Evidence remains inadequate regarding the benefits of participation in community gathering places, which is Japan’s primary strategy for preventing functional disability in older adults, in other domains of health and well-being. This longitudinal study examined the associations of participation in community gathering places with an array of subsequent health and well-being outcomes among older adults.n = 5 879 or 4 232 depending on the outcome). Our exposure was participation in community gathering places in 2016. We assessed 34 health/well-being outcomes in 2019 across 6 domains. We adjusted for pre-baseline covariates including prior outcome values in 2013.We used 3-wave data  from Japan Gerontological Evaluation Study .Compared with nonparticipation, participation in community gathering places was associated with some outcomes in the following 3 domains: physical/cognitive health , social well-being , and prosocial/altruistic behaviors  but also enhance other domains of human well-being, potentially by increasing social interactions. Translational Significance: Promoting participation in community gathering places is the primary strategy for the prevention of functional disability in Japan. Roles of community gathering places in promoting multidimensional health and well-being are understudied. This study demonstrates that participation in community gathering places was associated with some outcomes in the following 3 domains: physical/cognitive health, social well-being, and prosocial/altruistic behaviors. A community intervention with community gathering places may contribute not only to the prevention of functional disability but also to the promotion of health and well-being in some other domains.Aging populations are ongoing worldwide, and increasingly more countries must tackle the resulting major challenges to ensure that their health and social systems are well prepared for this demographic shift . Japan hParticipation in community gathering places is associated with various health-related outcomes, including physical function , physicaTherefore, the present study examined the longitudinal associations between participation in a community gathering place and wide-ranging subsequent health and well-being outcomes among older adults in Japan. We leveraged 3-wave data from a nationwide cohort study of Japanese older adults and adjusted for preexposure covariates, including preexposure outcome values, to reduce bias due to confounding and reverse causation. We adopted an outcome-wide approach  and holin = 137 736; response rate: 71.1%). In 2016, JAGES conducted a follow-up survey . JAGES randomly selected 12.5% (n = 9 833) of the respondents and distributed a questionnaire containing items regarding participation in community gathering places. These 9 833 individuals were categorized into 2 samples by linking them to 1) the 2019 follow-up survey containing information on self-reported outcomes  and 2) the national LTCI database containing information on the onset of all-cause mortality, dementia, and functional disability between 2016 and 2019 (n = 6 070). We excluded respondents with inconsistently reported age or gender between survey waves and improbable height (<100 cm or >200 cm) or weight values (<30 kg or >100 kg). Ultimately, we included 4 232 individuals for the 2019 survey-based outcomes and 5 879 individuals for the LTCI-based outcomes.We used 3-wave data from the 2013, 2016, and 2019 surveys of the Japan Gerontological Evaluation Study (JAGES) ,31, a naThis study was performed in line with the principles of the Declaration of Helsinki. Ethical approval for this study was obtained from the Ethics Committee at Chiba University  and the National Center for Geriatrics and Gerontology . JAGES respondents were explained that participation in the study was voluntary and that completing and returning the self-administered questionnaire meant agreeing to participate in the study.“How long have you been participating in salon activities at local governments and social welfare councils?” Participants were given the following answer choices: “never participated,” “used to participate but stopped,” “participated less than 1 year,” “1 year to less than 2 years,” “2 years to less than 3 years,” “3 years to less than 4 years,” “more than 4 years,” and “participating but for an unknown period.” We categorized the responses “never participated” and “used to participate but stopped” as not participating and the other responses as participating in community gathering places.Our exposure variable was participation in a community gathering place, taken from the 2016 survey. This variable was measured using the following question: Building on theorizing around multidimensional well-being and following a prior outcome-wide study in Japan, we examined 34 outcomes across 6 domains of health and well-being in 2019 (3 years after the exposure assessment) . These dData on death, cognitive disability (dementia), and functional  disability during the 3-year follow-up were obtained by linking the participants to registries maintained by local municipal governments recorded under the Japanese LTCI system ,38. CognWe obtained all covariates from the 2013 survey—3 years prior to the 2016 survey in which the exposure was assessed. We included the following preexposure characteristics: age, gender, years of education , household equivalized income , employment , marital status , living alone, ADL (dependent or independent), and population density . In identifying the population density of habitable land, we divided the population by the area of habitable land at the municipality level from national statistical data ,40. ThesTo reduce the possibility of reverse causation , we also adjusted for prior values of the outcomes, except for death, dementia, and functional disability as the participants did not have these conditions in the preexposure wave by design.SD)), and categorical variables are reported as numbers (percentages). We did not statistically compare covariates. Statistical tests are not appropriate to assess the presence of confounding  to allow the effect estimates to be interpreted as SD changes in the corresponding outcomes. Standard errors were clustered at the municipality district level to determine the potential correlation of the participants within the same district.We adopted an outcome-wide analytic approach ,32. Thisp-value cutoff for Bonferroni correction as p = .0015 (0.05/34).To address potential issues of multiple testing and increased risk for false positives resulting from the simultaneous assessment of the associations between participation in community gathering places and the 34 outcomes , we used Bonferroni correction . In thisThe self-administered questionnaires contained missing data; hence, using multivariate normal imputation, we created 20 imputed data and combined the estimates across imputations by using Rubin’s rule ,44.E-values for each exposure-outcome association .We also conducted 2 additional analyses. To evaluate the robustness of the estimated associations to unmeasured confounding, we calculated ociation . E-valuen = 4 232). Community gathering places participants were more likely to be female, have lower household incomes, be unemployed, and be single compared with nonparticipants. Overall, community gathering places participants reported better physical/cognitive health, except for self-rated health, BMI, and dyslipidemia in the prebaseline wave. They also had fewer prebaseline depressive symptoms and sense of hopelessness, higher life satisfaction with subjective well-being, higher social well-being (excluding frequency of going out), more pro-social/altruistic behaviors , and better health behaviors . Similar trends were found for prebaseline characteristics and prior outcome values in the study sample linked to national LTCI records , were involved in a hobby group more frequently , participated in senior citizens club more frequently , participated in learning or cultural groups more frequently , had greater number of friends seen within a month , and participated in volunteering groups more frequently in 2019 than nonparticipants. After Bonferroni correction, these associations remained below the p = .05 threshold. Compared with nonparticipation, participation in community gathering places was moderately associated with low diabetes incidence, low depression scores, better frequency of participation in a sports group, frequency of going out, frequency of meeting friends, frequency of participation in sharing of skills and experiences, health screening, and frequency of fruit and vegetable consumption. However, these associations were above the threshold of p = .05 after Bonferroni correction. There was little evidence of association between participation in community gathering places and other outcomes such as death, dementia, or functional disability.E-values, which indicated that the observed associations between participation in community gathering places and some outcomes were robust to an unmeasured confounder. For example, for the association between participation in community gathering places and hobby group participation, an unmeasured confounder would need to be associated with both the exposure and outcome by a risk ratio of 1.83-fold each  to fully explain the observed association and by that of 1.62-fold to shift the CI to include the null value.E-value for hobby group participation (1.62).This longitudinal study with a 3-year follow-up period examined the relationship between participation in community gathering places, which is the primary strategy for the prevention of functional disability in Japan, and subsequent health and well-being. There are 5 main findings. First, participation in community gathering places was associated with several social well-being outcomes, such as more frequent participation in a hobby group/senior citizens club/learning or cultural groups and a greater number of friends seen within a month. Second, participation in community gathering places was associated with more frequent volunteering. Third, in terms of physical/cognitive health, community gathering place participants had better higher-level functional capacity than nonparticipants. Fourth, there was modest evidence that participation in a community gathering place was associated with lower depressive symptoms scores and a higher frequency of fruit and vegetable consumption. Fifth, there was no strong evidence that participation in community gathering places was associated with other measures of subsequent health and well-being.The observed associations between participation in community gathering places and outcomes in social well-being domain are consistent with a previous study  wherein Similarly, volunteering, which was included in the pro-social and altruistic behavior domain, might be promoted by participation in community gathering places. Volunteers perceive that participation offers opportunities close at hand . In a suIn terms of the outcomes in the physical/cognitive health domain, community gathering place participants had better higher-level functional capacity than nonparticipants, and this result is consistent with the original aim of the community-based interventions  and the findings of a prior prospective cohort study . In our We did not find evidence of an association between participation in community gathering places and mortality, dementia onset, and functional disability during the 3-year follow-up period even though these outcomes are primary targets of the prevention of functional disability in Japan ,7. In prContrary to our findings, a previous study examined a similar study population of older adults in Japan and reported a significant association between participation in community gathering places and improvement in self-rated health by utilizing instrumental variable estimation . This inp = .05 after Bonferroni correction, our study showed the modest association of participation in community gathering places with lower depressive symptoms scores. Considering the robust evidence in the associations between social participation in older people and depression , cannot explain the observed association. In addition, we ensured that covariates were observed before the exposure assessment, so the over-adjustment of potential mediators is unlikely. Second, reverse causation cannot be avoided completely. For example, older adults who participated in community gathering places originally had a high level of functionality, resulting in participation in community gathering places. However, for this reverse causality, we took advantage of the 3-wave panel structure, which enables us to include prior outcome levels to reduce. Such control for baseline outcome does not eliminate the possibility of reverse causation but helps to mitigate it (n = 4 232) tended to be younger, more educated, and married and report higher income as well as better health/well-being in the prebaseline wave, compared with the sample of the data linking the 2013 wave and the 2016 wave (n = 7 612) and the analytic sample linking the 2013 wave, the 2016 wave, and the national long-term care insurance record (n = 5 879) . Nonetheless, we adjusted for a rich set of covariates, including prior levels of outcomes, taking advantage of the 3-wave panel structure. Moreover, our sensitivity analysis using igate it . Third, = 5 879) . Fourth,In conclusion, this study showed a wide range of evidence that participation in community gathering places promotes the health and well-being of older adults in Japan. Participation in community gathering places was associated with several social well-being outcomes, such as more frequent participation in a hobby group/senior citizens club/learning or cultural groups and a greater number of friends seen within a month. Furthermore, participation in community gathering places was associated with more frequent volunteering. Additionally, in terms of physical/cognitive health, participation in community gathering places had better higher-level functional capacity than nonparticipants. A community intervention with community gathering places, which is the primary strategy for the prevention of functional disability in Japan, may contribute not only to the prevention of functional disability but also to promoting other domains of human well-being by increasing social interactions. With restrictions on face-to-face contact during the coronavirus disease 2019 (COVID-19) pandemic, community gathering places were forced to suspend activities. After COVID-19-related deregulation, community gathering places will play a major role in restoring face-to-face interaction among older adults.igad084_suppl_Supplementary_MaterialClick here for additional data file.


