Intrapartum events leading to asphyxia at birth are among the leading causes of neonatal morbidity and mortality in Nepal. In response to this, the Nepal Ministry of Health and Population adopted Helping Babies Breathe (HBB) as a tool to improve neonatal resuscitation competencies. The effectiveness of HBB trainings has been well established. However, challenges remain in maintaining skills over time. Safa Sunaulo Nepal (SSN), with support from Latter-day Saint Charities (LDS Charities) designed an initiative for scaling up newborn resuscitation training and skills maintenance over time. This paper reports on the implementation of the SSN model of newborn resuscitation trainings and skill retention, and the changes in perinatal outcomes that occurred after the program. The program built capacity among facility-based trainers for the scale up and maintenance of resuscitation skills in 20 facilities in Madhesh Province, Nepal. A single external Mentor coached and assisted the facility-based trainers, provided general support, and monitored progress. Prospective outcome monitoring tracked changes in health metrics for a period of 14 months. Data was gathered on the neonatal health outcomes of 68,435 vaginal deliveries and 9,253 cesarean sections. Results indicate decreases in neonatal deaths under 24 hours of life (p<0.001), intrapartum stillbirths (p<0.001), and the number of sick newborns transferred from the maternity unit (p<0.001). During the program, facility-based trainers taught resuscitation skills to 231 medical personnel and supported ongoing skill retention. The SSN model for newborn resuscitation training and skills retention is a low-cost, evidence-based program focusing on facility-based trainers who are mentored and supported to scale-up and sustain resuscitation skills over time. Findings from the report are suggestive that the model had a substantial influence on critical neonatal outcomes. Future programs focused on improving neonatal outcomes may benefit by incorporating program elements of SSN model. The world has made phenomenal progress in reducing child mortality over the past three decades, but global progress was insufficient to universally achieve Millennium Development Goal (MDG) 4. Only one third of MDG countries, which included Nepal, reduced under-five mortality by two-thirds .While worldwide under-five mortality has declined considerably , the redIn Nepal, while the under-five mortality decreased from 133 deaths per 1000 live births in 1991 to 39 deaths per 1000 live births in 2016, neonatal mortality only dropped from 50 deaths per 1000 live births in 1991 to 21 in 2016 [Most neonatal deaths occur within the first week of birth . The firStrengthening the capacity and competency of healthcare workers to provide timely and appropriate newborn resuscitation is essential to addressing newborn deaths . To thisFollowing the successful piloting of HBB training in Nepal in 2013 , the theIn 2018, SSN, with financial and technical support from LDS Charities, designed a newborn resuscitation training, scale-up, and skill retention program centered on developing and maintaining the capacity of facility-based trainers to sustain the skills required to manage newborn emergencies. The goals of the program were to:Utilize evidence-based strategies for scaling up and maintaining resuscitation skillsImplement a cost-effective program for the scale-up and skill retentionMonitor the process with key indicatorsCompared to other provinces, Madhesh Province is the province in Nepal with the poorest performance in key health indicators including nutrition, teenage pregnancy, family planning coverage, newborn deaths and vaccination coverage. The NMR of the province in 2016 was estimated at 30 per 1000 live births against the national average of 21/1000, with this province accounting for the highest proportion of neonatal deaths in the country . These dUnfortunately, protracted political unrest persisting in the province since 2007, owing to dissatisfaction over province demarcation , resulteThe purpose of this paper is to describe the implementation of the SSN newborn resuscitation training, scale-up, and skill retention program in Madhesh province of Nepal and report changes in newborn outcomes that occurred after the time of program implementation.Ethical approval was obtained from the Nepal Health Research Council (Registration number 797/2018) for the newborn resuscitation scale-up and retention program, including data collection from the entire cohort of facilities under the program.We used a prospective cohort design to compare outcomes of birth cohorts in 20 hospitals pre- and post-implementation of the facility-based newborn resuscitation program in the Madhesh province. Data collection spanned a fourteen-month period from October 2020 to November 2021. Inclusion criteria captured facilities that provided delivery services 24 hours a day, 7 days a week and represented a significant proportion of the births in Madhesh province.To assess the effectiveness of the resuscitation skills scale-up and retention program, the first two months (October- November 2020) and the last two months (October- November 2021) of data collection were considered as baseline period and end-line period, respectively. In the baseline period, newborn resuscitation scale-up and support mechanisms were just beginning and included the HBB TOT, while the end-line period had the scale-up and support mechanisms well established.The newborn resuscitation training and retention program was conducted in Madhesh province, one of the seven provinces under the new federal structure in Nepal. An overview of the province is provided in The newborn resuscitation training and skill retention program was implemented in three phases . Detailsth- 30th November and the second TOT course from 2-5th December 2020. NTHC selected the facilities and trainers in coordination with the Provincial Health Directorate. The HBB TOT was facilitated by 10 Nepali trainers who used a HBB and Bleeding After Birth Complete (BABC) . The module builds the skills of healthcare providers working in clinical settings, including communication and teamwork, active management of the third stage of the labor, early detection and basic management of PPH, and advanced PPH care skills.) Learning Resource Package, developed by NHTC and SSN, as a field trial.The TOT phase focused on developing newborn resuscitation competencies of facility-based trainers with the first TOT held on 27A mix of public and private health institutions with large delivery services in Madhesh province participated in the program to improve and sustain neonatal resuscitation skills. Eighty eight facility-based trainer, candidates, representing 37 facilities, attended. Seventy-one out of the 88 (81%) were nurses by profession with the majority (45%) of the candidates working in their profession for one to five years. Forty-three out of 84 participants (51%) were from Secondary Hospitals, with 4 participants not completing the registration survey. Forty-six out of 84 (55%) indicated they personally attended up to 25 deliveries in an average month. Seventy-two out of 84 (86%) mentioned they resuscitated babies with a bag and mask as part of their current job.Validated, standardized tools were used to conduct pre- and post-knowledge tests of the trainers. The knowledge test had 18 questions with a passing score of 15. The average knowledge pre-test score was 16 while the average post-test score was 17 with 6% change in pre- to post-knowledge test. Eighty two percent of participants had a passing score or higher in pre-test with 94% passing the post-test. SSN and LDS Charities provided the new facility-based trainers with hard and soft copies of instructional materials such as flipcharts, provider guidebooks, and testing materials. Training equipment consisted of NeoNatalie manikins, Penguin suction devices, bag and masks, and stethoscopes. Clinical equipment, such as bag and masks, suction devices, and stethoscopes for the delivery rooms were also supplied.The facility-based trainer candidates were empowered to facilitate scale-up of resuscitation training to all physicians and nurses/midwives in their facilities and were expected to create an enabling environment for retention of learned skills.Following the TOT, 20 of the 37 facilities were selected for the active assistance with scale up and retention, based primarily on high delivery volume. An experienced HBB trainer with research experience was recruited to serve as a mentor, teacher, monitor of facility-based indicators, and administrative liaison for the cohort of 20 facilities . The scale-up and skill retention phase focused on facility-based trainers cascading resuscitation skills to staff in all 20 facilities, and then working to retain the learned skills, with the help of the equipment and materials provided by SSN and LDS Charities during the training of trainers.In the cohort of 20 facilities, the external Mentor assisted with facility-level scale-up of resuscitation training to all physicians and nurses/midwives. The Mentor also assisted with a) practice sessions, review meetings, and refresher training b) on-site coaching c) monitoring key indicators and d) liaison with administration. The Mentor was the driver for scaling up newborn resuscitation in the cohort of facilities through utilization of evidence-based methods to develop staff capacity.Vaginal delivery  was provided by all 20 facilities in the mentoring cohort, and 17 provided cesarean section delivery. The labor units in the hospitals were led by physicians and midwives and equipped to provide neonatal resuscitation at birth. Pediatricians led neonatal care units at Tertiary Hospitals, while in primary and Secondary Hospitals, sick newborns were managed in the pediatric unit, which was led by either medical officers or nurses/midwives.The facility-based trainers, under the supervision of the Mentor, conducted facility-level HBB trainings to physicians and nurses/midwives in the labor ward and neonatal care unit. Training also bridged newborn resuscitation knowledge and skill gaps among new staff due to staff turnover. The facility-based trainers encouraged daily practice sessions using low-dose high-frequency (LDHF) bag and mask ventilation practice in their respective facilities, recorded the practice performance, established of functional practice corners, and supervised regular staff practice and refresher training. Other interventions used by facility-based trainers for skill retention included weekly review meetings where resuscitation debriefing was done.and clinical equipment and liaising with hospital administration to create a conducive environment for skill retention. The Mentor was also responsible for obtaining monthly program data from the cohort of facilities.The HBB Mentor reviewed the practice logs and conducted Objective Structured Clinical Examinations (OSCEs)  and Bag and Mask Skill Check drills during a monthly monitoring visit. The Mentor also conducted a weekly telephone meeting with facility-based trainers and monthly in-person meetings with facility-based trainers, the nursing in-charge, and the medical superintendent to review the progress of HBB training and conduct further planning. Other activities included assessment of required support such as practice Quality improvement was jointly monitored by the facility-based trainers, the Mentor, and the hospital nursing supervisor. Together they observed the HBB skills of staff using a neonatal simulator during the Mentor’s regular and unannounced site visits and reviewed the data from the