Emerging evidence suggests that worldwide, between 30% and 50% of those who are infected with COVID-19 experience long COVID (LC) symptoms. These symptoms create challenges with return-to-work (RTW) in a high proportion of individuals with LC. To tailor rehabilitation programs to LC sequelae and help improve RTW outcomes, more research on LC rehabilitation program outcomes is needed.This study describes the characteristics and outcomes of workers who participated in an LC occupational rehabilitation program.A cohort study was conducted. Descriptive variables included demographic and occupational factors as well as patient-reported outcome measures . The main outcome variable was the RTW status at discharge. Descriptive statistics were calculated. Logistic regression examined predictors of RTW.t31=2.5, P=.02), the PDI , the FSS , the SF-36 PCS , the PHQ-9 , and the GAD-7 , there were no significant improvements in the PCFS, the overall mental component score (MCS) of the SF-36, or on the PCL-5. The availability of modified duties  and shorter time between infection and admission for rehabilitation  predicted RTW even when controlling for age and gender.The sample consisted of 81 workers. Most workers were female  and from health-related occupations . Only 43 (53%) individuals returned to work at program discharge, with 40 (93%) of these returning to modified duties. Although there were statistically significant improvements on the pain VAS  returned to work. Outcomes would likely improve with increased availability of modified duties and timelier rehabilitation. Additional research is needed, including larger observational cohorts as well as randomized controlled trials to evaluate the effectiveness of LC rehabilitation. Emerging evidence indicates that worldwide, between 30% and 50% of those who contract COVID-19 experience long COVID (LC) symptoms  . An inteIndividuals recovering from COVID-19 will increase demands for rehabilitation due to the prevalence and diversity of recognized LC sequelae -11. CommTo optimally tailor rehabilitation programs to LC sequelae and help improve outcomes of RTW programs, more research on LC rehabilitation is needed. This is especially true of rehabilitation programs that specifically aim to promote RTW. It is also important to explore whether certain individuals with LC fare better in rehabilitation than others, as this may identify potentially modifiable lifestyle or broader contextual factors that may facilitate the tailoring of rehabilitation services, thus increasing relevance and potentially improving RTW outcomes in this population.This study aims to describe the characteristics and outcomes of workers participating in occupational rehabilitation through Workers’ Compensation Board of Alberta’s (WCB-Alberta) Millard Health post-COVID rehabilitation program. We met this aim by (1) describing the characteristics of workers who accessed the program, (2) describing and comparing program admission and discharge data to determine whether there were significant changes in rehabilitation outcomes over the course of the program, and (3) comparing baseline and RTW status at discharge to determine what factors identified through admission data, if any, best predicted RTW status.The specific research questions (RQs) were as follows:RQ1: What are the descriptive characteristics of workers participating in WCB-Alberta’s Millard Health post-COVID rehabilitation program?RQ2: Are there significant improvements in outcomes between admission and discharge from the program?RQ3: Are worker descriptive characteristics or health status, identifiable upon admission, predictive of RTW status at discharge from the program?A descriptive cohort study was conducted using data collected by WCB-Alberta for regular program evaluation purposes.This research was approved by the University of Alberta’s Health Research Ethics Board (#Pro00113982).This study included data from workers participating in WCB-Alberta’s Millard Health post-COVID rehabilitation program. This program was created to help workers with compensation claims due to workplace COVID-19 exposure who developed LC return to regular work duties . The mulThe data set included information about all workers who contracted COVID-19 between March 2020 and mid-May 2021. To be included in this study, workers had to be at least 18 years of age and discharged from the aforementioned rehabilitation program. Workers who had not yet been discharged from the program were excluded as their outcomes resulting from program participation were not yet known. All workers had been discharged from the program prior to early January 2022.Anonymized data were extracted from provincial databases managed by WCB-Alberta Health Care Strategy. WCB-Alberta reports are electronic, and data from health care providers are automatically entered into databases. Reports are filed by health care providers at admission to, and discharge from, any WCB-Alberta program. Providers of the post-COVID rehabilitation program report on a variety of demographic, clinical, and occupational variables. Our team has previously conducted several studies using data from WCB-Alberta programs -26, and All data points were included in descriptive statistical calculations. This allowed us to obtain a clear picture of the demographics and general outcomes of the post-COVID rehabilitation program. No sample sizes were calculated, as all workers completing the post-COVID rehabilitation program were included .The data set included a variety of descriptive variables, including demographic factors , occupational factors , treatment factors , and mode of treatment delivery . Gender was treated as a categorical variable with 3 options: male, female, and undisclosed.Diagnostic and Statistical Manual for Mental Disorders Fifth Edition (DSM-5) posttraumatic stress disorder (PTSD) checklist (PCL-5) [Independent variables also included patient-reported outcome measures (PROMs) administered at the time of admission to the program. The PROMs included in this study were the Fatigue Severity Scale (FSS) , the Pos (PCL-5) . Table 1The outcome variable for this study was RTW status at program discharge. RTW status was chosen as the outcome variable of interest because previous research has shown that RTW status is impacted by LC and RTW is a primary goal of the rehabilitation program -17. RTW Data were analyzed using SPSS Statistics version 28 (IBM Corp). To address RQ1, we calculated the mean and SDs of any interval data  and the frequency of any categorical data .t tests for each variable collected upon admission to and discharge from the program to determine whether there were any significant improvements in outcomes. Wilcoxon signed-rank tests were performed if the dependent variable was not continuous .To address RQ2, we calculated descriptive statistics for the various PROMs. We calculated the mean and SDs of interval data and the frequency of categorical data. We performed paired-samples To address RQ3, logistic regression analyses were used to determine which variables , if any, were predictive of RTW status at discharge. Imputation techniques were used to address the high levels of missing data on the PROMs. We completed univariable logistic regression analyses to examine each potential prognostic factor. Due to the limited sample size, we were unable to build multivariable predictive models. However, we examined the potential confounding effects of age and gender on the significantly predictive variables. Relevant assumptions were tested.The data set included 81 workers who had been discharged from WCB-Alberta Millard Health post-COVID program  workers not completing at least 1 of the measures at admission or discharge. Only raw SF-36 data were available at discharge, thus preventing calculation of domain scores at admission. However, overall PCSs and MCSs for the SF-36 were logged at admission and discharge.t tests were run on those with complete matched PROM data . Due to the substantial amount of missing PROM data, we included all workers with complete data (the maximum number of matched pairs on any PROM in our sample was 39). Significant changes were noted on several measures , the PDI , the FSS , the SF-36 PCS , the PHQ-9 , and the GAD-7 . There were no significant improvements to the overall MCS measured through the SF-36 or the PCL-5 scores.Paired-samples measures . There wt test could not be carried out. Instead, a Wilcoxon signed-rank test was performed , suggesting that those with incomplete data had a lower likelihood of returning to work.Univariate associations between all potential predictors and the outcome of RTW are shown in In this cohort study of workers with LC participating in WCB-Alberta’s Millard Health post-COVID rehabilitation program, many worker outcomes significantly but modestly improved between admission and discharge. However, several key functional measures did not improve . Only a small majority of the sample returned to work (53%), and of these, 93% required modified duties. Those who identified at admission that modified duties were available in their workplace were 3.38 times as likely than those without available modified duties to RTW at program discharge, after controlling for age and gender. Workers with a longer time between symptom onset and program admission also had a lower likelihood of successful RTW.Our study found that the presence of modified duties in the workplace at admission to LC rehabilitation results in better RTW outcomes. Although we could not find other studies quantifying the relationship between modified duties and RTW with LC, the emerging literature suggests that individuals with LC would likely have greater chances of RTW if they have access to flexible, gradual RTW plans with modified duties. For example, Wong et al  completeThe importance of modified duties in LC rehabilitation is consistent with the broader field of occupational rehabilitation and work disability prevention, where modified work duties and RTW coordination are core components of rehabilitation and used to promote RTW . Early iTo the best of our knowledge, this is the first study examining the predictors of RTW among workers with LC, likely because of the novelty of the condition. However, previous research has examined RTW in individuals with chronic fatigue syndrome, which has been found to have an overlapping clinical presentation with LC . In a loThe primary limitations of this study are the large amount of missing data on the PROMs and the relatively small sample size. Completion of the PROMs was voluntary for patients in the program, which explains the sizeable amount of missing data. Missing data and a modest sample size limited our ability to build multivariate models and limited conclusions that could be drawn from our results. Having incomplete data on the GAD-7 was significantly associated with worse RTW, which suggests that those with missing data had a lower likelihood of returning to work. There are also likely unmeasured factors that influence both completion of the PROMs and RTW that should be further explored. Results are, however, important for individuals with LC due to the novelty of the condition and uncertainty around optimal rehabilitation approaches.Workers undergoing LC rehabilitation reported significant but modest improvements on a variety of PROMs, but only 53% of workers with LC returned to work at the time of program discharge. RTW outcomes would likely improve with increased availability of modified duties and timelier rehabilitation. Additional research is needed, including larger observational cohorts with additional variables as well as randomized controlled trials to evaluate the effectiveness of LC rehabilitation.