Bartonella henselae infection causes Cat Scratch Disease (CSD). Lymphadenopathy is the most common symptom and a small percentage of patients have systemic impairment. CSD can mimic malignancy and manifest atypically, therefore reliable serological testing has clinical importance. CSD is diagnosed if two of the following criteria are met: 1) the presence of clinical symptoms consistent with CSD; 2) the existence of antibodies against B. henselae IgM and/or IgG (1:256) . We aim to assess the accuracy and diagnostic utility of IgM and IgG in pediatric patients with suspected CSD.A retrospective, observational and analytical study was carried out from April 2022 through April 2023. Medical and laboratory records of patients with follow-up in the Infectious Diseases Department of a Children's Hospital in Buenos Aires (Argentina) were evaluated.We included 244 serum samples from patients with clinical suspicion of CSD using Immunofluorescent assay (IFA).Median age: 84 (IQR 48-132) months, 137 were female, 95% (233/244) had cat interaction.Twenty eight percent (70/244) were diagnosed with CSD based on serological evidence: 83,9% (58/70) had IgM +/IgG + (group 1); 10% (7/70), IgM-/IgG+ >1/64 (group 2) and 7,15% (5/70), IgM+/IgG – (group 3). The average time of symptom onset was 22,8 (6-90) days for group 1, 29,4 (11-90) days for group 2, and 11,4 (5-15) days for group 3.Lymphadenopathy was found in 87,1% (61/70) with or without systemic involvement and 6 % (4/70) had systemic involvement without lymphadenopathy.IgM had Sensitivity: 89%, Specificity: 97%, Positive Predictive Value (PPV): 92% and Negative Predictive Value (NPV) : 96%.Between 5-15 days after the onset of symptoms, IgM allowed us to diagnose 5 patients with CSD. The identification of IgM antibodies in CSD patients with systemic impairment has a great diagnostic performance. IgM remained positive after 90 days . We were able to diagnose CSD in 7 patients between 11 and 28 days following the onset of symptoms due to the presence of IgG 1:256 or higher. Combination of different methods  and a correct time of sampling, greater than 5 days, should be considered for rapid and accurate CSD diagnosis.All Authors: No reported disclosures


Delirium is among the most prevalent harmful events in hospitals that is associated with an elevated risk for severe outcomes such as functional decline, falls, longer length of stay, and increased mortality.To evaluate the impact of the implementation of a multi-component delirium program on the prevalence of delirium and the incidence of falls among patients staying on general medicine inpatient hospital units.A pre-post intervention study using retrospective chart abstraction and interrupted time series analysis.Patients were selected from adult patients that stayed at least 1 day on one of the five general medicine units in a large community hospital in Ontario, Canada. A total of 16 random samples of 50 patients per month for 8 consecutive months pre-intervention (October 2017 to May 2018) and 8 months post intervention (January 2019 to August 2019) were selected for a total of 800 patients. There were no exclusion criteria.The delirium program included multiple components: education of staff and hospital leadership, twice per day bed-side screen for delirium, non-pharmacological and pharmacological prevention, and intervention strategies and a delirium consultation team.Delirium prevalence was assessed using the evidence-based delirium chart abstraction method, CHART-del. Demographic data as well as fall incidence were also collected.Our evaluation showed that the implementation of a multicomponent delirium program led to a reduction in delirium prevalence and fall incidences. The reduction in both delirium and falls was the largest for patients in the ages between 72 and 83 years old and varied across inpatient units.A multi-component delirium program to improve the prevention, recognition, and management of delirium reduces the prevalence of delirium and fall incidence among patients in general medicine units.The online version contains supplementary material available at 10.1007/s11606-023-08238-9. Despite that up to 30–40% of cases is preventable5, it is often not recognized by clinicians in the early stages 10, and efforts to reduce the incidence of delirium are challenged by lack of delirium awareness; the conflation of delirium with dementia; and the absence of training and in-service education programs for physicians, nursing, and allied health staff.9Delirium is a common multifactorial condition among hospitalized patients that is associated with an elevated risk for severe outcomes such as functional decline, falls, longer length of stay, and increased mortality.11 and have been shown to reduce delirium incidence from 3% up to 30% in randomized trials as compared to usual care, 14 thereby improving the quality of life for patients and their families, while reducing healthcare costs and societal burden of delirium.15. These interventions often include the use of education, implementation of both non-pharmacological and pharmacological prevention strategies, and the support of inter-professional teams at the point of care to address potentially modifiable risk factors.17To address the multiple factors affecting the prevention and care for patients with delirium, multicomponent interventions are needed Our local hospital did not have a formalized delirium program. Therefore, based on the available knowledge, we developed, implemented, and evaluated a practical, evidence-informed multicomponent program for the prevention, early recognition, and effective management of delirium at a large community hospital.In this paper, we present the evaluation of a multi-component delirium program in a large community hospital serving a diverse population to understand the effectiveness of the intervention in reducing the number of delirium cases and falls analysed with pre-post Interrupted Time Series (ITS) design.The delirium program was implemented at Trillium Health Partners (THP), a large community hospital, in Mississauga, Canada, serving a diverse population of over one million people. With 1379 inpatient beds, the hospital provides the full range of acute care hospital services. In the 5 years leading up to this implementation, a few other initiatives related to delirium and falls were initiated at THP. First, the organization attained Registered Nurses Association of Ontario (RNAO) Best Practice Spotlight Organization (BPSO) certification (2012–2015), during which time the Prevention of Falls and Fall Injuries in Older Adults Best Practice Guideline (BPG) was implemented across multiple units. After this, the RNAO Delirium, Dementia and Depression in Older Adults: Assessment and Care BPG was implemented in conjunction with the delirium program activities (2015–2021). This BPG was intentionally launched concurrently with the work related to the delirium program. The BPG team supported the educational efforts for the delirium program. The journey to BPSO certification could have stimulated a culture of change and learning which could have had a positive influence on the implementation and uptake of the delirium program.18This evaluation studied charts from patients that stayed on one of the 5 general medicine units at one of the three hospital sites. Implementation of the delirium program in these units started in June 2018. This evaluation examines the occurrence of study outcomes within the pre-implementation period (October 2017–May 2018) and the post-intervention period (January 2019–August 2019). This manuscript follows the Revised Standards for Quality Improvement Reporting Excellence (SQUIRE) reporting guidelines.To change the existing model of delirium care in the organization, a team of administrators, clinicians, and scientists formed a project team and developed a multi-component delirium program based on current evidence. The developed delirium program intends to achieve three goals: (a) to prevent the onset of delirium, (b) to identify delirium when present, and (c) to improve the evidence-based management of delirium when identified.Before implementation of the delirium program on inpatient hospital units, the project team engaged with “local” leadership  and staff to tailor the program to the context of the units. The pre-implementation activities included, but were not limited to, current state mapping, recruitment and training of delirium champions on each unit, and the creation of a delirium data dashboard and screening rate score cards for the units.After the pre-implementation activities were completed, all clinical staff of the units were trained and the Delirium Program was implemented on the hospital units. The key components of the delirium program are the following: education on delirium for all staff involved, non-pharmacological and pharmacological delirium prevention strategies, delirium recognition with a bedside screener, and specific delirium management processes (order sheet) and strategies see Fig. . More deIn order to assess the implementation success of the delirium program, the two daily bedside delirium screening rates were calculated. The percentage of delirium screens done monthly for each of the 5 units was computed by dividing “the total number of delirium screens performed monthly per unit” over “the number of monthly bed days per unit, times 2” (times 2 since the delirium screen is done twice per day). The tracking of the delirium screening was done for 19 months after the start of the intervention for all patients that stayed on a unit in each given month to assess the implementation success; see Fig. 15 In order to assess the effectiveness of the multicomponent delirium program , we applied a pre-post evaluation study design using retrospective chart abstraction and Interrupted Time Series (ITS). ITS has increasingly been advocated as one of the more robust observational quasi-experimental designs for the evaluation of health system quality improvement interventions. The ITS design relies on data collected at multiple intervals over time before and after an intervention to establish a causal relationship between an intervention  and an outcome of interest .19 Based on Penfold and Zhang’s (2013), for our analysis, we considered a time period of 8 months before and after implementation of the intervention.20 For each month, we randomly selected a sample of 50 patients that stayed on any one of the 5 general medicine units. Patients were selected based on the month they were admitted to the hospital. For the pre-implementation period—October 2017 to May 2018—we selected 50 patients