practice logbook, on-site coaching, delivery and newborn logbooks, and refresher training.During the post-intervention phase, the facility-based trainers continued with interventions from the scale-up and retention phase. However, the Mentor did not support facility-based trainers in doing so. The Mentor obtained monthly program data during this phase.The primary outcomes included the pre-post difference in a) the intrapartum stillbirths and b) neonatal deaths within the first 24 hours of life. Stillbirths were considered fresh if they were not macerated. Secondary outcomes included differences in neonatal deaths after first 24 hours of life, the utilization of bag and mask ventilation, the number of sick newborns transferred from the maternity unit, and the percentage of staff trained with HBB.Monthly facility-level metrics included the number of vaginal deliveries, the number of caesarean sections, the number of intrapartum (fresh) and macerated stillbirths, the number of babies not breathing at birth, and the number of neonatal deaths less than and more than 24 hours of life. These were MoHP mandated metrics. In the tertiary level facilities, monthly facility-level data were derived from the health information department, which tabulated and reported MoHP-mandated metrics. In smaller facilities, the mentor gathered data from registers or logs maintained in the labor room and in the maternity ward. The data thus gathered was certified by the concerned health institution to ensure data quality.Additional facility level metrics that were not MoHP mandated included the number of sick newborns transferred from the maternity unit and the number of babies receiving assisted ventilation with bag and mask (B&M). Sick newborns transferred from the maternity unit were a proxy for all-cause newborn morbidity during the first days of life. These data were gathered from registers or logs maintained in the labor room and in the maternity ward.The hospitals in the cohort had no prior system of recording the number of babies receiving B&M ventilation for the pre-intervention period, although the hospitals reported practicing B&M ventilation. As these hospitals started recording this metric only after the HBB TOT, the sum of the measure from the first two months of the scale-up and retention phase (December 2020 and January 2021) was compared with the sum of measures from the post-intervention period for this metric only. Personal data of patients, such as demographic information, were not collected.Monthly monitoring reports generated by the Mentor documented the scale-up, facility support, and facility-level metrics, including the number of providers trained/retrained, maintenance of an equipped practice corner, low-dose high-frequency (LDHF) practice logs, completion of self-evaluation forms, review meetings held, and review of delivery and newborn logs. Since these metrics were not mandated by MoHP, the mentor collected these data on a monthly basis from the facility-based trainers, who were responsible for record keeping.Facility-level metrics were analyzed by comparing the baseline and endline measurements . The basInterhospital differences in perinatal outcomes were also analyzed by the type of the hospital. After the Mentor collected data into monthly reports, the Mentor conducted data quality and integrity checks. The monthly reports were forwarded to SSN and to LDS Charities with SSN conducting an initial review, analysis, and preparation of mandated reports. A Nepal-based research assistant combined the data into a master file, clarified missing variables with the Mentor, deleted variables missing significant data, changed text into appropriate numerical values, and conducted data analysis using SPSS version 21.The 20 facilities in the newborn resuscitation and scale-up program cohort represented a mix of public and private hospitals. The Government of Nepal has categorized public hospitals into different categories according to the level of government . AccordiAccording to the Health Infrastructure Development Standards 2017, Primary Hospitals in Nepal are mandated to provide normal delivery and comprehensive emergency obstetric and neonatal care (CEONC) . HoweverA total of 68,435 vaginal deliveries and 9,253 Cesarean deliveries took place at the 20 health facilities during the study period. Tertiary Hospitals accounted for more than half of the vaginal deliveries (51.54%), C-section deliveries (58.94%), neonatal deaths within 24 hours of life (53.59%), neonatal deaths after 24 hours of life (59.32%) and intrapartum stillbirths (62.14%). Sick newborns transferred from the maternity unit (40.49%), babies not breathing at birth (41.72%) and babies receiving bag and mask (44.44%) were also higher in Tertiary Hospitals as compared to other facility types. Outcomes according to facility type are listed in To test the hypothesis that baseline and endline means for perinatal outcomes were equal, a dependent samples t-test was done. Before preforming the analysis, the assumption of normally distributed difference scores was done to examine whether the assumption was satisfied. Data for each perinatal outcome satisfied the assumption of normally distributed pre-post difference scores as the skewness was <|2.0|and kurtosis <|9.0| .Since correlation between baseline and endline measures were significant at p-value < .001 , the depThe null hypothesis of equal baseline and endline means was rejected for neonatal deaths <24 hours t(19) = 6.212, P<0.001, intrapartum stillbirths t(19) = 5.225, p<0.001, and sick newborns transferred from the maternity/pediatric unit t(19) = 5.358, p<0.001. Thus, the endline means for neonatal deaths <24 hours, intrapartum stillbirths and sick newborn transferred from the maternity unit were statistically lower than the baseline means suggesting the potential impact of newborn resuscitation and scale-up program in the observed association.The first day neonatal mortality showed a declining trend,  with a dDuring the study period, overall intrapartum stillbirths decreased by 57% (p<0.001), from 200 during the baseline period to 86 in the follow up period .Sick newborns transferred from the maternity unit included their transfer to another unit of the hospital or to another hospital or discharged home. Sick infants transferred from the maternity unit was a proxy for all-cause newborn morbidity during the first days of life. Overall, sick newborns transferred from the maternity unit decreased by approximately 33% over time from 1093 in the baseline period to 729 in the endline period (p<0.001) .Inter-hospital difference in perinatal outcomes was observed for neonatal deaths within 24 hours, intrapartum stillbirths and sick newborns transferred from the maternity unit .Neonatal death within 24 hours of life was found to be significantly lower in Primary Hospitals (p = 0.0577) and Secondary Hospitals (p = 0.0239) during the endline period as compared to the baseline period. The decline was approximately 73% (p = 0.0577) in Primary Hospitals and nearly 64% (p = 0.0239) in Secondary Hospitals. The intrapartum stillbirths were observed to be significantly lower in Primary Hospitals (p = 0.0276) and Private Hospitals (p = 0.0136). There was an approximately 79% (p = 0.0276) decrease in the number of intrapartum stillbirths during endline period (n = 29) as compared to the baseline period (n = 6) in the five Primary Hospitals. The number of intrapartum stillbirths in the two Private Hospitals decreased by approximately 92% (p = 0.0313) from 13 in baseline to 1 in the endline period. Similarly, sick newborns transferred from the maternity unit decreased by nearly 27% (p = 0.0060) over time in Tertiary Hospitals.The monthly HBB scale-up and support measures were largely comprised of qualitative indicators. The scale-up of HBB resulted in 231 providers receiving the training during active mentoring. The facility-based trainers, with the assistance of the Mentor, cascaded the training in their facilities by training existing and new staff during the program, and holding refresher training sessions.At the end of the reporting period, all facilities reported fully functional practice corners that were equipped and utilized, were holding periodic review meetings, conducting self-evaluation surveys, and maintaining both delivery and newborn logs.SSN, with support from LDS Charities, set up a program to scale-up and maintain newborn resuscitation skills in Madhesh province of Nepal. This paper reports on the initiative, compares the newborn metrics and HBB scale-up activities from a cohort of facilities from Madhesh province, and analyzes the changes in outcomes associated with improving the quality of newborn resuscitation at the facility level.Analysis of baseline and endline data from this cohort of facilities suggests that the SSN program for the scale up and retention of newborn resuscitation skills was associated with marked decreases in the number of neonatal deaths within 24 hours, intrapartum stillbirths, and the number of sick newborns transferred from the maternity unit. Findings of this initiative correspond with several previous studies that have noted significant declines in intrapartum stillbirth , 33–36 aAs observed in other studies, neonatal deaths after 24 hours did not change significantly after the implementation scale-up and skill retention . A plausAnalysis of inter-hospital differences in perinatal outcomes suggest that resuscitation scale-up and retention had greater impact in Primary Hospitals in terms of reduction in 24-hour neonatal death and intrapartum stillbirths, as compared to other hospitals. Secondary, Tertiary and Private Hospitals may have more advanced technologies for newborn care and/or more specialized providers than Primary Hospitals. While the care in Secondary and Tertiary Hospitals is primarily provided by nurses/midwives, they may also have greater experience in newborn resuscitation due to frequent exposure to compromised infants based on both delivery volumes and referral center status. In Primary Hospitals, newborn care is often provided in relatively resource-constrained facilities by lower cadre health professionals, mostly by nurses, who may not have a foundation of knowledge and skills in newborn resuscitation. Hence, the greater effectiveness of scale-up and skill retention in Primary Hospitals may be a reasonable expectation. A study that compares perinatal outcomes in a first-level referral hospital before and after the implementation of HBB training has also shown that HBB training is effective in a local first-level referral hospital with few resources, such as Primary Hospitals in the context of Nepal, in improving key perinatal outcomes . SimilarNotably, 86% of facility-based trainers in the TOTs were already resuscitating babies in their current job at the time of training. Further, the pre-test scores demonstrated a good understanding of newborn compromise and resuscitation. Nevertheless, neonatal outcomes improved significantly in spite of the prior knowledge and experience. This emphasizes that training alone is insufficient to achieve gains in neonatal outcomes and needs to be followed by regular practice, mentorship, retraining, and monitoring—the main focus of our efforts.Run charts tracking perinatal outcomes over time showed considerable improvements towards the end of the post scale-up and skill-retention phase, indicating the possibility of continued improvements even after the external support for newborn resuscitation scale-up and skill retention ended. However, it is difficult to establish the long-term sustainability of the