Psychosocial interventions targeting the specific needs of people affected by younger-onset dementia are lacking. Younger-onset dementia refers to dementia where symptom onset occurs at less than 65 years old. Because of its occurrence in middle age, the impact on spouses is particularly marked and dyadic-based interventions are recommended. Music And Psychology & Social Connections (MAPS) is a novel online intervention, informed by the theory of adaptive coping by Bannon et al. (2021) for dyads affected by younger-onset dementia. MAPS combines therapeutic songwriting, cognitive behaviour therapy, and a private social networking group that focuses on the dyads. This will be a randomised controlled trial with a waitlist control. The primary aims are to assess whether MAPS improves depressive, anxiety, and stress symptoms in caregivers, with secondary aims to assess whether MAPS improves depressive symptoms in people with younger-onset dementia. The trial also aims to assess dyadic social connectedness; caregiver coping skills; and neuropsychiatric symptoms in people with younger-onset dementia. We will recruit 60 dyads to participate in a group-based weekly online program for 8 weeks facilitated by a credentialed music therapist and psychologist. Sessions 1 and 8 will include both caregivers and people with younger-onset dementia and Sessions 2–7 will involve separate group sessions for caregivers and those with dementia. There will be focus groups for qualitative feedback. Due to its online administration, MAPS has the potential to reach many dyads affected by younger-onset dementia.  Dementia is a progressive neurodegenerative condition that affects cognition and many areas of functioning. Younger-onset dementia (YOD) is characterised by symptom onset before the age of 65 years . YOD is Receiving a diagnosis of dementia during middle age can be devastating, with individuals reporting feelings of powerlessness, hopelessness, loss of self-identity, and social exclusion ,10,11. CThe majority of informal support and care is provided by partners of people living with YOD . YoungerFor dyads living with dementia, several psychosocial intervention studies have demonstrated positive outcomes for both the caregivers and the people living with dementia. Dyadic interventions described in the research include a combination of psychoeducation, cognitive-behavioural therapy (CBT), and strategies for managing cognitive deficits and neuropsychiatric symptoms in dementia. The Acquiring New Skills While Enhancing Remaining Strengths program (ANSWERS) is a six-week strengths-based program comprising modules covering psychoeducation of dementia, communication skills, managing memory and strategies, physical activity, and recognising emotions and behaviours . The controlled trial reported that caregivers in the intervention group had improved mental health with reduced depressive and anxiety symptoms, less dyadic strain and role captivity, and improved mastery compared to controls ; howeverThe Danish Alzheimer Intervention Study (DAISY) was a randomised controlled multi-component and semi-individualised intervention for people 12 months post-diagnosis of Alzheimer’s disease (AD) and their caregivers . In contWhile traditionally psychosocial interventions have been delivered face-to-face, online administration may have advantages in terms of flexibility and less time commitment due to minimal requirement for transportation . These aLooking to address the social isolation reported by both caregivers and people living with YOD, group programs may provide peer support and the feeling that “one is not alone” . TherapeAs far as we are aware, there have been no published interventions that focus on the dyad in YOD. Given the need to design psychosocial interventions that address the dyad as a unit, are accessible for busy caregivers, and are engaging and calming for people living with YOD, a combined music therapy and psychotherapy program delivered online, Music And Psychology & Social Connections (MAPS) was designed and will be tested using a pragmatic, wait-list control trial design. The present study aims to improve the mental health and social connectedness in caregivers and people with YOD, improve coping skills in caregivers, and decrease neuropsychiatric symptoms in people with YOD. The primary hypothesis is that the MAPS program will have a larger effect on improving depressive, anxiety, and stress symptoms in caregivers compared with standard care. Secondarily, we hypothesise that compared with standard care, MAPS will lead to greater improvements in: (a) depressive symptoms in people living with YOD; (b) the effectiveness and types of coping strategies utilised by caregivers; (c) levels of social connectedness in people living with YOD and their caregivers; and (d) the levels of neuropsychiatric symptoms in the people living with YOD.This pragmatic randomised waitlist control trial design with post-program focus groups will test the primary and secondary hypotheses with a 1:1 allocation ratio. People living with YOD and caregiver dyads will be randomised to one of two conditions: (1) MAPS; or (2) Waitlist control . Dyads rThe conceptual framework  underpinMAPS  is an 8-week online program for people living with YOD and their caregivers that embeds the adaptive coping model by Bannon et al. (2021), using a combination of therapeutic songwriting, cognitive-behavioural therapy, and social media participation .Private Facebook groups will provide space for group members to interact between sessions and develop adaptive coping and build connections through music and social media. The MAPS program addresses one adaptive coping topic each week . A musicA careful plan for the fidelity of the study design, treatment integrity, treatment differentiation, treatment receipt, and treatment enactment has been developed. A manual was developed prior to implementation as well as a fidelity checklist to be completed by all therapists at the end of each session. Sessions will be audio-recorded to monitor fidelity and a session will be randomly selected for fidelity assessment by a member of the research team who is not a facilitator. Individualised supervision and monitoring of therapists will be conducted fortnightly to address any challenges associated with program implementation according to the manual.Sixty dyads  living in Australia will be recruited. There is no restriction on the type of YOD. Participants will be recruited by advertising the study at the Royal Melbourne Hospital (such as the Neuropsychiatry YOD clinic), the Step-Up for Dementia Research Database, on social media, and through other forums such as Dementia Australia. Caregivers will be eligible to participate if they: (1) self-identify as a caregiver of a person living with YOD; (2) consider themselves in a long-term relationship with the person living with YOD ; (3) score either ≥14 on the Depression subscale of the Depression Anxiety and Stress Scale, DASS-21 , ≥12 on Interested and potential dyads will receive a phone call whereby the above criteria will be discussed to check eligibility for entry. Following the screening, informed consent will be obtained by caregivers and people living with YOD. Dyads will be randomly allocated a computer-generated number 0 or 1. If they receive a “1”, they will be randomised into the intervention MAPS group. Each intervention group will have a maximum of seven dyads. For those dyads who receive a “0”, they will be allocated to the waitlist control group and be invited to participate in MAPS following the completion of the intervention. All eligible participants will be administered the outcomes measures (see below).Demographic information , information about caregiving (duration and approximate hours per day), MMSE scores, treatments, and dementia type if known and severity  will be collected. To detect changes in anxiety and depression in caregivers (primary outcome), the DASS-21 will be administered pre- and post-program. The DASS is a 21-item scale composed of three sub-scales with 7 items each, measuring depressive, anxiety, and stress symptoms, and has good psychometric properties . Participants are asked to rate each item based on how they have been feeling the past week with a 0  to 3 (most of the time) scale for responses. The score is multiplied by 2 to make scores equivalent to the DASS-42 .Secondary outcome measures for the caregivers collected pre- and post-MAPS are:Coping: The Brief COPE  is a 28-Revised Scale for Caregiving Self-Efficacy:  is a 15-Social Connectedness: The Friendship Scale  is a 6-iSecondary outcome measures for the people living with YOD collected pre- and post-MAPS are:Social Connectedness: The Friendship scale , as descMental health: The DASS-21 , as descBehaviours using the Neuropsychiatric Inventory–brief form (NPI-Q) . This brDepression, using the Cornell Scale for Depression in Dementia, CSDD . This 19A process evaluation will be undertaken in order to gain a better understanding of participants’ experiences and the mechanisms of change. Focus group questions will explore participants’ reasons for joining and experiences of the program including any positive or negative aspects of the program, and what changes (if any) they noticed in the group, themselves, their partner, or their use of music. Questions will also focus on any perceived impact of the program on their relationships and feelings of connectedness (both between group members and within the dyadic relationship). The focus group will also include discussion around the continuation of the private Facebook group and if this is something participants wish to continue following completion of the research.All self-report measures will be collected online using REDCaP and stored electronically. Dyads successfully screened into the program will be contacted and invited to an online session where the pre-program measures will be completed. Post-MAPS quantitative outcome measures will be collected by members of the research team who are masked to allocation. Post-MAPS qualitative evaluation will be audio-recorded and transcribed for analysis.p < 0.05), we will require a sample size of n = 54 dyads. Accounting for 10% attrition, we aim to recruit 60 dyads. We thus anticipate approximately 9 “waves” of MAPS . As the program involves sequential weekly sessions, we will not be able to replace drop-outs during the program. For demographic analysis, we will use frequencies and descriptive statistics. Categorical tests such as χ2 will be used to compare groups on factors such as dementia types and gender. Paired t-tests will be used to compare pre- and post- primary and secondary outcomes and we will also calculate effect sizes to determine the size of the changes in DASS-21 and other measures. Statistical Program for Social Sciences (SPSS) version 27 (IBM) will be used for quantitative analyses. Qualitative analysis of focus group interviews will use Interpretative Phenomenological Analysis to synthesise their experiences, benefits, and limitations of participating in the project.Our primary outcome measure is an improvement in the DASS-21 (pre- and post-), with a 4-point reduction (SD of differences = 8). Using β = 80% (power) and α = 0.05 and medium effect size = 0.5 , reordering some of the topics , and creating a manual or workbook to be sent to participants in advance of the program. Caregivers have reviewed the content of the workbooks, which will be provided to the dyads and we have ensured that their suggestions have been incorporated.During the project, the PPI group will be consulted on all matters concerning implementation, consulting on recruitment approaches, and the development and design of the Facebook social networking component. They will also be involved in reviewing the revised program once the current pilot study has been completed and recommendations integrated into the final program design. The PPI will also have an opportunity to have input into the dissemination plan and how the songs created by participants might be shared and used to advocate for better services for people with YOD and their caregivers.This paper presents a protocol for a novel intervention combining therapeutic songwriting, psychological therapy, and social media, administered through an online platform for people living with YOD and their caregivers . Being manualised means that the program can easily be replicable and administered. Being online will enable flexibility, provide the ability to reach dyads who live in rural and regional communities as well considers the challenges associated with a COVID world. A closed social networking group will provide a platform for psychoeducation, sharing experiences, providing support, and providing opportunities for connection and interactions.Our protocol has some limitations. The intervention is not targeted to subtypes of YOD and hence the sessions are not specific to challenges associated with specific dementia types such as Alzheimer’s disease or frontotemporal dementia, but more about the psychosocial challenges faced within the dyad. However, due to heterogeneity of presentation in YOD with difficulties in obtaining a diagnosis, we feel that our intervention addresses the lack of interventions in this younger-onset space for people with dementia and their caregivers. Similarly, we only target those with mild/moderate severity so this intervention does not consider those who are in the advanced stages of dementia, who would have different dyadic and caregiving needs. In addition, as a dyadic intervention, this framework does not include the wider family or non-spousal caregivers.Living with and supporting a person living with YOD comes with unique challenges. Currently, there are very few psychosocial interventions aimed specifically at the dyad. Interventions need to be appropriate for the younger age group, be person-centred and address the relevant psychosocial issues. We have described a novel program involving both the caregivers and people living with YOD, using combined evidence-based strategies of therapeutic songwriting and psychological techniques administered online, with trained facilitators, aiming to improve mental health and social connections. If the program is successful, we anticipate that the program will be easily scalable and able to benefit more younger-onset dementia dyads.


