The 5-year graft survival rate of donor kidneys transplanted in the Eurotransplant Senior Program (ESP) is only 47 per cent. Normothermic machine perfusion (NMP) may be a new preservation technique that improves graft outcome. This pilot study aimed to assess safety and feasibility of this technique within the ESP.Recipients were eligible for inclusion if they received a donor kidney within the ESP. Donor kidneys underwent 2 h of oxygenated NMP with a red cell-based solution at 37°C, additional to standard-of-care preservation (non-oxygenated hypothermic machine perfusion). The primary outcome was the safety and feasibility of NMP. As a secondary outcome, graft outcome was investigated and compared with that in a historical group of patients in the ESP and the contralateral kidneys.P = 0.001). The incidence of immediate function was 64 per cent in the NMP group and 40 per cent in historical controls (P = 0.144). A significant difference in graft outcome was not observed.Eleven patients were included in the NMP group; the function of eight kidneys could be compared with that of the contralateral kidney. Fifty-three patients in the ESP, transplanted consecutively between 2016 and 2018, were included as controls. No adverse events were noted, especially no arterial thrombosis or primary non-function of the transplants. After 120 min of oxygenated NMP, median flow increased from 117 (i.q.r. 80–126) to 215 (170–276) ml/min  for donor kidneys transplanted in the Eurotransplant Senior Program. NMP is a safe technique and may improve the incidence of immediate function. A well powered study is warranted to confirm these results and to investigate the potential advantages of NMP on graft outcome.Potential to improve graft outcome Kidney transplantation is the only life-saving treatment for end-stage renal disease,,In the past decade, machine perfusion has regained interest as a promising preservation technique for deceased donor organs. Moers and colleagues,,,Although NMP is theoretically attractive, its application in deceased donor kidney transplantation is largely unknown, as only a few centres have published on this technique in a clinical kidney transplantation settingThis prospective, single-centre pilot study aimed to include 10 ESP recipients of a technically successful NMP procedure. Between 1 January 2018 and 1 December 2018, all waitlisted patients aged 65 years or above were asked to participate. Patients were excluded if they received a dual kidney transplant. Multiple renal arteries in the donor organ were not a contraindication for inclusion as arterial reconstruction could be performed safely before the NMP procedure. All kidneys were allocated according to the regular Eurotransplant rules based on blood-type compatibility and waiting time. All donor kidneys included in the study were suitable for transplantation based on standard criteria before the start of NMP. Both donation after brain death (DBD) and DCD kidneys were included. The study was performed in Erasmus Medical Centre, Rotterdam, the Netherlands, and approved by the local medical ethics committee . All recipients provided informed consent to participate in the study.®) Cold Storage Solution  to which 25 000 or 50 000 units heparin were added, depending on kidney-only or multiple organ procurement. After procurement, the donor kidney was stored and transported on pulsatile, non-oxygenated HMP using the LifePort®Kidney Transporter  or Kidney Assist Transport® , as this is standard of care in the Netherlands. In other Eurotransplant countries, kidneys are still preserved on SCS.The donor procedure was carried out in the donor hospital, according to the standard Eurotransplant retrieval procedure. For DCD donors, a 5-min period of ‘no touch’ after asystole was maintained, according to Dutch law. Thereafter, the donor was transported immediately to the operating room. The super-rapid recovery technique was used to perform aortic flush with at least 5 litres of ice-cold (0–4°C) Belzer University of Wisconsin . The kidney was then connected to the Kidney Assist.Upon arrival of the donor kidney at Erasmus Medical Centre, the kidney was disconnected from the HMP device under sterile conditions. Thereafter, acceptability for transplantation was assessed. The Kidney Assist  used for NMP provides pressure-controlled perfusion with a rotary pump. Perfusion was performed with an oxygenated, plasma-free, red cell-based solution, based largely on the perfusate, as described by Hosgood Oxygenated NMP was started at 37°C with 100 per cent oxygen at a pressure of 60 mmHg, which was increased manually if deemed necessary based on the colour of the kidney. Urine produced during NMP was recirculated to keep the volume constant, as this has been shown to maintain a more physiological perfusate composition and improved flow during NMPThe primary outcome of the study was the safety and feasibility of NMP. Any adverse events in the postoperative period or problems during NMP were recorded. Special attention was given to technical issues such as machine failure and inability to perform NMP or decannulation. Unfavourable short-term transplant outcomes, such as PNF, early rejection, graft infection and graft thrombosis, were also noted. Logistical issues were noted, paying particular attention to the duration of cold ischaemia time. The NMP procedure should not prolong cold ischaemia time, as this impacts graft outcome.Secondary outcomes were graft outcomes, defined as the incidence of immediate kidney function (no DGF/PNF), biopsy-proven acute rejection (BPAR) within 3 months, post-transplantation estimated glomerular filtration rate (eGFR), and graft and patient survival. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. For graft survival, both death-censored and uncensored graft survival were investigated. DGF was defined as the need for dialysis treatment in the first week after transplantation. PNF was defined as a never functioning graft and was diagnosed retrospectively 3 months after transplantation. Graft outcome was investigated and compared with that in two control groups. The first control group was a historical cohort of consecutive patients in the ESP transplanted without the use of NMP between 1 January 2016 and 31 December 2018. In this control group, cold preservation of the kidney was usually performed with HMP, and for incidental cases with SCS. To reduce bias by confounding, a second control group was formed consisting of the contralateral kidney of each included donor kidney, if that kidney was also transplanted.U test. Categorical variables were presented as numbers and percentages, and compared with the χ2 or Fisher’s exact test, based on expected and observed counts. For comparisons made with the contralateral kidney and for correlated measurements, the Wilcoxon signed rank test was used for continuous data and the McNemar test for categorical data. For the outcome eGFR, if graft failure had taken place, an eGFR of 10 ml/min was imputed. If a patient died with a functioning graft, the last observation of eGFR was carried forward. Survival analysis was performed using the Kaplan-Meier method and curves were compared with the log-rank test. Two-sided P <0.050 was considered statistically significant. All analyses were performed using GraphPad Prism® version 5.0  and IBM SPSS® Statistics version 25 .For baseline characteristics, continuous variables were presented as median (i.q.r.) values, and comparisons were done using the Mann–Whitney Between 1 March 2018 and 1 December 2018, 11 deceased donor kidneys transplanted into recipients participating in the ESP received 2 h of NMP. One protocol violation took place, as one of the donors was aged 63 years and 10 months; this became apparent only once the NMP procedure had started.Table 2. Seven of the 11 kidneys were retrieved from a DCD donor. The median age of donors and recipients was 71 (i.q.r. 66–72) and 71 (67–74) years respectively. The majority of patients (8 of 11) had received dialysis before transplantation, with a median time on dialysis of 22.5 (i.q.r. 14.3–45.3) months. Median total cold ischaemia time was 593 (i.q.r. 497–746) min, which consisted of cold ischaemia time until NMP plus a