newborn resuscitation program from this program, as the post scale-up and retention phase follow up was conducted for only two months. Towards the end of the program, the Mentor focused on transitioning to internal mentoring efforts through selection of one facility-based trainer per hospital as a focal person to continue the institutionalization of skill-retention and activities such as ensuring functionality of the practice corner, training new staff, encouraging daily practice sessions, and conducting refresher trainings. All 20 hospitals in the study cohort had a focal person appointed by the end of the program. Success of the internal mentoring efforts in achieving sustainability of the newborn resuscitation scale-up and skill retention program would also depend on continuous support from hospital clinical leadership.Newborn resuscitation training using HBB was first launched in Nepal in early 2012 under the sponsorship of LDS Charities. The program introduced the HBB curriculum to physicians, nurses, and hospital leaders under the MoHP . Since tA deterioration over time in the retention and the application of new life-saving skills by providers has been a major challenge to sustainability, mainly due to lack of motivation by, and lack of support for TOT graduates to scale-up HBB after initial training. We focused on assisting facility-based trainers to take the lead in gradually scaling up and sustaining the skills through on-the-job cascade trainings to all service providers, encouraging regular practice sessions, and refresher trainings.The external Mentor used evidence-based strategies for supporting and scaling up HBB training. These included monthly monitoring visits to review practice logs; conducting OSCEs and Bag and Mask Skill Checks; supportive supervision; weekly telephone meetings with facility-based trainers; and monthly in-person meetings with hospital clinical leadership to facilitate HBB skill retention by providers through necessary equipment and training support.To our knowledge, the interventions rolled out under this program for skills retention are unique to the country and offer numerous advantages to resource-limited settings like Nepal. First, the SSN and LDS Charities model for a newborn resuscitation scale-up program enabled improved assisted ventilation by encouraging hands-on low-dose high- frequency practice with a simulator for retention of learned skills. The model focused on the role of an external Mentor assisting the facility-based trainers in cascading HBB training to all providers, and holding practice sessions, on-site coaching, and refresher trainings. Evidence from other low and middle-income countries has also demonstrated that HBB training with frequent refresher training and on-the-job practice can positively impact the retention of knowledge and skills for newborn resuscitation and yield remarkable improvement in neonatal mortality outcomes .The model also emphasized the role of the Mentor in collaboration with local clinical leadership to establish a system for ongoing mentorship and supervision, and to foster policies that support institutionalization of HBB training. The crucial role of a dedicated Mentor in quality-improvement and scale-up has been acknowledged in the scale-up of various maternal and child health interventions .The SSN and LDS Charities model of newborn resuscitation scale-up proved to be a low-cost intervention. The cascade training approach by facility-level providers incurred much lower direct cost to SSN and LDS Charities by avoiding travel costs and Daily Subsistence Allowance (DSA) expenses. Similarly, indirect costs—such as loss of work hours by the hospital as part of sending providers for off-site training—was also remarkably reduced as the facility-level providers were trained while they were still on-the job. Further, the expense of the single, full-time Mentor was diffused among 20 facilities.Finally, a strength of the program was its reach from tertiary level hospitals to peripheral level and private health institutions with high volumes of deliveries in the province. These volumes constituted a huge proportion of the deliveries in the province, thereby influencing the clinical practice of newborn resuscitation at large scale.The resuscitation scale-up and skill retention efforts faced challenges due to the COVID-19 pandemic. The program took place when Nepal was hard hit by the global COVID-19 crisis. All the Tertiary Hospitals in the study cohort were designated as COVID-19 hospitals for the province. Similarly, Primary and Secondary Hospitals also faced the challenges of managing the cases of COVID-19 and providing essential health care services without concomitant increases in staffing. As part of the structural adjustment to the challenges posed by COVID-19, the facility-based trainers as well as providers in the study cohort underwent task sharing and restructuring to other units of the hospital. As a result, cascade training to facility-based providers occurred very sporadically, if at all, during three months of the scale-up and retention phase, from December 2020 to February 2021. Hence, the number of facility-level providers trained in the study period was lower than in other similar programs . Yet, imAnother challenge related to the data collection process itself. The program monitored progress by using limited indicators, most of which were tracked by the facilities for routine reporting to the MoHP and therefore less prone to error—neonatal deaths being one of those metrics. However, even though most of the facilities in the cohort tracked stillbirths, misclassification and underreporting of fresh stillbirths was widespread. Accordingly, delivery logs had to be reviewed to confirm accuracy in the classification of fresh stillbirths. Similarly, since the facilities did not track and report on resuscitation data for the MoHP, delivery logs had to be reviewed to obtain such data. Sick newborns transferred from the maternity unit—a proxy indicator for all-cause morbidity—were also not tracked by facilities as part of routine reporting to the MoHP. This necessitated a review of newborn logs to determine the number of sick infants transferred.Due to the design as a skill training and retention program, rather than a clinical study, there was no control/comparison group, which restricted the ability to establish the causality of the program on observed perinatal outcomes. This report describes the changes associated with newborn resuscitation scale-up on perinatal outcomes using routinely collected data, without establishing the causality, as in clinical trials. With this, we are unable to confirm whether the observed outcomes were solely attributable to the newborn resuscitation scale-up and skill retention program or to other changes at the facilities during the time period. Another limitation of the study relates to the use of routinely collected data. Our study utilized routinely collected facility-level metrics, obtained for the newborn resuscitation training, scale-up and skill retention program monitoring without a prior specific research goal. As such, data were not available for key maternal and fetal factors that may have significantly affected the findings in the study. Therefore, the study is unable to ascertain the role of maternal and fetal factors in the observed association. Hence, the findings from this report should be interpreted and generalized with caution.This report highlights that the SSN model of newborn resuscitation scale-up and skill retention could be a potential evidence-based, cost-effective model for improving perinatal outcomes in low-resource settings through building and sustaining in-facility capacity for resuscitation.This study shows that implementation of the SSN program for newborn resuscitation scale-up and skill retention is associated with reductions in neonatal deaths within 24 hours, intrapartum stillbirths, and sick newborns transferred from the maternity unit, and improved clinical practices in Madhesh province. The analysis confirmed that this approach to newborn resuscitation skill retention and scale-up is a simple, low-cost program focusing on facility-based cascade training in newborn resuscitation skills for providers using the HBB curriculum, LDHF practice, and subsequent mentorship. The program also demonstrated the role of mentorship in capacity building, liaison with clinical leaders, scale-up, monitoring, and quality enhancement with a single Mentor supervising and monitoring 20 facilities. To conclude, this model has the potential to significantly improve perinatal outcomes and could guide future programs to reduce perinatal outcomes for other resource-limited countries like Nepal.S1 Data(XLSX)Click here for additional data file. 9 Aug 2022PGPH-D-22-00883Assessing the effectiveness of newborn resuscitation training and skill retention program on neonatal outcomes in Madhesh Province, NepalPLOS Global Public HealthDear Dr. Robert,Thank you for submitting your manuscript to PLOS Global Public Health. After careful consideration, I feel that it has merit but does not fully meet PLOS Global Public Health’s publication criteria as it currently stands. Therefore, I invite you to submit a revised version of the manuscript that addresses the points raised during the review process.globalpubhealth@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pgph/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.Please submit your revised manuscript by Sep 08 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at Please include the following items when submitting your revised manuscript:A rebuttal letter that responds to each point raised by the editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.We look forward to receiving your revised manuscript.Kind regards,Rakesh SinghAcademic EditorPLOS Global Public HealthJournal Requirements:1. Please update your online Competing Interests statement. If you have no competing interests to declare, please state: “The authors have declared that no competing interests exist.”2. Please provide a complete Data Availability Statement in the submission form. If your research concerns only data provided within your submission, please write “All data are in the manuscript and supporting information files.” as your Data Availability Statement.3. We have noticed that you have uploaded Supporting Information files, but you have not included a list of legends. Please add a full list of legends for your Supporting Information files after the references list.  <font color="black"> Review Comments: </font> Reviewer #1: I am glad to review this paper entitled “Assessing the effectiveness of newborn resuscitation training and skill retention program on neonatal outcomes in Madhesh Province, Nepal.”I would like to congratulate the team for doing this project to improve the quality of care in resource limited settings and identifying the area where neonatal resuscitation programme was actually required. Decreasing neonatal mortality is really a great challenge in resource limiting settings. This research has utilized evidenced based strategies and implemented a cost-effective strategies/programmer to overall improve the neonatal outcomes in this province. This paper is well written and results are well expressed.Though this study was not a clinical study, some queries-1. Is there data regarding baseline characteristics of neonates in baseline period and endline period? As we know, there are various factors that can affect outcome of neonates within 24 hours and after 24 hours like maternal factors and fetal factors.2. It’s better to present the data in Table 4 as both number values and statistically significant observation for better understanding of results.3. Minor queries: Abstract section line no 35, please mention the full form of LDS Charities here as well.Reviewer #2: Yes , the manuscript is well written , clear and correct in most of its aspect and unambiguous. However, there were few grammatical errors which needs to be corrected and few numerical errors along with few minor changes , which I have attached as an attachment . 26 Aug 2022AttachmentResponse to Reviewers.docxSubmitted filename: Click here for additional data file. 23 Sep 2022Assessing the effectiveness of newborn resuscitation training and skill retention program on neonatal outcomes in Madhesh Province, NepalPGPH-D-22-00883R1Dear Dr. Clark,We are pleased to inform you that your manuscript 'Assessing the effectiveness of newborn resuscitation training and skill retention program on neonatal outcomes in Madhesh Province, Nepal' has been provisionally accepted for publication in PLOS Global Public Health.Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.globalpubhealth@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they'll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Global Public Health.Best regards,Rakesh SinghAcademic EditorPLOS Global Public Health***********************************************************Reviewer Comments:Reviewer #1: All comments have been addressedReviewer #3: All comments have been addressed