Immunoglobulin light chain (AL) amyloidosis may be caused by a B-cell non-Hodgkin lymphoma (NHL) rather than a plasma cell neoplasm in rare cases, which presents unique diagnostic and management considerations. NHL associated with AL will often have an IgM paraprotein; thus, this disease is termed IgM-related AL amyloidosis (IgM AL). The clinical presentation of IgM AL is more likely to involve the lungs, peripheral nerves, and soft tissue; cardiac involvement is less common. Patients with IgM AL amyloidosis should undergo a lymphoma-directed work-up including evaluation for nodal and extranodal disease. Additionally, patients with an IgM paraproteinemia should be screened for AL amyloidosis through history and physical examination. Treatment regimens active against underlying lymphoma, rather than plasma cell-directed regimens, are recommended. Historical response rates in IgM AL have been poor; prospective studies of novel antineoplastic regimens may improve treatment outcomes. Immunoglobulin light chain (AL) amyloidosis is a rare disease caused by extracellular tissue deposition of protein fibrils. AL amyloidosis is most often associated with an underlying plasma cell neoplasm, but is rarely caused by a B-cell non-Hodgkin lymphoma (NHL). When associated with NHL, there is often an IgM paraprotein present. This is known as IgM-related AL amyloidosis (IgM AL), and represents a distinct clinical entity with unique diagnostic and management considerations. Approximately 5-7% of patients diagnosed with AL amyloidosis will have IgM-associated disease . When coIgM AL may be associated with many different types of NHL, but it is most commonly associated with lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia (LPL/WM) 74%) . An asso% . An asPatients with IgM AL may first present with symptoms related to amyloidosis, IgM monoclonal protein, or lymphoma. In one review, the identification of a monoclonal IgM protein preceded the diagnosis of amyloidosis in about one third of patients . PatientIn patients with a known IgM monoclonal gammopathy, clinicians should evaluate carefully for signs and symptoms of amyloidosis when taking a history and conducting a physical examination. An estimated 7.5% of patients with LPL/WM are also diagnosed with AL amyloidosis at some point in the course of their disease .Neuropathy can pose a diagnostic dilemma, as this symptom is common in the general population and can be seen both in IgM monoclonal gammopathies as well as AL amyloidosis. Patients with neuropathy should undergo screening for other common etiologies such as diabetes, B12 deficiency, and alcohol use. Further evaluation includes nerve conduction studies, electromyography (EMG) and testing for anti-myelin associated antibodies (MAG) and anti-ganglioside antibodies. Monoclonal gammopathy of neurologic significance (MGNS) may be diagnosed if the following factors are present: symmetric sensory deficits, slow progression, length dependence, strongly positive anti-MAG antibodies, and prominent demyelination on EMG. Features less consistent with MGNS  should prompt a work-up for other diseases that may be associated with an IgM paraprotein and peripheral neuropathy, such as AL amyloidosis, POEMS , cryoglobulinemia, and Bing-Neel syndrome .The majority of patients will not require amyloid-specific evaluation beyond the history and physical exam. However, if suggestive symptoms are present, evaluation for potential amyloidosis should be pursued as detailed in the relevant review chapter. Of note, IgM MGUS can co-exist with other forms of systemic amyloidosis; presence of AL amyloidosis must be definitely determined in a biopsy specimen with mass spectrometry or immune electron microscopy .In addition to routine amyloidosis evaluation and staging, patients diagnosed with IgM AL should undergo an additional lymphoma evaluation. This differs significantly from patients with non-IgM AL who will undergo a workup for underlying plasma cell neoplasm. The initial evaluation includes the history and physical exam. Patients should be asked about the presence of B-symptoms, including night sweats, fever, or persistent weight loss. On physical exam, patients with IgM AL should have a thorough lymph node exam with particular attention paid to the cervical, supraclavicular, axillary and inguinal lymph nodes; the spleen should also be examined. Laboratory evaluation should include complete blood count (CBC), comprehensive metabolic panel (CMP), serum protein electrophoresis with immunofixation (SPEP/SIFE), quantitative immunoglobulins, serum free light chains, beta-2 microglobulin, lactate dehydrogenase (LDH), human immunodeficiency virus (HIV) antigen/antibody. Hepatitis B virus (HBV) serologies should be obtained given risk of HBV reactivation with rituximab therapy. Hepatitis C virus (HCV) serologies should be sent if there is a concern for splenic marginal zone lymphoma.The workup for AL amyloidosis, as well as LPL/WM, includes a bone marrow biopsy. Bone marrow samples should be sent for MYD88 testing and consideration of CXCR4 testing in addition to flow cytometry, immunohistochemical staining, and cytogenetic analysis. MYD88 gene mutation is present in over 90% of patients with LPL/WM and may helpful when the diagnosis is uncertain .Imaging should be obtained to evaluate for sites of NHL involvement, particularly the lymph nodes. Extranodal involvement may be present, but classic osteolytic bone lesions, as found in multiple myeloma, are less of a concern. Positron emission tomography/computerized tomography (PET/CT) is preferred for NHL staging evaluation, but computed tomography (CT) of the chest, abdomen, and pelvis with intravenous contrast can be a reasonable alternative in certain clinical situations . If lympMost prognostic evaluations of AL amyloidosis involve measures of cardiac dysfunction such as cardiac troponin or NT-proBNP. As cardiac involvement is less common in IgM AL, patients generally present with lower stage disease compared to non-IgM AL. Median survival of IgM AL is 49-78 months, similar to non-IgM AL . HoweverPatients with LPL/WM and amyloidosis have significantly worse overall survival than patients with LPL/WM alone  . The besThe overall goal of treatment is to eliminate the production of amyloid protein by targeting the underlying B-cell NHL. Typical plasma cell regimens are less effective in IgM AL, as they do not target the appropriate underlying clonal disorder . PatientWhile IgM AL has historically been treated with conventional chemotherapy alone , rituximab-based regimens along with bortezomib, immunomodulatory imide drugs (IMiDs), and Bruton’s tyrosine kinase inhibitors (BTKi) have been introduced into clinical practice and evaluated primarily in the form of small retrospective analyses and case series , 11, 12.In a small retrospective study with 27 patients, BR showed an overall response rate of 59%, with 11% of patients achieving complete response . BR is nIn a retrospective study of ibrutinib in 8 patients with IgM AL, only 2 (25%) achieved a hematologic response. Peripheral edema was described in 4 of 8 patients and atrial fibrillation in 2 of 8 patients . A subseAppropriately selected patients may be referred for autologous stem cell transplant. In a retrospective analysis of 38 patients who underwent transplant for IgM AL, response rates were high  . Over haWhile no standard treatment guideline exists, a reasonable approach may include BR as frontline treatment and a second generation BTKi at relapse. Determining how to best integrate and sequence autologous stem cell transplant remains a challenge due to limited data, with practices differing between centers. As we are treating an underlying lymphoma, induction treatment should be given prior to transplant consideration. Additionally, patients should be evaluated at specialty centers experienced with transplanting amyloid patients. However, less than a quarter of patients with IgM AL are transplant eligible at presentation .While uncommon, AL amyloidosis with underlying B-cell NHL is important to recognize due to its unique diagnostic and treatment considerations. Patients with IgM AL amyloidosis should be evaluated for presence of an underlying lymphoma. Additionally, patients with an IgM paraproteinemia should be screened for AL amyloidosis through history and physical examination. Treatment regimens active against underlying lymphoma are recommended, along with consideration of autologous stem cell transplant in appropriately selected patients. Historical response rates in IgM AL have been poor; future prospective studies of modern chemotherapy regimens may improve treatment outcomes.CB and CD both contributed to literature review, research analysis, and manuscript drafting. Both authors contributed to the article and approved the submitted version.