per month from 8 consecutive months in the period immediately prior to implementation of the delirium program in June 2018 (n = 400 patients). For the post-implementation period—January 2019 to August 2019—we selected 50 patients per month from 8 consecutive months starting 7 months after implementation of the delirium program to allow for the intervention to be fully implemented into practice (n = 400 patients). No stratification for unit or any other variable was used.Previous evaluations of multicomponent interventions about delirium often use post-intervention study designs with small sample size, thereby limiting the assessment of effectiveness and generalizability.The study population included 800 adult patients aged 18 years or older who stayed for a minimum of 1 day on one of the 5 general medicine units during the data collection period (pre- or post-intervention). There were no exclusion criteria. The patient records covering their entire stay, including time in the emergency room and on other units, were used.23, a brief delirium diagnostic tool that is accurate , with high inter-observer reliability.24The bedside delirium screening was done using the Confusion Assessment Method (CAM)25 The chart abstraction involved a detailed review of the full patient’s medical records  and was designed with the goal of maximizing sensitivity for identification of delirium.25 Information on acute changes in mental status, time and duration of such episodes, evidence of agitation and reversibility or improvement of the acute confusion, and scanning and auditing medical records for the key words/terms for delirium identification were abstracted. Appendix 25The presence of delirium was assessed based on either clear physician-diagnosis of delirium as documented in physicians’ progress notes, consults or discharge summary, or by the validated chart-based identification method CHART-del.23.The following outcomes were collected for each patient during their entire hospital stay from their medical chart: received a specialist consultation, use of restraint, safety attendant/sitter, had a fall, and whether or not a screening was done for delirium using the CAM Data collection was performed by a research assistant (SA) who was fully trained in the CHART-del evidence-based method. Calibration and training had taken place as part of one other large study using the same methods.26  for continuous values and counts (%) for categorical variables. Segmented regression was used to assess the impact of the multicomponent delirium intervention on the number of delirium cases and falls, by estimating the changes in level (and trend) in the post-intervention period compared to the pre-intervention period. Segmented regression analysis is a statistical method for modelling the interrupted time series data to draw more formal conclusions about the impact of an intervention on the measure of interest The THP Research Ethics Board approved this evaluation. Patients did not consent since the study operated under a waiver of patient consent because of the low risk of chart abstraction methodology.The characteristics of the patients in the pre- and post-intervention cohorts are reported in Table As a measure of the implementation success of the delirium program, the two daily CAM screenings were tracked for the medicine units. Figure p = 0.026, Std. error = 1.11). This is a relative reduction of 27.15% in the number of delirium cases per month. The estimate of the intervention effect did not change after adjusting the linear model for the negative autocorrelation in the error term, whereas it slightly reduced after accounting for the heterogeneity across units but remained significant  (see Appendix The average number of patients with delirium per month over 50 patients decreased significantly from 10.25 SD 1.83) before the implementation of the intervention to 7.38 (SD 2.39) after . This is a relative reduction of 18.97% in the number of falls per month. The estimate of the intervention effect did not change after adjusting the linear model for the negative autocorrelation in the error term, whereas the intervention effect reduced after accounting for the heterogeneity across units and became non-significant   before the implementation of the intervention to 11.8 SD 2.0) after (see Table .0 after .0 beforep = 0.01) and a 21% reduction in delirium among patients that stayed on Unit 3 (relative reduction 59.5%) (p = 0.03). Furthermore, we saw a 10.3% reduction in falls among patients that stayed on Unit 1 (relative reduction 41.2%) (p = 0.03). Although most other age groups and units saw a decrease in delirium and falls, none of the differences reached statistical significance, for some instances likely due to lack of power, since the study was not designed for this kind of explorative analysis, or due to a floor effect. Also of note is the large spread in delirium rates, from 10 to 35%, and falls, from 10 to 23%. Additionally, there is a large spread from pre-intervention to post-intervention in the absolute difference in delirium across the units: from an increase of 2% to a decrease of 21%; and for falls: from an increase of 2.5% to a decrease of 13.3% for falls   with the best uptake of the bedside screen did have the largest reduction in delirium rates which could indicate that when the program is successfully implemented it has the potential to significantly reduce delirium rates. Screening for delirium, however, was only one of the core components of the delirium program; therefore, caution needs to be taken with the generalization to the implementation success of the full program. Second, we noticed that the baseline delirium rate had a large variation across units. For some units where this rate was relatively low compared to other units, we did not see much change after implementation of the program, which could have been the result of a floor effect. Third, implementing an elaborate program is labor intensive as it involves many healthcare professionals coordinating multiple tasks. Studies show that the “readiness” of hospital units and the unit context  are key factors to the success of new programs.30 For future research, it would be interesting to measure these in order to expand the knowledge on which preconditions and key components contribute to success  using a mixed methods design.This multi-component delirium program was well resourced with the dedication of project leads, a dedicated project team, and the luxury of time to try things out. It remains a challenge with multicomponent interventions to pinpoint which components were key to the success on some units and which components were lacking on the less successful units. Previous research has shown the importance of education, champions, screening, and continuous support from hospital management.31 patient mobility,33 medication management34, and collaborative care, it is important to underline that it was not specifically designed to reduce length of stay.In our study population, the implementation of the delirium program did not change the length of stay, the use of safety attendants, or restraints. The length of hospital stay depends on a wide variety of factors that are related to, for example, the setting, clinical care, or logistics. Although the delirium program targeted some components related to these factors such as clinical pathways,35 which is a good start to have hospitals incentivize systematic screening and improve awareness; however, without a mechanism to respond to a positive delirium screen, this effort will fall short in improving delirium-related morbidities and mortalities.The implementation of delirium prevention programs within hospitals is currently at the discretion of hospital leadership and as a result not universally applied. Therefore, the creation of a standard delirium strategy within all acute care centers that focuses on components such as prevention, screening, and delirium management strategies that are evidence based is needed. Currently, hospitals in Ontario need to report the incidence of delirium25 Another limitation of the study was the use of aggregate data for each time point . Current ITS methods, including segmented regression, do not account for the heterogeneity among patients and across sites, which can imply loss of power.36 In order to address the problem, we implemented a recent proposal by Ewusie and colleagues called weighted segmented regression.38Unlike many other studies, no specific exclusion criteria were applied other than being hospitalized on a medicine unit. This allows for an increased generalizability of our findings to other hospitals’ medicine units. The use of chart abstraction in this study allowed data collection for both the pre-intervention period and post-intervention period providing data suitable for a strong evaluation design using ITS analysis. Other studies evaluating delirium prevention programs are often limited to data from the post-intervention period or report on other main outcomes than delirium. We do recognize that a limitation of the use of the chart abstraction method is that it is inevitable that some cases might be systematically mislabeled as either false negative or false positive. However, previous research demonstrated that the CHART-del method has a reasonable sensitivity and specificity and any under- or overestimation should be stable over time and temporal trends should remain meaningful.Future research might benefit from a larger sample size as well as the assessment of patient-related factors such as medical comorbidities or frailty to allow for segmentation of the patient population and de-aggregation of the data to identify who benefits and why. Furthermore, a deeper understanding of the implementation process will be key such as readiness for change, leadership involvement and endorsement, staffing ratios, and availability of real-time data to support practice changes. Together, this could increase our insights into what factors contribute to the successful implementation and sustainability of delirium programs.Our results demonstrate that the implementation of a multicomponent delirium program on general medicine hospital units is associated with reductions in delirium and falls, with the strongest effects seen in the most vulnerable patients. Hence, we believe that multi-component interventions focused on education and screening, with delirium prevention and management strategies, can have demonstrable impacts on changing patient outcomes, reduce harm, and improve practice.Supplementary file1 (DOCX 105 kb)Below is the link to the electronic supplementary material.