Background: The Health E Englewood Health and Wellness Program is a social determinant of health (SDoH) intervention developed to address social factors affecting the health of the North Hudson Community Action Corporation (NHCAC) patients’, a Federally Qualified Health Center located in Englewood, New Jersey. The main aim of this integrated wellness approach was to educate and motivate participants from the local community by strengthening the development of healthy lifestyles and providing the necessary tools for positive behavior change.Methods: Health E Englewood was a four consecutive week workshop series focused on three areas of health: physical, emotional, and nutritional wellness. The program targeted Spanish-speaking patients from NHCAC and was offered virtually via Zoom in Spanish.Results: The Health E Englewood program was launched in October 2021 with 40 active participants. About 63% of participants attended at least three of the four workshop sessions, with at least 60% of participants reporting improved lifestyle changes after the program. Additional follow-up data collected six months later also indicated evidence of the program's long-term benefits.Discussion: Social factors are the primary drivers of health outcomes. While many determinant interventions have failed to show long-lasting benefits, studying these interventions and their impact is crucial as it avoids “re-creating the wheel” inside health care and increasing costs. The World Health Organization (WHO) defines social determinants of health as “the conditions in which people are born, grow, work, live, and age, and the wider set of forces and systems shaping the conditions of daily life. These forces and systems include economic policies and systems, development agendas, social norms, social policies, and political systems” . The HeaIn the United States (US), efforts to improve health have traditionally focused on improving the healthcare system. However, studies have shown that health outcomes are largely determined by a range of factors, including genetics, health behaviors, social and environmental factors, and health care . In a stThere are many developed countries that spend more on social services than the United States. Despite significant spending, U.S. health outcomes are among the lowest for developed countries . MoreoveThe main aim of this integrated wellness approach was to educate and motivate participants from the local community by strengthening the development of healthy lifestyles and providing the necessary tools for positive behavior change. Our hope is that addressing more upstream social determinants will improve health outcomes, reduce inequities, and lower costs.Health E Englewood was a four consecutive weeks workshop series focused on three areas of health: physical, emotional, and nutritional wellness. Each of the four sessions was built upon skills to promote healthy living, including tips to get active, practical nutrition guidance, stress management skills, and budget-friendly healthy cooking tips Figure , Table 1The program targeted Black and Hispanic patients from NHCAC and was offered virtually via Zoom in Spanish and English. The recruitment of patients during routine clinic visits was coordinated by the population health team, medical assistants, and medical residents, who utilized a screening questionnaire for this purpose. Patients were eligible for the study if they expressed willingness to participate in weekly online workshop sessions conducted through Zoom and had access to a smartphone or computer with internet access to engage in the program. The resulting composition of the study comprised approximately 70% Hispanic individuals and 30% African Americans/Blacks.All participants received a welcome package that included Fitbit and Fitbit instructions, a portion plate, a healthy eating cookbook, a stress ball, a yoga mat, and Zoom information packets. All materials needed for the program were provided at no cost and delivered to patients’ homes Figure .Following the completion of the study, an immediate post-intervention survey was conducted to evaluate the efficacy of the interventions and gather participant feedback. Patients were then followed up after a six-month period. They were called via telephone, using a Spanish interpreter if needed. To assess the continued impact of the intervention and gather suggestions for its improvement, a similar post-intervention survey was administered to evaluate whether patients continued to benefit from the study.The Health E Englewood program was initiated in October 2021, with a total of 72 recruited participants, out of which 40 actively participated in the program. Among the participants, 63% attended a minimum of three out of the four workshop sessions. After a period of six months, a follow-up survey was conducted, with the participation of 15 patients. See Figures The Health E Englewood program targeted a vulnerable population of the NHCAC Clinic, with more than 50% of participants reporting improved lifestyle changes after the program and on follow-up six months after the intervention. Many similar programs have shown impressive benefits. For example, a long-term follow-up of patients registered in the ‘anticipatory care model’ revealed that this approach to medical care reduced the mortality rate in Glyncorrwg compared to a similar neighboring community in Europe . On the Another comparable investigation was undertaken by Alvear-Vega and Acuña San-Martín, delving into the impartial access to health care services through the Explicit Health Guarantees Plan (GES) of the Chilean population. Their findings indicate that the GES Plan effectively fulfills its primary objective of providing support to socially vulnerable groups with lower socioeconomic status. However, the study also revealed significant gaps in healthcare access among patients with certain medical conditions. These findings highlight the need for targeted interventions to ensure equitable access to healthcare services for all individuals, regardless of their specific medical conditions .The Health E Englewood program participants were recruited by the population health team, medical assistants, and medical residents using a screening questionnaire. This intervention was not a one-size-fits-all approach but was instead pioneered to be culturally competent with personalized guidance for barriers encountered . We beliWhile fine-tuning our intervention for a particular population proved beneficial in the immediate post-intervention period, additional follow-up data collected six months later also indicated evidence of the long-term benefits of the program. In the six-month follow-up survey, most participants believed that lack of time and motivation were the major obstacles to implementing what they have learned. Healthy cooking for a family was hindered by time constraints and individual meal preferences. However, many believed the portion plate was helpful as it was a tangible reminder of healthy portion size. As an unintended benefit, participants also built their own social network, in which they continued to share ideas even after the end of the program .A similar program, which encompassed a therapeutic lifestyle modification (TLM) program, was implemented with a six-month follow-up period. This program focused on women residing in a community in Korea. The TLM program consisted of health monitoring, counseling, health education, exercise, and dietary interventions. The researchers discovered that the positive outcomes of the program, particularly reductions in body weight and waist circumference, were sustained even six months after the intervention. However, similar to our intervention, it is important to note that not all aspects of the program demonstrated the same level of sustainability . These fAs part of our future interventions, we hope to focus on meal preparation and bulk cooking to accommodate busy schedules. The use of tangible reminders, such as storage containers, might be helpful. Also, we intend to return to in-person workshops as we believe some interventions, such as the Fitbit tutorial, would be better realized in person. Ideally, we would like participants to use a whole range of these techniques rather than just a few, since we believe that only then will the program have its full impact .One significant limitation of this intervention was that it had to be conducted virtually due to COVID-19 restrictions. As a result, patients who did not have access to the internet or suitable devices were unable to participate. This could have potentially excluded certain individuals who may have benefited from the program, especially those from lower-income households, elderly populations, or those residing in rural or remote areas with limited access to technology.Another limitation was the relatively high dropout rate, with 32 enrolled participants failing to attend any of the sessions. This could have been due to various reasons, such as scheduling conflicts, lack of motivation, or technical difficulties. Identifying and addressing such barriers is essential to improve the engagement and participation of individuals who may benefit from the program -18.Throughout the program, we have made extensive efforts to identify and address various barriers that may impede progress or hinder the achievement of our goals, as shown in Table Overall, it is crucial to recognize and address the limitations of these interventions to ensure that all potential beneficiaries have equal access to the program and maximize its impact. Social factors are the primary drivers of health outcomes. The ideal SDoH intervention is one that decreases per capita spending and has the greatest effect on total population health and well-being. Well-designed interventions tailored to those most in need can curb the overuse of our resource-constrained system. Although these techniques may be discussed with patients during routine visits with their primary care doctors, SDoH interventions play a vital role in healthcare by providing a supportive environment for patients to learn how to implement healthy lifestyle practices.