second short cold ischaemia time after NMP until transplantation (median 83 (34–167) min).Baseline characteristics are shown in Five donor kidneys had multiple renal arteries necessitating arterial reconstruction before transplantation. No technical problems occurred during NMP; in particular, no complications due to decannulation, arterial flow or machine failure were noted. Despite the high incidence of vascular multiplicity, no arterial thrombosis occurred during NMP or after transplantation. There were no cases of PNF, and all kidneys were demonstrated to be functioning. shows median flow, pressure, and intrarenal resistance during NMP for the 11 recipients, and Table 3 shows differences between perfusion parameters at the start and end of NMP. Median flow was 117 (i.q.r. 80–126) ml/min at the start of NMP, increasing significantly to 215 (170–276) ml/min at the end (P = 0.001). Median perfusate pH, lactate and sodium increased significantly, whereas glucose, potassium and calcium perfusate remained constant.Table 2 presents baseline characteristics for this control group in comparison with the NMP group. Donor BMI was significantly lower in the NMP group than in the historical controls (median 22.2 (i.q.r. 18.1–26.1) versus 25.6 (23.6–28.2) kg/m2 respectively; P = 0.043). Other baseline characteristics were not significantly different. Despite an additional second cold ischaemia time in the NMP group, total cold ischaemia time was similar in the two groups (P = 0.893).To select a larger reference control group, 53 consecutive patients in the ESP were selected, who had been transplanted between 1 January 2016 and 31 December 2018. Table 4. Seven of the 11 patients (64 per cent) in the NMP group had immediate kidney function, compared with 21 of the 53 patients (40 per cent) in the historical ESP cohort (P = 0.144). No PNF occurred in the NMP group, compared with four cases in the historical controls . The proportion of patients with DGF was 4 of 11 (36 per cent) in the NMP group versus 53 per cent in the historical controls (P = 0.320). Median duration of DGF was 15.5 (i.q.r. 8.3–98.5) days in the NMP group and 14.5 (5.5–26.8) days in the controls (P = 0.602). One of the four patients with DGF in the NMP group was pre-emptive and developed DGF as a result of atrial fibrillation with haemodynamic instability, requiring cardiopulmonary resuscitation followed by admission to the ICU. Fig. 2 shows similar creatinine and eGFR trajectories in the first week after transplantation and at 30 days in NMP and historical control groups. Groups did not differ in patient or (death-censored) graft survival, incidence of BPAR, or proportion of patients with an eGFR above 30 ml/min after 3, 6 and 12 months (Table 4). No differences in eGFR were observed between the groups at 3 months (P=0.510), 6 months (P=0.482) and 1 year (P=0.908) .Results of graft outcome in the NMP and ESP control groups are summarized in versus 40 (37–50) min for the contralateral kidney; P = 0.002). Total cold ischaemia time was similar (median 597 (512–795) versus 679 (574–700) min respectively; P = 0.867). DGF occurred in two kidney pairs in both kidneys, and in one pair only in the NMP kidney; biopsy of this kidney showed chronic damage with acute tubular necrosis without rejection. The 1-year death-censored graft survival rate was 100 per cent in the NMP group and 80 per cent in the contralateral kidney group . The 1-year uncensored graft survival rate was 86 per cent in the NMP group and 80 per cent in the contralateral kidney group (P = 0.637). The 1-year patient survival rate was 86 per cent in the NMP group and 75 per cent in the contralateral kidney group (P = 0.731) Rejection occurred in two kidney pairs in both kidneys and in one pair only in the NMP kidney. At 3 months, creatinine levels were determined for all eight kidney pairs and found to be similar between two kidney pairs . For four kidney pairs the creatinine concentration was lower in the NMP group, and for two kidney pairs creatinine levels were higher in the NMP group. The NMP kidney of donor 8 had a prolonged DGF based on acute tubular necrosis with discontinuation of haemodialysis after 3 months. Unfortunately, creatinine levels remained above 300 μmol/l. The NMP kidney of donor 5 experienced vascular rejection at the 3-month creatinine measurement; this recovered fully, with a creatinine concentration at 1 year of 120 μmol/l. Paired analysis showed a median 3-month creatinine level of 166.5 (i.q.r. 139.8–203.5) μmol/l in the NMP group and 176 (125.3–273.8) μmol/l in the contralateral kidney group (P = 0.779).Eight kidneys were eligible for comparison with the contralateral kidney, as one kidney was not transplanted (unknown reasons) and the other two contralateral kidneys both underwent NMP in this study. Second warm ischaemia time was significantly shorter in the NMP group (median 19 (i.q.r. 17–22) min This pilot study described experience with 2 h of NMP and supports the feasibility and safety of implementation of NMP in this frail patient group. No adverse events were noted during or after NMP. Moreover, analyses for graft outcome showed overall comparable kidney function in NMP and standard preserved kidneys, indicating the safety of NMP in this ESP group. An interesting finding is the observed difference in immediate function between NMP kidneys and the historical controls. Although this did not reach statistical significance owing to the small sample size, the magnitude of the difference suggests that the technique of NMP may be clinically relevant.P = 0.014). The impact of NMP on DGF is probably mediated by interference with ischaemia–reperfusion injury (IRI). ESP kidneys are more vulnerable to IRI, due to increased donor age and co-morbidity of the donor. Even though no active therapy was given during NMP, a recent studyThe results concerning the impact of NMP on the incidence of DGF are comparable with the first clinical study of 18 ECD–DBD donor kidneys by the Cambridge groupOne of the strengths of this study is the use of a paired analysis with the contralateral kidney as a control group. The comparisons made with the historical cohort are confounded; this was addressed by also analysing the outcomes for the contralateral kidney of the same donor. Another strength is that cannulation and attaching the kidney to the Kidney Assist was carried out by one surgeon, which reduces variability in this technique that may have affected quality of NMP. A limitation may be that the donor kidneys were stored for a short period on SCS after NMP for logistical reasons. This could have counteracted the benefit of NMP. However, this risk is deemed small as previous studies,Unfortunately, one protocol violation took place where one of the kidneys was from a donor nearly 64 years of age instead of 65 years or older. This may have affected graft outcomes, as the cut-off age for the ESP is 65 years. However, as the primary outcome was safety and feasibility, it was decided to include this patient in the analyses. Finally, a recent studyThe present study protocol differed slightly from that presented by the Cambridge group,A few adjustments could be considered to optimize the NMP procedure in the future. First, assuming that NMP of longer duration is beneficial, the addition of albumin may be recommended to increase the osmotic pressure, preventing oedemaet al.The findings of this pilot study support the performance of a larger study to explore further the potential efficacy of NMP to improve graft outcome. As a next step, the focus should be on exploring the safety of prolonged NMP and the possibility of administering therapy that specifically targets IRI. Currently, an RCT is being carried out in the UK, comparing NMP with SCS. This trial will help to identify biomarkers and perfusion cut-off values to define required length of perfusion. NMP not only has the potential to improve outcome in kidneys accepted according to current standards, but might also reduce discard rates, as Hosgood Coolsingel Foundation This study was funded by the Coolsingel Foundation (‘Stichting Coolsingel’). The funder was not involved in the research design, data collection, analysis, or manuscript preparation.