Accurately distinguishing between stable and unstable isolated distal radius fractures (DRF) in children allows for appropriate fracture-specific treatment. Although fractures with cortical disruption, displacement, or angulation are unstable, distinguishing stable buckle fractures (BF) from more subtle potentially unstable DRF is challenging. Our quality improvement project aimed to improve radiology reporting accuracy for these subtle fractures from 23% to 90% in a large tertiary pediatric hospital.Exams with a reported isolated distal radius fracture during baseline (January–March 2016) and intervention (April 2016–June 2019) were reviewed for accuracy. We introduced 3 types of interventions: radiologist education , a new standardized report template, and a measurement tool (“The 1 cm Rule”). In addition, a statistical process control chart tracked accuracy data to study process changes over time.During the baseline and intervention period, 22 and 480 radiographs, respectively, had either a stable BF or a potentially unstable isolated DRF. Each intervention type created a centerline shift. Overall, reporting accuracy increased from 23% to 90%. Most reports  used the template and standard terminology for reporting DRF.Radiology reporting diagnostic accuracy for distinguishing between stable BF and potentially unstable DRF in children increased to 90% through education, standardized reporting, and a measurement tool to enhance radiologist performance. Our institution plans to expand fracture-specific treatment practices with improved radiology reporting accuracy, including bracing and home management of stable BF diagnosed during an acute care visit. The standard of care has been to immobilize all pediatric forearm fractures in a splint or cast with orthopedic follow up. More recently, managing these injuries has become fracture specific. For example, treatment of the stable distal radius buckle fracture (BF), which manifests as a subtle bone deformity without cortical disruption, is trending toward home management with a removable wrist brace. In contrast, other clearly unstable or potentially unstable distal radius fractures (DRF) still require a splint or cast immobilization and orthopedic follow up.9Accurately distinguishing between BF and DRF at the time of diagnosis is imperative for appropriate treatment. At our institution, wrist or forearm radiographs are typically ordered by acute care triage professionals, with the final radiology report available to physicians at the time of management decision making. At baseline, most of our radiologists reported descriptive statements about DRF but did not provide a specific fracture diagnosis. Following a request from our orthopedic colleagues to make a specific diagnosis, radiology reporting accuracy varied. Accuracy was high for clearly unstable DRF, including displaced fractures, angulated fractures, or cortical disruption. However, the diagnosis was more challenging, and accuracy was low when radiologists relied on subtle morphologic differences to distinguish between BF Fig.  and poteUsing quality improvement (QI) methodology, our project aimed to improve the radiology report diagnostic accuracy for stable BF and subtle potentially unstable DRF in children 3–16 years, from 23% to 90% in 1 year.10Our institution consists of a large urban pediatric tertiary care hospital with 2 freestanding emergency departments and 8 urgent care centers in surrounding communities. The orthopedic case volume is high, with 22 pediatric radiologists providing 24/7 timely interpretations and reports for all orthopedic exams. This QI work was exempt from IRB review per institutional policy. Article preparation followed the Standards for Quality Improvement Reporting Excellence (SQUIRE) 2.0 guidelines.Final radiology reports are typically available to the acute care provider before discharge. During the baseline period, all DRF were casted. The preferred treatment for a stable BF was a splint or brace during the intervention period, although all clearly unstable or potentially unstable DRF were casted. During the baseline and intervention periods, all children diagnosed with an isolated distal radius fracture in an emergency department or urgent care center had a follow-up appointment in the orthopedic clinic within 1 week.Patient radiographic exams were identified via electronic medical records . For baseline data, we reviewed initial injury forearm and wrist radiographs with a reported radius fracture in children (3−16 years) evaluated in one of our emergency departments or urgent care centers between January 1, 2016, and March 30, 2016. Subsequent data searches provided exams from April 1, 2016, through June 30, 2019. We excluded exams with angulated or displaced distal third radius fractures, middle third, or proximal radius fractures or exams with >1 fracture, including ulna fractures. We also excluded exams initially interpreted by the first author (L.R.).Consensus established the final diagnosis between author L.R.  and author J.B.S.  and the treating orthopedic provider in the follow-up clinic. We defined a stable BF as an incomplete fracture with no cortical disruption and normal bone between the fracture and the physis Fig. A,B. We c11 The first intervention module reviewed fracture nomenclature and the morphologic criteria for BF diagnosis. Radiologists also learned of the institutional practice changes regarding treatment and follow up for BF versus other DRF. The module included a 12 question pretest and a 12 question posttest. The REDCap reminder feature ensured 100% participation. New radiologists who joined the group also completed this training during the intervention period. In September 2016, all radiologists completed a follow-up 26 case-based quiz with immediate feedback, including an explanation for each answer using the REDCap tool with 100% participation.11The interventions are outlined in the key driver diagram Fig. . In ApriIn December 2016, we created a standardized reporting template to improve diagnosis communication with the emergency department and urgent care providers. The new forearm and wrist template provided a menu of consistent “Final Impression” terminology for the 3 most common forearm fractures: radius fracture (nonbuckle), buckle fracture-distal radius, and both bone forearm fractures.9 In April 2018, based on measuring the fracture-physis-distance in over 200 children, we introduced “The 1 cm Rule” to our radiologists. This rule states an isolated distal radius fracture in a child is not likely to be a BF and should instead be considered a potentially unstable DRF if the fracture-to-physis distance is <1 cm,9 particularly in children 7 years or older. That month, all radiologists completed a third updated online training module, which included measurement instructions  attended live, and the remaining were able to access it from the department electronic shared folder.Throughout the intervention period, radiologists received individual feedback via email for incorrect diagnoses identified by orthopedic providers or during periodic peer review. They also received personal feedback for discrepancies noted at batch review .12 Annotated charts indicated the timing of interventions.The number of correct diagnoses was determined by comparing the radiology report diagnosis and the final diagnosis. We calculated accuracy using the number of accurate diagnoses as the numerator and the total number of DRF without cortical disruption or fracture lucency extending to the physis as the denominator. A radiology quality coordinator (MC) loaded accuracy data into a proprietary statistical process control charting template, which allowed the team to study process changes over time.13 Diagnostic accuracy was determined in monthly intervals. In addition to the monthly QI team reports and discussions, the data were presented to the Director of Quality Improvement and the Chief Medical Officer at our institution for periodic review.We utilized the American Society for Quality (ASQ) criteria for adjusting the centerline and control limits for the statistical process control chart. In addition, we reviewed the process stages for variations.P = 0.893).We reviewed 54 radiographs from the baseline period and 943 from the intervention period. After eliminating the obvious unstable DRF, 22 radiographs in the baseline period and 480 in the intervention period resulted. Patient age (3−16 years) and distribution were similar in the baseline and intervention groups with a mean of 9.6 ± 3.6 years and 9.6 ± 3.2 years, respectively . After a new reporting template with standardized terminology became available in December 2016, the centerline shifted to 72% (κ = 0.447). Finally, after introducing “The 1 cm Rule” in April 2018, the centerline shifted a third time to 90% (κ = 0.788). Average diagnostic accuracy for the last 10 months was 92% (22/24) for children (3−6 years) and 89% (122/137) for children (7−16 years). There were 17 (10%) false-positive diagnoses for BF during this time.Diagnostic reporting accuracy was 100% for clearly unstable DRF (32/32) and only 23% (5/22) for BF versus potentially unstable DRF during the 3-month baseline period. Diagnostic accuracy remained at 100% for clearly unstable fractures, including displaced fractures, angulated fractures, or those with cortical disruption 463/463), whereas reporting accuracy for stable BF and potentially unstable DRF increased with 3 process shifts during the intervention period  reports included the template or standard terminology for reporting an isolated distal radius fracture, either a BF or a nonbuckle type DRF.This project was part of a joint initiative with orthopedic surgery to provide fracture-specific care for stable BF and potentially unstable DRF in children evaluated and treated in a large tertiary hospital system. Although diagnostic reporting accuracy was very high at baseline for clearly unstable DRF, we aimed to improve radiology report diagnostic accuracy to distinguish between stable BF and subtle, potentially unstable DRF types using QI methodology. As a result, we increased diagnostic accuracy for these fractures from 23% to 90%.9 This rule discourages diagnosing a BF if the fracture-to-physis distance is <1 cm. After providing radiologists with this measurement tool, diagnostic accuracy improved to meet the 90% goal.Our process started with required education modules for all radiologists and, although not explicitly measured, individual feedback was ongoing throughout the intervention period. The second intervention replaced descriptive reporting with standardized reporting requiring clear and concise terminology within the radiology report’s “Final Impression” section. Because our radiologists were familiar with the format of standardized templates, this intervention was readily accepted. Our final intervention introduced the “1 cm Rule” after testing an observation that the cortical deformity of a stable BF tended to occur at a greater distance from the physis than nonbuckle DRF.At our institution, fracture-specific treatment for DRF began with BF bracing during the intervention period. Children (3−16 years) diagnosed with an acute BF in the emergency department, or urgent care was fitted with a removable splint or brace and discharged with a scheduled orthopedic follow-up appointment to confirm appropriate diagnosis and treatment. With improved diagnostic accuracy at the time of presentation, fewer children with BF required a change in diagnosis and management at the follow-up visit. We did not include fractures in children under 3 years because even the smallest commercially available braces are generally too large for young children. Also, we excluded fractures in older teens (older than 16 years) as BF does not typically occur in skeletally mature individuals.There were 17 potentially unstable DRF misdiagnosed and initially managed as stable BF during the intervention period. These were recognized within 1 week of diagnosis (during either radiology peer review or more often during the scheduled follow-up appointment in the orthopedic clinic). At that time, the fracture was casted with routine follow up for a potentially unstable fracture. There were no complications in this group.8 We plan to review the radiographs and reports of patients placed on this treatment pathway to ensure optimal patient care and continued reporting accuracy.After improving radiology reporting accuracy through this project’s interventions, follow-up instructions for acute BF versus other DRF are now fracture specific. Children diagnosed with an acute BF in one of our emergency departments or urgent care centers will be discharged with a removable brace and instructions for home management. The written discharge instructions include a list of indications to return for