General Practitioners (GP) are advised to opportunistically refer patients with overweight or obesity to a tier 2 weight management program, but few patients sign up after receiving the referral. Signing up to a weight management program is a behaviour, as such, behaviour change interventions are needed to increase sign ups. However, no research has explored the influences on signing up after an opportunistic referral specifically.To investigate the influences  on signing up to a tier 2 weight management service after receiving an opportunistic referral from a GP, using a theoretical framework to inform intervention development.Semi-structured interviews were conducted with 18 residents from the London borough of Hounslow who were eligible for the service. Interview guides were informed by the Theoretical Domains Framework (TDF). Data were analyzed inductively using Reflexive Thematic Analysis and Coding Reliability to identify influences on signing up, before being deductively coded to the TDF and grouped into themes.Eight theoretical domains were identified as influences on signing up. Fifteen sub-themes were developed and categorized as either a barrier (5), enabler (3), or mixed (7) influence. Beliefs about Consequences was the most frequently reported influence on signing up. Beliefs that were expressed the most often include how effective the program would be, whether the program is needed to lose weight and whether the program would be compatible with their lifestyle. Leveraging Social Influences and changing patient’s Knowledge could address these beliefs and provide a potential route for Behaviour change.The present study provides the first insight into behavioural influences on signing up for a weight management service opportunistically using a validated theoretical framework. This study has implications for intervention development in that public health researchers can identify intervention, content and implementation options based on the findings. Interventions targeting the key domains of Knowledge, Social influences and Beliefs about consequences would likely be the most effective because of their prominence and influence on other domains. FocusinThe next step is to identify influences on the target behaviour, using theory-based behavioural science frameworks. A growing body of evidence suggests that interventions developed with an explicit theoretical foundation are more effective than those lacking a theoretical base . The TheWithin the related literature, a subset of primary research has explored factors that act as barriers  or enablers  to patients joining lifestyle interventions more generally. Patients report many barriers to joining a program in general, including previous negative experiences, fear of the unknown, a lack of confidence and denial of a problem . The widopportunistic referral specifically. Instead, the participants in these studies had either been invited to join various programs in writing, via media adverts or sought out a program themselves. Furthermore, many of these programs were not tier 2 weight management programs, but rather lifestyle interventions more generally. Thus, the influences identified to date would not be relevant to this target behaviour and so their application in designing behaviour change interventions is limited. For example, an influence identified in the report “Awareness of programme” (Knowledge) would be an important influence on self-referral to a weight management program but would not be necessary to sign up in the context of an opportunistic GP referral.In 2018, a team of behaviour change experts produced a literature review for Public Health England where they mapped these influences to the TDF. The review found that the most common TDF domains that prevent program uptake are Social influences, Knowledge, and Emotion, which implies that people who do not have social support, have poorer knowledge, and negative emotions are less likely to join these programs. The most common domains that drove program uptake were Intention and Knowledge, which implies that people who intend to sign up and have better knowledge are more likely to join . HoweverIt is urgent that we develop a more thorough understanding of what influences the behaviour of signing up to a tier 2 service after being referred by a GP opportunistically. Recently, funding has been made available both from the NHS  and PublWhat are the influences  on signing up to a tier 2 weight management service after receiving an opportunistic referral from a GP?2.2.1.This was a qualitative study which analyzed primary research in the form of semi-structured interviews. Quantitative measures were used in the form of coding reliability. The methods are described in accordance with the consolidated criteria for reporting qualitative research (COREQ) checklist for qualitative research ; see Sup and the 2.2.Ethical approval was obtained from the University College London Research Ethics Committee (Project ID: 22079/001). Informed consent was sought via an information sheet and consent form present on the initial survey. All participants gave informed consent to take part in the research.2.3.The London borough of Hounslow was selected as the case study borough for this research. The borough of Hounslow is situated in West London, forming part of outer London and has a population of 272,976 . As of 2At the time of this study, Hounslow had successfully implemented a tier 1 weight management service and recently secured funding to introduce a tier 2 service. The first cohort of residents had signed up to the tier 2 service and were completing the 12-week program. Data gathered showed that the sign-up rate was low and that residents from the West of the borough, minority ethnic communities and men were under-represented, which reflects the literature more broadly .2.4.2 (classified as overweight). Residents are unable to participate in the service if they are (iv) pregnant, (v) suffer from an unmanaged co-morbidity, (vi) have an eating disorder or (vii) have had bariatric surgery in the two years prior. The advertisement also stated that eligible participants would be offered a small incentive (£10 Amazon voucher) to participate in the interviews should they be invited. Promotion ended and the survey stopped accepting responses in June 2022.Promotion started in May 2022. Participants were recruited from the population in Hounslow. Advertisements were created and shared by the borough of Hounslow via newsletters and social media channels. A recruitment team from the borough also handed out physical flyers to passers-by in the street . The advA total of 210 individuals completed the survey, of which 110 met the inclusion and exclusion criteria set out above. The primary researcher (CG) then prioritized 50 residents to be interviewed and contacted them via email to ask if they would be interested in taking part. A maximum-variation (heterogeneity) sampling technique was used to select potential interviewees based on BMI and demographic information . This approach was adopted to recruit individuals who are underrepresented in weight management programs. BMI was calculated by the primary researcher (CG) using individual’s self-reported height, weight, age, and gender on the “NHS Calculate BMI” tool . Twenty-Recruitment concluded after conducting 18 semi-structured interviews, guided by the concept of information power . Informa2.5.Semi-structured interviews were conducted in June 2022 via Microsoft Teams or Zoom by the primary researcher (CG). Since community-dwelling adults were recruited via advertisements, not following a recommendation from a GP, participants were emailed a one-page information sheet about the borough of Hounslow’s weight management program before the interview took place . Public A semi-structured interview guide was developed, informed by the TDF . The TDFEach interview lasted between 30 and 60 min. Fieldnotes were made after each interview to document reflections. The interviews were recorded and transcribed verbatim by a transcription agency. Transcripts were pseudonymized to remove identifiable information and returned to the researcher for analysis.2.6.Data analysis followed Braun and Clarke’s six phases of Reflexive Thematic Analysis  but incoReflexive thematic analysis was chosen to analyze the data because the method is flexible with regards to data collection, dataset size, analytic strategy , and allows for the incorporation of relevant theory to inform data analysis. Given that the aim of this research was to develop a thorough understanding of the target behaviour, the data was initially coded using an inductive, ‘bottom up’ approach, in which there was no attempt to fit the data to existing theory. Adopting this approach facilitated an understanding of different experiences, perspectives and meaning in a topic area that has not been widely explored in the past. This approach is in line with guidance from McGowan et al.  for asseConsidering that the findings may be used to inform intervention design, it was decided from the outset that coding would be performed at the semantic  level. Quality was conceptualized as accuracy and reliability of observations, and interrater reliability would be used to measure this. Thus, the research was underpinned by a realist ontology , which gAfter the inductively generated codes were deductively coded to the TDF, the TDF domains were used as the central organizing concept to group the data into candidate themes. A second interrater reliability check was performed to arrive at a consensus of what the candidate themes represent. After a satisfactory agreement had been reached, candidate themes were finalized and labeled as sub-themes. The sub-themes reflect a shared topic and aim to capture the diversity of meaning in relation to the target behaviour. Sub-theme names were developed which can be interpreted as domain summaries . The TDFFinally, following guidance from Braun and Clarke  on theme2.7.To ensure the reliability of the coding process, double coding was performed at both the inductive and deductive stages of data analysis . At the Although data analysis is described in linear terms, the process of the initial codebook development was iterative, and codes were further refined or broken down into a smaller number of codes if it was evident that they reflected more than one TDF domain.3.A total of 18 residents participated in this research. Eight themes and 15 sub-themes were developed from the semi-structured interviews. Each sub-theme was categorized as either a barrier (5), enabler (3) or mixed (7) influence. Mixed influences acted as a barrier for some but an enabler for others. 