A continuing professional development (CPD) program for pharmacists practicing in community and team-based primary care settings was developed and evaluated using Moore’s framework for the assessment of continuing medical education. The program had three components: online lectures, a two-day training workshop, and patient case studies. Knowledge (pre-post multiple choice test); attitudes, readiness, and comfort with applying pharmacogenomics in their practices (pre-post surveys); and experiences of implementing pharmacogenomics in practice (semi-structured interviews) were assessed. Twenty-one of 26 enrolled pharmacists successfully completed the program, and were satisfied with their experience. Almost all achieved a score of 80% or higher on the post-training multiple choice test, with significantly improved scores compared to the pre-training test. Pre- and post-training surveys demonstrated that participants felt that their knowledge and competence increased upon completion of the training. In the follow-up, 15 pharmacists incorporated pharmacogenomics testing into care for 117 patients. Ten pharmacists participated in semi-structured interviews, reporting strong performance in the program, but some difficulty implementing new knowledge in their practices. This multi-component CPD program successfully increased pharmacists’ knowledge, readiness, and comfort in applying pharmacogenomics to patient care in the short-term, yet some pharmacists struggled to integrate this new service into their practices. Pharmacogenomics is a rapidly evolving field, with pharmacists ideally positioned to lead its clinical implementation in practice. The pharmacogenomics curriculum content in North American colleges or schools of pharmacy has increased in the past 15 years, with much of the published research focusing on instructional design, student outcomes, and experiences associated with implementing pharmacogenomics into undergraduate Doctor of Pharmacy and post-graduate residency training programs . DetermiThe ability of traditional continuing professional development (CPD) programs to enhance the practice of health care professionals and improve health outcomes has been debated in health professions and pharmacy education literature. In a systematic review of the impact of CPD programs on providing clinical community pharmacy services, most cited their effectiveness in terms of knowledge or skill modification . Yet, asTo date, pharmacogenomics education for practicing pharmacists has been largely based on short in-person or internet-based programs . The impThe Pharmacists: Personalized Medicine Experts (PRIME) study was a prospective cohort study that consisted of two distinct phases. In phase one, we developed, delivered, and evaluated a pharmacogenomics CPD program (November 2015–January 2016) using the framework for planning and assessing continuing education (CE) described by Moore et al. . In the Pharmacists licensed to provide direct patient care in the province of Ontario who practiced primarily  in primary care settings were eligible to participate in PRIME. We used a broad definition of primary care settings that included community pharmacies, as well as interprofessional family medicine practices . Pharmacists practicing exclusively in hospitals, and pharmacy students/interns, were not eligible for the study. In addition, pharmacists already enrolled in another pharmacogenomics training program were not eligible.Participants were recruited through an email invitation. First, we contacted pharmacists who had previously participated in a study led by one of the co-principal investigators and had consented to be contacted for future opportunities. Second, we sent invitations to pharmacists who had already expressed an interest in participating in the project. Third, we invited pharmacists who had subscribed to the email distribution lists of the Leslie Dan Faculty of Pharmacy, University of Toronto Continuous Professional Development office; Ontario’s family health team pharmacists; and selected pharmacy corporations. Since the second study phase was planned as a feasibility study, we determined a priori that our maximum capacity for the CPD program was 25 participants. Participants were selected by the study team to obtain maximum variability with respect to geographic location in Ontario and practice settings.The curriculum was based on an assessment of the educational needs of pharmacists in pharmacogenomics, and the experience of the study investigators as clinicians and educators ,4. MooreA CPD program was designed with three distinct components, to be completed sequentially within a two-month period, with an emphasis on content intended to increase the participants’ knowledge and competence in the field of pharmacogenomics. Part 1 of the program, administered through the Blackboard learning management system used at the time of the study at the University of Toronto, consisted of three hours of online educational modules. Part 2 consisted of 12 contact hours in a two-day live training workshop. Multiple learning modalities were employed during the workshop, including lectures, facilitated discussions, case presentations, and role play scenarios. A summary of the session topics, and corresponding learning objectives, is included in The structure of the CPD program closely resembled the adaptation of Merrill’s approach to instructional design presented within Moore’s framework . This apThe CPD program participants also received support after the completion of the program itself. The Blackboard Learning Management system was used as a resource portal to provide participants with links to clinical guidelines and information about pharmacogenomics and mental health conditions, as well as a forum to discuss the cases through a discussion board. The formal training was supplemented with continuing support through an online community of practice, moderated by faculty members from the training program who had expertise in applying pharmacogenetics in clinical practice. Faculty members were also available to the participants for consultation with individual cases they encountered in the implementation phase.In the second phase of PRIME, pharmacists who successfully completed the CPD program sought to integrate pharmacogenomic testing into their existing primary care practices by identifying patients who may benefit from the service. For this purpose, patients were at least 18 years old and were either prescribed or switching to a new antidepressant or antipsychotic, or had a poor response or significant and repeated side effects to an antidepressant or antipsychotic. The patients provided a saliva sample for pharmacogenetic testing. The pharmacists conducted a comprehensive medication review with the patient, then reviewed the pharmacogenetic test results to discuss recommendations about antidepressant and antipsychotic treatment, as appropriate, with the patient. Moore’s 2009 outcomes framework proposes seven distinct levels that align with specific instructional designs . The outExisting materials from the Continuous Professional Development program at the University of Toronto were adapted to create a 63-item questionnaire to evaluate participants’ opinions of the training program. Items requested either open-ended or Likert-type scale responses from the participants, and were designed to measure their satisfaction with aspects of each component of the program, including the content and delivery, and to elicit suggestions for how the training program could be improved. A 20-item multiple choice test was developed and reviewed for content validity by subject matter experts within our investigator team, most of whom are experienced university educators. Each participant was given one attempt at the test. The participants undertook the test before accessing the online pre-workshop modules, and again after the training program was complete. The participants needed to achieve a score of 70% or greater on the post-program knowledge test to successfully complete the training. Of the 20 items included in the test, six were designed to evaluate declarative knowledge, and 14 were designed to evaluate procedural knowledge.This survey consisted of three parts and was administered simultaneously with the knowledge test, i.e., before and after the training program. In Part A, the pharmacists completed a short demographic questionnaire that included age, gender, years in pharmacy practice, post-graduate education, other certifications or specializations, practice setting, or other relevant informal training or work experience in pharmacogenetics. In Parts B and C, the pharmacists used five-point Likert scale responses to indicate their extent of agreement with 16 items. Part B items explored whether the pharmacists felt adequately informed about common issues in using pharmacogenomics information as part of patient care . Part C explored the pharmacists’ attitudes about the role of pharmacogenomics in clinical practice, and the suitability of the pharmacists in general to promote the uptake of its use in practice (intention to change—level 4). Part C also asked the participants to evaluate their own ability to apply this information in practice (self-reported competence—level 4). The survey was developed for this study based on a literature review of items from similar initiatives ,11 and aAll of the pharmacogenomics training program’s 21 participants received email invitations to participate in an approximately 30-minute long, semi-structured telephone interview about their overall experience with implementing pharmacogenomics into their practice. Pharmacists who expressed an interest in participating in an interview were contacted by phone prior to the interview to answer any questions regarding the interviews, and to obtain verbal consent. Interviews were conducted by a pharmacy resident between February and April 2017, and were audio recorded and transcribed verbatim.Summary statistics are reported as means and standard deviations for continuous data and counts, and as percentages, medians, and min/max for categorical data. Paired t-tests were used to compare before-and-after scores on the knowledge test. The data collection method for the Self-Assessment Survey did not allow pairing; therefore, unpaired t-tests were used to assess change. P-values less than 0.05 were considered to be statistically significant. All statistical analyses were conducted using IBM SPSS Statistics Version 23.0.Qualitative data management software  was used to organize interview transcript data and to assist with thematic analysis. Transcripts were inductively coded by the interviewer and a pharmacist graduate student. Themes and patterns within the coded data relating to participant performance (Moore’s level 5) in delivering pharmacogenetic clinical services in the PRIME program were identified and interpreted. A third investigator reviewed several coded transcripts and their analysis, to enhance the ‘trustworthiness’ of these findings.With respect to prior training in pharmacogenomics, all of the pharmacists disagreed with the statement “Pharmacogenetics was an integral part of my undergraduate pharmacy school curriculum”. When asked to estimate the number of hours of training received in the past, the mean was 2.1 . Seventeen (43%) of the pharmacists reported they had received no training whatsoever, and three (8%) of the pharmacists reported receiving 10 or more hours.Interest exceeded initial expectations, with 143 pharmacists applying to participate within the first 48 hours of advertising. From this group, 26 pharmacists were selected for the training program. All 26 completed the early online training, 24 attended the live training workshop, and 21 successfully completed the entire training program. All withdrawals were due to personal circumstances. Satisfaction using the feedback