Background: COVID-19 pandemic lockdowns led to the closure of most in-person pulmonary rehabilitation programs in Australia. Text message programs are effective for delivering health support to aid the self-management of people with chronic diseases. This study aimed to evaluate the implementation of a six-month pre-post text message support program (Texting for Wellness: Lung Support Service), and the enablers and barriers to its adoption and implementation. Methods: This mixed-methods pre-post study used the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework to evaluate the Texting for Wellness: Lung Support Service, which is an automated six-month text message support program that included evidence-based lifestyle, disease-self management and COVID-19-related information. Reach was measured by the proportion of participant enrolments and demographic characteristics. Adoption enablers and barriers were measured using text message response data and a user feedback survey . Implementation was evaluated to determine fidelity including text message delivery data, opt-outs, and intervention costs to promote and deliver the program. Results: In total, 707/1940 (36.4%) participants enrolled and provided e-consent, with a mean age (±standard deviation) of 67.9 (±9.2) years old (range: 23–87 years). Of participants who provided feedback, (326/707) most ‘agreed’ or ‘strongly agreed’ that the text messages were easy to understand (98.5%), helpful them to feel supported (92.3%) and helped them to manage their health (88.0%). Factors influencing engagement included a feeling of support and reducing loneliness, and its usefulness for health self-management. Messages were delivered as planned (93.7% successfully delivered) with minimal participant dropouts (92.2% retention rate) and low cost ($AUD24.48/participant for six months). A total of 2263 text message replies were received from 496 unique participants. There were no reported adverse events. Conclusion: Texting for Wellness: Lung Support Service was implemented quickly, had a broad reach, with high retention and acceptability among participants. The program was low cost and required minimal staff oversight, which may facilitate future implementation. Further research is needed to evaluate the efficacy of text messaging for the improvement of lung health outcomes and strategies for long-term pulmonary rehabilitation program maintenance. Chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), chronic asthma and bronchiectasis, are among the most common non-communicable diseases worldwide . In 2017Globally, 91% of people own a mobile phone . In AustA mixed-methods  evaluation of a six-month pre-post text message support program for people with chronic respiratory disease during the COVID-19 pandemic was conducted using the enhanced Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework . The stuParticipants were eligible if they were: (i) an adult (≥18 years), (ii) diagnosed with a chronic respiratory disease, (iii) had an Australian mobile phone number, and (iv) able to provide informed e-consent in English. Participants were recruited from 29 April 2020 to 1 February 2021 through paid and unpaid advertisements on social media , paid radio advertisements, and through unpaid strategies including the Lung Foundation Australia , and emails from lung disease organizations and rehabilitation programs. Potential participants were instructed to either click a secure weblink, text the word ‘Lung’ to the study mobile phone number, or scan a Quick Response (QR) code, which would lead them to the secure study website that contained the participant information sheet, e-consent form and privacy statements that detailed how participants’ personal information would be stored securely to maintain confidentiality and be used only for research purposes. After providing e-consent, participants completed demographic data . Next, participants registered their preferred name (‘nickname’) and mobile number into the automated text message delivery software, which initiated the first message in the program.Participants received a ‘welcome to the study’ message, which encouraged them to save the study mobile number in their phone. Participants then received four to five text messages per week (free-of-charge) for six months. The message delivery was automated, delivering messages at random times and on random days to minimize habituation . The mesThe program was two-way , and participants were informed they would receive a response within 72 h. One message asked a direct question about how they heard about the program . For safety, a member of the research team monitored replies and responded when appropriate. Participants could opt-out at any time by replying ‘STOP’ or requesting to unsubscribe and they were removed from the program within 72 h. The final message included a secure weblink to a user feedback survey regarding the acceptability and utility of the program (described in detail below). This text message was resent by the research team after one month if participants had not completed the survey. Reach and representativeness was evaluated using the percentage of people who enrolled in the study after visiting the study website (n enrolled/n visited study website × 100) and participant demographics, including age (years), sex , smoking status (current smoker yes/no) and postcode. Postcode was used to determine participants’ Index of Relative Socio-economic Advantage and Disadvantage (IRSAD) , which cEfficacy for improving health outcomes was evaluated in a multi-centre randomized controlled trial , includiAdoption enablers and barriers were evaluated at the setting-level based on where participants were recruited, and the participant-level based on: (i) text message response data: the number, and content of text message replies, including text, emojis  or ‘reactions’, which occur when a participant clicks a text message and clicks ‘like’, ‘love’, or ‘emphasise’ and; (ii) user feedback survey: 13 questions, including 11 5-point Likert scale questions (1 = strongly disagree to 5 = strongly agree) regarding the perceived usefulness of the program , participants’ motivation to manage their health , whether participants shared the program with family, friends or medical professionals, and participants’ preferences for program characteristics . The survey also included two free-text questions regarding what participants liked most and least about the program, and suggestions for improvement. Staff-level adoption included evaluating the number of text message replies that required a staff response and estimated staff time.Implementation and Maintenance was evaluated by the fidelity of the intervention including: (i) Text message delivery data (29 April 2020–8 August 2021): The number of text messages successfully delivered or unsuccessfully delivered (bounced); (ii) retention rate and percentage of opt-outs (n opt-outs/n baseline × 100); (iii) direct intervention costs, including delivering the text messages, monthly fees for the automated text message delivery software and advertising fees; and (iv) cost of staff time to monitor and respond to incoming text message, at an annual salary of AUD$78,760 ($AUD43.27/hour).Categorical data, including the text message delivery data and quantitative feedback survey data, were summarised by frequencies and percentages and continuous data were summarised as means and standard deviations. Text message responses and free-text feedback survey responses were independently coded into themes using the framework approach of two researchers , and any disagreements were reviewed by a third reviewer (RR) and discussed until an agreement was reached . Within 1.5 months of the Australian COVID-19 lockdown on 23 March 2020, ethics approvals and legal review were obtained to adapt the integrated text messaging program  into theA total of 1940 individuals visited the study registration website and 707 unique participants provided e-consent and completed the demographic data  and 70% (496/707) of participants replied at least once. The most common replies were ‘thank you’ , simple replies or emojis , and the sharing of personal experiences . Participants also shared how they had heard about the program ; nearly half of participants heard about the program through paid and unpaid social media advertising including Facebook  and Instagram . Other participants heard about the program through unpaid advertisements including Lung Foundation Australia , and from their healthcare professionals . Other replies included reactions to the message such as ‘like’ or ‘love’  or complimenting the program , and some asked questions about the study, lung health or where to get additional support  (see examples in User feedback survey: 326/707 (46.1%) participants completed the user feedback survey , and quaThe thematic analysis of free-text survey responses mirrored the quantitative data, revealing two main factors influencing engagement: (1) experiencing healthcare support, and (2) usefulness of the program for managing health . Sub-theBox 1THEME 1. EXPERIENCING HEALTHCARE SUPPORTFeeling supportedJust letting me know you were always there to support me—Female, age 41, Major CityIt feels like someone is out there who truly cares and can depend on—Male, age 64, Major CityIt had the knack of providing the right support at exactly the right time—Female, age 64, Inner Regional AustraliaMental health benefits of feeling less aloneAlthough I’m aware the messages were generated electronically, it made me feel less alone. The support provided has been wonderful and I’m very grateful for being involved—Female, age 64, Major CityI felt so much less alone by receiving these tips that though generic felt written in a very caring way specifically for me. Great for my mental well being too—Female, age 70, Major CityI felt alone with my condition before I subscribed to the messages—Female, age 64, Inner Regional AustraliaTHEME 2. USEFUL FOR MANAGING MY HEALTHInformativeVery informative and I learnt some new things I was unaware of—Female, age 69, Inner Regional AustraliaThe messages gave me valid information, but not overloaded it—Female, age 70, Very Remote AustraliaLearnt some coping tips didn’t know. Main one, when breathless bend forward with arms resting in front of you—Male, age 70, Major CityEasy to understandThey were easy to understand and gave easy to follow instructions when needed—Female, age 65, Major CityEven people with basic reading skills can follow these—Female, age 65, Major CityGentle health reminders that motivated behaviour changeIt was daily reminders of good things to do for myself that would help my quality of life. I thought they were great