assessment. However, patients with a stable BF will no longer require routine formal orthopedic follow up. This practice eliminates potential lost work and school time and is desirable for children and families.13 with small incremental changes. Rather, we tracked our progress, changing the algorithm in stages with larger changes.One limitation of this project is that the medical records were searched in batches, each with slightly different search parameters due to information system-search software changes. The 3 centerline shifts occurred within the period of search batches and not between them, suggesting that batched record searching did not contribute to improved reporting accuracy. The search parameter differences might account for variation in monthly volumes as a repeat search of 3 months in the midintervention period identified additional children with DRF. However, including these other exams did not affect the diagnostic accuracy (73% vs. 74%). Another limitation is that we did not utilize the traditional Plan-Do-Study-Act technique,Finally, fracture-specific practice patterns may not be generalizable to other institutions. For example, in our hospital system, a staff pediatric radiologist reviews acute care musculoskeletal radiology exams within minutes; thus, the final radiology report guides treatment and discharge planning. Although this rapid radiology reporting may not be feasible in other acute care settings, training clinical providers to distinguish between these fracture types is possible. Also, our institution has a robust focus on QI with leadership support, a strong culture of patient safety, and abundant resources for QI work, which may not exist in other institutions.A quality initiative increased diagnostic accuracy for stable BF and potentially unstable DRF in children through education, standardized reporting, and a measurement tool to enhance radiologist performance. In addition, our institution plans to expand fracture-specific treatment practices with improved radiology reporting accuracy, including bracing and home management of stable BF diagnosed during an acute care visit.The authors thank the teaching staff and other participants at our institution’s Quality Improvement Scientific Writing course, especially the numerous article reviews and suggestions provided by Anja Zann, MD.The authors have no financial interest to declare in relation to the content of this article.


PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen that was recently found to be expressed by malignant melanocytic lesions but not by benign ones, thus resulting useful in this diagnostic field. PRAME could also be expressed by some normal tissues and nonmelanocytic tumors, suggesting as caution should be adopted to use PRAME as a “pan-melanoma” marker for the differential diagnosis with other malignant tumors. Until now, PRAME expression was exclusively investigated through single staining with a monoclonal antibody targeting PRAME and with double staining for Melan A/PRAME found to be useful in specific diagnostic sets. Herein, we studied the expression of PRAME in 40 melanocytic lesions and 23 nonmelanocytic ones using PRAME, Melan A/PRAME, and novel double staining for HMB45/PRAME. Although our results need to be validated, they support the adoption of HMB45/PRAME, alone or in combination with PRAME and Melan A/PRAME, as a helpful marker in the diagnosis of melanocytic neoplasms with a high concordance rate between primary melanoma and corresponding metastases.PRAME ( PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen that was firstly identified by autologous T cells in patients with metastatic melanoma (M).PRAME  and DS (Melan A/PRAME and HMB45/PRAME). IHC was performed on 3 μm thick sections of formalin-fixed, paraffin-embedded tissue on the BenchMark ULTRA automated immunostainer . In both DS, PRAME nuclear staining was visualized with DAB , whereas Melan A and HMB45 cytoplasmatic staining were visualized with FastRed  to minimize difficulties in interpretation due to cytoplasmic melanin pigment. To enhance PRAME brown signal in the DS, a further step with an amplification kit was added . IHC protocols, clone antibodies, and other technical data are summarized in Table Of the 23 M and MM tested, 21 (91.3%) were scored as 3+  and/or 4+ . Conversely, 13/17 76.5%) N and NN lacked any staining (0), and only 4/17 (23.5%) showed PRAME immunoreactivity in a minor population of melanocytes (1+). The nonmelanocytic tumors chosen as negative controls were completely negative (0) (Table % N and N


Introduction: While pharmacogenomic (PGx) testing is routine in urban healthcare institutions or academic health centers with access to existing expertise, uptake in medically-underserved areas is lagging. The primary objective of this workforce education program is to extend access to didactic, case-based and clinical PGx training for pharmacists serving rural Minnesota and populations experiencing health disparities in Minnesota.Methods: A PGx workforce training program funded through the Minnesota Department of Health was offered through the University of Minnesota College of Pharmacy (COP) to pharmacists working in rural and/or underserved areas in the state of Minnesota. Learning activities included a 16-week, asynchronous PGx didactic course covering PGx topics, a 15-min recorded presentation, an in-person PGx case-based workshop, and a live international PGx Conference hosted by the University of Minnesota COP and attendance at our PGx Extension of Community Health Outcomes (ECHO).Results: Twenty-nine pharmacists applied for the initial year of the program, with 12 (41%) being accepted. Four (33%) practiced in a hospital setting, four (33%) in retail pharmacy, two (17%) in managed care, and two (17%) in other areas. The majority had not implemented a PGx program as part of their practice, although nearly all responded definitely or probably yes when asked if they expected their organization to increase its use of PGx testing services over the next three years. All participants either strongly or somewhat agreed that this program helped them identify how and where to access clinical PGx guidelines and literature and improved their ability to read and interpret PGx test results. Eight participants (67%) strongly or somewhat agreed that they expected to increase the number of PGx consultations in their practice, while ten (83%) strongly or somewhat agreed they would be able to apply what they learned in this program to their practice in the next six months to a year.Discussion: This novel PGx training program focused exclusively on pharmacists in rural and/or underserved areas with a delivery method that could be accomplished conveniently and remotely. Although most participants’ organizations had yet to implement PGx testing routinely, most anticipated this to change in the next few years. Precision medicine is an innovative approach to preventing and treating diseases using an individual’s genetic makeup and lifestyle . PharmacThere are several barriers that limit widespread implementation of PGx, despite its potential in improving medication therapy management and reducing costs . PGx is CYP2D6, HLA) and make the utility of PGx of even greater value.Effective use of PGx information in the care of patients requires pharmacists to be adequately versed and confident in the use of genomics, understand the relationship between genomics and drug action, understand when and how PGx should be applied, and be able to communicate the benefits and limitations of PGx to their patients and other health professionals . As a prThe University of Minnesota College of Pharmacy, with funding from the Minnesota Department of Health, has developed a certificate granting PGx training program aimed at practicing pharmacists in rural and underserved populations in the state of Minnesota. Several unique underserved communities reside in Minnesota, such as American Indian, US Hmong, Karen and Somali. In addition, nearly 10% of its population live in rural areas . The priA PGx training program was offered through the University of Minnesota College of Pharmacy to Minnesota licensed pharmacists working in rural and/or underserved areas in the state of Minnesota . ApplicaThe overall objectives of the PGx workforce training program are shown in The clinical didactic course presented the concepts of the science underpinning PGx, exploring how pharmacogenes are known to affect human therapeutics and highlighted content related to clinical practice. These topics included an introduction to the human genome and pharmacogenes, clinical PGx resources and guideline ) development, and PGx in psychiatry, opioids, proton pump inhibitors, NSAIDs, cardiology, oncology, HLA, and pediatrics. Additional topics included how PGx pertains to genetic exceptionalism; health equity; PGx testing panels; educating patients in PGx; regulatory considerations; ethical, legal, and social issues; clinical decision support and implementation of PGx in a large health system . ParticiThe national PGx conference was a CE-bearing international conference which has been hosted by the College of Pharmacy every other year since 2016. The first part of the conference was a one-day in-person clinical case workshop (6.75 h), while learners also attended a 2-day conference following the case workshops which could be attended in-person or virtually (12.25 h). Topics and drugs covered in the workshop and conference are shown in At the conclusion of the didactic portion of the program, participants were asked to complete a short survey developed by the program staff and faculty to assess the program, changes in their own PGx knowledge and attitudes, expected changes to their clinical practice based on their participation, and current barriers to PGx implementation in their current practice setting.A total of 12 out of 29 applicants were accepted into the inaugural program and all completed the certificate program. The next cohort begins in January 2023. Common reasons applicants scored low by the admission committee were not working with a rural or underserved population, not practicing in an environment that would allow for implementation of PGx, or having a personal statement that did not strongly describe why they wanted to participate in the program. All participants had a PharmD degree. Four (33%) reported working in a hospital pharmacy, four (33%) in community pharmacy, one (8%) in a clinic, two (17%) in managed care, and two (17%) as “other.” As seen in Prior to starting the program, when asked if their clinical practice had implemented a PGx program, eight (67%) responded No, two (17%) responded Yes, a small pharmacy-led program, and three (25%) noted they were currently in the process of implementing a PGx program. When asked if their organization used PGx in clinical care, four (33%) responded Yes, seven (58%) No, and one (8%) that they did not know. Half of participants stated their organization ordered fewer than 10 PGx tests per year, one that they ordered 100 or more, and five stated they did not know. Similarly, when asked how often they use PGx-guided care in their practice, half responded Infrequently, four stated Never, one Monthly, and one Weekly.Responses related to an individual’s level of understanding and future plans for PGx are shown in I recommend (it) to any pharmacist wishing to learn more about this exciting aspect in pharmacy.”• ““It was a great experience and I learned a lot.”• “Gaining knowledge of the available resources will allow me to continue to implement changing guidelines in my current practice. The PGx ECHO sessions  were really great - being able to discuss real patient cases with clinicians currently practicing with PGx data was invaluable.”• “Overall this was a great course. I was extremely grateful to have the opportunity to learn more about PGx in this setting. I feel it really helped to catch me up on information that was not taught during my time in a PharmD program. It was something I was interested in, but would have found overwhelming to self-teach without this base.”• “Loved the opportunity to participate in this course. Most of it was real word applicable, held my interest, was applicable to patient care, and didn’t feel like busy work or straight memorization.”