2. To explore the reason for this difference we undertook a detailed technical comparison of the commonly used Europe Against Cancer (EAC) BCR::ABL1 reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assay in European Treatment and Outcome Study (EUTOS) reference laboratories (n = 10). We found the amplification ratio of the e13a2 amplicon was 38% greater than e14a2 (p = 0.015), and the amplification efficiency was 2% greater (P = 0.17). This subtle difference led to measurable transcript-type dependent variation in estimates of residual disease which could be corrected by (i) taking the qPCR amplification efficiency into account, (ii) using alternative RT-qPCR approaches or (iii) droplet digital PCR (ddPCR), a technique which is relatively insensitive to differences in amplification kinetics. In CML patients, higher levels of BCR::ABL1/GUSB were identified at diagnosis for patients expressing e13a2 (n = 67) compared to e14a2 (n = 78) when analysed by RT-qPCR (P = 0.0005) but not ddPCR (P = 0.5). These data indicate that widely used RT-qPCR assays result in subtly different estimates of disease depending on BCR::ABL1 transcript type; these differences are small but may need to be considered for optimal patient management.Several studies have reported that chronic myeloid leukaemia (CML) patients expressing e14a2  BCR::ABL1 is the primary driver of chronic myeloid leukaemia (CML) but this chimeric gene exists in several different isoforms that need to be recognized for optimal patient management [BCR::ABL1 mRNA transcripts, both of which encode a 210 kDa BCR::ABL1 protein (p210), are characterized by splicing of BCR exon 13 or BCR exon 14 to ABL1 exon 2, and are designated as e13a2 and e14a2, respectively [BCR exon 14 is 75 bp in size and thus the e14a2 mRNA encodes an additional 25 amino acids compared to e13a2 [BCR::ABL1 fusions involving different BCR and/or ABL1 exons; recognition of these cases is important for their clinical management [BCR::ABL1 transcript type expressed by individual patients is determined largely by the precise positions of the genomic breakpoints on chromosomes 22 and 9 [For routine molecular monitoring of response to treatment, most laboratories use the Europe Against Cancer (EAC) reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assay, or variants thereof, which use a single primer pair/probe combination to detect and quantify e13a2 and/or e14a2 in the same procedure . Whilst BCR::ABL1 have an inferior molecular response to treatment at multiple timepoints compared to those expressing e14a2 [Several clinical studies have indicated that patients expressing e13a2 ng e14a2 –11, althng e14a2 . The posThe study described here was designed to investigate the possibility that the observation of higher measurable residual disease (MRD) levels in e13a2 patients could be due to differing efficiencies in PCR amplification between the two transcripts, which is a crucial parameter in RT-qPCR .BCR::ABL1 assay  three sets of primers and probes: set 1 was specific to e13a2 [BCR::ABL1 [BCR::ABL1 qPCR were performed at each site according to local procedures and included the use of laboratory-specific conversion factors (CF) to express results on the International Scale (IS) according to the protocol detailed in R of the local BCR::ABL1 assay exceeded 1.5 fold of the interquartile range of all laboratories [BCR::ABL1 [BCR::ABL1, results were considered relative to this transcript type.14 reference laboratories from the European Treatment and Outcome Study (EUTOS) for CML network that routinely use the EAC to e13a2 , set 2 uCR::ABL1  and set CR::ABL1  (ii) 1 sratories . The finratories  and WHO CR::ABL1  are bothBCR::ABL1 junction sequence as well as parts of the ABL1, BCR and GUSB genes that are used commonly as a reference to control for variation in sample quality and RT-qPCR efficiency. The plasmid is supplied as 6 different concentrations over a range of 10 to 1 × 106 copies/µL and is commonly used as a calibration standard by laboratories performing molecular monitoring for CML [BCR::ABL1 fragment in place of e14a2  or e13a2 (KCL-22) into a BCR::ABL1 negative cellular background (HL60). Dilutions of each cell line were targeted to contain approximately 10, 2, 0.4, 0.08, or 0.016% BCR::ABL1/ABL1, which was confirmed by RT-qPCR prior to distribution. The initial dilution was generated by adding 6 × 105BCR::ABL1 expressing cells (K562 or KCL-22) to 6 × 107 HL60 cells, which were then further serially diluted into HL60 cells at a concentration of 1.5 × 106 cells/ml. Cells were lysed in RLT buffer  according to the manufacturer’s instructions to generate final cell lysates samples containing approximately 5 × 105 cells in 600 µL of lysis buffer.A five-fold dilution series was prepared by diluting BCR::ABL1 and ABL1 assays according to locally established procedures [BCR::ABL1 %IS kit , according to the manufacturer’s instructions. Both cell line and plasmid material were tested, however as ddPCR experiments can become saturated at very high levels of template copy number, only 4/6 plasmid dilutions were used for ddPCR experiments, spanning a concentration range of approximately 1 × 101 to 1 × 104 copies/µL. The ratio of BCR::ABL1/ABL1 was calculated from the reported copy number of each target.ddPCR was performed using EAC-based ocedures , or withR) and (ii) amplification efficiency (E) as previously defined [R values (designated ARC) were calculated [We measured two parameters to assess the performance of e13a2 and e14a2 amplification: (i) the amplification ratio . Patients shown to be co-expressing both e13a2 and e14a2 were excluded (n = 7), leaving a total of 145 cases in the final analysis . Patient samples were analysed using RT-qPCR assays for BCR::ABL1 and GUSB [BCR::ABL1 [BCR::ABL1 assays used for RT-qPCR and ddPCR both co-amplified e13a2 and e14a2. Results were expressed as %BCR::ABL1 (RT-qPCR or ddPCR copies) / GUSB (RT-qPCR copies). Results were not converted to the International Scale as the %BCR::ABL1 / GUSB values greatly exceeded 10%.A cohort of CML patients at diagnosis were identified  that is applicable to both RNA and DNA samples, as well as the kinetics of disease reduction [Sequential prospective monitoring of MRD at both the mRNA and DNA levels for a subset of 81 CML patients  has been described previously . Finallyeduction  as descrComparisons between groups were performed using the Mann-Whitney U test. Paired comparisons were performed using the Wilcoxon signed-rank test, with Bonferroni correction for multiple tests where appropriate. RT-qPCR and ddPCR measurements were also compared using Bland-Altman analysis  with theBCR::ABL1 amplification by RT-qPCR by the widely-used EAC protocol, we undertook a detailed multicentre performance evaluation using control materials according to the schema shown in Supplementary Fig. BCR::ABL1/ABL1 copy number ratio is 1:1 regardless of plasmid concentration, the median laboratory specific amplification