prompts—Female, age 68, Inner Regional AustraliaIt reminded me of the very small things I can do to make a difference to my own lung health and wellbeing. Encouraged me to challenge myself and not get disheartened—Female, age 70, Major CityThey form a reassurance that exercise, diet, other simple strategies like breathing and recovery are in my control, and can benefit my condition—Male, age 66, Major CitySUGGESTIONS FOR PROGRAM IMPROVEMENT:CONTROL OVER PROGRAM FEATURESProgram lengthThe only negative thing is that it has finished and I will no longer receive my comforting, helpful messages any longer—Female, age 62, Major CityLoved the program, could only be improved by extending the program—Female, age 66, Major CityThe program should be ongoing: it is good for staying motivated—Male, age 68, Outer Regional AustraliaMessage frequencyI received daily messages… on the odd busy day I did ignore them till after work but always looked at them in the evening…so maybe an option of how many messages a week would be my only note—Female, age 54, Inner Regional AustraliaToo many messages. Sometimes up to 4 consecutive days. Preferable to have less and be able to focus on one thing more slowly—Female, age 77, Major CityMore detailed informationI would like to see some advice about condition specific actions. Keeping it general weakens the type of help that this can provide—Male, age 66, Inner Regional AustraliaCould be more new information instead of basic information which people with COPD already know. It was useful as memory jogger—Male, age 74, Major CitySome messages needed a little more detail—Female, age 71, Inner Regional AustraliaBased on the free-text survey feedback, some participants expressed a potential benefit of having control over program features, including the length of the program and message frequency, to suit their schedules and support needs. Some participants also wanted more details within the messages or specific practical advice regarding their lung health .Fidelity: 83,573 text messages were sent from 29 April 2020 to 8 August 2021; 78,301 (93.7%) were delivered successfully, 5203 (6.2%) bounced, and 69 (<0.001%) were pending (neither delivered nor bounced). The retention rate for the program was 92.2% (652/707). Fifty-five (7.8%) participants opted out; 53 participants opted out by replying ‘STOP’ and two sent a text message reply requesting to opt out. Reasons for opt outs are summarised in Cost: The direct intervention costs of delivering Texting for Wellness: Lung Support Service to 707 participants was AUD$8269.84, including text message costs (AUD $6685.84) and automated message delivery software (AUD$1584). Advertising costs were AUD$5416.15, including social media (AUD$2916.15) and radio advertising (AUD$2500). Estimated costs for staff to monitor incoming messages and send minimal replies  was AUD$3623.86. Together, the total cost of promoting, delivering, and staff monitoring the program was AUD$17,309.85 or $24.48 per participant for six months.The period of the COVID-19 pandemic and its associated lockdowns has been a challenging time, especially for people living with chronic respiratory diseases whose in-person pulmonary rehabilitation programs were cancelled across Australia. The integrated text messaging  program The use of digital technologies to deliver self-management programs for people with chronic respiratory conditions is an emerging area of research. Texting for Wellness: Lung Support Service was delivered solely by text messaging, as planned, with a high retention rate , minimal cost (AUD$24.48/participant for six months) and had a broad reach, with participants signing up from within a diverse age range (23–87 years old) and socioeconomic backgrounds and from all states and territories across Australia, including both urban and rural communities. This is representative of those who have chronic respiratory diseases in Australia . This stThis study found that Texting for Wellness: Lung Support Service was feasible for overcoming common barriers to the implementation of health self-management support programs for people with chronic respiratory disease, including health literacy levels, insufficient healthcare practitioner time, resources or skills,  and psycThis study is not without its limitations. Firstly, as this program was offered as a service, completion of the feedback survey was optional. The high retention rate  suggests participants liked the program, yet the user feedback survey had a 46% response rate and therefore the feedback may not be representative of all participants. A recent systematic review has demonstrated that online surveys have a response rate of around 46% and therefore this study is consistent with prior research . FurtherTexting for Wellness: Lung Support Service was rapidly implemented and had a broad reach, with high retention and acceptability among people with chronic respiratory conditions. Factors influencing engagement with the program included experiencing continued healthcare and its usefulness in health self-management. The program was low cost, factoring in both program delivery and staff time, which may assist with future implementation. Further research is needed to understand whether text message support improves health outcomes for people with chronic respiratory conditions and strategies for long-term program maintenance.


The benefit of vital involvement (VI) in dementia care is largely unknown. The purpose of this study is to demonstrate VI elements in a creative group storytelling program for persons living with dementia (TimeSlips). After offering 6 weekly storytelling sessions for 4 small groups in a memory care community, we interviewed participants (n = 21), family members (n = 2), and care associates (n = 6) to obtain feedback on the program. Themes from narratives in the audiorecorded and transcribed interviews suggest that participants enjoyed the program, enacting their personal values, strengths, and interests, and incorporating their past and current experiences, as supported by their sociospatial environment . When paired with the VI practice, creative group storytelling has potential to magnify favorable outcomes for participants with dementia, who may express more fully their meaningful engagement with their inner  and external  world.


Monitoring is critical to gauge the effect of environmental management interventions as well as to measure the effects of human disturbances such as climate change. Recognition of the critical need for monitoring means that, at irregular intervals, recommendations are made for new government-instigated programs or to revamp existing ones. Using insights from past well-intentioned  attempts to establish and maintain government-instigated monitoring programs in Australia, we outline eight things that should never be done in environmental monitoring programs (if they aim to be useful). These are the following: (1) Never commence a new environmental management initiative without also committing to a monitoring program. (2) Never start a monitoring program without clear questions. (3) Never implement a monitoring program without first doing a proper experimental design. (4) Never ignore the importance of matching the purpose and objectives of a monitoring program to the design of that program. (5) Never change the way you monitor something without ensuring new methods can be calibrated with the old ones. (6) Never try to monitor everything. (7) Never collect data without planning to curate and report on it. (8) If possible, avoid starting a monitoring program without the necessary resources secured. To balance our “nevers”, we provide a checklist of actions that will increase the chances a monitoring program will actually measure the effectiveness of environmental management. Scientists and resource management practitioners need to be part of a stronger narrative for, and key participants in, well-designed, implemented, and maintained government-led monitoring programs. We argue that monitoring programs should be mandated in threatened species conservation programs and all new environmental management initiatives. Good monitoring is fundamental to sound ecological management, threatened species recovery, and environmental reporting Gardner, . MonitorUnfortunately, poorly designed and poorly implemented monitoring programs have characterized many large-scale environmental management initiatives around the world, including agri-environmental schemes  so that the impact of the program can be determined. Australia’s multi-billion dollar Natural Heritage Trust program that, in part, aimed to promote widespread replanting efforts is but one of many examples ANAO, . Some liWe argue that for most new conservation initiatives and large, periodic environmental management programs, it is critical to set explicit measurable objectives that can then contextualize and inform the design of the monitoring that is required to evaluate the management program’s success or progress towards that success. Considering monitoring in initial program inception and design enables accurate costing of monitoring and ideally enables a “before investment” baseline to be measured. This improves the chances that monitoring will be properly designed, maximizing the chances of detecting a clear signal of management. A general rule of thumb is that approximately 10% of the total budget of management programs should be dedicated to monitoring the effectiveness of a program , where the fundamental aim is to generate, store, and share large amounts of data, especially using new kinds of sensor technologies, but without data collection being guided by well-crafted questions that would support improvements in programs , and this precludes developing and then establishing monitoring programs that can effectively answer such questions. Good questions can be relatively simple, such as: Is a population at a particular site increasing? Is a particular management action such as weed control reducing the impact of weeds on species of interest? or Is a target species doing better at sites that are being managed compared to sites that are not? For example: Is placing more woody debris along creeks leading to an increase in the number of frogs compared to places where debris are not being added?Monitoring should address questions that are management-relevant, that can improve management decisions and actions if answered, and that can provide rigorous evidence of the effect of management interventions. In a sobering example, Russell-Smith et al.  lamentedThe key questions being addressed in a monitoring program may need to change over time, especially given the rate and magnitude of change currently being experienced in ecosystems