tool was received from 23 participants, though not every question was answered by every participant. In general, participants felt that the program met their expectations  and that the length of the training program was appropriate . They were satisfied with the training experience; 90% (n = 18/20) agreed or strongly agreed that the caliber of instruction was high, and 95% (n = 19/20) agreed or strongly agreed that the organization of the program was very good, with 95% (n = 18/19) agreeing or strongly agreeing that they would recommend this course to colleagues. Areas for improvement were noted in terms of the formatting and readability of the course handouts, providing access to more resources to facilitate self-directed learning, and additional practice in applying the training program’s concepts .p < 0.001), from a total possible 20 points. The distribution of test scores is shown in The mean score on the knowledge test before the program was 11.2 (SD 2.4), and was 17.3 (SD 1.6) on completion of the program  located in both urban and rural parts of Ontario. Eight of the 10 pharmacist interviewees had provided clinical pharmacogenetic services for at least one patient. Pharmacists reported increased knowledge and competence after completing the pharmacogenomics CPD program. “I feel that I definitely have a better understanding than I had before. I definitely have more resources that I’ve learned about through this process. So if I were to be asked a question, I think I can be able to find the right resources to provide some opinion.”Many shared examples of applying the knowledge and skills that they had practiced in the CPD program to situations they encountered in their practices, such as identifying patients who would benefit from pharmacogenomics services, making and implementing pharmacotherapy recommendations based on pharmacogenomics results, and providing patient education. However, some pharmacists reported that some personal discomfort with providing pharmacogenomics services persisted until after they had cared for a few patients in their practice. Some of this discomfort was attributed to pharmacogenomics testing interpretation being an inexact process requiring clinical interpretation and decision-making. “Especially with some of the first patients that I had, it just took me a while to feel comfortable myself with all of that. So let alone, sort of potential knowledge gaps that I had too. So not only getting comfortable in understanding what the results mean and how to apply that to the patient but also the knowledge gaps with regards to... I mean, like CANMAT  guidelines for anxiety and depression and all of those subcategories, I found that I really had to refresh myself. Obviously wanting to recommend what was first line.”Other participants with early successes reported this as motivator to continue. “Well, I can tell you that I got three more referrals from that physician. So I think once you kind of see some of that success that also kind of buys into the approach as well.”Despite the objective gains in understanding, comfort, and competence evident from the CPD program surveys, some pharmacists shared that they lacked confidence in their real-world ability to recommend or refer patients for pharmacogenomics testing. Still, other participants described a need for additional training if they were to continue offering the service beyond the context of the study, and for the resources and support from study personnel. “I think I would want to personally study a little bit more now that I have an understanding. I think I have a very general understanding and have been able to at least talk about the reports. But if I were doing it on my own, I would want to be a little bit more up-to-date. Like…because you know, being part of the study, I always felt that if I had any questions, I can reach out to somebody who is an expert. But if I were doing it on my own then I would expect that my level of understanding should be higher.”Furthermore, these participants postulated that their recruitment of patients into the study and incorporation of pharmacogenomics testing into their practices would have been enhanced by increased comfort and competency in providing pharmacogenomics services. The PRIME CPD program was successful in equipping pharmacists as personalized medicine experts, as evidenced by short-term improvements in knowledge tests, self-reported competence, and the demonstration of application in a practice setting. We used an established curriculum planning framework in our program design, with the goal of equipping pharmacists with the procedural knowledge to enact level 5 (performance) in Moore’s framework. We used blended and active learning strategies, incorporated several embedded application opportunities, and our program was designed by an interprofessional team. Since our training program was developed, consensus-based pharmacogenomics competencies have been published to guide pharmacy education in this field . Our CPDOur evaluation perspective is unique in this field, as there are few examples in the pharmacy continuous professional development field of examining level 5 (performance outcomes) of Moore’s framework ,14, and Limitations of our study are noted. First, we used convenience sampling to recruit pharmacists to participate in our training program and are uncertain how many pharmacists received our invitation to participate in the study through the channels we used to distribute the invitation. According to the Canadian Institute for Health Information, there were approximately 10,000 pharmacists practicing in Ontario’s community pharmacies in 2015 . Second,A recent qualitative interview study of community pharmacists delivering pharmacogenetic services identified five themes relating to self-described educational needs: (1) pharmacogenomics education and training, (2) active learning to build confidence, (3) robust clinical resources to effectively implement pharmacogenomics services, (4) a team-based approach throughout implementation, and (5) a readily accessible network of pharmacogenomics experts . We beliSince our program was developed, an update to Moore’s framework has been published . In thatThe PRIME CPD program increased both knowledge and competence, and improved performance in providing clinical pharmacogenetic services for most participating pharmacists, particularly in the short-term. Future iterations of the program would be enhanced by the additional integration of implementation science theory and approaches into curriculum design to address the challenges encountered by pharmacists as they incorporate this new service into their existing practices.


Different combinations of these modes could describe a range of ways of relating to the program, including a nonsocial interaction, a semi-social interaction, and a semi-social relationship. A person-to-program bond is explained by the model as an experienced supportive social presence, enabled by making come-alive and a positive program interaction.Health interventions delivered online (self-guided web-based interventions) may become more helpful through a person-to-program “working alliance.” In psychotherapy, the working alliance signifies a therapeutically useful client–therapist relationship and includes an emotional bond. However, there exist no theories of how program users relate to online programs, or that explain a person-to-program bond theoretically. Addressing this gap, we conducted qualitative interviews with and collected program data from users of a self-guided web-based intervention. Taking a grounded theory approach, the analysis arrived at a model of relating based on two relational modes— Online health interventions may dramatically change how health care is provided by providing high-quality, individualized care without the expensive use of human resources, available to anyone with the access to the internet, anytime and everywhere. Often called “eHealth” or “mHealth” programs, these computerized interventions can be completely automated and have repeatedly proven to be effective . HoweverThere is evidence suggesting the existence of a person-to-program alliance . For exaHowever, there is no consensus of exactly what a person-to-program alliance is—what elements it includes. In psychotherapy, the alliance is often defined as comprising three elements: (a) that client and therapist agree on the goals of therapy ; (b) agreement on the therapeutic tasks toward that goal ; and (c) the emotional bond, or “the nature of the human relationship between therapist and patient” , p. 254.On a behavioral level, people do seem to respond to computers as if they were other humans in a variety of situations, as demonstrated in a series of experiments conducted by N = 9) who had used a self-guided web-based intervention for quitting smoking. The intervention mainly consisted of an interactive, tailored website on which the participant could navigate through different pages. Nevertheless, the authors found that participants could “project human qualities” to the program and interact with it as if it were a person. Some of the data excerpts clearly demonstrate this . In a different study, N = 14) who used a self-guided web-based system. The system was placed in their homes, served a variety of health purposes, and participants could call the intervention, upon which the intervention answered with a human voice (recorded by an actor). Participants could respond by pressing numbers on their phone. The authors found that participants formed three types of relationship to the web-based intervention: “feelings of love” (N = 3), described as talking about the program as a person ; “feelings of guilt” (N = 9), described as feeling judged or lectured by the program; and “ambiguity and ambivalence.” In this latter category, six participants talked about the intervention as a machine, one participant talked about the intervention as “he” instead of “it,” and four participants expressed ambiguity as to whether they were interacting with a person or a program.On a more cognitive and emotional level, there are vivid examples in the literature of program users sometimes thinking of self-guided web-based interventions as other human beings . Two of The evidence that these studies report may be the experiences of a few unique individuals. Furthermore, How do the users relate to the intervention?In sum, there is a need to improve our understanding of the working mechanisms of self-guided web-based interventions , and oneWe chose grounded theory  because The study was conducted within a critical realist perspective . That is“Endre” (“Andy”) is a Norwegian, self-guided web-based intervention for quitting smoking designed to support a working alliance . Some imAndy consists of a phase of preparing for quitting smoking and a follow-up phase after the user has quit. In the standard version, the preparation phase consists of 10 different session over 10 days, followed by a follow-up phase of 14 different sessions over 4 weeks. The actual number of sessions each program user receives is tailored to individual use, as the program adapts to how often the user logs on. Once the user has quit, she or he enters a follow-up phase in which she or he in addition to web-based sessions also receives text messages from Andy in the evening, asking whether she or he has been smoke-free that day. If the user reports a lapse, she or he is given access to a special session aimed at preventing the lapse from becoming a full-blown relapse to smoking. A typical session consists of Andy greeting the user, introducing today’s quitting-related topic, and asking a topic-related question, which the user must answer by choosing a multiple-choice alternative. Sometimes the user is asked to write his or her answer in a textbox. Some of these user-generated texts are presented to the user at a later