ratio . Overall, amplification of e13a2 was 2% more efficient than e14a2, although this difference did not reach statistical significance  and e14a2 (74 bp). In contrast to the EAC assay, we found the AR for the specific assays to be higher for e14a2 in 7/10 laboratories, but the difference overall was not statistically significant  dilutions were calculated using the local EAC qPCR assay and either the e13a2 or the ERM-AD623 e14a2 plasmid standard curves used to assign copy numbers (runs 5 and 6). If the performance of the assay was similar for both transcript types, then the transcript type of the standard curve should not affect the calculated BCR::ABL1/ABL1 values. For all dilutions, the results  were higher when calculated using the e14a2 standard curve, compared to using the e13a2 standard curve . Bland-Altman analysis of the difference between the average log10 ddPCR and RT-qPCR results for both transcript types combined showed a bias of −0.11 ,  for monitoring of ions n = 0. Bland-n = 145), we used both RT-qPCR and ddPCR to measure %BCR::ABL1/GUSB at diagnosis. Using RT-qPCR, the %BCR::ABL1/GUSB was significantly higher for patients expressing e13a2 compared with those expressing e14a2 . Concordant with the findings of other groups, the time to MMR was shorter for patients expressing e14a2 compared to e13a2, although the difference was not significant in our relatively small series of cases  for both mRNA and DNA assessments showed noticeably less difference between transcript types  entation , 11, proentation  or cytogentation . HoweverBCR::ABL1 and reference gene copy numbers are estimated by interpolation of sample Cq to a standard curve derived from calibrated control reagents, and BCR::ABL1 copies are reported as a percentage of the reference gene, commonly ABL1, BCR or GUSB [R between e13a3 and e14a2  did not find any impact of transcript type on the achievement of MMR or MR4, although they did find that e14a2 patients were more likely to achieve MR4.5 at 48 months [With RT-qPCR,  or GUSB . A diffe or GUSB , which i or GUSB . Our res4a2 Fig. . We were8 months .BCR::ABL1 RT-qPCR test result assumes the equal performance of multiple separate amplifications (BCR::ABL1 and reference gene for the sample and a 6-point standard curve such as ERM-AD623). This may be a reasonable assumption when comparing like-for-like samples and calibrators, however the commonly used ERM-AD623 plasmid calibrator contains the e14a2 target sequence [BCR::ABL1 RT-qPCR assay performs depending on the transcript type. It is unsurprising, therefore, that the use of a standard curve containing a different target amplicon may skew the results of an experiment. Indeed, we observed inflated BCR::ABL1 values from e13a2 expressing cell lines when an e14a2 calibrator was used, compared to results obtained using a matched e13a2 calibrator , which is consistent with an e13a2 standard curve that is amplifying more effectively than the e14a2 standard curve. Although the application of laboratory-specific CFs helps to mitigate against this difference, the increase in variation of the results suggests that CFs may not be fully optimised for the e13a2 transcript. Recent work by Dominy et al [BCR::ABL1 are based on e14a2, which likely accounts for the relative lack of assay optimisation for e13a2. In theory these issues could be addressed by production of e13a2-based reference materials that would enable assay optimisation , estimation of E and correction of results. The ‘Pfaffl method’, for example, is frequently used in relative quantitation experiments [A typical sequence . As we asequence  have shony et al  also inveriments  and has eriments , 33. HowBCR::ABL1/GUSB levels at diagnosis were apparently elevated in e13a2 cases compared to e14a2 when using RT-qPCR, but no difference was seen with ddPCR. The negative bias in RT-qPCR e14a2 amplification when compared with ddPCR is consistent with reduced efficiency of the e14a2 EAC assay as the source of experimental error. It is important to note that variations in laboratory protocols, including the use of different reference genes, are likely to lead to variable levels of bias (if any) between transcript types in different laboratories, and testing centres with concerns should undertake their own internal investigations to determine the performance of their assays for both e13a2 and e14a2 BCR::ABL1.An alternative approach is to use ddPCR, a technique which is relatively insensitive to differences in amplification efficiency as well as having other advantages such as producing results that are less variable that those produced by RT-qPCR and the lack of requirement for a standard curve –37. Our BCR::ABL1 variants [When RT-qPCR results were normalized to pre-treatment levels, there was no difference between transcript types with respect to achievement of a 3-log reduction in levels of disease, and no difference in the α or β slopes was apparent (Supplementary Fig. variants , it is ovariants , 40 but BCR::ABL1 transcript type. This issue is almost certainly not limited to the EAC primer/probe set, but likely affects other assays with similar differences in amplicon sizes between e13a2 and e14a2. It is important to emphasize, however, that the discrepancy is subtle and, although its consequences are apparently detectable in some large studies [In conclusion, there is a growing body of evidence that points to discrepancies in the performance of the EAC RT-qPCR assay in relation to  studies –11, the  studies . NeverthSupplemental Material


Researchers have begun to change their approach to training in the biomedical sciences through the development of communities of practice (CoPs). CoPs share knowledge across clinical and laboratory contexts to promote the progress of clinical and translational science. The Congressionally Directed Medical Research Programs’ (CDMRP) Ovarian Cancer Academy (OCA) was designed as a virtual CoP to promote interactions among early career investigators (ECIs) and their mentors with the goal of eliminating ovarian cancer.t-tests for Time 1 and Time 2. Qualitative data were analyzed for themes to discern which aspects of the program were useful and where more attention is needed.A mixed-methods approach (surveys and interviews) was used to evaluate the effectiveness of the OCA for the eight ECIs and five mentors. Quantitative analysis included internal reliability of scales and descriptive statistics for each measure, as well as paired sample Preliminary analyses reveal several trends, including the importance of training in grant writing to the ECI’s productivity, as well as the value of peer mentorship.The results show that the OCA was an innovative and effective way to create a CoP with broad implications for the field of ovarian cancer research, as well as for the future of biomedical research training. As the need for investigators in translational and team-based science increases, so has an interest in developing mentorship programs