• Participants were also invited to provide written feedback, which included the following from separate individuals.Participants were asked about what barriers in their clinical practice could hinder their ability to implement what they learned. These included resources devoted to the scalability of implementing PGx, insurance coverage/reimbursement of testing and appointments with a pharmacist, lack of access to patient medical records/PGx test results, lack of organizational interest, and current level of evidence for prior authorization criteria and exceptions.One unique challenge for this first cohort was the timing in regards to the global COVID-19 pandemic. Pharmacists in rural areas in particular struggled at times to balance staffing shortages during a surge in cases with the demands of completing the program. Faculty teaching in the course also teach PGx content in the PharmD program and a programmatic challenge was adapting lectures intended for delivery to students for working professionals.PGx is a promising innovation to improve medication safety and efficacy, but it will not be fully realized until the broader healthcare workforce is adequately prepared. It is vital that PGx not be available only to those in larger metropolitan areas from large healthcare organizations, but to intentionally and strategically create programs for pharmacists caring for rural and underserved populations. This PGx workforce training program of pharmacists is unique in that it includes not only lectures from PGx content experts, but also includes a full day of case-based learning, participation in a novel PGx ECHO program, and a two-day PGx conference with presentations from PGx experts. As shown by survey of the first cohort to participate in this certificate, their overall education level increased, with future plans to offer or enhance PGx guided care at their respective institutions.etc.,, in order to participate. Employers were also not expected to pay for their education to minimize the imbalance for well-funded vs. underfunded organizations, 2) the program is attempting to create over time a community of PGx-trained practitioners throughout the state by using a cohort model and by requiring PGx ECHO and conference participation, 3) it is offered by a public, land-grant university rather than a professional organization.Knowledge and attitudes of PGx in healthcare professionals is well described, with most individuals acknowledging the importance and value of PGx but also expressing their own discomfort in interpreting and applying results . The AmeTo date, the majority of large PGx implementation programs have been limited to larger institutions . PGx in While Dorfman et al. focused on providers working in rural areas, Stegelmeier et al. 7-item survey focused on adult individuals filling a prescription at a community pharmacy in a rural area. A total of 52 individuals completed the survey. The clear majority in this group were taking a prescription medication, while average responses reflected a neutral to agree response in regards to their understanding of what PGx is, their interest in PGx, and a belief that PGx could help them. On average, this group expressed they would be willing to pay just $51 out of pocket for PGx testing, but generally did agree that PGx testing is valuable . While iAlthough Minnesota has excellent healthcare, it also has considerable health disparities between whites and people of color and American Indians . ReachinBeyond clinical implementation, research efforts to identify novel variants that may impact PGx are also needed In February of 2022, the Right Drug Dose Now Act was introduced to the United States Congress, with the purpose of updating the National Action Plan for Adverse Drug Event Prevention . This biAdequate PGx education of clinicians, including pharmacists, physicians, nurse practitioners, physician assistants, and registered nurses will be critical moving forward as PGx continues to be implemented. In order to avoid worsening rural/urban health disparities, and those seen in underserved populations, it is critical that this education extend to all healthcare professionals working with these populations. Directly engaging these communities in PGx certificate training programs is one method to increase the knowledge and understanding of not only foundational PGx knowledge but also PGx implementation so all individuals can benefit from PGx informed care.


While rural physicians are the ideal candidates to investigate health and healthcare issues in rural communities, they often lack the required skills, competencies, and resources. As a result, research skills development programs are crucial to help ensure communities receive the quality of care they deserve. Memorial University of Newfoundland created a research skills development program called 6for6 to empower and enable rural physicians to research solutions to community-specific health needs. 6for6 program delivery was exclusively in-person until 2019. However, with limitations introduced due to the COVID-19 pandemic, organizations around the globe needed to respond quickly. As we work to return to a post-pandemic environment, program administrators and educators worldwide are unsure whether to retain or remove the changes made to programs to adapt to the pandemic restrictions. Therefore, this work addresses the impact of the online delivery model in two areas: 1) attainment of competencies ; and 2) participant experiences, defined as the ease of attendance, the capacity to interact with team members and peers, and challenges or barriers associated with navigating program resources.We compared the effect of an online delivery model pivoted to adapt pandemic restrictions with the original model (primarily face-to-face) on the acquisition of learning competencies and participant experience using a mixed-methods study. Various data collection methods, such as a pre-post program survey, post-program focus group, and structured observation, were utilized.From 2014 to 2021, 35 physicians attended the program (30 face-to-face and five online). The Wilcoxon-sign-rank test did not show any significant differences in the participants’ median change of research competency scores who attended face-to-face and online learning, respectively: knowledge , attitudes , and skills . Flexibility and accessibility were key aspects of participants’ experiences during the online model. Comparison with previous years demonstrated no significant challenges with the virtual delivery model, yet participants struggled with mentorship challenges and learning-life balance.Although presenting some unique challenges, the online model did not negatively affect learner competencies. Likewise, it provided opportunities for rural physicians to attend learning sessions and interact with experts and peers while remaining in their communities. Rural physicians are well-positioned and often motivated to conduct community-based research , 2 but fWith the onset of the global COVID-19 pandemic in early 2020, organizations worldwide implemented various safeguards. As a result, we quickly pivoted the program at Memorial to an online-only delivery model for 2020-21. Now, more than a year after the start of the pandemic, we are undertaking a comparison of two delivery models (primarily face-to-face vs. entirely online) to help determine the ideal future delivery model. This work will provide a foundation for other organizations that are preparing to return to a new, post-pandemic work environment.Our purpose was to assess the impact of the online delivery model in two areas: 1) attainment of competencies ; and 2) participant experiences, defined as the ease of attendance, the capacity to interact with team members and peers, and challenges or barriers associated with navigating program resources. To explore these questions, we undertook a mixed-methods study approved by the provincial Health Research Ethics Board.The team consisted of the core program team  and the teaching team . The core program team was involved in all aspects of program conceptualization, design, and analyses, whereas the teaching team was focused solely on program delivery. Program participants were individually paired with expert researchers, or mentors, to help them with the curriculum content and with integrating the content into their research plans. The participants regularly met with their mentors to develop their projects, and in turn, develop a productive working relationship. Mentors were carefully selected, with consideration given to factors such as expertise, time availability, and experience. Since 2022, program alumni have acted as mentors for new participants, which highlights the full-circle nature of this program. All mentors are provided mentorship support through expert-guided face-to-face discussions with the core team, resources like coaching strategies, and a sample timeline for meeting program outcomes.The research skills development program, 6for6, is developed around an adult learner-centered approach using a blended learning model and is tailored to the needs of physicians practicing in rural areas of Canada. Six participants per year gain various research competencies and enhance their writing skills while developing their own research idea (the capstone project).The program utilizes both synchronous (instructor-led) and asynchronous (self-paced) content. The synchronous content comprises six structured, face-to-face sessions delivered at the main Memorial campus in St. John’s. The asynchronous content is a number of dedicated self-learning activities and assignments, including readings, tip sheets, workbooks, writing exercises, and online resources.The team invited various subject-matter experts  to help with each of the six face-to-face sessions. The core team developed the session goals and learning objectives in consultation with subject-matter experts using the anchored delivery model . The proDuring the spring, summer, and fall of 2020, the core team quickly pivoted and adapted to pandemic restrictions and so developed an online-only delivery model for the 2020-21 group .The first step was converting the face-to-face (synchronous) content into an online format. The core team completed this conversion internally. A priority was determining how to incorporate these elements into a virtual model ; this included conducting an environmental scan to determine the best approach for delivering the content online. The team also completed an extensive literature search to identify any related evidence.The next step was reviewing course content to determine any required changes. The team completed internal and external consultations, including education design experts, subject-matter experts, and 6for6 alumni. Given that the rurally-based participants and team members had varying access to reliable internet, the team sought input from the 2020-21 group to help ensure the best possible experience. The team also mapped each course concept with corresponding modes of delivery to determine the best use of available resources and to maintain the core components of 6for6, including participant interaction and engagement, while working within pandemic restrictions. To assist with this, the team utilized the Capability Assessment Framework to help determine institutional capability for pivoting online . As noteAs part of the inaugural online year, we also asked participants about their home technology  and familiarity with online programming. Subsequently, we provided training in navigating online platforms such as WebEx and D2L (Desire2Learn), Memorial’s online learning platform, and a toll-free telephone option as a backup. We also recorded online sessions to share with participants via D2L. These online components were additions not previously available when the mode of delivery was primarily face-to-face.The pre-and post-program survey measures self-assessed research competency, which is a subjective measure of the relationship between knowledge, attitudes, and skills of an individual that combine to produce results . The catn = 35) were encouraged to attend a focus group at the end of the last program session; to date, 35 rural physicians have participated. Two third-party researchers with expertise in qualitative research methods facilitated this session. The focus groups were semi-structured; participants were asked about advantages and disadvantages of the program, suggestions to improve program delivery, and important takeaways, among other questions. Focus groups were held in-person until we were required to pivot to an online format for the 2020-21 cohort (due to the COVID-19 pandemic). This focus group was conducted via Zoom. Participants were asked additional questions about the virtual nature of the program, such as pros and cons related to online delivery. These additional questions were approved by the provincial Health Research Ethics Board.We conducted the post-program focus group as part of the final session with each group from 2014 to 2021. All participants’  using a five-level Likert Scale. We estimated participants’ scores for competencies as total scores obtained by each participant on the questions related to each competency  divided by the total possible score for each competency and multiplied by 100. We summarized research competencies using mean, standard deviation (SD), median, and interquartile ranges (IQRs). We performed a Wilcoxon signed-rank test to examine any statistical difference in knowledge, attitudes, and skills before and after the program and any differences between face-to-face and online delivery models using score changes between pre-and post-program. We performed analyses in the R version 4.1.1  statistical software package to obtain the results. We considered a For qualitative analysis, we utilized a thematic analysis of the post-program focus group and structured observation to extract comprehensive information regarding learner experiences. Extracted observational data in this study was integrated as confirmatory research. In other words, structured observation data was used to corroborate research findings in this study. We transcribed the focus group discussions verbatim, and qualitative data experts undertook the thematic analysis. A researcher with expertise in qualitative analysis described the scope and content of each developed theme. The researcher then established the final themes, compared them with the data and coding set to ensure accuracy, and discussed them with the core team to reach a consensus. The extracted themes from previous cohort focus groups  associated with research competency, networks, and connections, were considered a basis for analysis of the focus group and structured observations performed using the online delivery model.n = 29) for the pre-program survey and 76.7% (n = 23) for the post-program survey. Respondents were 56.7% (n = 17) female and 43.3% (n = 13) male; 83.3% (n = 25) family physicians and 16.7% (n = 5) other specialists.Thirty participants attended the program (six participants per year for five years) during face-to-face delivery. The response rate during this time frame was 96.7% (n = 6). Respondents were 80.0% female and 20.0% male; 80.0% family doctors and 20.0% other specialists.During the one year of online delivery, five participants attended the program. There was one drop-out early in the program (p < 0.001), attitudes (p < 0.05), and skills attainment (p < 0.001) were statistically significant , attendees strongly emphasized the program’s key role in expanding their research competency and networks and connections, providing them with a unique opportunity to incorporate research skills into their daily lives as rural physicians. Analysis of the post-program focus group during the pandemic illustrated several benefits of the online-only delivery model, including the ease of attending the learning sessions  and the capacity to interact with team members and peers  while also pinpointing some challenges or barriers associated with navigating program resources .Due to geographical and professional isolation and a shortage of time and funding, rural physicians constantly struggle with a lack of accessible and contextually-relevant research training programs. 6for6 addresses the gap between research and clinical practice for rural physicians. Nevertheless, face-to-face sessions over six weekends (Friday and Saturday only) during one year demands significant travel for attendees. The virtual version of the program; however, provided flexibility and accessibility for busy rural physicians who may not be able to find time for the program in their busy schedules otherwise:I really liked that it was virtual. I know that this was intended to be an in-person session, but I found that really added a bit of flexibility to it and made it a lot easier to accommodate it. I don’t think I would have been able to attend all of the sessions in-person, if that’s how it went; just with work scheduling stuff … you know, there’s the things that we do together.”“Attendees have considered the lack of a supportive research system as one of the barriers to conducting research for anyone practicing in rural and remote areas. An undeniable impact of 6for6, other than building research capacity  and productivity , is building professional research networks and connections, which includes facilitators, researchers, the program coordinator, mentors, librarians, and colleagues:I’ve lived in [remote areas] for most of my career, right? And so, how to connect was my main preoccupation; that felt like the biggest barrier and I feel like that barrier is gone now. Right, so it’s not necessarily skills but it’s like plugging in and knowing who to ask and how to find them in the end and just feeling like there are fewer barriers.”“The primary requirement to build this professional circle of support is having rich peer-to-peer and mentor-participant communication. While one might assume that the virtual format may challenge engagement, communications, connections, and weaken supports, participants noted they had a substantial amount of interaction and effective communication with team members under the virtual delivery format:[A]nd I was like quite surprised right off the bat at the intimacy that the virtual still allowed us, you know.”“Furthermore, participants applauded the cooperation and teamwork among peers during the program’s online delivery. In addition to increasing interactivity and finding comfort in knowing that other people shared in their struggles , it also helped ensure that participants all remained motivated in their respective projects:We’re all in fairly similar situations we have busy clinical work and family life and otherwise, so you know, knowing that we’re all sort of trying to balance it all and learn from each other has been really great.”“One of the program goals is to uncover and modify the barriers and difficulties caused by the program curriculum and structure. Even though the majority of participants were satisfied with their mentor-mentee relationship and found it to be a helpful aspect of the program, time zone differences and mismatched mentors were considered challenges. Time zone differences between the participants and their mentors contributed to rescheduled meetings and delays. In addition, one online participant felt that they were not matched with the most appropriate mentor for their project; a concern that was not immediately noticed by the study team due to the online program delivery:I really thought I was coming in and doing a quantitative study. That was my idea, so I was paired with someone qualitative which I think was like both good and bad, right?...I was like trying to figure out how to do my study and like, I think probably a month or two of just like really trying to jam my square peg into a round hole and I think, partly because I really felt like there was an expectation that I was going to do qualitative research because I’m paired with a qualitative research partner”.“The mentor-mentee selection is based on the participant’s research question and the mentor’s expertise. We strive to make the best selection possible for both the mentor and mentee; however, communication style, availability, and clinical background, among many other factors, can affect this relationship. When the 6for6 program was delivered exclusively in-person, the core team was able to monitor for these factors and mediate the mentor-mentee relationship, as required. Mentorship issues can arise in both the in-person and online delivery models; however, it is much more difficult to monitor and mitigate these issues during online program delivery.Workload and time frame have been regularly monitored, evaluated, and reframed during the in-person model of the program. Although the online delivery model provides participants with the opportunity to attend the classes while being at home, attendees not only have to complete all the required asynchronous content and assignments of the program, but also meet commitments outside of the program. This comes with feeling overwhelmed by the course commitments while trying to balance home and work responsibilities.[W]here sometimes the assignments or information was coming out really close to when the sessions were going to be, or the deadlines; I found that pretty tricky, for you know as an adult learner who’s like trying to balance other commitments.”“The respective challenge is unique to the online delivery model, as face-to-face delivery included allotted time for participants to work on 6for6 material. In addition, participants who attended the face-to-face program were able to step away from other obligations for the weekend of the session and focus solely on their research projects:Things that I think made a difference for me … creating time and space. My clinic is closed, I’m here, and I’ve never been more productive around scholarly work than those two or three days that I’m here because I’m not distracted and people are priming my brain.”““Get out of your space, and … you think differently, work differently, have different experiences, I’m a different practitioner now because of that.”Unlike participants who completed the in-person program, participants in the online-only group were simultaneously dealing with their professional obligations and challenges  and home-related responsibilities , which at times interfered with their course engagement and productivity. In-person program delivery provides participants the opportunity to have dedicated time away from their other responsibilities to focus on their research. We also noted that time zone differences resulted in less engagement by participants, particularly due to interweaving with family responsibilities. Regardless, any additional educational activities will cause a busy clinician to become even busier, whether delivered online or in-person.Many organizations will be seeking answers as they prepare to return to a new, post-pandemic work environment. So, what is the optimal model of delivery moving forward for supporting participant needs? Is it a return to a traditional in-person program delivery model, continuing with an online model, or a combination of both? Of course, if we remain restricted by the pandemic impacts, there is no option but to remain online. However, if lifted, it becomes imperative to determine if virtual delivery models are as effective and acceptable for our participants and program faculty as a face-to-face modality.Our assessment suggests that the online delivery model, while presenting its own unique challenges for both team members and participants, did not negatively impact the attainment of self-reported research competencies, and we were able to support the learning needs of the rural participants. These results echo the findings of existing literature, noting a lack of material difference between in-person and online delivery models , 12 whilOur findings should be interpreted in light of their limitations. It should be noted that this study was limited to just one year of data on the online-only delivery model, which was rapidly assembled due to the uncertain pandemic regulations and consequently delivered over a condensed time frame. Ideally, the curriculum would have continued for 12 months with adequate preparation time. Although our assessment did not show any difference in self-assessed research competencies by delivery model, a non-inferiority design study would better support whether face-to-face and online delivery are equivalent. We also did not have sufficient data to support statistical analysis for assessing competencies before and after online delivery.Admittedly, the online curriculum included some deficiencies , which would not have been a significant issue in a non-pandemic year. Furthermore, face-to-face delivery included time allocation for self-paced research activities while the participants were on campus. In addition, the pandemic conditions may have influenced participant satisfaction with the online delivery model .One of the goals of our rural research capacity building model is to empower rural practitioners to be change-makers in their communities by investigating contextually relevant health issues . We contAs program developers and organizers prepare for a new normal, ideally with fewer restrictions, these questions will become increasingly relevant to ensure the best program for participants while working within the boundaries of a post-pandemic workplace. In our case, one option would be to utilize a hybrid model of delivery, including the best aspects of both the online model and the original face-to-face model. Among other benefits, this would allow our participants greater flexibility to stay in their communities when they are most needed while still offering some advantages of a face-to-face model.While this study focuses on rural physicians participating in a research skills development program in Canada, the results will have global applicability for any organization seeking to determine an optimal delivery model for distributed clinicians and, ultimately, will also help ensure positive participant outcomes in many sectors.