Northwest Medical Physics Center (NMPC) is a nonprofit organization that provides clinical physics support to over 35 radiation therapy facilities concentrated in the Pacific Northwest. Although clinical service is the primary function of NMPC, the diverse array of clinical sites and physics expertise has allowed for the establishment of structured education and research programs, which are complementary to the organization's clinical mission. Three clinical training programs have been developed at NMPC: a therapy medical physics residency program accredited by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP), an Applied Physics Technologist (APT) program, and a summer undergraduate internship program. A partnership has also been established with a major radiation oncology clinical vendor for the purposes of validating and testing new clinical devices across multiple facilities. These programs are managed by a dedicated education and research team at NMPC, made up of four qualified medical physicists (QMPs). The education and research work has made a significant contribution to the organization's clinical mission, and it has provided new training opportunities for early‐career physicists across many different clinical environments. Education and research can be incorporated into nonacademic clinical environments, improving the quality of patient care, and increasing the number and type of training opportunities available for medical physicists. To the best of our knowledge, there is currently no published literature regarding the design and execution of these types of medical physics programs in an environment where the main emphasis is clinical service. There are unique administrative and resource management challenges in an environment that is not fundamentally designed for research and education. This paper is intended to provide a template for other interested medical physics service groups, using a theoretical framework based on guiding learners to build progressing levels of clinical skills, competence, and performance.2To understand the benefits of an education and research program in a medical physics group whose primary mission is clinical service.To understand the design and execution of clinical training and research programs in a nonacademic environment.3A theoretical framework is a foundation that helps situate scholarly work within a theoretical context or model.4Northwest Medical Physics Center (NMPC) is a nonprofit organization that provides clinical physics support to over 35 radiation therapy facilities. NMPC is composed of approximately 50 physicists and dosimetrists who are based at facilities ranging from small, community‐owned cancer centers to large hospital systems offering multiple radiation treatment modalities. The primary focus of NMPC staff has been the provision of clinical physics and dosimetry support in radiation oncology, as well as project work that includes therapy and diagnostic shielding design, linear accelerator (linac) commissioning, and many types of auxiliary radiation therapy imaging and treatment systems. However, the wide range of clinical sites and associated treatment technologies also provide excellent opportunities for clinical training and research. The nonprofit status of the organization has enabled the development of a structured educational and research mission, which is complementary to its clinical services.Three clinical training programs have been established at NMPC: a medical physics residency program accredited by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP), an Applied Physics Technologist (APT) program, and a summer undergraduate internship program. In addition to these programs, a structured approach has been taken to clinical research. A partnership has been established with a major radiation oncology clinic vendor for the purposes of validating and testing new clinical devices across multiple facilities. All these programs are managed by a dedicated education and research team of four qualified medical physicists (QMPs). The expansion of the group's clinical mission to include education and research was enabled by its nonprofit status; however, these programs have enhanced clinical services, improved the quality of patient care, and are consistent with the goals of the Medical Physics 3.0 Initiative, which seeks to expand the practice of medical physics.4.1NMPC established a residency program in radiation therapy physics in 2005. This program was CAMPEP‐accredited in 2009, becoming the first nonacademic institution to achieve accreditation. The recommended guidelines for clinical medical physics residency programs are discussed in American Association of Physicists in Medicine (AAPM) Report No. 249.NMPC currently has six designated clinics for residency training, although residents visit other sites to assist with commissioning projects, system upgrades, and annual linac quality assurance (QA). Residents currently rotate through three of the designated clinics as main sites during their time in the program. The schedule of a recently graduated resident is included in Figures In addition to their training objectives, residents are expected to take on QA responsibilities at each clinic once they achieve an appropriate competency level. Within the first few months of starting at a clinic, residents are expected to perform weekly chart checks, monthly linac QA, patient‐specific intensity modulated radiation therapy (IMRT) QA, and daily HDR afterloader QA without personal or direct QMP supervision.Per CAMPEP standards, the NMPC residency program is governed by a residency steering committee currently composed of six physics faculty and two non‐physics faculty members. Experienced physicists interested in mentoring activities typically occupy faculty positions for a 5‐ to 7‐year term. These faculty rotations allow for the provision of varied expertise and fresh perspectives to the residency program. The non‐physics faculty members, a dosimetrist and a physician, are employees of NMPC client clinics. The NMPC residency committee meets twice a year to review changes to the program and the progress of the residents.The residents are evaluated quarterly by physics residency faculty members; each resident undergoes a 2.0−2.5 h oral exam each quarter, designed to test their clinical knowledge as well as prepare them for the American Board of Radiology certification exams. The oral exam is performed remotely using MS Teams , allowing the participation of faculty based at multiple, geographically distributed clinical sites. Residents are expected to submit a written report on each clinical objective prior to this exam. Any questions that the resident fails to answer satisfactorily in the exam must be addressed in a follow‐up report. In addition to these exams, each resident has bi‐weekly virtual meetings with a faculty member from a clinic other than where the resident is based for that rotation. These meetings allow faculty to determine whether the resident is meeting their training objectives and provide the resident with a regular point of contact for feedback, independent of their on‐site mentor.The NMPC residency is self‐funded, and resident presence may be explicitly included in the legal contract language for a given clinical site. NMPC has found residents provide a welcome extra set of hands to staff physicists, many of whom express interest in the opportunity to help train residents, who will progress to become future colleagues. Clinics that may initially be somewhat skeptical about hosting residents recognize the value‐added contribution of the resident after they leave for the next rotation and look forward to hosting the next resident.4.2NMPC's APT Program was designed as a 1‐ to 2‐year training program for individuals who had recently completed an undergraduate degree in the physical sciences or engineering. This program provided the opportunity to explore a career in medical physics prior to applying to graduate school. The APT acquired hands‐on experience in radiation therapy physics, assisting QMPs in day‐to‐day responsibilities as well as larger clinical projects in busy radiation oncology departments. Prior to 2018, the NMPC APT program was an informal, ad hoc hourly paid position. The program was converted to a formal, salaried position with benefits in 2018, and a QMP was assigned as an APT manager. The intention was to improve the educational and mentorship experience of the APT program, so it would be consistent with the NMPC education mission. A single APT was enrolled in the program at a time. Recruitment efforts were targeted at 4‐year colleges with physics and engineering departments in Oregon and Washington states. The APT program was retired in 2021 due to financial constraints.Each APT was assigned to a base clinic in Washington state, where they worked on routine clinical responsibilities, such as patient‐specific QA and linac QA, under direct or personal supervision of a QMP. The level of APT supervision was broadly based on the Medical Physics Practical Guidelines (MPPG) 3.A.4.3NMPC has recruited undergraduate physical science and engineering students as clinical interns on an ad hoc basis since 2005. A more formal internship program was started in 2018 using the AAPM Summer Undergraduate Fellowship Program (SUFP) as a template.4.4Research has not been the primary focus of physics staff at NMPC, although the group has cultivated a robust performance history in clinical development going back to the institution's founding , has emphasized the need for competency‐based training for radiation oncology resident education, including the tracking of entrustable professional activities (EPAs).The NMPC residency uses the Typhon All Health Student Tracking System  as a cloud‐based platform for logging resident clinical activities. Typhon platforms have been used for logging competencies, assessments, feedback, and training hours for other health care providers, including physicians,One of the major strengths of the NMPC residency is the incorporation of multiple clinical sites and commissioning projects to allow the resident to view not only different equipment, procedures, and workflows, but also to facilitate the resident participating in different clinic cultures  commissioning, on‐board imaging (OBI) commissioning, data‐collection automation, and end‐to‐end‐testing. These routine QA and commissioning responsibilities provide the resident with valuable clinical experience and allow them to make a significant contribution to the clinical mission of NMPC. This work helps relieve the workload of the on‐site physics team, allowing them to focus on clinical activities exclusively reserved for QMPs. It also helps demonstrate the value of the resident to clinic administration, which may be initially skeptical of hosting a trainee physicist in a nonacademic environment. The expected resident travel schedule is discussed with all residency candidates at both the initial phone interview and the final video conference interview stages, as well as at the AAPM residency fairs. NMPC's multi‐institutional approach encourages residents to experience a range of different clinical environments, and therefore shares similarities to “hub‐and‐spoke” model residencies that are designed to take advantage of multiple clinical sites. To the best of our knowledge, the majority of currently available hub‐and‐spoke model residencies are affiliated with major academic centers,Medical Physics and International Journal of Radiation Oncology, Biology, Physics as well as National Council on Radiation Protection and Measurements (NCRP) and International Commission on Radiation Units and Measurements (ICRU) publications. With the longstanding nature of the NMPC residency, a large electronic repository of required reading materials has been compiled over the years the residency has been accredited. This library of materials is limited for educational purposes within the nonprofit educational scope of the residency and is shared with incoming residents through fair‐use guidelines. Additional books, reading materials, and other resources required by the residency or for preparation for board exams are budgeted for by NMPC and reimbursed up to $500 per year per resident.One potential challenge of a nonacademic residency program is access to publications commonly provided to residents at academic institutions, such as journal article access and books. To address this issue, NMPC pays for AAPM and ASTRO membership for its residents. These organizations offer access to peer‐reviewed journals such as 5.2The number of applications for the APT program varied from 10 to 15 per year during the time period 2018−2021. Three recently graduated physics students were successfully recruited and trained during this time. APTs have presented work at national conferencesThere is currently no literature available detailing the APT experience. Research in other undergraduate science, technology, engineering, and math (STEM)‐based fields has shown that