worldwide, and the diversity and interaction of the factors driving change. In these cases, an adaptive monitoring approach  the ability to actually answer the key questions being posed see “”, accounnot adequate monitoring, even if those points are a long way apart. This is because there can be an almost infinite number of different trajectories for a line between two points , the particular attributes or variables being targeted for measurement, and the method of measurement . Therefore, because a monitoring program worked in one place or on a given species does not mean it will automatically work again under a different set of circumstances. Of course, this does not mean there are not valuable lessons to be learned from other programs—but rather that context is critical. Therefore, we argue there is a need to be wary of adopting ‘standard’, ‘generic’, or ‘multi-purpose’ monitoring protocols or any protocol applied elsewhere without critically evaluating whether they appropriate to achieve key objectives. For example, typical multi-species programs using randomly selected sites in space monitored across seasons are not optimal for many species. In the case of the threatened Brush-tailed Rabbit-rat Some government-initiated monitoring programs attempt to employ generic approaches that are characterized by an ill-informed fascination with new and emerging technologies that are poorly suited to the entities that need to be monitored. A classic example was the Australian Government’s roll-out of Cybertracker technology to record geo-locational information under the Indigenous Protected Area, Working on Country and National Heritage Landscape programmes Wilson, . To the Critical evaluation may reveal that some elements of a standard protocol might be fit for purpose, others not. An example of these kinds of issues is the PPbio monitoring protocol that was developed in tropical South America  descriptions of meta-data and field survey protocols, enabling work to be continued by others. This is especially critical when the management of a monitoring program is transitioned to a new leadership team.Many monitoring programs make serious over-commitments at the outset and are unable to deliver on them, or they deliver on them poorly. For example, some monitoring programs try to monitor too many things or too many time-intensive measurements for a given entity (see the example below). This can lead to the sampling burden becoming unsustainable or result in insufficient data being collected for useful inference about anything. We argue it is better to monitor a smaller number of entities well than a large number poorly. Decisions about which entities make that subset should be guided by the questions being posed, available budget, statistical design, and practical realities associated with field sampling . Much of the uncertainty about how much monitoring could and should be achieved can be addressed using thoughtful consideration of the costs and effort required to complete various levels of sampling and a priori power analysis  at 1,656 sites, many remotely located across the entire province  as has been applied in the case of seabirds on islands which can be logistically and financially challenging to access  responsibility to properly curate those data, and make them widely available, and ensure they are discoverable by the public and future land managers and researchers, including those who wish to maintain or re-establish a long-term study. Part of this responsibility lies with the funders themselves—to ensure that supporting the data curation and storage as well as analysis and public reporting of results is as essential as supporting the monitoring itself. A centralized, national facility to collect, curate, analyse, and provide access to biodiversity data collected during monitoring attached to major government investments in environmental management would ensure that information is not lost between the end of one program and the beginning of the next. Such a facility could support many functions relating to environmental management , creating a mismatch between objectives, outcomes, and resourcing. As stated above, monitoring is rarely properly funded, usually the last item considered in budgets, and the first thing cut when there is a budget problem , https://www.sustainableaustralianbeef.com.au/) will likely fail because there is a paucity of well-designed environmental monitoring throughout the large areas of the Australian continent subject to livestock grazing  such as the Natural Heritage Trust, Caring For Our Country, The Biodiversity Fund, the National Landcare Program, and threatened species recovery programs ANAO, . InadequWe recognize there is no such thing as a perfect monitoring program, but we suggest that at least considering the eight “nevers” in this article and their solutions Table  will helWe argue that the culture leading to poor quality monitoring in Australia (and many other parts of the world) needs to change in line with public expectations so that the benefits of conservation programs can be demonstrable, auditable, and rigorously reported and that the causes of failure can be discerned and corrected ANAO, . In areaPart of the solution to the perennial problem of limited monitoring or poorly designed monitoring is the development of stronger scientist-policy maker and scientist-manager partnerships. This is essential to ensure that scientific and statistical principles of design and practice can be injected into new proposals to instigate new large-scale government-led monitoring programs and efforts to renovate existing programs to increase their effectiveness and robustness. This is a call for some scientists to dispense with the notion that monitoring is second rate science. There is also a role for policy makers and resource managers (as well as scientists) to look more broadly than their regions, states, or nationally and discern what monitoring programs have worked and not worked where and “steal” the good innovations that are effective . The Bureau of Meteorology has successfully prosecuted the case for supporting the collection and analysis of long-term climate and weather data. An equivalent agency responsible for environmental and conservation monitoring programs would be a major positive step towards rectifying past problems. In fact, the Australian Academy of Science has recommended a new institution akin to the Bureau of Meteorology to support monitoring of new government-led environmental management initiatives (Australian Academy of Science, Poorly designed and/or implemented monitoring programs have characterized many large-scale environmental management initiatives around the world. Based on our collective experiences in an Australian context, we outline eight things that should never be done in an environmental monitoring program if the aim is for it to be useful. Failure to address these key issues will mean that institutionalized, large-scale environmental management programs will often continue to repeat past mistakes and will squander effort, resources, and goodwill. We balance our “nevers” with a checklist of actions (see Table


The assessment of consumer behavior in brand-choice models may be greatly influenced by accurately modeling and evaluating a brand-loyalty parameter. The most well-known approaches for estimating brand loyalty employ a household’s past purchase data and account for habit formation with a single smoothing parameter that indicates the weight assigned to households’ current decisions versus their distant shopping history. In this study, we present a method for estimating time-varying smoothing parameters for heterogeneous households. We estimate smoothing parameters for American households from 2014 to 2017 using Nielsen Homescan data for the US beer retail market. Using this more flexible method, we discover that the smoothing parameter varies significantly among households and time frames (for the same households). We next include a brand-loyalty index based on this approach into a brand-choice model of the American beer retail market, demonstrating that this new method improves estimation results. Brand loyalty, defined as a state-dependent persistence for a specific brand regardless of potential price changes, is essential for understanding consumers’ decision-making processes  to differentiate them from competitors Aaker . CustomeAccording to marketing literature, loyalty is a biased reaction that is persistent over time and evident in the historical patterns of an individual, a family, or a business unit Mellens et al. . To diffJacoby and Chestnut  define bThroughout the years, other scholars have somewhat adjusted this definition Assael . Based oBehavioral loyalty focuses on purchasing patterns and the proportion of times a purchaser chooses the same product or service in a specific category compared to the total number of purchases made by the purchaser in that category defines customer loyalty . From here, we follow the procedure outlined in Fig. Using these estimated smoothing parameters, we can calculate the brand-loyalty index as a household-specific variable, add that to the Mixed Multinomial Logit model, and check for improvement in fit and explanatory power as the final step. To estimate r et al.  to accomWe expand If we now renameIn a rich data set, if we treat  as an eqentclass1pt{minimathen use  to replat) using  we need ribed in . If we rribed in , which is).Using , we can n is the number of brands. While our initialization is different from Guadagni and Little . Nielsen selects a geographically and demographically representative sample of US households. Households use a home scanner to keep track of purchases of food and related commodities, including the quantity purchased, the amount paid, and the date. Purchases consumed before returning home are often not scanned and are not included in the data set. Einav et al.  evaluateSince we began this investigation, the United States has been struck by COVID-19, and the pandemic has also affected the retail beer sector. The consumption of beer off-premises has increased significantly (30%) , these top eleven states consumed 60% of all beer consumed in the United States. Because the top 2% of brands vary by state, we study each state independently. Figure For computational convenience, we focus on these top 2% brands. If more than 90% of a household’s consumption portfolio is from the top 2% brands, we include that household in our data set. In discrete choice models, combining various alternatives into one outside option can distort parameter estimates and result in misleading predictions Stafford . InvestiWe investigate households who purchased at least twelve times