point, in a different “conversation” in which Andy “remembers” something the user has said previously. Next, Andy will respond to the user’s answer, and the “conversation” will go back and forth, ending by Andy summarizing today’s session and bidding farewell.The study was conducted in Norway and is based on two different types of data from two different subsamples: an interview sample and a noninterview (“reflection note”) sample. For both samples, we recruited people who wanted to quit smoking with the help of a web-based intervention. In the following, we will describe the two samples separately.N = 16) was recruited via the researchers’ social network on Facebook, a popular discussion forum in Norway (“Underskog”), and a local general practitioner’s (GP) office. This convenience sample of 16 participants was fairly heterogeneous, including both men (N = 5) and women (N = 11), varying in age (32–70 years), and holding different occupations . Some participants had stopped using the program while still preparing for quitting, some completed the program, some had successfully quit smoking, some had not, and yet others had relapsed. Thus, this study sample was diverse on several parameters, and the ensuing model is based on and includes these different perspectives. Three of the participants were distant acquaintances of the interviewer (Marianne T. S. Holter); this did not seem to affect the data negatively.The interview sample (N = 55) participated through “reflection notes,” a special type of written activity in the program described below. These participants were originally recruited for a different, quantitative study, but they consented to the current use of their program data. They were recruited through Healthy life centers in several Norwegian municipalities as well as through advertisements on Facebook, Google, and online newspapers. The first 112 participants who consented were included in a sample pool for the current study, from which we theoretically sampled (N = 10) and women (N = 45) of different ages (25–66 years) and with different levels of education (ranging from primary school to a higher university degree of 4 years or more).The noninterview sample . The other eight participants were interviewed over the telephone, as they lived in other parts of the country. All interviews except three were audiotaped; in these interviews, a recording device was for various reasons not available, and the interviewer instead made notes, careful to separate quotes from notes.After the first six interviews, we made considerable changes to the interview guide. These first interviews served two purposes: data collection for the current study and gathering feedback for program improvement. However, we experienced substantial challenges in getting rich data on how the participants related to the program, leading us to revise the interview guide. In the revised interview guide, the participants were first asked to give a free account of their experiences. Next followed a section where the participants and interviewer together reflected on questions of relating to Andy, both active in the discussion from their unique vantage points, ultimately seeking general knowledge about the processes under study . It is this written material that is referred to as “reflection notes.”Reflection notes were included in the later stages of the study to increase its validity through methodological triangulation , and to We used grounded theory  to analyThe iterative process of interviewing, inductive coding, sorting, case analyses, and memo-writing gradually moved us toward a more deductive phase, in which we tentatively sketched out a model. The model, in turn, informed a new codebook of focused codes, which was used to re-code all the transcriptions and code new material . The modThe ethical aspects of the study were formally approved by the Norwegian Center for Research Data . Prospective participants were given written information about the study, including the right to confidentiality, to anonymity, and to withdraw at any point. Not all participants returned a written consent form; however, oral informed consent was given at the beginning of the interview by all participants.As part of researcher reflexivity, some aspects of the researchers’ background and experience may be of importance for the study. The authors’ background is from psychology, self-guided web-based programs, and counseling. Following our critical realist perspective, we acknowledge that this background necessarily has influenced what we have seen as relevant processes in the data, although we have strived for openness and inclusiveness. Another relevant aspect of our collective background is that Marianne T. S. Holter has previously worked part-time at the Norwegian Quit Smoking Line. This clinical experience with the study population was never mentioned to the participants, but probably contributed to building a rapport in the interviews.Furthermore, Andy was designed and developed by Håvar Brendryen and Marianne T. S. Holter. This was an asset during data collection and analysis, because the self-guided web-based intervention that was the focus of the study was intimately familiar to us. However, we have been vigilant to counter any threats to the validity of the study as a cause of this role duality, both in data collection and in analysis. The validity threat related to data collection was related to the fact that Holter, who had co-developed the intervention, also conducted the interviews, and that participants may talk more positively about the intervention as a cause of that. Although we did not inform participants about this role duality, some nevertheless assumed this to be the case. In these situations, Holter made it clear that her current role was as an interviewer-researcher interested in all aspects of the participant’s experiences. The validity threat related to data analysis was that our role in development might motivate us to portray Andy in a favorable light. Feelings of pride or disappointment did indeed arise in different situations, and this is something we have regularly examined in reflexive memos. By reflexively confronting these feelings whenever we feared that they might influence the study, we believe we have focused on the participants’ perspectives and stayed true to the data. Perhaps even more importantly, the model we present does not concern how well participants liked the intervention or how “good” it is; the relational modes and patterns we present can be combined with both positive and negative program experiences. Hence, we do not believe Holter’s dual role as a program developer/interviewer has influenced the data noteworthy.making come-alive and keeping un-alive. As all the interviews were conducted by Marianne T. S. Holter, as well as most of the analysis, some of the text is written in her voice. All texts in quotation marks are data excerpts. Excerpts are anonymized and de-identified.In retrospect, our evolving understanding of the processes under study can be said to have gone through three phases. In the following, we will account for each of these phases and the inductive emergence of the two main categories: After only a few interviews, it became clear that some participants did indeed experience Andy as a person, spontaneously describing this self-guided web-based intervention “a friend” and “a therapist.” We coded these instances with “experiences Andy as a person.” Initially, this was what preoccupied us analytically. However, it was equally clear that other participants described their experiences as similar to using any other app or computer program. At first, this made me react with disappointment—after all, referring to Andy as a computer program is accurate, a factual description of the intervention. Therefore, participants who talked about Andy as a program did not seem to relate to the intervention at all, making these interviews seem without value for the present study. Despite the seemingly irrelevance of experiencing Andy as a computer program, we were reluctant to leave these interviews out of the analysis at this early stage. One reason for this was that experiencing Andy as a program seemed to be the opposite of experiencing Andy as a person, and that leaving it out of the analysis would therefore be untruthful. Another reason was that despite our initial dismay, we were also fascinated by the fact that the participants could make sense of their interaction with the program in such different ways. The intervention was highly interactive and tailored to individual use; nevertheless, it was also standardized in its way of interacting with the participants. That this same pattern of interaction could be experienced as either a person or a program caused us to consider whether experiencing Andy as a program might entail something more than just being the taken-for-granted experience. Therefore, the code “experiences Andy as a program” was introduced. Introducing this code slowly facilitated a shift in our thinking, and we increasingly started thinking about experiencing Andy as a program as an important part of the analysis.relating (which seemed to be more about experiencing Andy as a person than experiencing Andy as a program), we instead turned to analyzing ways of making sense of the program interaction, a mind-shift which we found to open up for complexities, which we kept coding for inductively.The continuing analysis revealed several complexities that the simple dichotomy of person or program could not account for. Taking a step back from One such inductive code was “getting embarrassed over one’s own personification.” When talking about Andy as a person, several participants would laugh or giggle, suggesting a degree of embarrassment over talking about an inanimate computer program as something alive. This struck us, because similar embarrassment signifiers can also be found in the existing qualitative eHealth literature. For example, Another early code was “artificial nature revealed,” which was used to code passages where participants expressed that sometimes it became “obvious” that Andy was a computer program. On the surface, it might seem like these participants simply experienced Andy as a program. However, if it suddenly became apparent that Andy was a program, what had it been up until then? Other observations of complexity included the fact that participants who talked about Andy as a person at the same time were fully aware that Andy was a program. Furthermore, some participants seemed to have an experience of writing “to” someone else “behind the program”  that would read what they wrote, whereas others talked as if they were interacting directly with Andy. This added to our increasing acknowledgment of the complexities involved in relating.1 This seemed an accurate description of how some participants were experiencing Andy: Andy was not simply a program, nor quite a person, but rather, both program and person—and at the same time, neither. Therefore, “betwixt and between” was another early code. Participants would also sometimes find it difficult to explain exactly “what” Andy was to them or how they experienced the program. This indecisiveness would sometimes be verbalized by participants who said that it was hard to describe. Other times the uncertainty was apparent in speech that came slowly, involving much on-the-spot reflection, including unfinished words and sentences. These interview passages were marked with the code “hard to verbalize,” and seemed to, like “betwixt and between,” indicate something that breaks down established boundaries or categories and for which one therefore lacks appropriate language.As our understanding evolved with increased complexity, so did the interviews, and in some interviews, participants described Andy as sort of both a program and a person. To further our understanding of this