immersive field experiences result in higher levels of translational outcomes and deeper levels of understanding than classroom learning or experiential learning field trips.The APTs who participated in the program did not yet have extensive medical physics or general research experience at the time of admission to the program, but graduated with at least a year of real‐world clinical experience with the goal of providing a supporting foundation at the lower levels of Miller's pyramid on which to build. To do so, the APT program provided a blended educational environment including project‐based learning5.3Although recruitment for the summer undergraduate internship has been suppressed since 2020 due to COVID‐19 restrictions, the intern program has proven very popular, with as many as 45 complete applications to the program in 2019. Five undergraduate students have completed 10‐week summer internships at NMPC since 2018. Of those five students, one intern presented their project work at the 2020 Radiosurgery Society Meeting;AAPM offers similar undergraduate internship experiences through their SUFP and Diversity Recruitment through Education and Mentoring Program (DREAM), formerly the Minority Undergraduate Summer Experience Program. AAPM has offered paid support for talented undergraduates to conduct mentored research since 2001. The current SUFP and DREAM programs offer 10‐week paid internship experiences for undergraduate students by pairing each student with a mentor to guide them in medical physics research and/or clinical responsibilities. Published results showing high satisfaction rates from both the mentors and student graduates.5.4The Varian SRS phantom project had a synergistic relationship with NMPC educational and clinical responsibilities. It allowed the intercomparison of SRS practices across multiple clinical sites. It also gave clinical sites another method for validating the integrity of their SRS treatments, which was used as a justification for spending clinic time on this project in discussions with clinic administrations. The dosimetric and geometric SRS data acquired across six linacs established baseline data for future SRS commissioning on new machines. It also served as an excellent teaching tool for one of our residents, who played a significant role in data collection for this research.The Varian SRS phantom became commercially available for clinical users in 2021. The development and commissioning work performed with the phantom was presented at the 2021 AAPM and ESTRO annual meetings.Collaborations between academia and industry across many medical and STEM‐based fields are not new, with academic‐industry partnerships (AIPs) supported with established national funding mechanisms including the National Institutes of Health's Academic‐Industrial Partnerships for Translation of Technologies for Diagnosis and Treatment R01 Research Project Grant.6NMPC has successfully established three formal clinical training programs. A structured research and development program has also been established in collaboration with a major clinical vendor. Notwithstanding the retirement of the APT program and the COVID‐19 restrictions placed on the internship program, all these programs have made a significant contribution to the clinical service mission of NMPC, as well as providing training opportunities for early‐career medical physicists across many different clinical environments. These programs are described using the widely recognized lens of Miller's Pyramid, in which learners  build from a foundation of acquiring new knowledge and skills, proceed to demonstrating understanding of that knowledge, then progress to demonstrating how to apply concepts in practice, and finally, performing independently in real‐world situations. Clinical medical physicists can and should seek to expand their traditional role, especially in the context of a shortage of QMPsAll the authors have made significant contributions to the design and administration of the education and research programs described in this paper. Jessica Fagerstrom and Thomas Brown were responsible for writing the paper. All authors have reviewed the paper and were given the opportunity to provide edits prior to submission.The authors declare no conflicts of interest.


The Butterfly Girls (BFG) Study is a culturally and developmentally appropriate online obesity prevention program for 8–10-year-old Black girls designed with key stakeholders in the Black community. This multi-methods investigation, conducted with parent–child dyads who participated in an outcome evaluation of the intervention, aimed to understand parent and child reactions to the program. We were particularly interested in understanding perceptions regarding its cultural and developmental appropriateness, relevance and acceptability. Program participation and survey data  were analyzed. Participation data demonstrated high adherence in treatment and comparison groups. Descriptive statistics were calculated for survey data and highlighted the socioeconomic diversity of the sample. Post intervention surveys included two fill-in-the-blank questions for parents  and one for children (n = 32). Comments were analyzed using structured thematic analysis. The majority of the feedback from child participants was complimentary and many found the program relatable. Among the parent responses, the majority found the program to be beneficial in its educational nature and in promoting behavior change. This multi-methods analysis suggests that the BFG program was perceived as beneficial by parents while being culturally and developmentally appropriate and engaging for young Black girls, highlighting the importance of co-collaboration in program development.  Obesity prevalence in the United States is at an all-time high. Between 2017–2020, obesity prevalence among 2–19-year-olds was 19.7% . This diTo effectively address disparities and reduce obesity risk, convenient, accessible and personally relevant interventions are needed. Online interventions offer one possible route of providing convenience and accessibility given that internet access has increased for all racial and ethnic groups  and usagAddressing obesity-related disparities in Black girls is a key aspect of designing programs to achieve health equity. Health equity is evident when everyone is equally positioned to be as healthy as possible . EnsurinTo develop effective interventions for under-represented youth, cultural factors need to be considered to help ensure the appropriateness and relevance of program content and structure ,20. ThisThe Butterfly Girls program (BFG) was designed to address the inequities in obesity prevalence among Black girls. The program was developed using a community-engaged approach with the Black community in the greater Houston, TX area. The purpose of this paper is to report parent and child reactions to the program. Although described in detail elsewhere , the proThe BFG program was adapted from an earlier pilot intervention consisting of a summer day camp, followed by an internet component to promote maintenance of change . The intDuring adaptation of the BFG intervention , communiBlack girls, 8–10 years old living in the greater Houston, TX area, were recruited using standard procedures and the volunteer database at the Children’s Nutrition Research Center. Eligibility criteria included 8–10-year-old Black girls with a personal email address, internet access and a parent or legal guardian who was willing to allow them to participate and would themselves participate in the parent component of the program . While gThis paper reports parent and child reactions to, and child participation in, an intervention designed using community-engaged research. Data for this paper included parent and child quantitative and qualitative data from baseline and post 1 (immediate post-intervention) data collection time points. Surveys were completed online using a private password. As part of baseline data collection, parents completed demographic surveys describing personal and home characteristics. The characteristics included total household income, highest level of household education, parent race and ethnicity, parent gender and the number of adults living in the household including themselves. At post 1 (immediately after their daughter completed the intervention), parents of girls randomized to the treatment or comparison group were eligible to complete a process evaluation survey. The survey included two open-ended questions. The first question required a yes/no response: “Would you recommend this program to other parents?” followed by, “Please tell us your reasons for recommending or not recommending the program to other parents”. At the end of the survey, parents were given an opportunity to provide additional information: “Please use this box for any additional comments you may have”. For the girls, program participation data was automatically collected in each session as girls logged in and interacted with the program. At post 1, girls randomized to the treatment or comparison group were eligible to complete a process evaluation survey with one open-ended question: “If there is anything you would like to tell us about the characters, their voices, the story, or the program, please type it in here”. Survey responses were analyzed using descriptive statistics . A structured analytic approach was used to code parent and child data . Prior tThree hundred thirty parents completed the demographic survey . Nearly Parents (n = 205) responded to the survey question as to whether or not they would recommend the program to other parents and provided reasons for such a decision. Overall, 98.1% of the parents said that they would recommend the program to other parents. Of these, 184 parents responded to the question, “Please tell us your reasons for recommending or not recommending the program to other parents” and 65 parents responded to “Please use this box for any additional comments you may have”. Responses to both questions were separately coded and grouped into six categories: benefits, compliments, suggestions, barriers, data collection and requests. Results are summarized by question below, supported by representative comments to provide context and insight. Verbatim comments are shown to provide additional insight. To ensure categories accurately captured parent comments, responses could be coded into multiple categories, depending on response content. For the question: “Please tell us your reasons for recommending or not recommending the program to other parents”, 213 comments were grouped into five categories . The catThe majority of the comments noted the education-related benefits of the program. For instance, parents often stated that the program added “educational value to both parents and kids on living healthily” or generally described it as informational, using words like “informative” and “great information” or made the parents aware of their current dietary habits by using phrases such as “it [the program] helps me and my daughter realize what we ate”. Comments on behavior change indicated that the program was motivational and encouraged healthy eating and physical activity. One parent noted that the program provided “great motivation for healthy changes”. Another parent said, “this program is [a] good way to encourage girls to get and stay active”. Child agency was defined as enhancing self-confidence regarding health choices. For instance, one parent said the program will help “children make better choices for themselves and encourage their friends”. Another said it helps “girls have a positive body image”. Comments related to family time often focused on the program being a bonding opportunity as indicated in this comment: “this program brings mothers and daughters closer”. Another parent said the program helped them “think about the type of foods I was purchasing for my family and some ways we could improve as it relates to eating and just spending quality/active time with the kids”, indicating that the program itself was a bonding experience and helped encourage bonding outside of the time spent on the program. Responses coded under general were not specific enough to be subcategorized. They typically stated something like “great program for young girls” or that “other parents can benefit from this program”. Compliments contained the second largest category of responses (n = 58). These responses were further sub-categorized as compliments about their overall experience (n = 31) and program-specific compliments (n = 27). Responses that were complimentary of the overall experience indicated that parents felt positive about their time in the program. One parent indicated that it was a “great experience for [their) child] and good interaction between parent and child”. Another parent described their overall experience as “relevant to issues in our society with African Americans, engaging and convenient”. Several of the comments described their experience in BFG as being engaging or “fun”. Program-specific comments tended to focus on the information related to health and nutrition provided by the program. For example, a parent said, “I find the program very informative and kid-friendly. The language use is clear and precise and on the level that children understand”. Few comments (n = 3) were coded as suggestions. One parent indicated that they thought the program would be better if children were asked to watch the videos and repeat the information to the parent in their own words rather than having parents watch the videos with them. They thought the program could be turned into a reading and writing assignment to “sharpen critical thinking skills”. Another parent wished the program had been offered in-person. Similarly, few comments (n = 2) were coded as barriers. Both were time-related. One parent said, “great program, but time consuming”, while the other said the program took “a lot of time and effort”. Only one comment focused on the data collection experience. This comment described the parent’s awareness of the importance of data collection for healthy lifestyles. There were no comments coded as requests, which were defined as asking for consideration of some type or changes they would like to see in future iterations of the program. . Compliments were further sub-coded as compliments on the overall experience (n = 32), program (n = 4), or staff (n = 3). Compliments on the overall experience tended to be general, e.g., one parent said “it’s a wonderful program”. Compliments on the program focused on how “interactive” parents found it or on the “ideals” exemplified in the episodes. Comments on the staff described their interactions as positive and found it helpful to have reminders from the research team to complete episodes.Parents also viewed the program as beneficial (n = 20 comments), further grouped into four subcategories: motivation for behavior change (n = 11), educational (n = 5), child agency (n = 2) and family time (n = 2). The majority of the comments were related to behavior change. For example, many of the comments given by parents were similar to this statement: “the program helped us reinforce what we’re trying to do as a family”. One parent said that they added more fruits and vegetables to their meals and enrolled the children in physical activity programs following program completion. Additionally, parents commented on the educational aspects of the program saying that they learned more about “good food habits” and considered the program to be a resource. Agency was mentioned by two parents. For example, one noted that her daughter is “very proud about her part in the study… It is now great to see how she compares what she has learned from the videos…to life as she sees it and is able to see how either herself or other(s) can make better choices”. Family time was also mentioned by a few parents. As one parent commented: the program “opened up a dialog between the two of us (mother and daughter) about changes we could and should make to our families’ diet.”Fourteen responses were coded as suggestions. Suggestions were further subcategorized as positive (n = 8) or negative (n = 6). Several of the positive responses called for expansion of the program in some way: for example, two parents suggested expanding the age range and one suggested targeting the program to low-income families. Negative responses primarily focused on the videos, ranging from parents asking to expand the videos in order to demonstrate more ways to add vegetables into diet, to the need for better technical quality and more realistic character voices. Shortening the time commitment needed to complete the dietary recalls was also suggested.Very few comments (n = 3) focused on barriers. Two parents indicated that they did not have sufficient time to incorporate more of the lifestyle changes they had wished to incorporate, while another indicated they faced a financial barrier to buying produce. Finally, one parent indicated that they were unable to get the rest of the family interested in making lifestyle changes suggested in the videos. Two responses were coded under data collection. Both were coded as negative. One parent indicated that the diet recall survey “wore out” her daughter due to issues with attention span . The other parent indicated that the activity tracker was uncomfortable for her daughter to wear . Two comments were coded as requests. One parent requested a focus on promoting independence such as including an activity where the child shops for recipe ingredients. Another parent indicated a desire to have similar programming for a son. After completing baseline data collection, 342 girls were randomized to condition: 114 to the treatment (full intervention) condition, 114 to the comparison condition (animated stories only) and 114 to the waitlist control condition. Episode completion for all groups was automatically cataloged as girls navigated the online program. The majority of girls assigned to the treatment (53.5%) and comparison (68.4%) conditions watched all 10 episodes, while few girls in the waitlist control condition did so (4.4%) . Girls (n = 32) provided responses for the question “if there is anything you would like to tell us about the characters, their voices, the story, or the program, please type it in here”). Responses were grouped into five categories: compliments, relatability, complaints, requests and benefits. Results for each category are summarized below and in The category receiving the most comments was compliments (n = 32). Comments were grouped into three subcategories: storyline (n = 13 comments), characters (n = 13 comments) and overall program (n = 6 comments). In general, girls felt positive toward the storyline. One girl liked how the story was put together and another found the plot “easy to follow along with”. Another girl simply said, “I love everything about the stories”. Compliments regarding characters generally focused on positive attributes they admired in the characters such as strength, confidence, or athleticism. For instance, one girl described the characters as “strong, confident, peaceful and more”. Several girls expressed positive reactions to the overall program, most frequently focusing on the fun they had while participating in the program. For example, one girl commented that the program was “fun, creative and easy to read”. Ten comments from nine girls were coded as relatability, defined as the child feeling positively represented by the story, feeling the overall experience was inclusive, or feeling represented by the characters. Comments were further grouped into reactions to the characters (n = 9) and the overall program (n = 1). Findings indicate that girls felt connected to the characters, particularly those who shared a common interest with the girls and looked like them. For example, one girl stated, “I like the characters because they relate to me because I like butterflies and fashion”, while another said, “[the girl characters] remind me of my friends and cousins”. Finally, another indicated that she related to the program saying that participating in the program made her feel part of a “special group”. Five comments were coded as complaints. The comments were further grouped into reactions to the voices (n = 2), storyline (n = 1), program (n = 1) and characters (n = 1). Findings were varied. Two girls found the voices “weird”. One girl wished the girls had been shown going to school. Another girl had technical difficulties in finishing an episode. Lastly, one girl indicated disliking the character who “berated her friends”. Four comments were coded as requests. These comments related to reactions to the program (n = 2), characters (n = 1), or storyline (n = 1). Requests were varied. One girl wished to taste the recipes she did not get to try during the program. Another girl indicated a desire to repeat the program with a different story stating that she would “love to do it again with a different story”. Regarding the comment related to characters, one girl wished for a change to a character’s role in the storyline requesting that they played for a different soccer team. Similarly, one girl indicated a desire for nicer antagonists . Lastly, two comments were coded as program benefits. One girl said, “it was great how the butterfly girls taught me to stay active”. The other girl stated that the program gave her the opportunity to interact with computers.Parent/child pairs (n = 342) participated in the Butterfly Girls program promoting healthy diet and physical activity behaviors for 8–10-year-old Black girls. The program was developed using community-engaged research with multiple stakeholder groups, including 8–10-year-old Black girls, their parents and community representatives. Girls randomized to the treatment or comparison groups demonstrated high levels of program participation. This study aimed to understand parent and child reactions to the program following community engagement during program development. Future papers will utilize machine learning to detect patterns in diet, physical activity and body weight change following the BFG program. Parent and child comments indicated high connectedness to the program and that it was viewed as an educational and motivational resource. Results also provide evidence that a program designed with key stakeholders from the community for whom the intervention is intended can result in high program participation. This suggests that co-design approaches, such as community-engaged research, are essential for programs designed to attain health equity.The demographics of the study sample were socioeconomically diverse with 43.0% of parents earning $41,000 a year or less and 38.8% of parents earning over $61,000 a year. However, the majority of the households represented had an individual with at least a college degree. The fact that education status did not necessarily predict the socioeconomic diversity of the sample is consistent with other studies in minority populations that have shown that income disparities can persist despite educational status ,30. Program dose was relatively high with 68.4% of the girls in the comparison group and 53.5% in the experimental group watching all of the BFG episodes, suggesting an acceptable program dose. Alternatively, girls in the wait-list control group watched few episodes. A community-based obesity prevention program for parents and children with longitudinal interactions with research staff reported similar attendance to those in our treatment and comparison conditions, with an average attendance of 64.0% of sessions .Striking differences in program dose were observed among the groups, which may partially be explained by participation reminders. While girls in the treatment and comparison groups received reminders to log on, those in the waitlist control group did not. Girls in the treatment and waitlist control groups received the same intervention, with the only difference being participation reminders, suggesting that reminders can enhance participation. The literature supports the importance of participation reminders in program adherence. Shumaker et al.  and RobiThe qualitative findings from the girls indicated connectedness to the characters and positive perception of the overall storyline and characters. These findings support the importance of community-engaged research when developing interventions for under-represented children. Collaboration with minority populations in the research process allows for the cultural sensitivity the girls’ comments highlighted . The girThe qualitative responses from the parents indicated that they found the program to be beneficial, primarily as an educational resource and secondly as a motivator for behavior change, and was an overall positive experience. Parental perception is of particular importance given that parents can be a powerful determinant of children’s health behaviors ,36. PareThe BFG Program had several limitations. Perhaps in part due to the developmental maturity of participants, only 32 children responded to the qualitative prompts in the Post 1 timepoint survey. Furthermore, there is a possibility that responses for parents and children to qualitative prompts were self-selecting in that only those who had significant experiences in the BFG program gave an answer. Further, parental educational status was relatively high, which may limit generalizability. However, the socioeconomic status of parent participants was diverse which may lessen this concern. Finally, it is possible that the Hawthorne effect influenced participation given that participants received phone calls from researchers if they failed to watch an episode . DespiteThis study provides evidence that a co-design approach via collaboration with key community stakeholders can encourage program engagement, as evidenced by high program participation rates and positive reactions to the program. These findings suggest that a co-design approach is an important component of programs designed to achieve health equity.