3.1.3.1.1.Participants held beliefs about whether the program would be effective at helping them lose weight and improve their health if they did sign up. Some participants believed that the program would produce many of the intended health, wellbeing, and weight loss benefits, which acted as an enabler to signing up:“… the good things is reducing weight, and getting the knowledge and the understanding of healthy eating exercise programmes, what to do, and the benefits of it all” .In contrast, other participants believed that the program would not successfully help them lose weight, which acted as a barrier to signing up:“Again, I’m not quite sure how effective it would be” .Tied to this, these participants often expressed a preference for other weight loss programs or strategies that they believed would produce more effective results than this program.The sub-themes “Understanding benefit of the program” and “Others experience with weight management programs” are related in that these influenced participants belief about the efficacy of the program.3.1.2.Participants held beliefs about whether they would need the support of the program to lose weight if they did sign up. One of the biggest barriers to participants signing up was the belief that they can manage their weight independently without the support of a program:“For me it’s not a case of something is deficient or anything else, it’s just bad habits that I do get through. Like I do not require intervention” .They often described that they already know what is contributing to their weight gain and the steps that they need to follow to lose it. In contrast, other participants described that they struggle to manage their weight independently, and do need the support of a program to lose weight:“Of course, every time I tried to lose weight on my own or manage my own weight … the opposite would happen … I realized that I’m not able on my own to maintain a healthy, to maintain my weight for long” .The sub-theme “Trust in GP and their recommendation” is related in that participants were more likely to believe that the program was necessary if they trusted their GP.3.1.3.Participants held beliefs about whether the program would be compatible with their lifestyle and existing schedules if they did sign up. The times, dates and locations of the classes were often described as factors that made the program compatible or incompatible. Some participants described that the program would not be compatible, because they had other work or childcare responsibilities, which acted as a barrier to signing up:“Some of the classes are physically going to the place and I would not be able to do that personally because I do not, I would not be able to find childcare for the times that they wanted you to” .Other participants described that the times, dates, or locations of the classes would work well for them, which acted as an enabler to signing up:“I do travel around Hounslow anyway, I live in Feltham so it’s not a problem” .3.1.4.Participants believed that they would experience negative emotions such as stress or anxiety if they were to participate in the program, which acted as a barrier to signing up. Participants described that they were worried about being judged or feelings of shame because of their weight:“I think it’s just because it’s a shame thing, I’m not very active, that kind of thing, so nobody needs to see me at my worst” .Other participants believed that being on the program would trigger their anxiety:“So there’s obviously the flipside of whilst the accountability’s good, it can also be negative because it can trigger my anxiety if I’ve not been able to do it, for whatever reason” .Participants also expressed worries in relation to procedures that would need to take place on the program, such as feeling uncomfortable if someone were to measure their weight in front of others.3.2.3.2.1.Having practical information about the program  acted as an enabler to signing up whilst in the GP clinic. If this information was provided to participants, it would enable them to sign up in the moment:“I plan within the next couple of days what I’m going to do. So, if I’ve got that timetable in front of me and I can go, “OK, I can meet at that time”” .Participants described that they needed this information to determine whether it would be feasible for them to accept the referral because they had work, childcare or other responsibilities to consider:“I would just need more details, as someone who works shifts, about the timing of it” .3.2.2.Participants held misconceptions about who weight management programs are meant for, which acted as a barrier to signing up. A common misconception was that weight management programs are only meant for people with obesity, and not overweight:“Is it anyone who’s, even if you are five kilos overweight, you can do it? I do not know. I do not know. My understanding was that you’d have to be quite overweight” .Other common misconceptions were that weight management programs are specifically meant for people who are immobile, old, retired, have mental illnesses or substance abuse issues. Participants also thought that weight management programs are meant for people who have medical issues, such as diabetes or high blood pressure, since the program is recommended by the GP:“if it’s through your GP, I … would assume like it’s a, you know, solving a medical issue rather than promoting like a healthy lifestyle” .The sub-theme “Fit for the program” is closely related in that people’s misconceptions determined whether they felt like a good match for the program.3.2.3.Understanding how the weight management program would improve their health and weight acted as an enabler to signing up. Participants described that they wanted to understand from the GP how the program would benefit them:“I want to talk about with the GP to say “why are you recommending the programme? What do you think I’ll get out of it?”” .If they understood how the program would help them or fill a gap that they were missing, they were more likely to sign up. Many participants described that they would not sign up if they did not understand how the program would benefit them, because they did not want to feel like they were only being referred to tick a box:“I would assume that there is a reason that they are offering it and [if] I am convinced that it’s not just a tick box. I am probably, like 95% likely to sign up” .3.3.3.3.1.How important weight loss is to participants influences whether they sign up to the program. If weight loss was important to them, this acted as an enabler to signing up. Certain factors made weight loss more important, such as having suffered from weight related health problems in the past:“They said to me that I was diabetic and it almost killed me. Now I’m pre-diabetic. For me, it’s top on the list” .Some participants also described that their ethnicity puts them at risk of developing weight related illness, which makes it more important for them to be on a program.In contrast, other participants described that their weight was not a concern or a priority for them which acted as a barrier to signing up. They often described other priorities which were more important to them such as work, exams, or family obligations. These participants described that they would not sign up to the program because they need to focus their time and attention elsewhere:“So I’ve started a new role with the same employer, that’s my priority at the moment, exercising is not. Weight management is not” .Some participants described that their current weight determines how important it is to lose weight and that if they were to become heavier, weight loss would be considered more important.3.4.3.4.1.Participant’s trust in the GP and their recommendations, or lack thereof, influences whether they sign up. Some participants described that they do not trust what the GP recommends, which acts as a barrier to signing up:“I do not know because, mm, I feel as if, like I said before, there’s always that issue where I cannot always trust his view” .Not trusting the GP was often linked to previous negative experiences with healthcare professionals. In contrast, other participants described that they do trust the GP, which acts as an enabler to signing up:“It’s important to listen to the professionals regardless of what I’m seeing, what I feel myself. I think it’s important” .Some participants described that there is one healthcare professional in particular that they have a good relationship with or who knows their medical history well that they would likely listen to if they made the referral:“If they know you then you trust them more. So, you know, if my actual proper GP who would know me versus a locum, if my actual, proper GP recommended it, then I would pay more attention” .This sub-theme is closely linked to the sub-theme “Need for the program”, in that participants who trusted the GP’s recommendation were more likely to believe that the program was necessary for them:“I would definitely be taking their advice on stuff because they are right, at the end of the day, you know. I know that my weight at the moment is not great and I need to do something about it … So if they suggested something that could be done … they know better” .3.4.2.Many participants knew of others who had been on a similar weight management program in the past. Witnessing their weight loss journey impacted how likely they were to sign up to this program. Participants had often heard negative feedback from others about similar programs, or had noticed that as soon as the program had ended, others had put the weight back on again:“I’ve known a lot of people who have done these sort of … programmes and I’ve never known anyone to keep it off” .This acted as a barrier to signing up. In contrast, other participants described that they know people who have had a very positive experiences on similar programs, which encourages them to try it for themselves:“I saw results from that, from a friend as well. So, then I was like “Oh damn, that works.” And they have got results that I wanted, so yeah, absolutely” .3.5.3.5.1.Whether participants feel like a good fit for the program influences sign up. This sub-theme is closely related to “Misconceptions of who weight management programs” are for as participants knowledge of who joins these programs ultimately led them to feel like a match for the program (or not):“I suppose I would feel a bit awkward being there, if I do not like have – if I’m not at like high risk of like a heart attack” .Participants who did not hold misconceptions were more likely to feel like they are the type of person who would be on the program, which acted as an enabler to signing up:“Yeah, I am the type of the person that would sign up to it, definitely.” .like minded others” . Many younger participants described that being in a class with older people would make them feel uncomfortable, and similarly older participants described they would feel out of place if they were in a class with only young people. Participants also discussed this from a cultural perspective. Women who wear coverings described that they would not be the right match for a program where men were also participating, because it would be uncomfortable and impractical to cover whilst exercising.Part of what makes participants feel like a good fit for the program is being in a group with “3.6.3.6.1.Participants described negative emotions that they would experience in the GPs clinic, which acts as a barrier to signing up. Some participants described that receiving the referral would be offensive or make them feel disappointed in themselves. Other participants described that they would feel worried that something was wrong with them:“I’d feel worried and concerned that there was something wrong with me, physically, that I needed to go and do this” .Participants also described that they imagine signing up to the program would make them feel stressed or trigger anxiety:“… it would be like a thought in the back of my mind where it’s like a do you really want to put yourself through the stress and the anxiety of doing that” .3.7.3.7.1.Participants described that the financial implications of joining a program would prevent them from signing up. They described that despite the program itself being free, they would still find it challenging to cover the associated costs, such as having to buy gym clothing, pay for parking, petrol, or childcare:“Also the cost of petrol. That sounds really petty but that’s not petty anymore, you know, why am I going to waste my petrol driving to an exercise class if I can do it online” .Participants who were in full time employment described that they would need support from their employer to be able to sign up, mostly in the form of paid time off to be able to attend the various classes:“If it falls within my working day, my employer has to support me 100 percent” .3.7.2.Needing time to think, plan and discuss acted as a barrier to participants signing up in the moment. Participants described that they would need to be given time to read and process information:“I think I would not make a decision right there and then, I would definitely say, you know, can I have all the information first and then think about it and then sign up” .Other participants described that they would want to sit with the GP and talk through the particulars of the program. In some cases, this was perceived to be problematic because of the short appointment time that patients have with their GP:“… you have not got the time, in