particular experience, we employed a sensitizing concept in our analysis : “betwixAt this point, we knew that we were observing complexity that needed to be accounted for analytically. Furthermore, we had a growing concern that for the most part, participants who had described Andy as a person had done so unsolicited, not as a response to the questions in the interview guide. Although these unsolicited descriptions added to the data’s validity, it also worried us that there might be aspects to the users’ experiences that our interview guide was not adequately tapping into. To address these concerns, we decided to make some methodological refinements, which included changing the interview guide (as described in the “Method” section) and adding reflection notes as an additional data source. Reading through the reflection notes of the 116 participants in the reflection note pool, we theoretically sampled participants whose reflection notes explicitly or implicitly indicated a way of relating to Andy. That is, we sampled reflection notes that indicated Andy as another social actor  or referred to Andy as an un-alive thing . Reflection notes in which ways of relating were not indicated were excluded .thinking within and thinking about But yes, when you put it like that, I’m thinking—and you’re talking about Equipped with a refined interview guide and two new sensitizing concepts, the next interview I conducted became a turning point in the analysis. The participant consistently talked about Andy as a computer program. However, I came to the point in the interview guide where there was a hypothetical question which sounded, “If Andy had been a person, what do you think he would say about you?” The participant replied, “‘She,’ I thought it was a ‘she.’” To accommodate the participant, I rephrased the gender of Andy indicated in the question to “she,” paying no further attention to it then and there other than sensing a small sense of puzzlement. It was not until after the interview that this puzzlement took shape: why would this participant, who apparently only thought of Andy as a computer program, nevertheless think it more appropriate to call the program “she” instead of “he”? Recall, the Norwegian name of the intervention (“Endre”) is masculine . I had chosen the name and had made all the program texts thinking that I was creating the “voice” of a male character. Thus, I knew there was nothing designed into the program to suggest that Andy was This interview revealed that it was possible to make sense of the program interaction in one way within program sessions and in another way when thinking about the program outside of program interaction. The participant called this an “illusion,” and we made this an early code (“agrees on illusion”). This interview was a turning point also because it brought to the surface something we had sensed for some time: that participants might see the program interaction as containing elements of both program and person (even if they do not explicitly articulate this).relational modes that we called making come-alive—thinking of Andy as a person—and keeping un-alive—thinking of Andy as a program . Our effort to turn these relational modes into relational categories caused us to make four new codes: “making come-alive about” (thinking about Andy as a person), “keeping un-alive about” (thinking about Andy as a program), “making come-alive within” (experiencing Andy as a person within program sessions), and “keeping un-alive within” (experiencing Andy as a program within program sessions). We re-coded all data material with these codes, developed the categories analytically through memos, and theoretically sampled in interviews . What caused greater worry was that some participants’ experiences did not seem to fit within either relational category. For example, some participants talked about Andy as a program most of the time—but could suddenly in a sentence refer to Andy as “him,” or laughingly say something that portrayed Andy as a person. The participant was talking about Andy and not engaged with the program, so they were not “accepting an illusion.” Nor did these few instances of making come-alive seem to qualify as “creating a secret companion,” but it did not seem accurate to categorize such a participant as simply using a self-help tool. In sum, it was difficult to fit participants into relational categories without defying the complexity of their experiences.In a serendipitous moment of turning the analysis inside-out, we realized that instead of trying to reduce the complexity we were observing by forcing all participants into mutually exclusive relational categories, we could retain the complexity by focusing on the relational modes making come-alive and keeping un-alive. The relational modes could still be combined with relational situations to form typical relational patterns, as we illustrated in a final iteration of the evolving model. This model could explain all existing and incoming data in terms of how a participant related to Andy, and therefore we considered it theoretically saturated. The model will be accounted for below.relational modes: making come-alive and keeping un-alive. When keeping un-alive, the self-guided web-based intervention was experienced as an inanimate object incapable of thinking and feeling, to which the participant had no relationship. In this relational mode, they described Andy as a “program,” a “tool,” a “machine,” a “computer,” a “robot,” a “standardized scheme,” or a “product”; somewhere they could “fill in” information, or like a “questionnaire.” Andy was a thing, not a social actor. Therefore, when keeping un-alive, participants would sometimes think of their interaction with other social actors, the people “behind” the program (the designers or the researchers), as exemplified by one participant: “I keep thinking about how you’ve sat down and made this program! There’s quite a lot of work put into this!” .Participants related to Andy with two making come-alive, the self-guided web-based intervention was experienced as a social presence capable of thinking, feeling, and acting on its own accord. In this relational mode, the other social actor of the interaction was not the designers or researchers, but Andy—evidenced by participants referring to Andy as “someone” (as opposed to “something”). This “someone” “cared,” “understood,” and “supported” participants. They attributed to Andy the ability to “keep an eye” on them, have “expectations,” “have faith in me,” and “wish me well”; someone “positive,” “interested,” and “very nice”; someone who refrained from an ability to act negatively . In reflection notes, making come-alive was expressed by referring to Andy as “you,” as exemplified by the following participant: “The funny thing is that I like talking to you, you give me pictures and metaphors I haven’t thought about myself” .In contrast, when supportive social presence. This is of significance for the subsequent discussion of a potential person-to-program emotional bond.When making come-alive, it was also of significance whether participants experienced the interaction with Andy positively or negatively. There were a few examples of participants experiencing Andy negatively, leading to Andy being described as “quarreling,” “doubting,” or failing to follow up on appointments. However, the recurring experience was of Andy as a nonsocial interaction, a semi-social interaction, and a semi-social relationship. Participants who experienced a nonsocial interaction kept un-alive both when thinking about the program and within their program experiences. In interviews, this was revealed through joint exploration, in which these participants expressed genuine bewilderment and incomprehension over the thought of experiencing the program sessions as conversations. Instead, they would describe interacting with Andy as “talking to myself,” “mapping” behaviors and patterns, or using a “helpful tool.” One participant said, “Then and there, when I’m answering the questions, it’s . . . maybe more like talking to myself? . . . Yes, maybe more like initiating thought process, I think would be more accurate to say” . Reflection notes confirmed that some participants kept un-alive also when actively engaged with the program. Although they were answering Andy’s very personal question, “How would you describe working with me,” these participants would nevertheless refer to internal change processes and call Andy “the program,” as exemplified by one participant:Like a hidden part of my personality. Nothing is new, all the thoughts about smoking and quitting smoking have been thought before, just in a different way and sequence. I get to structure my thoughts and approach free from stress. My subconsciousness is working when I’m not working with the program. The combinations of making come-alive and keeping un-alive could be described with three typical relational patterns: a semi-social interaction, keeping un-alive when thinking about the program but making come-alive within program sessions. These participants would agree to “play along” then and there—but leave the alive-making once they left the session. A semi-social interaction often involved a tension between making come-alive and keeping un-alive, an ambiguousness of the program being both a social actor and not a social actor at the same time. Sometimes, participants struggled to verbalize this, but some would describe Andy explicitly as being “in the borderlands,” a “robot psychologist” or a “digital friend.” One participant explained the ambiguity this way:It’s funny, because it becomes kind of a relationship in quotation marks . . .. What can I say . . . something in-between a program and a person, if you get what I’m saying? That it’s . . . almost neither nor. Other participants experienced a In reflection notes, ambiguity was expressed in participants’ use of quotation marks, almost as if to keep an element of un-aliveness to expressions that suggested making come-alive. This is illustrated in the following: “Nice to have a ‘friend’ who gets how hard it is to quit smoking and who helps me liberate thoughts about quitting” .semi-social relationship, in which they substantially made come-alive also when thinking about the program even when not interacting with it. In the semi-social relationship, participants seemed to experience Andy as a social presence that lingered even after the session was over. To these participants, Andy was a positive social presence held in their minds as someone who could “be there” for them or “look after” them, sometimes assigned with different (human) social roles: an “understanding friend,” a “secret friend,” a “tutor,” a “psychologist,” or a “therapist.” We call this a relationship because the experience of Andy as a supportive social presence lasted beyond the immediate interaction and seemed to involve more substance. Exemplifying this, one participant wrote the following at the end of the intervention: “It’s been nice and I’ll miss you” . One participant said that she could imagine what Andy looked like, indicating that she would picture “him” in her mind: “He has light hair. And he’s . . . perhaps 35. Not drop-dead gorgeous or anything, but a little thin . . . Very friendly looks. Yes. A friendly guy” . Another participant wrote, “I completely forget that you’re a program” .Finally, some participants experienced a kind of like a person,” “almost like a friend”), or by expressing embarrassment over making come-alive through laughing and giggling. Whether making come-alive or keeping un-alive, there was nothing in the participants’ accounts suggesting that their use of these relational modes was intentional or volitional.However, a semi-social relationship also included elements of keeping un-alive, and ambiguity was sometimes expressed through verbal modifiers , two participants could not be categorized . The