to support early career investigators (ECIs), who are often defined as being within the first 3 years of their first faculty position  ,2. MentoHowever, the world of clinical and translational science is slowly changing as researchers have started to reimagine collaborating within virtual communities of practice (CoPs). Traditional CoPs were designed as groups of people who met face-to-face , but theThe purpose of this paper is to describe the preliminary qualitative and quantitative evaluation data collected during the period 2015–2020 for a new mentorship program devoted to the development of a community of ovarian cancer investigators by CDMRP’s Ovarian Cancer Research Program (OCRP), known as the Ovarian Cancer Academy (OCA). This academy was intentionally designed as a virtual CoP to support ECIs during the nascent phase of their independent research careers, while focusing on basic, translational, and clinical aspects of ovarian cancer research. Evaluation of this program began in 2015 with the goal of collecting data to facilitate improvements in the OCA and also to promote the advancement of ovarian cancer research. By providing a description of how the OCA’s virtual mentoring program was designed, as well as by sharing preliminary evaluation data collected on an early cohort in the program, it is hoped that other biomedical research training programs will be inspired to design their own virtual CoP as an alternative to more traditional mentorship programs.In 2009, the Ovarian Cancer Research Program of the Congressionally Directed Medical Research Program within the U.S. Army Medical Research and Development Command of the Department of Defense  initiated a new biomedical research training program, the Ovarian Cancer Academy (OCA). The OCA was created in recognition of the need to increase the number of investigators committed to ovarian cancer research. ECIs selected for participation in this Academy were selected for their past research contributions to the field of ovarian cancer research, as well as based on their proposed plans for future innovative research in the field of ovarian cancer.The OCA is unlike other programs, many of which focus solely on supporting mentees through the development of mentor/mentee relationships . Rather,The ECIs choose their mentor(s) based on their professional needs. The ECIs wrote their mentors into their grants as co- or sub-PIs to provide protected time for mentorship and career guidance. The OCA did not formally evaluate how ECIs made decisions about who to invite as mentors; however, several possible reasons were given to ECIs in making this decision including ensuring professional compatibility, mentor’s expertise in the area of ovarian cancer research, mentor’s ability to help the ECI navigate their home institutions, and name recognition in the field of ovarian cancer research. In each case, it was the responsibility of the ECI to choose their mentors and determine when and how they would meet to achieve the goal of securing external funding.The OCA’s basic design included monthly meetings where mentors, mentees, invited guests and speakers meet via Webex, alongside annual meetings, where ECIs were trained in grantsmanship and other professional skills. Being virtual has allowed the program to leverage interactions with internationally recognized scientists, a design recommendation shared by other clinical and translational science mentoring programs . During This preliminary evaluation was designed as a mixed-methods study, which is considered an appropriate design for virtual CoPs  and was n = 8) and their primary mentors (n = 5), were included in this study. The cohort mentees were 52% female, 62% Asian, and 75% assistant professors with a mean age of 43 years (SD = 3.92). Of the five mentors in the sample, 60% were male, 80% were White, and 80% were full professors at the onset of the study. Additional demographics are presented in Table Thirteen individuals, representing the first OCA cohort , mentees were given their first survey (baseline) and were subsequently administered a survey every six months thereafter for 5 years, totaling 11 surveys during their OCA participation. Anonymous links to the survey were distributed to participants via email. Mentee surveys contained 12 metrics to evaluate the effectiveness of the program. Surveys took approximately 45 min to complete. Mentor evaluations began in October of 2016, one year into the OCA program for a total of 9 survey time points. Mentors were given an abbreviated survey version that assessed only their mentoring role and program satisfaction. In addition to these surveys, we also collected data on publications and grant funding obtained by this mentee cohort over the last 5 years.For qualitative data collection, exit interviews were completed with study participants in the summer of 2020, corresponding to the completion of the 5-year OCA program by the first mentee cohort. Exit surveys consisted of open-ended questions focusing on benefits and challenges, as well as expectations and results of the program. Each interview lasted approximately 30–45 min. Interviews were conducted virtually by an independent evaluator using Microsoft Teams. After each interview, the transcript was downloaded, cleaned for analysis, and then checked against the original video recording for accuracy.In addition to demographics, the mentee survey contained 12 metrics to assess over time five major categories of variables germane to the goals of the OCA: psychosocial wellness, research skills, mentoring competency, and patient-centered research, as well as overall program satisfaction. Given the large number of variables, measures were chosen for their brevity, validity evidence when available, and relevance to the investigators’ objectives for participants in the OCA. On some occasions, items were deleted if they represented duplication between metrics. Information regarding instruments can be found in Table t-tests for Time 1 and Time 2. Mentors’ quantitative data are not included for this initial cohort because of the  low response from mentors; we anticipate including mentor data in future studies as more cohorts complete the program. Data on number of publications and number of grants and dollar amounts were extracted from NIH RePorter (https://reporter.nih.gov/) and PubMed (https://pubmed.ncbi.nlm.nih.gov/), respectively.Quantitative survey analyses were completed and imported into IBM SPSS Statistics Software program (SPSS), version 26. Because of the large number of time points and small number of mentee participants (with missing participant data for some time points), we combined time points such that we compared “early program responses” , labeled Time 1. Later time points used were the last, most complete set of responses we had from a participant, anywhere between 40 and 60 months which served as Time 2. Statistical analyses included internal reliability of scales and descriptive