Lefkowitz et al. Nature Communications 10.1038/s41467-023-42848-5 (2023)2-adrenoceptors”1. In their critique2, they state that our study concludes that intrinsic sympathomimetic activity (ISA) is the mechanism responsible for the beneficial actions of carvedilol and that this is incorrect. First and foremost, we neither concluded definitively that ISA explains the superior clinical profile of carvedilol nor do we suggest any changes to the well-established, beneficial clinical practices. We did not intend to make inferences between the mechanism of carvedilol action and its clinical significance. Our statements considering any potential in vivo and clinical implications of our work were purely speculative and meant to stimulate further research and discussion. The pertinent question in Benkel et al.1 is rather to illuminate how carvedilol, a widely used beta blocker that works by inhibiting β1-ARs, activates cellular signaling via the β2-AR subtype. Specifically, we state in the abstract “beyond blockade of β1-ARs, arrestin-biased signaling via β2-ARs is a molecular mechanism proposed to explain the survival benefits. Here, we offer an alternative mechanism to rationalize carvedilol’s cellular signaling”.We thank Dr. Robert Lefkowitz and co-authors for their comments on our article “How carvedilol activates β2-ARs and find that G-proteins but not arrestins initiate all detectable cellular signals in these conditions. Others postulate arrestin-biased agonism for carvedilol at the β2-AR4 and hence a debate is sparked on how precisely carvedilol activates this β-adrenoceptor subtype. We certainly stand by all conclusions presented in our published work1, and we explain below how a thorough comparison of the data contained in Benkel et al.1 with those referenced by Lefkowitz et al.2 along with enhanced semantic precision will help resolve the apparent confusion and provide a unified explanation of events.Herein, we can only reiterate that we established novel and recapitulated previously used cellular systems to bring about carvedilol signaling through β2-AR in engineered cells and even in primary neonatal cardiomyocytes must not be confounded with the clinical relevance and value of β-blockers that may or may not display varying degrees of ISA. ISA was originally coined to describe the ability of β-blockers to also stimulate β-ARs to some extent and this partial activation may become manifest as elevation of cAMP, heart rate, or force of contraction7. As pointed out by Lefkowitz and co-authors2, there is clinical consensus from a number of post-myocardial infarction trials carried out in the 1970’s and 1980’s that β-blockers with too much ISA are not beneficial and may even increase mortality of heart failure patients2, in apparent contrast to the only study cited in Benkel et al.1. However, Lefkowitz et al.2 do not mention that the study cited by Benkel et al.1 was published in 1990 and so made reference to several of these earlier trials as well as unveiled that a subgroup of high-risk patients not enrolled in these trials did indeed benefit from mild ISA9. Thus, whether ISA may be beneficial or not is likely dependent on the degree of ISA, the selected patient population, and, finally, the involved β-receptor subtype.We are keen to stress that the molecular mechanism underlying carvedilol activation of the β1 we use the term ISA to refer specifically to the weak activation induced by carvedilol through the β2-AR , and we employed cellular conditions that allow both detection of this weak activation and its mechanistic dissection. For the above reasons, our discussion on the clinical significance of ISA in Benkel et al.1 is short and entirely speculative. Clinical implications were not the focus of our work.In Benkel et al.2 correctly point out that carvedilol stimulation of β-ARs is variably detected across species and experimental paradigms. For instance, in untransfected HEK293 cells which express low (physiologic) levels of β2-AR, carvedilol neither elevates cAMP nor stimulates phosphorylation of ERK/MAP kinases. It follows that overexpression systems are clearly demanded to study the low efficacy carvedilol signaling in the HEK cellular context. We appreciate the comment2 that “carvedilol does indeed promote some very low level of cAMP accumulation provided that receptor levels are raised dramatically by overexpression and that high concentrations of carvedilol are used”. In fact, the authors state that “The concentrations of carvedilol used in Benkel’s overexpressing cells, 10 micromolar for many studies, and above one micromolar in most, are well above the plasma levels the drug ever achieves clinically.” We are well aware that elevation of cAMP but also phosphorylation of ERK/MAP kinases (pERK), require such high carvedilol concentrations as well as overexpressing cells. The same high concentration of carvedilol, 10 micromolar, and β2-AR overexpressing cells was used in the paper of the Lefkowitz group  to coin the unique mechanism of carvedilol action: stimulation of β-arrestin signaling. Given the notion that carvedilol stimulation of low-level functional responses in HEK293 cells requires β2-AR overexpression, it is even more surprising that some very recent investigations, referenced in ref. 2, study cAMP production at endogenous β2-AR expression but pERK in β2-AR overexpressing cells10. This clearly highlights the need for a very careful choice of experimental setup when designing studies to investigate biased signaling, as well as a careful interpretation and discussion of the results obtained from such experiments.Lefkowitz et al.2-AR activation by carvedilol is not only observable by us and others in recombinant cells  overexpressing the β2-AR12, but also in embryonic cardiomyocytes with endogenous β2-AR expression1, and even in explants from human ventricular myocardium7. We appreciate the comment of Lefkowitz and colleagues that the ISA of carvedilol is detectable in only one out of seven human explants, clearly attesting to both (i) its predominant action as β-blocker and (ii) the ability to also activate β-receptors to some extent. Given that low efficacy β2-AR activation is quite variably detected for carvedilol13, it is very likely cellular context-, patient- and disease-dependent. In our neonatal cardiomyocyte preparation, we recorded very slow and low-level cAMP elevation , but carvedilol enhancement of spontaneous cardiomyocyte beating was only observable in cells with spontaneous beating ≤60 bpm (as stated in the legend), and after blockade of β1-ARs with the β1-preferring blocker CGP-20712A . Thus, our experimental setup is distinct from many other studies that did not observe ISA in the endogenous context, as we deliberately needed to create cellular conditions that are permissive for detection of low-level β2-AR activation. Whether low-level β2-AR activation or any other mechanistic attribute is responsible for the beneficial actions of carvedilol in the clinic is clearly beyond our discretion.Low efficacy β1, we chose to use engineered HEK293 cells, depleted by CRISPR/Cas9 of either G-proteins or β-arrestins, to investigate the molecular details underlying the low-level carvedilol signaling. Because HEK293 cells have been used to coin the unique mechanism of carvedilol signaling3, and because such cells are by far more amenable than primary cells to genetic manipulations and to the identification of the involved signaling components, engineered HEK293 cells are the line of choice to disentangle why apparently comparable experimental settings may lead to such disparate mechanistic conclusions: G-protein versus arrestin signaling.In Benkel et al.1 determined cAMP elevation and phosphorylation of ERK/MAP kinases in HEK293 cells overexpressing the β2-AR and lacking either G-proteins or arrestins, Lefkowitz et al.2 and the few additional studies referenced therein only used arrestin-depleted cells but did not take advantage of the G-protein-depleted counterparts. We believe this is necessary for two reasons: first, arrestin-depleted cells only allow to investigate arrestin contribution to G-protein-driven signals; second, G-protein-depleted cells are a prerequisite to visualize the suggested arrestin transducer function, i.e., the ability of arrestins to promote signaling in their own right and independent of functional G-proteins. If this is not done, mechanistic conclusions on a signaling driver role of arrestins must not be drawn and may likely be erroneous and misleading.We believe that a thorough look at experimental details and original data obtained in such engineered cells is likely to provide a plausible explanation. While Benkel et al.4. However, to truly unmask the arrestin transducer function, experimental paradigms would require genetic deletion or pharmacological inhibition of heterotrimeric G-proteins and β-arrestins. Unfortunately, studies like these are still scarce18, although they are now technically feasible due to the advent of gene editing technologies yielding mammalian expression hosts with either targeted deletion of the α subunits of the four G-protein classes18 or arrestins18. Along with G-protein class-specific inhibitors such as pertussis toxin, FR900359, and YM25489021, as well as naturally arrestin-biased receptors that internalize but do not signal through heterotrimeric G-proteins22, these engineered cells offer a widespread and useful approach to discriminate, unambiguously, transducers of receptor signals from proteins that assist but do not drive signaling on their own. The collective experimental evidence gathered with such genome-edited cells nicely illustrates that carvedilol used at high concentrations in β2-AR overexpressing cells4 actively promotes signaling in a process that is G-protein-dependent and arrestin-assisted.Looking ahead, enhanced semantic precision will also be indispensable to solving the problem. The term “arrestin signaling” was coined to reflect the independent transducer function of this protein family and to differentiate the arrestin pathway from the canonical G-protein-mediated signal transduction. However, the very same term, arrestin signaling, is also used to denote the arrestin contribution to G-protein-initiated signal transduction, which is mechanistically distinct. Indeed, arrestin contribution to G-protein-initiated signaling explains both diminished pERK upon reduction of βarr1/2 expression and enhanced pERK1/2 in βarr1/2 KO cells upon βarr1/2 re-expression after GPCR stimulation2-AR. The reason why carvedilol shows a superior profile in clinical practice remains entirely speculative and needs to take into account all properties of this β-blocker, including but not limited to its interaction with α-adrenergic receptors23.Controversy exists in every field of science and is essential to spur new ideas and scientific progress. This communication focuses on the controversy surrounding the molecular mechanism that underlies low efficacy carvedilol activation of the β