per year (regular purchasers) in each state. As expected, the number of regular purchasers is higher in more populated states. Prices, even for the same brands, change in different states. We can find similar beer brands and types standing among the top brands in all the states. Bud Light . For observations, we look at the purchased prices, discounts, and containers recorded for each brand in a time span around the purchase date. In the first step, we look at the county level and search for the missing brand information in 8 days. In other words, if the missing brand has been purchased 4 days prior or 4 days after the purchase occasion, we will use all the observed information in that time span to form the discrete distribution as the likelihood distribution.If a brand has not been purchased in the mentioned 8-day period, we expand the geographical area (from county to state) and the time span (from 4 to 7 days). Following the same pattern, we expand the geographical area to region and then to the total sample and the time span to 15 days and 6 months, if needed.In addition to some household characteristics collected directly from Homescan, we construct other transaction variables based on the Homescan purchase data. We record each brand’s price and construct variables related to beer type (or flavor), purchased volume, amount purchased on promotion, product container information, and ultimately a brand-loyalty variable.p values in the last column show that not all the states medians are equal.Table To illustrate how our technique generates smoothing parameters that vary across households and over time, we developed a graph displaying lambda distribution in different states. Figure To demonstrate the relevance of heterogeneous smoothing parameters, we compare the new proposed brand-choice model with varying smoothing parameters and an alternative model with the classic, constant smoothing parameter. We build two separate models using beer retail market data from 2014 to 2017 (3 years). The preferred model calculates each household’s brand loyalty for each brand on each purchase date using the newly estimated smoothing parameters and incorporates this index into the MML brand-choice model. We compare this preferred model to a restricted model that incorporates a loyalty index that relies on a constant smoothing parameter of 0. 75 across different states. To account for potential price endogeneity, both the preferred and restricted models also include the estimated residuals from the auxiliary price equation that is part of the control function approach  and Bayesian Information Criterion (BIC), which test the additive explanatory power of the new brand-loyalty variable. Figure The other factor which significantly affects brand choices is seasonality. Like other factors, seasonality works differently across states, even for similar brands. We can observe these differences by looking at the visualized summary of the seasonality effects in Fig. We have demonstrated that increasing the heterogeneity of the smoothing parameter that serves as the basis for a brand-loyalty index is computationally viable and increases the explanatory power of an estimated brand-choice model. Accurately assessing and quantifying brand loyalty among households may benefit manufacturers and retailers primarily by enabling them to better target their client base and quantify the effects of brand loyalty. However, it may also benefit policymakers by allowing for more exact welfare estimation due to mergers that change brands’ availability.Additionally, this model can be applied to other scenarios requiring a comparable degree of heterogeneity in state-dependent variables. For example, enhanced heterogeneity could improve political party polling or simplify risk assessment for insurers, banks, and lenders. Thus, a significant implication of our study is that it advocates for the inclusion of heterogeneity in different state-dependent variables in other empirical situations.When we apply the model to the US beer retail market, we discover how brand loyalty has a significant impact on brand choices. Thus, having a precise measure of brand loyalty and tracking its progress over time will help firms enhance their segmentation and targeting strategies. Consistent with earlier research, we observe a significant effect of marketing mix factors.By definition, the smoothing parameter describes how households weigh their experiences over time. By utilizing such a parameter, one may ascertain who will remember their feelings and who will forget. Here, more precise data provides marketers with a useful tool for segmentation, targeting, releasing a new product, or even rebranding.Accurately measuring brand loyalty and analyzing trends in brand-loyalty variations will assist market planners in predicting demand, simulating segmentation, and formulating effective positioning strategies. In the digital era, tracking loyal consumers, discovering their purchase patterns, and making appropriate plans are now feasible. For example, to lunch new products, learning about customers’ brand loyalty in different regions and various markets would benefit the industry and help market analysts to optimize their approaches toward new markets. While identifying the model, this new time-varying smoothing parameter assisted us in achieving greater accuracy than previous models, albeit at a cost. Calculating these new smoothing parameters is computationally intensive and requires a significant amount of computing power, especially when working with big data. While consumer databases continue to grow in size, models must be adaptable and scalable (Braun and Damien


A novel program was implemented in an effort to optimize the blood pressure taking skills of medical and pharmacy students, in collaboration with older individuals in Detroit. Under the supervision of Interprofessional faculty, pharmacy and medical students provided blood pressure screenings at the popular Riverwalkers program, a community exercise program designed for older Detroiters. Prior to volunteering at the program, students were required to complete the AMA blood pressure modules to develop proficiency in blood measurement best practices. Over the course of two months, 72 students provided blood pressure screenings for 79 older individuals during 266 distinct encounters. We believe this program can serve as a model for other professional schools, as it efficiently accomplishes several distinct


Racial/ethnic minority and immigrant caregivers of persons with dementia experience high rates of psychosocial stress and adverse health outcomes. Few culturally tailored mobile health  programs were designed for these vulnerable populations.This study reports the development of a culturally tailored mHealth program called Wellness Enhancement for Caregivers (WECARE) to improve caregiving skills, reduce distress, and improve the psychosocial well-being of Chinese American family caregivers of persons with dementia.Community-based user-centered design principles were applied in the program development. First, the structure and curriculum of the WECARE program were crafted based on existing evidence-based interventions for caregivers with input from 4 experts. Second, through working closely with 8 stakeholders, we culturally adapted evidence-based programs into multimedia program components. Lastly, 5 target users tested the initial WECARE program; their experience and feedback were used to further refine the program.The resulting WECARE is a 7-week mHealth program delivered via WeChat, a social media app highly popular in Chinese Americans. By subscribing to the official WECARE account, users can receive 6 interactive multimedia articles pushed to their WeChat accounts each week for 7 weeks. The 7 major themes include (1) facts of dementia and caregiving; (2) the enhancement of caregiving skills; (3) effective communication with health care providers, care partners, and family members; (4) problem-solving skills for caregiving stress management; (5) stress reduction and depression prevention; (6) the practice of self-care and health behaviors; and (7) social support and available resources. Users also have the option of joining group chats for peer support. The WECARE program also includes a back-end database that manages intervention delivery and tracks user engagement.The WECARE program represents one of the first culturally tailored social media–based interventions for Chinese American caregivers of persons with dementia. It demonstrates the use of community-based user-centered design principles in developing an mHealth intervention program in underserved communities. We call for more cultural adaptation and development of mHealth interventions for immigrant and racial/ethnic minority caregivers of persons with dementia. Currently, more than 6 million Americans aged ≥65 years are living with Alzheimer disease or related dementias (ADRD) . More thAsian Americans represent the fastest-growing racial group in the United States; they accounted for 7% of the total US population in 2020 and are projected to reach 12% in 2050. Chinese Americans represent nearly a quarter (23%) of the Asian American population . The litMost of dementia care is received at home where family caregivers play a central role but often lack the knowledge and skills to perform caregiving duties to meet the needs of persons with dementia. Chinese caregivers tend to keep problems within the family and do not seek external help because of the stigma associated with dementia or cognitive impairment . The isoTo date, few interventions have been conducted to serve the needs of Chinese American caregivers of persons with dementia. Specifically, in a recent systematic review, only 2 interventions targeting Chinese American caregivers were identified . One wasOut of nearly 4 million Chinese Americans, more than 70% are foreign-born . Over 3 More than 95% of Chinese Americans own a smartphone . SimilarTo address the literature gap and public health needs, our team developed a WeChat-based intervention called “Wellness Enhancement for Caregivers” (WECARE) for Chinese American family caregivers of persons with dementia. This paper reports the process of developing the WECARE program and the design features of this social media–based intervention.The study was conducted from September 2021 to April 2022 with the goal of developing a culturally tailored WeChat-based intervention to improve the psychosocial well-being of Chinese American family caregivers of persons with dementia. The development of the WECARE program consisted of 3 steps. First, with experts’ input, we designed the structure and curriculum of the WECARE program based on existing