remaining 69 participants could roughly be categorized as following: 12 expressed a nonsocial interaction, 34 expressed a semi-social interaction, and 23 expressed a semi-social relationship. Of course, these numbers should be interpreted with caution: because they combine two highly different data sources, because the study was not designed to estimate how these relational types are represented in the population, and because the boundary between the categories are not absolute. The reason for reporting them is to support the following claims: (a) that both making come-alive and keeping un-alive were normal relational modes for this study sample, (b) that most participants engaged in making come-alive at least some of the time, and (c) that neither relational pattern was unique to just one or two individuals.making come-alive  and keeping un-alive . Using these relational modes to a varying degree, participants exemplified different relational patterns, forming a landscape ranging from a nonsocial interaction , to a semi-social interaction , to a semi-social relationship .The purpose of this study was to develop a theoretical model of how people relate to self-guided web-based interventions and to discuss the implications of this model for a potential emotional bond of a person-to-program alliance. Regarding the emotional bond, we wanted to theoretically explain how it can be possible to experience an emotional bond to something one knows to be an inanimate computer program. In pursuing this purpose, we conducted a grounded theory study  with theWhen making come-alive, participants experienced Andy as a person, confirming previous findings of how people can sometimes think of self-guided web-based interventions as human beings . The proHowever, does the experienced supportive social presence of a semi-social relationship amount to a person-to-program emotional bond? The emotional bond of the alliance was previously defined as involving complex, positive social emotions that assume another social actor who can think and feel. Participants with a semi-social relationship to Andy experienced Andy as such a supportive social presence, attributing to Andy the ability to feel (“care”), think , and act . It seems reasonable to call this a type of emotional bond, enabled by making come-alive and experiencing the interaction positively. Thus, 23 of the 69 participants in the current study expressed a type of emotional bond to Andy.knew they were interacting with an inanimate computer program, they nevertheless experienced Andy as a supportive social presence—temporarily blurring out the boundaries between real and not real in a form of “play” or “illusion.” Considering making come-alive—and the emotional bond it can facilitate—from this perspective makes it less mysterious and controversial. It becomes possible to consider an emotional bond as a potentially common way of relating to a self-guided web-based intervention.Why so many participants experienced an emotional bond might be explained if we consider making come-alive as a form of “transitional experience” . TransitThis proposition is supported by the other reports of what we may now define as a type of emotional bond to three other self-guided web-based interventions: “Laura” , “Dit DiThis is also a question of the proposed model’s transferability  to otherinteraction, which may be a useful concept for describing a hitherto unnoticed group of program users. While many users of self-guided web-based interventions will talk about these interventions as inanimate computer programs, the proposed model suggests that a proportion of these users may nevertheless make come-alive within the immediate program interaction. Given a positive program experience, these users may in the moments of using the program experience it as a supportive social presence, able to understand, care for, and support them. However, whether these passing experiences of a supportive social presence can be described as an emotional bond is a question that we are hesitant to answer. Another possible area for future research is therefore whether a person-to-program emotional bond is dependent on the experience of the program as a supportive social presence also after and between program sessions, or whether perhaps these are two different types of emotional bonds.We have so far focused the discussion on one element of the proposed model, namely, the semi-social relationship, which confirms and extends on existing research. However, this study also documents the possibility of experiencing a semi-social Another contribution this study makes is by conceptualizing keeping un-alive as a way of relating. We have suggested ways in which the proposed model can be used to explain the experiences of people who use self-guided web-based health interventions. However, to achieve such a feat, the model must first of all be a valid representation of the experiences of the current study’s participants. Given our critical realist perspective , we beliHowever, the study has certain limitations. Three interviews were not audiotaped, causing loss of detailed data for these participants. Another limitation is related to the study being based on a convenience sample (as opposed to a more strategic sample), which was one reason why the model cannot explain whether different relational patterns were related to participant characteristics such as gender, age, or how long they used the intervention. Furthermore, although we suggest that experiencing a person-to-program emotional bond is likely to be a common way of relating to self-guided web-based intervention, normality cannot be ascertained with this type of study design, as it would require a larger-scale quantitative study. Nor does this model include possible consequences of different ways of relating in terms of their clinical significance or effects on program use and engagement. These questions were not possible to pursue in the current article due to the scope of accounting for and developing the presented model of relating. In a separate publication , we presThe present study also has several strengths, including the methodological refinement process we undertook, as well as the previously accounted for efforts to increase validity. Following the recommendations of One practical implication of the proposed model is that to facilitate an emotional bond, an intervention should support making come-alive, but also be experienced positively and as supporting. Another area in which the model may have practical implications is in how the emotional bond of a potential person-to-program alliance is measured: The model suggests that an emotional bond is possible, but dependent on making come-alive, which alternates with keeping un-alive. Thus, whether a person filling out an alliance-measure rates the program as a supportive social presence  depends on whether she or he is making come-alive in that specific moment.It is our belief that the proposed model of relating in automated therapy can be useful for addressing currently unanswered questions of how self-guided web-based health interventions work. The proposed model suggests that experiencing an emotional bond may be one common way of relating to self-guided web-based interventions, but that there also are other ways of relating that call for further research. The current study also raises other questions concerning how different relational modes and patterns arise (related to characteristics with the program user as well as the intervention) and what their consequences are. However, we believe the study’s main contribution lies in proposing a set of concepts for describing how people relate to self-guided web-based interventions, which may be used as a stepping stone for further research into potential associations between relating and change. These efforts may be further facilitated through the theoretical explanation provided of the person-to-program emotional bond, which may be tested and elaborated, and hopefully lead to an increased understanding of whether a working alliance plays a role in the change facilitated by automated therapy.


Ml5.2 Le Teil earthquake in France reveals slow nucleation at depth that migrates to the surface and propagates northward with a velocity of Although moderate‐size earthquakes are poorly studied by lack of near‐fault observations, they can provide key information about larger damaging earthquakes. Here we propose a new approach, inspired by double‐difference relocation, that uses high‐coherency waveforms recorded at neighboring sensors, to study the preparation phase and dynamics of moderate‐size earthquakes. We validate this technique by analyzing the 2016,  Stereometry uses stereoscopic effect to study intermediate‐size earthquake sourcesStereometry retrieves finite fault rupture parameters such as direction, length, and speedStereometry can reveal the activity of a single fault patch before an earthquake When avAnother way to estimate some finite fault earthquake source properties is by using a dense seismic network with the back‐projection technique which maps the spatiotemporal distribution of high‐frequency radiations along the fault  component of the source function Heaton,  observedD is much larger than the two stations separation and much larger than the rupture length, we can estimate the rupture length Δtrs1 and Δtrs2 between the first and the last high‐frequency pulse emitted by the source at station Δts1s2lastpulse−Δts1s2firstpulse=Δδt, we obtain: p is the ray parameter between the rupturing point and the barycenter of the station pair, Following a double‐difference approach (δxscosArs−δyssinArs)≠0 means that the earthquake cannot be at the vertical of the stations or that the earthquake and the two stations are not colinear . However, to keep high coherencies between the waveforms, we need to avoid frequencies too high for which scattering and attenuation dominate. Therefore, stereometry should be performed on the lower end of the high‐frequency component of the source where the temporal resolution is enough to separate broad pulses associated with each source but not enough to isolate the shorter pulses associated with the ramping up and down of the slip of each patch.We show three other station configurations  in the 33.1To illustrate the use of seismic stereometry on real data we chose a well‐studied earthquake with strong directivity, surrounded by a dense network of seismic stations. The 2016, a Figure . This ruP wave attenuation To resolve details along the 2 km rupture length, we need wavelengths smaller than 1 km, which means frequencies above 5.5 Hz, taking P wave on the vertical components , P1 and P3  is similar to the time shift of P3, indicating that they originate from the same area on the fault: The second asperity.P2 is likely the P wave signal originating from the start of the rupture of the second asperity. The time delay between P1 and P2 would suggest a rupture velocity of the first asperity of about 2 km/s .Beside key source parameters, stereometry analysis of the Borrego Springs earthquake can inform us about potential source processes. The time shift of the second P coda, with specific M1.8 foreshock event : ANZA Regional Network. International Federation of Digital Seismograph Networks. Dataset/Seismic Network. https://doi.org/10.7914/SN/AZ. The data from stations AL01 and AL05 will be available via the RESIF portal under FDSN code XW after 2022. We used the quaternary fault database for the United States from the USGS (https://earthquake.usgs.gov/hazards/qfaults/). The cross‐wavelet transform function developed by Mao et al.  / CC BY.The PY network data are from UC San Diego 2014): Piñon Flats Observatory Array. International Federation of Digital Seismograph Networks. Dataset/Seismic Network. o et al.  and used014: PiñoSupporting Information S1Click here for additional data file.