ten minutes, to… because if the GP said “have you thought about this?” then he’d need to tell me when is it, when does it start, there’s no cost in it, you have to have this much time and I want to know when’s it start, where do I have to go and so I’d have all the questions” .3.8.3.8.1.Being ready to join a weight management program influenced participants perceived capability to sign up. Participants described that being in a good place in their lives allows them to focus on their health and bettering themselves, which acted as an enabler to signing up:“I would need to be in a good place. Like at the moment, I’m doing reasonably OK so I’m in the place where I could focus on that. Because when I’m not in the best mindset … it’s just more about surviving when I’m in that mode than it is about bettering” .They described that signing up to a program and starting the weight loss journey is the hardest part of the process, and so it was something that they needed to be in a good place to be able to do:“… that’s probably the biggest one is, is this the right time for me? Am I ready, in my life, to do something like this? … because if you are not, what’s the point?” .4.The present study provides the first comprehensive assessment of influences on the behaviour of signing up to a weight management service opportunistically, drawing upon a theoretical framework that can inform intervention development. Due to the opportunistic nature of the target behaviour, many barriers to patients accepting weight management support from a GP in the related literature did not influence behaviour in this context. Instead, this study found that the domain of Beliefs about consequences was the most frequently reported influence on signing up. Whether Beliefs about consequences acted as a barrier or enabler was largely driven by the domains of Social influences and Knowledge, providing a potential route for behaviour change. Other domains that influenced the target behaviour include Goals, Emotion, Environmental context and resources and Beliefs about capability. The findings from this study make several novel contributions to the science, and are discussed in more detail below, in the context of the related literature. The findings have theoretical, practical, and clinical implications. First and foremost, the findings can be used to develop targeted interventions aimed at increasing the number of patients living with overweight or obesity who agree to join a tier 2 service after receiving a referral.Participants hold many beliefs about what would happen after signing up to the program, which influences whether they ultimately would. Beliefs that were expressed the most often include how effective the program would be, whether the program is needed to lose weight and whether the program would be compatible with their lifestyle. The finding that Beliefs about consequences is the most influential domain on the behaviour of signing up is aligned with the health behaviour change literature in general. Conceptual frameworks underlying models of health behaviour such as the health belief model , protectThe results pose a potential solution to this challenge, in that they find that the domains of Social influences and Knowledge largely influence whether Beliefs about consequences act as a barrier or enabler to signing up. Thus, changing patients’ knowledge, and leveraging social influences, may be two ways to lead them to hold positive beliefs about the consequences of signing up. The links between these domains emerged in various ways in the data. Firstly, this study found that the domain of Social influences influenced Beliefs about consequences in that participants described that if they trust the GP providing the referral, they are more likely to believe that the program is needed and subsequently sign up. Furthermore, they described that there are certain healthcare professionals that they trust more than others and would be more likely to sign up if the referral came from them. Unfortunately, many participants in this study also described that they have had negative experiences with healthcare professionals in the past, who have made them feel at blame for having excess weight. This weight stigma is still pertinent in the healthcare system  and may Another barrier that many participants reported was feeling like they were not the right fit for the program, which reflects the domain of Social/Professional Role and Identity. Similar to changing beliefs about consequences, addressing patients’ sense of belonging and fitting in with others in the program can be challenging. However, the study identifies a potential solution, as the domain of Knowledge was found to influence Social/Professional Role and Identity. In general, participants were unsure who the weight management service was intended for, and were unaware that individuals with overweight could join the program. Many held the belief that the program was only intended for individuals with obesity, illness, or pre-existing medical conditions. Upon reviewing the one-pager provided , particiGoals was another highly influential domain on the behaviour of signing up. All participants described that signing up would largely be influenced by how important weight loss is to them. Similar findings have been reported in the related literature . ParticiThis study found that the domain of Environmental context and resources acted as a barrier to signing up, in ways that are both in line with and contribute to the related literature. An intervention targeting opportunistic sign ups overcomes many of the physical barriers to patients receiving weight management support from a GP (such as transportation and the density of GP practices) since the behaviour would occur whilst already in the GP’s clinic. As such, these influences were not relevant in this context but are still barriers  which laFinally, the domains of Beliefs about capability and Emotion were also found to influence sign up, although amongst fewer participants. Similar to the physical barriers described above, an intervention targeting opportunistic sign ups overcomes various Beliefs about capability barriers such as believing that they would be unable to log on to a website or travel to the service to sign up, since the GP would complete the referral for them. Accordingly, participants in this study did not doubt their physical capability to sign up but were concerned about their psychological capability. This emerged through the need to be ready for change to sign up. Participants described that having strong mental health and being in a good place in their lives would make it easier for them to sign up, because they felt this would help them manage the difficulties associated with being on a program. Emotion also acted as a barrier to signing up. Participants reported negative emotions that they might experience in response to hearing the GPs recommendation, such as anger, frustration, anxiety or feelings of guilt. The study conducted by Aveyard et al.  found th4.1.a priori accounts of what would influence sign up in this context. However, this is also a limitation in that the participants in this study did not communicate with or verbally receive a referral from a GP. As described above, research has shown that talking about weight with patients is a highly sensitive topic, and that using the incorrect terminology, having a negative attitude, and having stigmatizing material on display (such as magazines or posters) can lead to an avoidance or delay in seeking medical care and worsen health outcomes  to understand influences on the target behaviour. Using the TDF allows these findings to be used to inform intervention design following the steps of the Behaviour Change Wheel . A furthoutcomes . Thus, poutcomes .4.2.This study has implications for the systematic development of behaviour change interventions targeting opportunistic sign ups to weight management programs. It finds that eight TDF domains are influential on whether participants sign up to weight management programs after receiving an opportunistic referral from a GP. Following the stages of the BCW, a valuable next step would be to identify intervention options followed by content and implementation options based on the findings . These fIn order to increase sign ups, interventions targeting the domain of Beliefs about consequences would likely be the most effective and could do so via the domains of Knowledge and Social influences. Focusing on the domain of Knowledge, the Theories and Techniques tool  can be uThe results also have clinical implications in that they may help GPs to develop a better understanding of the information that patients will be looking for before signing up and what their thought process may be. Public Health England  recommenFinally, these findings have theoretical implications and extend the science in this area. Guidance has been produced for GPs on how to have the referral conversation with patients , 34 base4.3.Future research should aim to develop an understanding of influences on subsequent behaviours that are necessary for patients to utilize weight management programs. This study explored influences on the behaviour of signing up to a weight management program but signing up does not guarantee that patients will attend or complete the program. This is evident in the research conducted by Aveyard et al.  where on5.In conclusion, an intervention focused on increasing the number of patients who sign up for a tier 2 service after receiving an opportunistic referral from a GP has the potential to have a significant impact on the uptake of tier 2 services. This study aimed to explore the factors that influence this target behaviour and is the first to do so using a theory-based behavioural science framework, the TDF. Accordingly, the results indicate that patients’ internal beliefs about the consequences of signing up pose the biggest barrier to doing so. Public health researchers can use the results mapped to the relevant TDF domains to identify intervention options and develop effective content and implementation strategies by following the stages of the Behaviour Change Wheel. The findings from this study suggest that interventions targeting the key domains of Knowledge, Social influences, and Beliefs about consequences are likely to be the most effective at increasing the number of patients who sign up to a tier 2 service opportunistically due to their prominence and influence on other domains.chiara.gericke.20@ucl.ac.uk.The datasets presented in this article are not readily available due to the sensitive nature of the data, data sharing was not requested or granted from the Research Ethics Committee. Requests to access the datasets should be directed to The studies involving humans were approved by Ethical approval was obtained from the University College London Research Ethics Committee (Project ID: 22079/001). Informed consent was sought via an information sheet and consent form present on the initial survey. All participants gave informed consent to take part in the research. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.CG, SR, and DD’L conceived and designed the study. CG collected the data and wrote the first draft of the manuscript, analyzed the data, and revised the manuscript with contributions from DD’L. All authors contributed to the article and approved the submitted version.This research was not covered by a grant or award. However, the London Borough of Hounslow covered the research costs associated with this project.SR is employed by the London Borough of Hounslow and has a professional relationship with the setting of interest, however, her role in the study was limited to contributing to the initial research proposal. The research was conducted independently by researchers  from University College London.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.https://www.frontiersin.org/articles/10.3389/fpubh.2023.1226912/full#supplementary-materialThe Supplementary material for this article can be found online at: Click here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.