statistics for each of the measures, as well as paired sample Qualitative interviews for mentors and mentees were imported into Dedoose, a cloud-based software program, to be analyzed by an independent evaluator using latent content analysis . The datThe qualitative analysis indicates that the OCA program was highly valued by both mentors and mentees. Participants described the program as a way for mentees to become more intentional about their research, receive feedback from other experts working in the field, and to learn the skills they need to be successful within and beyond the laboratory or patient bedside. In the following sections, strengths of the OCA from the perspective of the ECIs are presented, as well as areas in which the program needs further development.Participants indicated that the OCA’s individual DOD CDMRP OCRP-sponsored funding (‘ECI Awards’) were helpful to their overall development because it allowed participants to focus on building a program of research without having to worry about funding. As one participant explained, “A lot of funding opportunities are much shorter, which makes it really hard to kind of settle in” (Participant3). Participants indicated that having a funded laboratory allowed them to refine their research goals, identify potential grants, and kick start their nascent research programs. Funding also helped expand their laboratory capacity, as this participant explained, “The funding has definitely been instrumental in shaping my lab, getting things done, and getting students” (Participant5). Participants also explained that not having to worry about securing additional funding for a period of time allowed them to focus on their own professional development as scientists. Mentors corroborated this finding indicating that many of the junior awards available to researchers are only for 2–3 years making the OCA funding incredibly helpful, “My mentee was able to write one small grant application and then be able to get [a] five year grant, which really made all the difference in terms of the successful career that he has now” (Participant9).Additionally, being able to develop as a professional was an unanticipated benefit. Having reduced pressure to secure additional funding meant they could focus on the continued development of their research program and build a support network that would endure long after their participation in the program ended. For example, this participant explained, “I think that [what was most valuable] was both the funding aspect of it as an early career investigator and also the community aspect… I didn’t realize how strong the community would be at the time I was applying” (Participant3). Having a supportive community was important because it reduced isolation, but also provided technical support when participants needed it. One participant described it as “a family where we help each other” (Participant8), suggesting that both personal and professional relationships were created. Mentors also thought the community building was important because it created a safe and collaborative atmosphere for participants, which is a departure from other programs or scientific meetings where attendees compete with each other. In the OCA, there was no need for competition because everyone was there for the same purpose, to support the work of ECIs in ovarian cancer research, as one mentor explained, “The Academy is very ideal because everybody gets along so well. I mean, you see very little friction in the Academy meetings… [because] they’re all in the same mode there” (Participant12).Participants also liked that while participating in the program their success was tracked, which helped them to reflect on what they have accomplished throughout the year and make plans for the following year. For example, one participant indicated she liked that the OCA tracked the grants she applied for, including ones that were funded and ones that were turned down. She also liked that the OCA was interested in her publications, committee work, and her other professional development activities. Again, this gave her a sense that there were others in her community tracking her development who could help her think through areas she may need to strengthen as an ECI moving toward independence.Additionally, the ECIs problem-solved everyday issues in dealing with their institutions or departments, as this one shared, “[The OCA was valuable] to not just connect with [others] scientifically, but [to hear about] the nuts and bolts of how they were doing within their own institution’s department.” Another participant described how having a community was useful to quickly move through issues in ways that have the potential to impact productivity. Participating in a virtual CoP normalized communication in ways that were not available face to face, “We talk frequently [via] a chat room. Whoever has problems, technical issues, or you know, when we applied for grants, we face difficult questions, and so we talk to each other [about it]” (Participant8).Finally, participants described the high-quality mentoring they received on how to conduct ovarian cancer research. As one participant explained, “People don’t really realize how much it means for us to have that kind of support and mentorship in place” (Participant6). Mentors took their roles seriously and spent considerable time supporting mentees in their research. The protected time they received from being a co- or sub-PI on the ECI’s grants helped ensure mentors could focus on the needs of the mentee, as this mentor explained, “It is nice to have a little bit of protected time, I take my mentoring very seriously and so I meet with all my mentees. I would say that 25% of my week right now is [spent mentoring]” (Participant13).ECIs also expressed that they grew as mentors themselves. For example, one participant indicated that through the mentoring relationship they learned about the importance of being a team player. Whereas previously he did not take his role on a team as seriously as a leadership role, the OCA helped him realize the importance of this, “Even when you are not the leader of the group, you need to be a good team player [and] you need to care about the team” (Participant1). Others described learning about their responsibility to others in different ways. For example, another participant shared, “[The OCA] really taught me more about mentoring, how to become a better mentor, how to navigate interactions with mentees, and how to get the most out of interactions with mentors” (Participant6).In summary, the OCA’s first cohort of ECIs to be evaluated found that the program’s funding, networking and community building, and also expert mentoring, were extremely helpful to their growth and development as ECIs in the field of ovarian cancer research. These results were substantiated by the participants’ mentors who felt that the program was successful in helping participants successfully launch