While 3.5 million breast cancer survivors in the USA are indicative of promising disease-free survival, many experience adverse effects in recovering from treatment. Evidence-based exercise programs may be a low-cost, easily disseminable solution to the challenge of recovering from adverse treatment affects. Therefore, after establishing efficacy in a large randomized controlled trial, we developed the Strength after Breast Cancer (SABC) program and the accompanying online course for clinicians interested in physical therapy to learn to deliver this rehabilitative exercise program to individuals with breast cancer. We surveyed clinicians who took the course to assess implementation of the program in outpatient rehabilitation clinics.Ninety-six clinicians completed the survey between June and December, 2017 (24% response). Guided by Proctor’s implementation outcomes framework, the respondents were asked if they had implemented (adoption) and are still implementing the program (sustainability), and which programmatic components they implemented (fidelity). Respondents were asked how many patients completed the program (reach), how patients got into the program (reach), the program’s delivery format (appropriateness), and whether clinics were reimbursed by third-party payers (cost). Finally, respondents were asked what barriers they faced in delivery of SABC (feasibility) and whether others in the clinic completed the course (penetration).p > .05) in reported barriers between those who implemented the program and those who did not.Seventy-six percent of respondents implemented SABC and among those, 93% (68/73) were still delivering it. All programmatic components were implemented by over two thirds of respondents (67–95%). On average, the program was delivered to 13 patients per clinic by the time respondents took the survey. Most patient referrals were from oncology clinics (50%). The majority of clinicians delivered SABC one-on-one (96%) and 72% of clinics were compensated via third-party payers. Major barriers were lack of referrals from oncologists (40%) and clinic’s competing demands (33%). We found no differences (Fisher’s exact test Our findings suggest that the online training was sufficient to successfully implement the SABC program in outpatient rehabilitation clinics with high levels of adoption, fidelity, reach, and capacity for sustainability. Information on patient acceptability, cost-effectiveness, and how to overcome implementation barriers are still needed. Contributions to the literatureEvidence-based guidelines recommend regular exercise to recover after breast cancer treatment and ease adverse treatment effects but few US women have access to exercise rehabilitation programs in the communities they live.After establishing efficacy in a large randomized controlled trial with 295 breast cancer survivors, we developed the Strength after Breast Cancer (SABC) program, an online course to train clinicians interested in exercise rehabilitation to deliver SABC to their patients with breast cancer in outpatient rehabilitation clinics.Our findings suggest that the online training was sufficient to successfully implement the SABC program in outpatient rehabilitation clinics with high levels of adoption, fidelity, reach, and capacity for sustainability.There are more than 3.5 million women in the USA who have undergone treatment for breast cancer . AlthougEvidence-based guidelines from the National Comprehensive Cancer Network , the AmeBased on these promising findings, our group adapted the PAL intervention into the Strength after Breast Cancer (SABC) program  and deveParticipants were 96 clinicians who completed the SABC course online in 2015 and responded to our implementation assessment survey in 2017.http://klosetraining.com/course/online/strength-abc). Requirements to complete the course included being a licensed physical or occupational therapist, physician, or registered nurse. In addition, exercise professionals were offered the opportunity to have their credentials and experience with patients with cancer reviewed to discern eligibility. Upon registration and payment ($120), participants received a username and password; they had 3 months of access to the course. The 4-h course covered all aspects of setting up and running the SABC program including how to obtain referrals from oncology clinicians, screen potential patients, coordinate with a certified lymphatic therapist, educate patients about lymphedema, teach the 4-session exercise program, instruct patients on how to log their progress, motivate patients to perform exercises, handle logistical considerations, and manage discharge and wrap-up. The course also provided all the materials needed to set up the program in clinics, including PAL trial results, lymphedema education session in PowerPoint format, lymphedema risk-reduction guidelines, exercise instructions with photos, decision tree for tracking adherence, self-check list for program objectives, guidance for support staff, helpful information about billing codes, and weight training workout logs.The online course was created by Dr. Kathryn Schmitz, in collaboration with Guenter Klose, and provided in 2015 through a popular online platform for physical therapy continuing education . Using REDCap, a secure web application for building and managing online surveys and databases, an initial email was sent to all individuals that included an invitation to complete the survey, information explaining the purpose of the survey, a link to access the survey online, and a statement about the confidentiality of their responses. Two weeks later, an email reminder was sent to those who had not yet responded the survey. The 10-min survey was conducted between June and December, 2017. No monetary incentive was offered to complete the survey. The survey response rate was 24%. The study was approved by the Institutional Review Board of the Penn State College of Medicine.Klose Training and Consulting provided a list with the emails of those who completed the course . We used the Fisher’s exact test in the latter set of analyses exploring implementation barriers due to the small size of some cells. We analyzed survey data using Stata 14.0 .Seventy-six percent of respondents implemented SABC in their outpatient rehabilitation clinics and among those, 93% (68/73) were still delivering the program by the time they took the survey Fig. . The majp > .05) in reported barriers between those who implemented the program in clinics and those who did not. We also found no differences (p > .05) in barriers noted by implementers with low reach (< 13 patients) versus those reporting high reach (≥ 13 patients). The majority of respondents (83%) took the course as continuous education and more than one third (37%) reported that other therapists (range 1–10) in their clinics also completed the SABC online course. Respondents said patients with breast cancer used dumbbells of different weights (84%) for resistance exercise at home, followed by household items like soup cans (53%), resistance bands (29%), adjustable dumbbells (15%), and other equipment (7%). Only 15% of respondents said their clinics provided the resistance equipment to patients.The major barriers reported to delivering the program in clinics were lack of referrals from oncologists (40%), competing demands of physical and occupational therapists, administrators and front desk staff (33%), and logistical difficulties  for measuring implementation, particularly fidelity. Self-reported measures introduce the possibility of participation bias, where those therapists who implemented the SABC program were more likely to respond to the survey than those who did not. This could have contributed to the high adoption and fidelity rates reported by respondents. We also need additional data about two critical dimensions of fidelity: implementer adherence to program’s protocols and competence in delivering the program . In addiExercise is an effective way to manage common adverse effects of breast cancer treatment, and the SABC course proves a valuable tool to implement an evidence-based exercise program for patients to receive those benefits. Our findings suggest that the online training provided to clinicians interested in physical therapy successfully led to implementation of SABC in outpatient rehabilitation clinics, with high levels of reach, adoption, and fidelity. Because any new interventions will not be effective if they are not implemented well, the promise of SABC cannot be advanced without special attention to implementation science. Research is still needed to further understand implementation outcomes of this program, especially acceptability at the patient level and provider level, as well as what can be done to increase reach through engagement of oncology care teams.