Endobronchial ultrasound (EBUS)‐guided tissue acquisition (TA) performed by transbronchial needle aspiration (TBNA) is the main diagnostic procedure in mediastinal and hilar lymph node (LN) biopsy. EBUS‐guided intranodal forceps biopsy (EBUS‐IFB) and EBUS‐guided cryobiopsy can achieve higher diagnostic yield of lymphomas, uncommon tumors, and benign diseases. However, these techniques require the creation of a tract to insert biopsy devices, which may result in critical complications. Here, we report a rare case of airway stenosis (AS) that occurred after EBUS‐TA for mediastinal LN biopsy. An 80‐year‐old man had multiple pulmonary nodules and an enlarged mediastinal LN. EBUS‐TBNA and EBUS‐IFB were performed for histological diagnosis. Cutaneous adnexal carcinoma (CAC) was diagnosed. The patient underwent chemotherapy. Four months later, he was hospitalized for AS due to a tracheal tumor with dyspnea. Chest computed tomography and bronchoscopy revealed that the tracheal tumor was caused by invasion from the biopsied LN into the tracheal lumen by tract seeding (TS) caused by EBUS‐TA. Cryotherapy was performed. The tracheal tumor was pathologically consistent with CAC and is currently under control with radiotherapy. TS‐associated EBUS‐TA is rare but may increase in frequency with aggressive tissue sampling techniques. Bronchoscopists should perform EBUS‐TA with awareness of the potentially serious complications. We report a rare case of airway stenosis that occurred after endobronchial ultrasound (EBUS)‐guided tissue acquisition (TA) for mediastinal lymph node biopsy. Tract seeding associated EBUS‐TA is rare but may increase in frequency with aggressive tissue sampling techniques. Bronchoscopists should perform EBUS‐TA with awareness of the potentially serious complications. Endobronchial ultrasound (EBUS)‐guided tissue acquisition (TA) performed by transbronchial needle aspiration (TBNA) is the main diagnostic procedure for mediastinal and hilar lymphadenopathies given its safety and minimal invasiveness.Here, we report a rare case of airway stenosis (AS) that occurred 4 months after EBUS‐TA for mediastinal LN biopsy.An 80‐year‐old man with a 100 pack‐year smoking history was referred to our hospital for treatment of multiple pulmonary nodules and an enlarged mediastinal LN. He had previously undergone excision of a 3‐cm left axillary tumor, and cutaneous adnexal carcinoma (CAC) was diagnosed. He was medicated for hyperuricemia and reflux esophagitis and had no allergies. His laboratory results were normal, including coagulation test results Table . LN metaWe present a rare AS case caused by TS complicated by EBUS‐TA. The largest retrospective study on EBUS‐TBNA reported a 1.2% incidence of complications, mostly including bleeding and infections without TS.In the gastrointestinal field, endoscopic ultrasound‐guided TA (EUS‐TA) via gastric and duodenal tracts have been performed worldwide for pancreatic and biliary tract tumors and gastrointestinal submucosal tumors, even before EBUS.However, newer techniques, such as EBUS‐IFB and EBUS‐cryo as well as newer EBUS‐TBNA needles with fabricated needle tips for core tissue sampling and 19‐gauge EBUS‐TBNA needles, may create a firmer and larger tract than the standard 21‐gauge or 22‐gauge EBUS‐TBNA needle.Here, clarifying the main reason for AS after EBUS‐TA was difficult; the involvement of the size of the tract created by EBUS‐TBNA and EBUS‐IFB cannot be ruled out. However, AS due to TS has not been reported, even in EBUS‐cryo,In conclusion, we report an EBUS‐TA‐complicated AS case. Bronchoscopists should perform EBUS‐TA understanding that aggressive tissue sampling can have potentially serious complications.The authors declare that they have no competing interests.


The Monte Carlo (MC) method is a powerful tool for modeling nuclear radiation interaction with matter. A variety of MC software packages has been developed, especially for applications in radiation therapy. Most widely used MC packages require users to write their own input scripts for their systems, which can be a time consuming and error prone process and requires extensive user experience. In the present work, we have developed a graphical user interface (GUI) bundled with a custom-made 3D OpenGL visualizer for PHITS MC package. The current version focuses on modeling proton induced positron emitting radioisotopes, which in turn can be used for verification of proton ranges in proton therapy. The developed GUI program does not require extensive user experience. The present open-source program is distributed under GPLv3 license that allows users to freely download, modify, recompile and redistribute the program. These widely used MC packages have their own specific scripting syntaxes and format for setting up the simulation of radiation transport, such as geometry, material, source and tally definitions. Preparing the input scripts for these widely used MC packages are actually time consuming and error-prone processes and require user experience.Monte Carlo (MC) simulation is an established tool which is extensively employed in simulation of nuclear radiation transport in matter, thanks to that the stochasticity of radiation interaction with matter can be conveniently considered in MC models . The MC 1H, 12C and 16O are the commonest elements found in body tissues, with 12C and 16O being able to produce 11C and 15O/13N, respectively, which are positron emitting radioisotopes and in turn generate annihilation photons within the patient’s body. It is remarked that 1H does not produce a stable positron emitter and will not be considered in most investigations.Interest in proton therapy has increased in recent years. In proton therapy, high energy protons are used to deliver doses to tumors. As a result of the interaction between high energy protons with tissues, the tissue elements would be activated . 1H, 12Cet al. [13N positron emitters for proton range verification due to its low energy threshold that peaks at around 12 MeV. In their previous study, water-like gel and tissue-like gel phantoms were irradiated and scanned using an in-room positron emission tomography (PET) system. The proposed method was interesting and promising in that it could be used to enhance the effectiveness and accuracy of proton therapy. We refer interested readers to Cho et al. [13N) for verification of proton ranges without requiring extensive user experience in MC method and code scripting. The present open-source program is distributed under GPLv3 license that allows users to freely modify, recompile and redistribute.Previously, Cho et al.  proposedo et al. . ConsideThe present program can be divided into six main parts: (i) the main program, (ii) GUI control callback, (iii) GUI callback function, (iv) PHITS script generator, (v) linear interpolation and (vi) proton range subroutines. The main program and all the subroutines were written in the FORTRAN90 programming language. The OpenGL 3D plotter program was written in the C++ programming language that read the output of the main GUI program to plot the 3D structure. The developed GUI program is shown in Box X, Box Y and Box Z , which were placed in an air sphere centered at the origin  with the user defined radius Air Rad (in cm). The variables Xmin, Xmax, Ymin, Ymax, Zmin and Zmax  represented the tally region within the modeled rectangular parallelepiped. The variable NZ (integer number) defined the number of mesh slices along the z-axis  at which the beam of protons is launched with a source radius defined by the Beam Rad (in cm) variable. It is possible for the users to change the beam size by defining Beam Rad, which is essentially the proton beam radius. The modeled geometry and tally region are shown schematically in maxcas (integer number) and maxbch (integer number), respectively. The users could choose seven different materials: (i) water [The present program simulated a rectangular parallelepiped with user defined dimensions, i) water , (ii) wai) water , (iii) Pi) water , (iv) boi) water , (v) luni) water , (vi) adi) water , and (vii) water . The prei) water . The mat−38 to 1038. Another limitation would be the format of the numbers in Fortran. The core of the present GUI program that generates the entire PHITS script requires number formatting for writing the PHITS script. The current format of the GUI variables enables the users to input geometry sizes up to four digits and less than 2000 cm in length and tally region up to three digits (i.e. 999 cm); these can be easily increased depending on the user demand by changing the format length and recompiling the program. The control callback subroutine handled the asynchronous callback when the corresponding button was pressed. The callback subroutine read all the user inputs from the GUI, converted characters to either real or integer numbers and called the PHITS script generator subroutine. The PHITS script generator subroutine handled the generation of PHITS input code with specific formatting and syntaxes built into the PHITS script