themselves in the early phases of their research careers, as this one indicated, “The success rate is going to be pretty substantial, and I think it speaks to the role of the Academy in helping foster the early phases of career development for those individuals” (Participant11).Although participants felt there were many areas of strength, a subtler theme showed the need for more skill development on grant writing. ECIs indicated that what was provided in the OCA was very helpful, as this one expressed, “the grant writing and grant review process is particularly strong” (Participant3). However, the mentors and mentees expressed concern that once they left the program, they wouldn’t be able to secure their own funding, even though several had already secured additional funding at the time of the exit interviews. They also expressed that conducting team science was challenging, given that they had their individual research projects they needed to attend.Additionally, the inclusion of patient advocates in the OCA was perceived differently by physician vs. non-physician scientists. Some felt that these interactions were exceptionally rewarding because this was an aspect of ovarian cancer research for which they had little previous experience, such as this one, “We got a lot of opportunities to interact with consumers and patient advocates, which generally we don’t get. The OCA was a very good platform to get to know the ovarian cancer patients and what they went through” (Participant7). Mentors also felt that this was a benefit, explaining, “I’ve been in ovarian research for 15 years and actively involved in a number of meetings addressing ovarian cancer …to actually see the advocates, I think has been extremely valuable” (Participant12). However, other ECIs indicated they would like even more regular opportunities to interact with these community members because of how powerful their stories were in shaping their research, as this ECI shared, “I kind of want more interaction with the patients and patient advocates” (Participant6).In summary, after participating in the OCA, participants thought that more opportunities for grant writing and grantsmanship development, with potentially even greater inclusion of patient advocates in activities of the program would be useful. Although these components were already included in the design of the OCA, participants felt they were beneficial to their career development and wanted even more opportunities to grow and learn from such experiences.Internal reliability was calculated using Cronbach’s Alphas. Table P < 0.05) occurred between Time 1 and Time 2. This was anticipated given the small n for the first year. However, many measures displayed an increase in mean scores between Time 1 and Time 2 in the directions predicted. Table Because we used combined time points as detailed in the analysis plan, there was no missing data in Time 1 and Time 2 comparisons. Still, no statistical significance  institutional resources , b) training , c) conflicting demands , and d) relational factors  are addressed, ECIs experience both extrinsic success  and intrinsic success (e.g. career satisfaction) . FindingIn moving forward, the OCA will continue to collect data to evaluate the next cohort of ECI’s in this program, which is funded through 2025, with the potential for even longer-term support. The next CoP iteration will make design changes to the evaluation methods, including six-month interviews to explore how the careers of these ECIs change over time, including navigating obstacles and overcoming scientific and organizational challenges. Specifically, we will also explore how ECIs navigated obstacles as a result of the COVID-19 pandemic, asking how the pandemic affected their ability to adhere to a research plan, their outlook on future funding, and home and work-life balance, such as caring for children and/or ill loved ones.Additionally, we would also like to make changes to the survey administration. Because the OCA was a new program, it was challenging to get participants to consistently respond to the surveys. The five mentors who were mentioned in this manuscript were the only five to complete every time point’s evaluations, whereas the others only responded intermittently. Therefore, in the next iteration, given the number of metrics included during the quantitative assessment, each metric will be reviewed to determine its overall contribution to understanding the ECIs’ experience in this program. The goal will be to shorten the survey’s length with the hope that more of them will be completed.In another vein, although the OCA was intentional in recruiting patient advocates that would be helpful to the ECI’s research agenda, we did not fully evaluate the advocates’ experiences in the program. Rather, advocates were selected based on their commitment to ovarian cancer research and their willingness to help our scholars. In addition, they were chosen because many of them were interested in supporting racially underrepresented populations, or were racially underrepresented themselves. Initially, we viewed these advocates in a supporting role, but after the evaluation, we have reframed our view and realize that their experiences should be a part of the formal evaluation, both to gain a more holistic view of the program, as well as ensuring a sense of belonging. Stakeholder engagement is extremely important at every stage of translational science, and a bidirectional approach, in which knowledge is actively constructed, discovered, transformed, and extended between advocates and mentees equalizes the power hierarchy in translational work and makes for better science. Although the OCA award does not provide funding to train and orient patient advocates, going forward, we plan to give greater thought to how we might engage with advocates differently.And finally, we noted that the same degree of racial underrepresentation that is seen in biomedical research , more ge


The R32 program seeks to ensure that individuals at high risk for adverse health outcomes are identified, engaged, and linked to needed services. The program pays particular attention to identifying individuals with risks related to mental health, memory, nutrition, food insecurity, and emergency department or inpatient hospitalizations. Key performance indicators were tracked, including the number and proportion of participants whose needs were addressed by R32. Results indicate that the program has succeeded in engaging the vast majority (>90%) of individuals with specific risk factors and connecting them with needed services. Viewed in the context of managed care plans, this level of performance is noteworthy and would earn the program a 5 Star rating – the highest rating available. Findings underscore the strong advantage offered by having a wellness nurse and wellness coordinator embedded on site in senior housing and using this platform to manage prevention and care services to residents.