evidence-based behavioral interventions for persons with dementia. Second, using a community-engaged user-centered design, we developed the multimedia components of the WECARE program that used the built-in functions of the WeChat app; we also developed a back-end database to manage intervention delivery and track user engagement. Finally, the complete WECARE program was refined after a beta test in target users.The study protocol was approved by the Institutional Review Board of the George Mason University (IRB1849712). Informed consent was obtained from all participants prior to data collection. Given that this study was focused on protocol development, we did not collect participants’ personal information including their demographic data.We first conducted interviews with 4 experts in the fields of ADRD, caregiving, cultural adaption, and mHealth intervention development, with 1 expert from each field. We sought input from the experts on (1) how to apply existing theories and evidence to enhance caregiving skills and reduce psychosocial stress among underserved family caregivers, (2) how to adapt evidence-based caregiving interventions for Chinese American caregivers, and (3) how to identify and prepare for potential barriers and facilitators during the intervention delivery.The experts also suggested that the curriculum design be based on evidence-based interventions proven to be effective in minority and underserved caregivers of persons with dementia. Specifically, we used the Resources for Enhancing Alzheimer’s Caregiver Health II for its major domains of the intervention , BuildinFollowing the principles of community-engaged user-centered design  while deWhen the complete WECARE program was ready, we tested it among 5 target users. Of these 5 Chinese American family caregiver participants—1 man and 4 women—all had limited English proficiency and were recruited by our community partner. Participants were invited to a conference room and received the WECARE program on their WeChat accounts to test its navigation and the functions of the back-end database. During the test, participants were encouraged to “think out loud” and share their feedback while going through the program components. Participants were asked to check if all program components were delivered at prescheduled times and if all program components could be opened without problem. Meanwhile, research staff monitored all user activities on WECARE’s back-end database. All interviews were conducted in Chinese or Mandarin and audio recorded, and detailed notes were taken while observing users’ navigation behaviors. The research team discussed users’ feedback, addressed the glitches reported in the test, and further refined the program.WECARE is a 7-week program with each week focused on a theme and the final week for summary and additional resources. These themes include (1) facts of ADRD and caregiving; (2) enhancement of caregiving skills; (3) effective communication with providers, care partners, and family members; (4) problem-solving skills for caregiving stress management; (5) stress reduction and depression prevention; (6) practice of self-care and health behaviors; and (7) social support and available resources. The 7 major themes were derived from the evidence-based programs (see Step 2). The curriculum schedule is detailed in The content of the WECARE program was adapted for Chinese American culture based on input from our stakeholders, and the following changes were made. First, we ensured that the language translation reflected Chinese values and tradition. For example, following the tradition of respecting seniority, Chinese participants did not like the literal translation of “care recipient” or “care partner”; instead, they preferred to use “the elder” (“Lao Ren” in Chinese) to refer to the care partner, which we adopted in the WECARE program. Second, program components specific for our target users were added. For example, given that many Chinese caregivers have limited English proficiency, we added a section on how to communicate with health care providers with a practical checklist as well as a list of terminologies commonly used in medical encounters and dementia care. Additionally, as many Chinese caregivers have limited knowledge and use of formal care and support services , we addeThe WECARE program consists of multimedia components to engage users and enhance understanding. Considering that many caregivers are older adults and many have lower levels of health literacy, each article is accompanied by an audio recording, so participants with vision impairment can listen to audio recordings for most of the WECARE content. We also included many short videos (3-5 minutes) adapted from other caregiver interventions with subtitles for illustration. Culturally relevant characters, storylines, and background music are embedded in all program components.As WECARE is delivered via the popular WeChat social media app, the built-in functions of social networking in WeChat were used to enhance social support among participants. For example, participants were invited to attend staff-moderated group meetings scheduled at week 3, week 5, and week 7 and welcome to share their personal experiences during the course of WECARE. Participants could also initiate their own “group chat”; in a group chat, they could “friend” any fellow caregiver participant for a private chat. Prior to the group meetings, participants agreed to the protocol that all participants in the group meetings address each other by first names only and that no personal information discussed in the meetings be shared with other people outside the group.Along with developing the front-end program components of WECARE, we also created an interactive web-based application to serve as the back-end database to manage intervention delivery and monitor user engagement. This interactive website has 3 core functions: (1) storing information on every participant enrolled, including characteristic and user preferences; (2) pushing the program components based on user preferences and response ; and (3) tracking program receipt and responses. User engagement indicators tracked in the database include whether a program component is opened, how many times the program is opened or played, and how much time is spent on each component. This study reports the process of developing WECARE, a culturally tailored social media–based intervention to enhance caregiving skills and reduce psychosocial distress in Chinese American caregivers of persons with dementia, and its key features. Community-based user-centered design principles were applied in the intervention development. We first crafted the structure of the WECARE curriculum based on existing evidence-based interventions and input from experts. Second, working closely with key stakeholders and through an iterative design-discuss-revise process, we developed culturally tailored multimedia program components at the frontend and an interactive database for intervention delivery and user profile management at the backend. Finally, we conducted a beta test of the complete WECARE program in target users and further refined it. The resulting WECARE is a 7-week mHealth program. Through subscribing to the official WECARE account, users could receive 6 multimedia articles pushed to their WeChat account each week for 7 weeks. Users could also use the built-in functions of WeChat for social networking. The back-end database automatically pushes program components with a preset schedule and tracks user activities on WECARE.The WECARE program represents one of the first culturally tailored mHealth programs for Chinese American caregivers of persons with dementia. The health disparities experienced by minority and immigrant caregivers of persons with dementia have been exacerbated during the COVID-19 pandemic. There is an urgent need to adapt evidence-based interventions for wider dissemination in underserved populations. The cultural adaptation and digitalization of evidence-based interventions, such as developing the WECARE program as described in this paper, could be an effective approach to address the literature gap and public health needs.When adapting and developing mHealth interventions, we need to consider the mobile use behaviors of the target population. The popular social media apps used by minority populations can serve as an efficient channel for intervention delivery . The WECCultural sensitivity is critical for developing interventions for minority populations. A community-engaged user-centered design is an effective approach for the cultural adaptation of evidence-based programs. Using this approach, we made substantial changes in the WECARE program components in response to the input of our stakeholders and target users. The resulting program reflects the values, needs, and practices of Chinese American caregivers of persons with dementia.The WECARE program features multimedia components of audio recording, short video clips, pictorial messages as well as automatic and interactive delivery based on user preferences and responses. The built-in functions in WeChat such as “private chat,” “group chat,” and “video chats” facilitate social networking and enhance social support. Literature suggests that mHealth programs with multimedia features and social networking functions are likely to engage target users, especially those with lower levels of health literacy . The desThe back-end database has the functions of user profile management, the automatic delivery of program components, and user activity tracking. These functions are similar to another WeChat-based intervention and enable potential scale-up and long-term follow-up . The useFirst, the beta test of the WECARE program was based on a small sample of 5 target users. The development was a rigorous process following community-engaged user-centered design principles  with inpIn conclusion, this paper reports the development process and key features of the WECARE program—a culturally tailored, linguistically appropriate, and interactive social media–based interventions to improve caregiving skills and reduce psychosocial distress among Chinese American caregivers of persons with dementia. As the US population becomes older and more diverse, an urgent need exists for more culturally sensitive mHealth interventions for minority and immigrant caregivers of persons with dementia. We advocate for more research and practice of the cultural adaptation of evidence-based program for digital delivery, capitalizing on the widespread use of smartphones and highly popular social media apps, to meet the needs of racial/ethnic minority and immigrant patients with dementia and their caregivers.