ETV6-ABL1 gene fusion is a rare genetic rearrangement in a variety of malignancies, including myeloproliferative neoplasms (MPN), acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). Here, we report the case of a 16-year-old male diagnosed with a MPN, 7 months post-completion of treatment for Burkitt leukaemia. RNA sequencing analysis confirmed the presence of an ETV6-ABL1 fusion transcript, with an intact, in-frame ABL tyrosine–kinase domain. Of note, secondary ETV6-ABL1-rearranged neoplastic diseases have not been reported to date. The patient was started on a tyrosine kinase inhibitor  and, subsequently, underwent a 10/10 matched unrelated haematopoietic stem cell transplant. He is disease-free five years post-transplant. Definitive evidence of the prognostic influence of the ETV6-ABL1 fusion in haematological neoplasms is lacking; however, overall data suggest that it is a poor prognostic factor, particularly in patients with ALL and AML. The presence of this ETV6-ABL1 fusion should be more routinely investigated, especially in patients with a CML-like picture. More routine use of whole-genome and RNA sequencing analyses in clinical diagnostic care, in conjunction with conventional cytogenetics, will facilitate these investigations. ETV6-ABL1 gene fusion is a rare genetic rearrangement in a variety of malignancies, including myeloproliferative neoplasms (MPN), acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML) /46,XY[2]  showed a white blood cell (WBC) count of 101 × 1046,XY[2] .9/L, with a significant left shift, eosinophilia (2.92 × 109/L), monocytosis (4.38 × 109/L), thrombocytopenia (100 × 109/L), and no peripheral blasts. The patient was asymptomatic. Viral workup was negative, and EBV serology was consistent with past infection. There was no travel history. Bone marrow aspirate (BMA) revealed marked hypercellularity with significant eosinophilia and an absence of elevated blasts consistent with a myeloproliferative disorder. Immunophenotyping showed no abnormal cell population. FISH analyses were negative for MYC, PDGFRA , and PDGFRB  gene rearrangements, and the karyotype was normal. Molecular analysis was negative for the BCR-ABL1, FLT3-ITD, JAK2 V617F, and CALR variants.A CBC 7 months after the completion of therapy showed WBC 29.2 × 109/L over 3 months, accompanied by persistent thrombocytopenia (range 50–100 × 109/L). The patient became progressively symptomatic with fatigue, generalized bone pain, as well as significant spontaneous bruising. He was started empirically on Hydroxyurea 25 mg/kg/dose, which normalized his WBC count and improved his symptoms within one month.The leucocytosis increased to 192 × 10ETV6-ABL1 fusion transcript, with an intact, in-frame ABL tyrosine–kinase domain.Whole-genome sequencing of his MPN BMA sample was performed on an Illumina HiSeqX platform with a depth of 22X, and RNAseq was performed on Illumina HiSeq 2500, with a depth of 294X. Structural variant analysis from whole-genome sequencing showed a dispersed duplication event of approximately 600 kb from ABL1 to PRRC2B (9q34), inserted into the ETV6 locus (12p13)  was suggestive of a cryptic insertion of a portion of the ABL1 locus into one chromosome 12 at 12p13 (ABL1 gene rearrangement was present in 193/200 (96.5%) interphase cells. Interphase FISH analysis with a dual colour breakapart probe for the ETV6 locus  did not show ETV6 gene rearrangement in this patient, and metaphase FISH with subtelomeric probes for 9q and 12p yielded normal results, suggestive of the insertion of ABL1 into ETV6 rather than rearrangement by translocation. FISH analysis with a dual colour breakapart probe for ABL1  demonstrated that the 3′ portion of ABL1 was inserted into 12p13 on the derivative chromosome 12, with the 5′ portion of ABL1 remaining on the derivative chromosome 9  and, subsequently, underwent a 10/10 matched unrelated haematopoietic stem cell transplant. He is disease-free five years post-transplant.ETV6-ABL1-rearranged hematologic malignancies are rare entities [ETV6-ABL1 is found in <1% of all children and adults diagnosed with ALL and is less frequently in AML. The exact incidence of CML-like ETV6-ABL1 neoplasms is unknown, due to the lack of systematic screening [entities ,5. The fentities  and “CMLentities . ETV6-ABETV6-ABL1 FISH probe available, and the commonly used BCR-ABL1 or ETV6-RUNX1 probes can miss ETV6-ABL1 [ABL1 breakapart FISH probe would better enable the detection of all the ABL1 gene rearrangements, including ETV6-ABL1. RT-PCR analysis can also produce false negative results unless the exact breakpoints are known. RNAseq has been increasingly recognized as the most useful diagnostic tool for these cases [Conventional clinical diagnostic tests often fail to detect this fusion, given that there is no commercial TV6-ABL1 . An ABL1ETV6-ABL1 aberration can present in the form of immature lymphoid or myeloid neoplasms raise a number of possible pathogenetic mechanisms. First, it is possible that this patient had independent but simultaneous bi-lineage disease with two clones: the MYC-positive Burkitt leukemia and the ETV6-ABL1 MPN, the former being controlled by the initial Burkitt-targeted chemotherapy, allowing the other partially treated clone with ETV6-ABL1 to expand following therapy completion. Of note, our patient had marked eosinophilia at the presentation of both the Burkitt leukemia (1.01 × 109/L) and the ETV6-ABL1 MPN (4.67 × 109/L)—a finding that is commonly associated with MPNs and not with Burkitt disease [ETV6-ABL1 MPN in the Burkitt leukemia sample due to low sensitivity; the lack of RNA for in-depth RNAseq did not allow us to confirm or refute this hypothesis. Of note, no pathogenic variants were identified on germline analysis to suggest an underlying cancer predisposition syndrome, which must be considered in the setting of two independent primary tumors.The unique presentation of our patient and the fact that a 1.01 × 9/L and tETV6-ABL1 was an early clonal event that occurred in a common hematopoietic progenitor cell, followed by a second hit in the MYC, resulting in the initial Burkitt leukemia. However, we would have expected the clonal presence of the ETV6-ABL1 fusion in the diagnostic Burkitt leukemia specimen in this circumstance.The second possible molecular mechanism is that the ETV6-ABL1-rearranged neoplastic diseases have not been reported to date. Furthermore, such an early secondary malignancy in a paediatric patient after exposure to alkylators would be very unlikely, as the latency is typically several years post-completion of therapy [Alternatively, the MPN may have been a therapy-induced secondary event associated with the alkylator chemotherapy included in the treatment of Burkitt leukemia. However, secondary  therapy .ETV6-ABL1 fusion in haematological neoplasms is lacking; however, overall data suggests that it is a poor prognostic factor, particularly in patients with ALL and AML [ETV6-ABL1 MPNs, although multiple reports advocate for the early introduction of first and/or second generation TKIs [ETV6-ABL1 gene fusion [ETV6-ABL1-driven chronic myeloid leukemia who initially responded to imatinib but who rapidly deteriorated over the following 2 weeks and required conventional chemotherapy [ETV6-ABL1-associated neoplasms, via the restoration of signalling through the phosphoinositide-3-kinase (PI3K)/Akt/mTOR and mitogen-activated protein kinase (MAPK) pathways [ABL-class fusions, such as BCR-ABL1, it is well-established that point mutations in the kinase domain of BCR-ABL1 are the prevalent mechanisms of resistance to ABL kinase inhibition  [BCR-ABL1 independent resistance) [Definitive evidence of the prognostic influence of the  and AML . There aion TKIs ,14,15. Re fusion . It shouotherapy . The mecpathways . With restance”) . In otheistance) ,21.ETV6-ABL1-associated neoplasms. The presence of this fusion should be more routinely investigated, especially in patients with a CML-like picture, particularly as it can prompt therapy with a tyrosine kinase inhibitor, as in the patient presented here. More routine use of WGS and RNAseq analysis in clinical diagnostic care, in conjunction with conventional cytogenetics, will facilitate these investigations.Further detailed molecular studies of other patients with the same genomic abnormalities will provide insight into the pathogenesis and clinical course of