Small bowel Crohn’s disease (CD) strictures can lead to debilitating obstructive symptoms and the deterioration of quality of life. Imaging modalities such as intestinal ultrasound (IUS) are invaluable in the diagnosis of strictures. The use of IUS in CD is rapidly growing, is cost-effective, easily repeatable, and similar in accuracy to magnetic resonance enterography. Evidence for medical management of fibrostenotic CD has been limited to anti-tumor necrosis factor biologics. Studies on the efficacy of other biologic therapies for strictures such as ustekinumab, a p40/interleukin 12 and 23 inhibitor, are lacking.The objective of this study was to evaluate the efficacy of ustekinumab in the treatment of small bowel strictures on IUS.This retrospective cohort study evaluated the IUS changes of terminal ileal (TI) CD strictures at baseline and 12 months following ustekinumab initiation from 2016 to 2020 at a single tertiary care center. Strictures identified were defined as 1) increased bowel wall thickness (BWT) > 3mm, 2) narrowed luminal apposition, and 3) presence of pre-stenotic dilation (PSD) or the inability to pass the colonoscope through the narrowed area. Changes in sonographic parameters  were recorded at baseline prior to initiation of ustekinumab and compared 12 months after treatment. Differences from baseline to 12 months were paired within-person and statistical analysis was performed using paired T-tests for continuous variables and McNemar’s test for categorical variables.n = 10) were male, median age was 49 years (Q1-Q3: 33-63 years) at initial scan, with median CD duration of 10 years (Q1-Q3: 8-20 years). The majority of TI strictures were surgically naïve . Between pre- and 12-month post ustekinumab therapy scans, there was significant improvement in BWT , however there was no significant difference in the presence of peri-enteric inflammatory fat (p = 0.10), mean stricture length , and mean stricture lumen diameter  (Table 1). There was also no significant difference in the presence of stricture-associated peri-enteric fat , stricture-associated hyperemia  or dysfunctional peristalsis  (Table 1).Of the 18 patients identified, 55% (Our study is the first to report the efficacy of ustekinumab in small bowel CD strictures using IUS at baseline and 12 months. This study shows that although ustekinumab leads to improvement in overall sonographic appearance of bowel thickness, it does not improve luminal narrowing nor PSD, two hallmark criteria of fibrostenosis. More extensive studies with larger sample sizes evaluating ustekinumab, or combination therapies, are required to identify their role in stricturing CD.NoneNone Declared


My health for life program.Chronic disease is the leading cause of premature death globally, and many of these deaths are preventable by modifying some key behavioural and metabolic risk factors. This study examines changes in health behaviours among men and women at risk of diabetes or cardiovascular disease (CVD) who participated in a 6-month lifestyle intervention called the My health for life program is a Queensland Government-funded multi-component program designed to reduce chronic disease risk factors amongst at-risk adults in Queensland, Australia. The intervention comprises six sessions over a 6-month period, delivered by a trained facilitator or telephone health coach. The analysis presented in this paper stems from 9,372 participants who participated in the program between July 2017 and December 2019. Primary outcomes included fruit and vegetable intake, consumption of sugar-sweetened drinks and take-away, alcohol consumption, tobacco smoking, and physical activity. Variables were summed to form a single Healthy Lifestyle Index (HLI) ranging from 0 to 13, with higher scores denoting healthier behaviours. Longitudinal associations between lifestyle indices, program characteristics and socio-demographic characteristics were assessed using Gaussian Generalized Estimating Equations (GEE) models with an identity link and robust standard errors.The p < .001 for all) but not risky alcohol intake. Modelling showed higher average HLI among those aged 45 or older  with vocational educational qualifications  while being male, Aboriginal or Torres Strait Islander background, or not currently working conferred lower average HLI scores .Improvements in HLI scores were noted between baseline  and 26-weeks  which corresponded with increases in fruit and vegetable consumption and decreases in takeaway frequency (While participants showed improvements in dietary indicators, changes in alcohol consumption and physical activity were less amenable to the program. Additional research is needed to help understand the multi-level barriers and facilitators of behaviour change in this context to further tailor the intervention for priority groups.The online version contains supplementary material available at 10.1186/s12889-022-14056-1. Chronic disease poses the greatest threat to global health, with a higher morbidity and mortality rate, than do all other causes contributing to around 41 million deaths each year . The ramThe development of chronic disease is underpinned by varying risk factors, including both non-modifiable  and modifiable health behaviours –3, 5 witAddressing chronic disease is important for the 2030 Agenda for Sustainable Development, specifically Sustainable Development Goal (SDG) target 3.4 calls for a one-third reduction in premature mortality from chronic disease by 2030 . To accehttps://www.lifeprogram.org.au/), the Queensland Government invested in a large public health program, My health for life. The program, aims to reduce the risk of cardiovascular disease and diabetes in priority groups, such as those at high risk of developing chronic disease, Aboriginal and Torres Strait Islander People and culturally and linguistically diverse people, through supporting individuals to make changes to their health behaviours. The program targets multiple modifiable health behaviours associated with increased chronic disease risk, therefore to assess the joint association of the multiple modifiable health behaviours targeted by the program, a healthy lifestyle index (HLI) score was created by combining dietary, alcohol and tobacco smoking, and physical activity indices to form a composite score. To understand the effectiveness of the program, the purpose of this paper is to examine changes in the primary outcome  in participants of the My health for life program.Modifiable health behaviours including diet, alcohol, tobacco smoking, and physical activity are linked with physical and psychological symptoms including pain, fatigue and depressive symptoms . Among pMy health for life program is a novel, multi-component program that aimed to reduce chronic disease risk factors among adults at risk of diabetes or CVD in the state of Queensland, Australia. The Queensland Government funded program was developed by an alliance of health organisations led by Diabetes Queensland including Stroke Foundation, Heart Foundation, Queensland Primary Health Networks, Ethnic Communities Council of Queensland and Queensland Aboriginal and Islander Health Council . Details about the program are here https://www.myhealthforlife.com.au/.The https://www.myhealthforlife.com.au/risk-assessment). A range of marketing and communication activities were undertaken to lead potential participants to the online health