generator. The generated PHITS script from this subroutine was saved into an input file and the callback subroutine initiated the PHITS MC package through a system call with the generated input code. It is remarked that for automatic PHITS MC run, users would need to have PHITS installed on their computers.After the user entered the inputs through the GUI, the program read all entries as characters, which were then converted into either real or integer numbers depending on the specific variable. The parameter limits are based on the user inputs for each variable that will be read by the GUI program in 256 characters string and then converted to single precision 4-byte real numbers which has seven digits of accuracy and a magnitude range from 10http://www.srim.org/) for incident proton energies ranging from 20 to 250 MeV. All the proton range data obtained from SRIM that were implemented into the program can be found on: https://figshare.com/articles/software/Development_of_PHITS_graphical_user_interface_for_simulation_of_positron_emitting_radioisotopes_production_in_common_biological_materials/17054864. These data were implemented into the proton range subroutine and interpolated  to the nearest user defined incident proton energy. Using the obtained proton range, another output file would be generated containing the maximum projected range which would then be used by the OpenGL plotter program. Snapshots from the OpenGL 3D plotter program are shown in The OpenGL 3D plotter program read the output from the GUI program. The linear interpolation and proton range subroutine were called from the callback function subroutine upon plotting. The interesting feature here was the visualization of proton ranges in 3D Cartesian coordinates, which was displayed along with the modeled phantom, tally region and axial mesh slices. The GUI program wrote the dimensions of the modeled phantom, tally region and number of axial mesh slices into output files. In addition, data on proton ranges for the seven different materials shown in Box X, Box Y, Box Z) and air sphere radius (i.e. Air Rad) will be filled into RPP and SO in the surface card of the PHITS script by the program. The source card with proton projectile will also be automatically generated by the program and the user input beam radius (Beam Rad) and incident energy (i.e. Energy) will fill the source card accordingly. The product tally card with all its commands will also be generated by the program and the variables Xmin, Xmax, Ymin, Ymax, Zmin, Zmax and NZ will fill the tally card. The tally card option for generating output plots in the eps image format will be turned on automatically by the program so that users can easily view the simulation output results. The GUI program and all its source code can be found at: https://figshare.com/articles/software/Development_of_PHITS_graphical_user_interface_for_simulation_of_positron_emitting_radioisotopes_production_in_common_biological_materials/17054864.In the present GUI program, a loop function was implemented that prevented overwriting of the output code and results generated by the PHITS MC package; this would be particularly useful when users aimed to simulate a large number of cases/scenarios. The generated PHITS input script was numerically numbered and PHITS MC package outputs would be named with the user defined energy and material for ease of recognition and post processing. The present GUI program generates the entire PHITS script for proton irradiation of homogenous phantoms composed of seven different materials: (i) water, (ii) water gel, (iii) PMMA (acrylic), (iv) bone equivalent, (v) lung equivalent, (vi) adipose equivalent, and (vii) gel dosimeter. The user can intuitively change the parameters and immoderately run PHITS and see the output results. The present GUI program has the ability to execute PHITS by clicking a button and the users can immediately view the output results. The program generates all tally cards such as; title, parameters, source, material, surface and tallies automatically. The command for geometries that are RPP and SO for rectangular parallelepiped and air sphere centered at origin, respectively, will be printed in the PHITS script automatically. The user defined rectangular parallelepiped dimensions,  80 MeV protons irradiating 20 × 20 × 20 cm3 gel dosimeter phantom, and (iii) 235 MeV protons irradiating 15 × 15 × 30 cm3 bone equivalent phantom. The normalized dose and production of positron emitting radioisotopes versus depth were determined for every test case. In addition, the 3D plot was generated using the OpenGL 3D plotter program.Three different test cases were considered to validate the present GUI program: (i) 110 MeV protons irradiating 10 × 10 × 40 cmThe test results from the present GUI program for three different cases have been shown in http://theis.web.cern.ch/simplegeo/) is an interactive solid modeler that would help users design complex geometries for FLUKA, MCNP and PHITS MC packages, PHITS Interactive Geometry viewer in 3D (PHIG-3D) (bundled with PHITS MC package) that is commonly used for visualization of 3D geometries by reading PHITS input file; while this tool can enlarge, reduce and rotate geometries prepared in the PHITS input script. Another notable feature for defining geometrical features would be SuperMC (https://github.com/chunshen1987/superMC) that enables the conversion of a CAD file to the PHITS input format. These tools have higher flexibility; however, it would be rather difficult to be operated by beginners. There are also a variety of GUI programs developed for other MC packages such as Vised  that was developed for the MCNP MC package, which enables visualization of the MCNP input script, geometrical debugging and visualization of particle tracks in a variety of applications [http://geant4-resources.com/Geant4GUI/G4GUI.html) that is developed for Geant4 MC package. It has the ability to determine particle tracks, mean free path and dose deposition in almost any element from the periodic table, however, common biological materials that are of most interest in medical applications were not considered. In addition, Wisp can only determine dose and mean free path, while the production of radionuclides as a result of irradiation was not considered. The EGS Windows (https://rcwww.kek.jp/research/egs/user.html) is another general-purpose 3D viewer for the use EGS5 MC package; this tool is only for visualization of geometries and does not offer input script generator. Unlike other tools that would only assist users to generate 3D geometries, the present GUI program generates the full PHITS script and assigns numerical values to each command based on user inputs. Users do not need to install the present GUI program (as it is a portable executable software) or interact with any scripts or codes.The main difference of the present GUI program is that it generates the entire PHITS script and it is not limited to geometries and materials definition; this makes the present program easy and simple even for novice users. The user can intuitively change the parameters and immoderately run PHITS MC package and see the output results. This feature is especially good for pedagogical applications and medical staffs in clinical studies. Some notable tools such as SimpleGeo 13N, 16O15O and 12C11C nuclear reactions produced 13N, 15O and 11C radioisotopes, respectively. The present GUI program automatically generated the tally card for scoring the production of these positron emitting radioisotopes. This was indeed useful for users as it reduced the time for preparing the input script and prevented any potential errors in tally definition. As reported previously [13N peak was close to the actual Bragg peak and therefore it could be used for verification and monitoring of proton range during radiation therapy. This would be particularly useful for benchmarking the experimentally obtained results from PET systems using the MC method.The results shown in 5a and 5a and Snapshots from the developed OpenGL 3D plotter program is shown in In the present work, an open-source GUI program was developed for the PHITS MC package for proton irradiation of a homogeneous phantom made of most commonly used biological materials. The users could choose seven different materials: (i) water, (ii) water gel, (iii) PMMA, (iv) bone equivalent, (v) lung equivalent, (vi) adipose equivalent, and (vii) gel dosimeter to study the proton interaction, dosimetry and production of positron emitting radioisotopes. In addition, the present GUI program was coupled with a dedicated OpenGL 3D plotter program. The users could visualize the modeled geometry and proton range within the modeled phantom. The present GUI would reduce the possibility of errors and the time needed in preparing input scripts for proton irradiation and proton induced radioisotopes. In future works, we aim to further develop the present GUI and the OpenGL 3D plotter program by considering various types of ionizing radiations, geometries and materials for the PHITS MC package.