Recent studies underline the need for research on approaches to encouraging healthy listening habits. This study aims to develop and evaluate an online hearing loss prevention program; and examine its influence on the participants’ use of hearing protection, hearing loss prevention knowledge, attitude towards noise, and program useability and adherence.The study was conducted in the county of Västra Götaland, Sweden, from March through October 2021. The program included four modules focused on hearing and hearing loss prevention and was accessible to the participants for four weeks. In total, 75 participants completed the program which was evaluated using the Youth Attitude to Noise Scale and four additional self-designed questionnaires. The questionnaires were deployed before and immediately after program completion.The findings indicate that the program may influence the participants’ attitudes toward noise and the use of hearing protection. The participants who completed the program perceived high useability and increased hearing loss prevention knowledge. This program is most needed to promote healthy hearing. Future studies should target specific groups with this program and evaluate its long-term effects. Not allA recent systematic review showed that unsafe listening is highly prevalent in young individuals aged 12–34 years . ExperieShaping knowledge and addressing health consequences are important components when promoting health behaviour change . For exaOnline interventions may improve the accessibility of hearing health care and can be a cost-effective way change of listening habits . Such inOur aim was threefold: a) to develop an online HL prevention program (oHLPP), b) to investigate the program adherence, and c) to evaluate the oHLPP within the group of participants who completed the program. We wanted to investigate whether the oHLPP could increase the perceived knowledge of HL prevention among participants who completed the program and enhance their hearing protective behaviour between pre-and post-intervention, for the total group, and between subgroups related to age and HL/No HL. The participants were divided into 20–65y, representing the working-age category/professionals, and ≥ 66y representing the non-working population as 65 is the retirement age in Sweden. Recreational activities may dominate in this part of life .2The study was conducted in the county of Västra Götaland, Sweden, March–October 2021. The study was approved by the Swedish Ethical Review Authority (Dnr. 2020–01966) and conducted using an experimental design where all participants received the same intervention, and the outcomes were assessed over time.2.1The oHLPP was created by experienced clinically practicing and research audiologists with knowledge of online interventions and HL prevention. The program was developed using the Sweden's national Health Care Platform (HCP). The oHLPP consists of four modules, each underpinned with components and modalities aimed to increase and reinforce HL prevention knowledge see .Table 1IIntroductory summaries and quizzes were used throughout the oHLPP except for week 1. This effectively promoted repetition of the information, which facilitates knowledge acquisition and may help identify knowledge gaps while building confidence in knowledge retention . FurtherEach module took approximately one hour to complete, and all content was printable except the videos. To encourage program adherence, weekly notifications were sent through the HCP to inform users that new content was available. The HCP also contained a message service allowing program users to contact the research team directly with questions or feedback. After completing the oHLPP, users were encouraged to use their newly acquired hearing preventive knowledge in their everyday life by summarizing the benefits of HP-use and pointing out important take-home messages.A pilot group of 12 participants  with self-reported HL, n = 2 (age 66 and 72) and without self-reported HL, n = 10  evaluated the first version of the oHLPP verbally and/or by written feedback to the research team. These participants were personal acquaintances of the research group and were contacted via phone, text message, or social media. The pilot group had access to the oHLPP for two weeks and was asked to address questions regarding the content of the program, its relevance, comprehensibility, text quantity, and level of overall adversity. In addition, the online prevention program was evaluated regarding its structure, usability, length, layout, and utility.The oHLPP was perceived as relevant and comprehensive, and the content was generally perceived as easy to understand. The pilot group had a positive view of the layout of the program and found it easy to log in and navigate through the pages. The pilot group suggested improvements such as: extending the number of videos, condensing some of the text information, including introductory text to the quizzes for the participant to better understand the purpose and having the program accessible for four weeks, with one module presented each week.Based on these suggestions, redundant text was removed, and additional videos and introductory texts were included with the quizzes. After this revision, the new version was shared with the pilot group, and no further changes were suggested.2.2The inclusion criteria for the oHLPP evaluation were for the participant to be ≥ 18 years of age, and to have access to the HCP. Participation was voluntary, and the participants could at any time withdraw from the study.First, an invitation letter and a consent form were sent to 600 hearing aid users who had been diagnosed with HL by an audiologist at the Hearing Organization, the County of Västra Götaland. Second, a volunteer sampling using advertisements through different social media-  and county websites were used. The participants were encouraged to visit the oHLPP program. Lastly, without using any advertisement, the oHLPP was available for those actively searching for an online program to participate in. Volunteers who returned a signed consent form with a request for additional information about the study were contacted by phone. A summary of the recruitment process can be found in The outlines of the questionnaires deployed pre- and post-intervention can be found in Appendix 1,2,3,As the HCP requires personal data authentication, age and gender were collected through the platform. These demographics together with information on hearing aid use from the recruitment process and responses on questionnaires deployed pre-intervention see  are presThe oHLPP was accessible to the participants for as long as the data collection continued. Though designed to last four weeks, the participants themselves decided on the appropriate study pace. The research group was able to monitor the participants’ online activity through the HCP, for example when a participant activated a new module. If participants printed out the information, online monitoring was not possible.2.3Program adherence was investigated using descriptive statistics. A ranking approach  was usedDue to a lack of validated questionaries measuring attitudes toward noise for an older population, the Youth Attitude to Noise Scale (YANS) was used even though validated for individuals below thirty years of age . The sub33.1The demographics and hearing-related information of the participants collected using questionnaires on hearing and knowledge pre-intervention see and 2 ca3.2A total of 75 participants completed the oHLPP. Those who did not respond to questionnaires pre-and/or post-participation were excluded from that specific analysis. Accordingly, 70 participants evaluated HP-use, 69 the outcomes measured with YANS, and 67 evaluated perceived knowledge and the usability of the oHLPP.Never , and by Hearing Organization in Region Västra Götaland, Sweden.Andreas Thulin: Conceptualization, Methodology, Writing – original draft, Software, Investigation, Writing – review & editing, Visualization, Formal analysis. Kim Kähäri: Conceptualization, Methodology, Writing – original draft, Supervision. Milijana Malmberg: Conceptualization, Methodology, Writing – original draft, Software, Investigation, Writing – review & editing, Visualization, Supervision, Data curation, Project administration, Funding acquisition.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.