check including television advertisements on regional and metropolitan television channels, outdoor advertising on billboards and bus shelters, Facebook advertising and print advertisements in local newspapers and a motoring club magazine. Eligible participants were identified using adapted risk assessment tools  [To recruit people at-risk of developing chronic disease, Stroke Foundation staff undertook health checks at community events and workplaces across the state of Queensland, health clinicians undertook health checks in clinical settings  and potential participants undertook a health check online via the website (USDRISK)  or AbsolUSDRISK) ). The prUSDRISK) . High rin = 245, 63.0%), with a small number contracted to a Pharmacy . In total, 264 facilitators (face-to-face or THC) delivered at least one program and had a variety of backgrounds in Allied Health (Dietetics or Exercise Physiology), Nursing, Pharmacy, Health Promotion, Counselling, Aboriginal Health Work or Multicultural Health Work. Retention of facilitators that delivered at least one program was 61.7% (n = 163). Retention of provider organisations that delivered at least one program was 81.8% (n = 112). All provider organisations received financial payment to deliver the face-to-face program, paid on a per participant basis.The program offered is either the face-to-face group-based program (GBP) or one-on-one telephone health coaching (THC), with participants choosing the most suitable option for themselves. The GBP consists of small groups of 6–8 participants, delivered by a trained facilitator in a community setting running for approximately two hours and the THC offering is delivered one-on-one via telephone in house by the lead organisation, Diabetes Queensland with a trained facilitator  running for approximately one hour. Potential provider organisations for the face-to-face program responded to a call for expressions of interest to deliver the program. The organisations nominated qualified and experienced health professionals for training by the program implementation team as a facilitator for the delivery of the face-to-face program with 136 approved providers engaged to deliver the program. Diabetes Queensland recruited the telephone health coaches to work in house through a standard employment recruitment process of qualified and experienced health professionals or through identification of appropriately qualified and experienced existing health professional staff. In total, 408 health professionals attended facilitator training with 403 completing training to become a certified facilitator. Of these, 389 were trained and certified to deliver face-to-face groups, and 14 were trained and certified to deliver the THC program. Training of facilitators included completion of prior reading, attendance at a two day face-to-face training course and successful completion of all assessment. All facilitators are required to maintain accreditation through participation in professional development activities on an annual basis. Training and certification of facilitators was conducted be the My health for life program implementation team. Most facilitators were contracted to an Allied Health Service  with session 6 (related to maintenance) occurring at around 24 weeks. The program, underpinned by the Health Action Process Approach (HAPA), aimed to develop knowledge, skills, and strategies to adopt positive lifestyle behaviours, while educating participants on different risk factors, including healthy eating, alcohol, tobacco use, and physical activity. Session activities target modifiable health behaviours using behaviour change techniques  as outli–5 with sMy Health for Life program between July 2017 and December 2019 who contributed weight, diet, alcohol, smoking and physical activity data towards the composite healthy lifestyle index (HLI). Participants consented to participate upon commencement in the program and completion of the first survey. Telephone health coaches or program facilitators assisted participants to enrol in the program. Ethical approval was granted from the Darling Downs Health Human Research Ethics Committee (HREA/2021/QTDD/72406) and Griffith University (GU Ref No: 2021/143) before accessing de-identified, secondary data.This paper draws upon survey data from 9,372 participants of the This study uses a pragmatic non-randomised, time–series analysis adopting observational, goal-based and pretest–posttest design for the program evaluation  and vegetables , intake of sugar-sweetened drinks  and take-away consumption  . The dieThe alcohol and tobacco index, based on the health guidelines for drinking alcohol , comprisFor the physical activity component, a single indicator was used. The variable, derived from the Active Australia Survey, was collapsed to form a single trichotomous variable indicating being sedentary (no points), insufficiently active (1 point), and sufficiently active for health (2 points) .Details of the scoring for each indicator is in Supplementary Table My health for life program. However, while excess weight was a primary outcome for the study, it was not included in the healthy lifestyle index as it could have been an intermediate factor between modifiable health behaviour and health outcomes [2 representing normal weight, 25–29.9 kg/m2 representing overweight, 30–39.9 kg/m2 representing obesity and >  = 40 kg/m2 representing extreme obesity. Sex-specific waist circumference was grouped according to increased risk (94-101 cm in men and 80-87 cm in women) and greater increased risk (> 102 cm in men and > 88 cm in women). Both measures were included in this analysis to adequately capture adiposity. BMI is an adequate measure of adiposity for clinical purposes [Overweight and obesity are associated with around 8% of Australia’s burden of disease  and was outcomes . Neverthoutcomes  with a Bpurposes .Adjustment was made for other covariates including socio-demographic characteristics , Culturally or Linguistically Diverse (CALD) background, and employment ), relati2) tests and ANOVA with statistical significance set at α = 0.01 and clinical significance achieved with percentage differences greater than 10% [Statistical analyses were performed using SPSS  version 23  and STATthan 10% .Before undertaking multivariate analysis, the patterns of missing data were examined. For the primary outcomes, the amount of missing data at Session 1 varied from < 1% on dietary and alcohol indicators   = 285.15, p < 0.01), sex  = 22.34, p < 0.001), retirement (χ2(16) = 328.41, p < 0.001), higher educational attainment (χ2(16) = 79.10, p < 0.001), and greater relative advantage  = 124.93, p < 0.001). Socio-demographic characteristics by HLI quintile are further outlined in Table Baseline bivariate comparisons of the healthy lifestyle index showed that healthy lifestyle was associated with age  = 16.41, p < 0.01) aged 45 years or less (χ2(2) = 67.36, p < 0.01) with primary or secondary school education (χ2(8) = 16.93, p = 0.03).Overall, three-quarters of participants were female, most were aged 45 years or older (> 80%), around two-thirds reported a secondary school or certificate/diploma level education, and half were employed outside the home. Some modest but statistically significant differences were noted with attrition highest in men (p < 0.001) and vegetables increased over time  while the frequency takeaways decreased. Risky alcohol