A growing body of literature supports the efficacy of the health–social approach for the implementation of complex interventions to enhance self-care health management among community-dwelling older adults. However, there is little research on how interventions with this approach are implemented and disseminated in a real community setting.This pilot study adopted an effectiveness–implementation hybrid design to 1) evaluate the effectiveness of a community-based Health–Social Partnership Program (HSPP) and 2) explore the reach, adoption, implementation, and maintenance of the HSPP in the community. Potential participants were recruited if they were aged 60 or above, owned a smartphone, and were cognitively competent. The participants received nurse-led case management with support from a social service team. Factors that hindered or facilitated the program delivery were examined to determine the implementation outcomes and sustained effects of the program. Data were collected at pre-intervention (T1), immediately post-intervention (T2), and 3 months post-intervention (T3).2 = 12.28, p ≤ .001). Barriers to widespread program implementation included manpower shortage, lack of experienced staff, and unpredictable environment, whereas facilitators, as suggested by the older adults, providers, and community staff members, included regular communication between the research and service teams, recruitment of participants through community centers with the support of the research team, and seamless partnership among the health–social partnership team members. Strong implementation fidelity was achieved with zero attrition rate.Ninety-two older adults joined and completed the program. The recruitment rate was 76.7%. A significant interaction effect was found for the mean self-efficacy scores from T1 to T2 .This study was registered at The online version contains supplementary material available at 10.1186/s12877-022-03463-z. Contributions to the literatureImplementing, sustaining, and scaling up health promotion programs for older adults in the community setting are challenging but imperative to improve public health outcomes.This study is the first to involve key stakeholders, including the managers and frontline staff members of a local community center, to contribute to the implementation of a self-care health management program for community-dwelling older adults.The findings provide preliminary information on the facilitators of and barriers to implementing and sustaining a health–social partnership program for older adults in the community.The population of Hong Kong, as in most countries, is aging. It is predicted that by 2038, 31.9% of Hong Kong’s population will be over the age of 65 .The effect of the pandemic affecting program adoption was reiterated by the center staff members and the manager. They mentioned that the pandemic led to significant changes in operation and service delivery, including re-deployment of staff which increased existing workload. Overall, these changes affected the planning and delivery of the new program:“We had a few meetings before the program launched. However, due to the pandemic, we have had to change the recruitment procedure, reschedule the duties of our staff, and revise the logistics of the program. All of this has increased our workload as we also need to make similar changes to other programs.” – [Community center staff manager].Further to the above, the center staff manager highlighted key issues which served as barriers to implementing new programs and continuing with existing ones. These issues included limited staff strength to run a new program in addition to existing ones, availability of trained staff to deliver the program, limited government support in increasing the staff strength, and financial constraints. Put together, these issues adversely impacted on sustaining existing programs and successfully implementing new programs. Additionally, from the providers’ perspective, it was critical to have healthcare professionals specifically trained to deliver the program; a lack of which can adversely impact the planning and implementation of the program:“Manpower is the biggest issue for the center. While the research team has provided us with a nurse and research assistants, we still need additional staff to run a new program. Even for our regular programs, we need financial support from the government to hire a registered nurse and clerical staff.” – [Community center staff manager].“This program requires an experienced and skilled nurse to monitor the health conditions of the participants, provide optimal and individualized interventions, and handle emergency situations. It will be more difficult to meet the standard of the program if the nurse is not specialized in community or elderly care. A nonspecialized nurse would need more guidance and training.” – [Provider].Forging collaboration with the healthcare professionals at the community served as a facilitator for the adoption of the program among participants. Existing relationship and trust between community center staff and the older adults which may have existed for a while can potentially lead to participants accepting any recommendation from the staff. In this way, the community center staff will serve as gatekeepers and by including them in the study, participants are assured of good outcomes:“You said you are a university staff member. How can I trust you? There are so many swindlers in the world. However, if a community center staff member called me and recommended the program to me, I would immediately join the program without hesitation.” – [Participant].The participating manager re-echoed a need to reach out to all staff members and promote the program among them. In this way, staff members are kept abreast with firsthand information about the study as well as offering an opportunity to respond to other issues they may have so they can in turn be able to participate in the program:“Instead of us calling the members, it would be better if the research team could organize a briefing session in the community center. In the briefing session, the research team could talk about the aims, benefits, and requirements of the program. The research team members are the ideal people to answer questions from our members regarding the details of the program.” – [Community center staff manager].Staff manager participants highlighted building consensus and communication as key ingredients to facilitate the adoption and implementation of a new program. Participants reiterated that this involved good-faith efforts to attain unanimous agreement between the research and service delivery teams to facilitate smooth implementation of the program. Participants recounted and reflected on previous experiences with the research team in a positive light and felt this may help to drive the collaboration forward to support the adoption of the program:“There were a lot of things to discuss before we could adopt the program here. Whether the mission and vision of the program are consistent with ours, the logistics and manpower issues, the equipment and instruments needed… The research–service team members have to reach a consensus before the program can be launched smoothly. In fact, we think that our experience of working with the research team was good because we had several fruitful discussions beforehand.” – [Community center staff manager].Regarding communication, the providers’ comments echoed the opinion of the community center staff manager, although the providers’ main focus was the interaction among the health–social partnership team members. The providers noted a need for constant communication across the service delivery team before, during, and after the implementation of the program:“Regular communication among the health–social partnership team members is crucial before the commencement of the program, as well as during and after the program. We learned to clearly understand each other’s working styles, roles, and responsibilities. When any participant’s condition changed, we could revise our action plans and protocols during our group meetings. The revised protocols are stored in the community center for reference.” – [Provider].A research team member, who did not participate in the intervention procedure, joined the Zoom meetings with the NCM and CWs at least twice weekly to evaluate the intervention fidelity using a performance checklist (Additional file The maintenance effects of the program were measured by evaluating the primary and secondary effectiveness outcomes 3 months after the completion of the program. No significant changes were observed from T1 and T2 to T3 in any outcome, although the numbers of unscheduled hospital admissions, unplanned general out-patient department visits, general practitioner visits, and emergency department visits, and the total number of health service uses, for the intervention group were lowest at T3 Figs. , 7 and 8In recent years, researchers and policymakers around the world have emphasized the importance of successfully implementing health promotion programs in the real-world setting to improve public health. To do so, research must extend beyond evaluating the program’s effectiveness, to include the program’s reach indicators, adoption rate, implementation strategies, and sustainability. This translational study is one of the first to adopt a hybrid design in evaluating both the effectiveness and implementation outcomes of a community-based health-social partnership program. It demonstrated that the uptake of an HSPP for community-dwelling older adults could be successfully achieved with good reach, positive preliminary effectiveness, and high implementation fidelity in a non-governmental organization. These findings provide preliminary information on effective strategies for the implementation of self-care health management programs that can inform global policies and guide international health priorities to mitigate the chronic disease epidemic among community-dwelling older adults.Despite difficulties in recruiting and engaging older adults into the program during the COVID-19 pandemic, the research team was able within 1 year to recruit a representative sample of community-dwelling older adults with similar demographic and clinical characteristics, including education level, chronic conditions, and number of health service uses. In addition, no differences were observed between older adults who participated in and completed the program and those who opted out. One reason for this high level of reach was the support of the community center staff during the recruitment process. The literature suggests that the recruitment of older adults is most successful when a person familiar to them promotes the program, such as the staff members of a community center that the older adults visit daily; these persons can arouse the interest of the older adults and assuage their concerns regarding participation in the program, thereby enhancing the recruitment rate and the reach level . FurtherOur findings are consistent with studies that have identified several major barriers to widespread implementation of health programs among older adults, including manpower shortage, lack of experienced staff, and presence of an unpredictable and critical environment such as the COVID-19 pandemic. This study demonstrated that providing structured training workshops to the center staff, health and social care providers, and research assistants assigned to collect data or provide social calls can facilitate program implementation. The theoretical knowledge and practical skills covered in the workshops were necessary for the staff, providers, and research assistants to understand the purpose and content of the program, define roles of the team members, and conduct the interventions and necessary procedures in the program. A standardized training manual with a detailed protocol for the content compiled by the research team and validated by content experts can also be kept at the community center for use by new staff members tasked with program implementation; this can help sustain the program in the community over the long term. In addition, although the program was challenged by the COVID-19 pandemic, the research and service teams worked collaboratively according to a contingency plan to ensure that the program was successfully implemented for community-dwelling older adults in these critical times. Modifying the eligibility criteria to specifically include smartphone users, changing the delivery mode of providers from home visits to Zoom meetings, and providing IT support for both the providers and older adults are some contingency steps that can be deployed when face-to-face meetings with health care providers are not feasible. Our positive preliminary findings can guide policymakers and governments to allocate extra incentives and funding and designate additional manpower to non-governmental organizations to promote the health self-management of community-dwelling older adults.A notable strength of this study is the inclusion of various key stakeholders in the design and implementation of a novel program that ensures the delivery of a well-rounded program of care. The process evaluation phase of the study provides further support for the preceding quantitative phase that helps to attain a greater explanatory power regarding the implementation of the program.While the preliminary findings were encouraging, this study is not without limitations. First, this was a pilot study that included only one community center. Thus, although the reach level was high, this small study setting limits the generalizability of the findings. Second, due to the COVID-19 pandemic, the intended implementation strategies, such as home visits and data collection at the center, could not be carried out. Third, the study included only the older adults who own a smartphone and have Internet coverage at home. The findings may thus not be generalizable to those who have lower socioeconomic status and live in rural areas. While smartphone usage is more prevalent among older adults in these few years, future studies are recommended to include contingencies, such as lending smartphones to the older adults from the community center, receiving donations from smartphone companies, or replacing video call by phone call, to accommodate older adults who lack smartphones to avoid creating or perpetuating health disparities.This was a pioneer study to evaluate the translation of an HSPP in a community setting using a hybrid type-1 effectiveness–implementation design. The study fills a major gap in the literature on elderly care services by identifying strategies that facilitate effective implementation of older adult-targeted programs in the real-world setting. While there were barriers to and delays in the uptake of the program, the program showed reachability and preliminary effectiveness. The findings can inform the design and execution of health self-management programs and strategies for community-dwelling older adults.Additional file 1. Study flow of the programmeAdditional file 2.