intake . Finalles < 10%  increaseHowever, while there were general trends towards healthy lifestyle behaviours over the program period, attrition might have influenced prevalence and therefore data were imputed. To assess the robustness of imputation, the original and imputed healthy lifestyle indices summary statistics are provided. Point estimates for the HLI (range 0—13) did not change at each time point with the average HLI at Session 1 being 8.6 (SD = 2.1), 9.6 (SD = 1.9) at Session 5 and 9.9 (SD = 1.9) at Session 6.p < 0.001; Model 2: β = 0.96, 95% CI = 0.89, 1.03, p < 0.001; Model 3: β = 0.98, 95% CI = 0.91, 1.05, p < 0.001) and this was sustained at Session 6 .The results of Gaussian Generalized Estimating Equations which incrementally adjusted for program characteristics (Model 2) and personal background (Model 3) are shown in Table p < 0.001) and program mode  significantly influenced HLI scores though following adjustment for background socio-demographic factors (Model 3) mode was no longer significant (p = 0.076). Findings showed that being retired , aged 45 or older , and having a certificate or diploma  or bachelor’s degree or higher  conferred a higher average HLI while being male, Aboriginal or Torres Strait Islander background, or not currently working conferred lower average HLI scores .Model 2 examined the additive effect of program characteristics. In Model 2, number of sessions attended  though around one-third (37%) of participants consumed an average of 5 or more alcoholic drinks in one session and this was largely unchanged over the program period. Finally, at baseline 19% of participants reported being sedentary and 46% were insufficiently active for health. Over the program period, the proportion of people meeting physical activity guidelines increased, though at Session 6, only 53% reported being sufficiently active for health. Percentage changes using predicted probabilities in individual health behaviours from Session 1 to Session 6 are illustrated in Fig. % though My health for life program, which aimed to reduce the risk factors of chronic diseases among at-risk populations. When compared with the lifestyle indicators of Queenslanders more generally, My health for life participants reported lower compliance with recommended daily fruit consumption, higher baseline average single occasion risky drinking, and low physical activity levels that were sufficient for health [My health for life program period, the proportion of participants meeting recommended health behaviour guidelines , in some instances, was greater than is reported by Queensland adults [This paper explores changes in primary health outcomes of participants from the r health . Notablyd adults .2) in ‘at-risk’ populations, is associated with a significant reduction in disease burden [My health for life program participants has the potential to have a significant impact on the burden of chronic disease. The reduction in BMI for program participants is similar to previous literature which demonstrates the potential for programs targeting multiple health behaviours to contribute to reduction in BMI and waist circumference [During the intervention, the proportion of participants in the extremely obese, obese, categories decreased from Session 1 to Session 6 while those in the normal weight range increased from 9 to 13%. Overweight and obesity is the fourth highest risk factor for burden of disease in Australia. A large proportion of total disease burden can be prevented avoiding or reducing exposure to risk factors including tobacco use, overweight (including obesity), dietary risks, and alcohol use. Overweight including obesity accounts for 8.4% of the burden of disease in Australia . Obesitymference . This shmference .Dietary indicators improved over time, with many participants increasingly likely to meet recommended fruit and vegetable intake at Session 5. In this study 73.5% of participants were meeting dietary guidelines for fruit consumption, whereas in Queensland, it is estimated that around 2.1 million (53%) adults were meeting recommendations for fruit consumption. Around one quarter (25.7%) of participants in this study were meeting the recommendations for vegetable consumption, compared to only 320,000 (8.0%) of Queensland adults meeting recommendations for vegetable consumption . ImportaIn 2019 in Australia there were 11.6% of the adult population who smoke tobacco daily , compareWhile smoking and alcohol consumption rates in this group were lower than the Australian population at baseline, there were improvements across the life of the program.There were general improvements in participants’ physical activity behaviour between Session 1 (34.1%) and 5 (58%), though only around half of participants were sufficiently active for health at program completion, returning to lower levels (53.3%). At baseline for this study there was a considerably smaller percentage of participants who were sufficiently active for health (34.1%), than that previously reported for Queensland adults aged 18–75 years  and Australian adults more broadly (45%) , 52. ThiThe results from this study are consistent with the growing body of research showing the effectiveness of lifestyle interventions on improving modifiable health behaviours. Key components of these interventions include the use of motivational interviews to allow participants to set their own intentions and goals , 54, strThe intervention was associated with improvements in healthy lifestyle indicators which contributes new information to this research area. While participants showed improvements in dietary and smoking indicators, changes in alcohol consumption, and physical activity were less amenable to the program. Conducting additional research will help understand the multi-level barriers and facilitators of behaviour change in this context to further tailor the intervention for priority groups.This paper has several limitations to acknowledge. First, a pragmatic non-randomised, time–series analysis adopting observational, goal-based, and pretest–posttest design features underpins the program evaluation. The absence of a control group, which would be extremely challenging to establish given the size and intent of the program, could impact on the ability to make causal inferences about the impact of the intervention of health indicators, however, where possible program results are compared to Queensland and Australian rates of behaviour. Participants enrolled in a lifestyle modification program, are potentially highly motivated to improve their health regardless of the intervention which may impact on the positive outcomes of the program. Second, akin with many longitudinal studies, missing data were present in around 42% of participants at Session 5 and 58% of participants at Session 6 and this might have impacted the magnitude of outcomes and the representativeness of the sample . To accoAdditional file 1: Supplementary Table 1. Healthy lifestyleindex construction. Supplementary Table 2. Sensitivity analysisof the longitudinal modelling of a HLI using Gaussian Generalized EstimatingEquations with an exchangeable structure and robust standard errors (with andwithout adjustment for baseline excess weight). Supplementary Table 3. Associations between participant characteristics and missing data at baseline. SupplementaryTable 4. Proportion of missing data from indicators at sessions 1-6.