Strong partnerships between academic health professions programs and clinical practice settings, termed academic-clinical partnerships, are essential in providing quality clinical training experiences. However, the literature does not operationalize a model by which an academic program may identify priority attributes and evaluate its partnerships. This study aimed to develop a values-based academic-clinical partnership evaluation approach, rooted in methodologies from the field of evaluation and implemented in the context of an academic Doctor of Physical Therapy clinical education program. The authors developed a semi-quantitative evaluation approach incorporating concepts from multi-attribute utility analysis (MAUA) that enabled consistent, values-based partnership evaluation. Data-informed actions led to improved overall partnership effectiveness. Pilot outcomes support the feasibility and desirability of moving toward MAUA as a potential methodological framework. Further research may lead to the development of a standardized process for any academic health profession program to perform a values-based evaluation of their academic-clinical partnerships to guide decision-making. Strong partnerships between academic health professions programs and clinical healthcare practice settings, termed academic-clinical partnerships, are essential in providing quality full-time clinical training experiences ,2. UnforDecreased availability of student placement slots may require academic programs to increase their volume of clinical partners. A growing quantity of clinical partners reduces the ability of an academic program to maintain, enhance, and evaluate quality partnerships. Interactions between partners are often suboptimal, triggered by issues needing resolution rather than a drive for mutual engagement ,7. To adWhat is unclear, however, are the precise conditions and factors that promote strong academic-clinical partnerships. Such constructs have not been operationalized to date and there is no model by which an individual program may assess its priorities. The concept of partnerships remains undefined as well, referencing both legal affiliation agreements and operational relationships guiding placement processes. The inherent variability in academic program missions, resources, operations, student clinical education needs, and academic faculty skills and experiences suggests that partnership priorities are likely not the same for every program.This case report aims to present one academic DPT clinical education program’s pilot implementation of a values-based academic-clinical partnership evaluation approach, rooted in methodologies from the field of evaluation.Study subjects were not human but programs; therefore, neither approval by the institutional review board nor obtainment of the informed consent is necessary.To establish a baseline, the authors as clinical education faculty members in the DPT program at the University of Minnesota began with an informal assessment of their existing partnerships. A subjective ‘grade’ of A, B, C, or D was assigned to each partner based on interactions with that partner from 2015 to 2020 . PartnerThe authors then sought a way to quantitatively evaluate partnership factors to determine the extent to which existing clinical partners supported the program’s priority values. These values were aligned with the academic program’s mission, vision, and operational resources. Because health professions literature did not offer a systematic process to perform this evaluation, the team explored methodological processes in the field of evaluation. The faculty identified an evidence-based decision-making framework with potential called multi-attribute utility analysis (MAUA) ,9 Suppl. This frAs a pilot study, the academic clinical education faculty opted to incorporate evaluation principles associated with MAUA to assess the feasibility and desirability of conducting a full MAUA for partnership prioritization in a future study. None of these steps had been implemented in partnership literature to date.First, the authors considered partnership literature, program faculty perspectives, institutional context, and professional experience to generate their priority partnership list. Ten attributes were selected as follows: setting , level variety (early versus advanced learners), frequency (over a year), location , state (in- versus out-state), relationship with clinical education team , relationship with program/university , relationship with students , administrative burden (on program), and student burden . Each attribute was operationalized as noted with parenthetical examples.Next, the direct method was used as described in MAUA to assign importance weights to each attribute by allocating a total of 20 points among the 10 prioritized attributes based on their perceived relative importance . An iterThird, the additive approach was used to calculate the total utility, or effectiveness, of each partnership by summing the points for all attributes. The final point system indicated 20 as the highest partnership effectiveness score and 0 as the lowest. An institution-specific final rubric was created, termed the Clinical Partner Prioritization Rubric (CPPR) .An initial CPPR score was determined for 142 distinct clinical partners A, with aThe clinical education team used CPPR data to guide initial actions. The team reviewed partners with the lowest CPPR scores and determined whether attribute utilities were changeable or unchangeable. For those with multiple unchangeable circumstances , affiliation agreements were terminated, and the sites were removed from the partner list. For those with changeable circumstances , meetings were scheduled to discuss partnership growth opportunities. The team also reviewed partners with the highest CPPR scores and developed strategies to strengthen collaborative placement planning and clinical faculty training.These actions taken following the first CPPR analysis resulted in a revised CPPR mean score of 11.46/20 and a reduction in total partners evaluated from 142 to 113 . Again, The CPPR evaluation was completed again one year later. Actions following this CPPR analysis resulted in an aggregate CPPR mean score of 11.66/20 and a reduction in total partners evaluation from 113 to 107 . In the Raw response data are available from Pilot outcomes support the feasibility and desirability of moving toward MAUA as a potential methodological framework for evaluating academic-clinical partner relationships. The semi-quantitative evaluation approach developed in this pilot incorporated evaluation concepts rooted in MAUA methodology, successfully enabling academic clinical education faculty to create and consistently apply a values-based prioritization process specific to the institutional context.Over the course of one year, data-informed actions resulted in the elimination of lower-scoring academic-clinical partnerships and increased relationship-building with highly aligned clinical partners, leading to improvement in overall partnership effectiveness. Continued research may lead to the development of a standardized process by which any academic health profession program could perform a values-based evaluation of their academic-clinical partnerships to guide decision-making in partner relations. Further research is needed to assess the utility of MAUA for academic-clinical partnership evaluation over time and across institutional contexts. Questions remain regarding comparisons of priority partnership attributes across academic programs and professions, optimal frequency of partner evaluation, cutoff scores to objectively stratify levels of partnership effectiveness, and potential for a variant of this process for clinical partners to evaluate their priority values in academic-clinical partnerships.Findings in this case study begin to address national clinical education challenges cited in the literature. Further exploration of strategies and structures supporting strong academic-clinical partnerships is needed to advance knowledge regarding the conditions that promote strong clinical training of health professionals.


BCR gene located on chromosome 9q34 and the ABL1 gene located on chromosome 22q11. Thus, mimicking the initiation process of translocation, we induced CRISPR/Cas9-mediated DSBs simultaneously at the breakpoints of the BCR and ABL1 genes in a granulocyte-macrophage colony-stimulating factor (GM-CSF) dependent human leukemia cell line. After transfection of two single guide RNAs (sgRNAs) targeting intron 13 of the BCR gene and intron 1 of the ABL1 gene, a factor-independent subline was obtained. In the subline, p210 BCR::ABL1 and its reciprocal ABL1::BCR fusions were generated as a result of balanced translocation corresponding to the Ph chromosome. Another set of sgRNAs targeting intron 1 of the BCR gene and intron 1 of the ABL1 gene induced a factor-independent subline expressing p190 BCR::ABL1. Both p210 and p190 BCR::ABL1 induced factor-independent growth by constitutively activating intracellular signaling pathways for transcriptional regulation of cell cycle progression and cell survival that are usually regulated by GM-CSF. These observations suggested that simultaneous DSBs at the BCR and ABL1 gene breakpoints are initiation events for oncogenesis in Ph+ leukemia. (200/200 words).The Philadelphia (Ph) chromosome was the first translocation identified in leukemia. It is supposed to be generated by aberrant ligation between two DNA double-strand breaks (DSBs) at the  BCR gene and the ABL1 gene at each breakpoint [BCR gene is fused to exon 2 of the ABL1 gene, which encodes p210 BCR::ABL1 fusion protein [BCR gene is fused to exon 2 of the ABL1 gene, which encodes p190 BCR::ABL1 fusion protein [Chromosomal translocation is among the most common chromosomal abnormalities observed in leukemia, and is highly involved in leukemogenesis. It is supposed to be generated as a result of aberrant repairs of two simultaneous DNA double-strand breaks (DSBs) at different portions of the chromosome. The Philadelphia (Ph) chromosome was the first chromosomal translocation identified in cancer. It was discovered in 1960 by Nowell PC and Hungerford DA as an abnormal minute chromosome in chronic myeloid leukemia (CML) patients . It was eakpoint , 5. Ther protein . In BCR: protein . BCR::AB protein . Of clin protein . Tyrosin protein –19.BCR::ABL1 gene mutations on TKI sensitivities, a murine IL-3-dependent Baf3 cell line transduced with human BCR::ABL1 cDNA by retrovirus vector has been generally used [BCR::ABL1 cDNA was retrovirally transduced [BCR::ABL1 cDNA into NOD-SCID mice [BMI1 cDNA induced ALL progression [BCR::ABL1 under diverse promoters, leukemia progression has been widely confirmed [BCR::ABL1 was also evaluated in the endogenous locus of mouse bcr gene promoter. Notably, B-cell leukemia was developed in knock-in mice of p190 BCR::ABL1 cDNA [BCR::ABL1 [For functional evaluation of tyrosine kinase activity of BCR::ABL1 and pharmacogenetic evaluation of lly used , 21. A bansduced . AlthougCID mice , simultagression . In tranonfirmed –27. The BL1 cDNA , while lCR::ABL1 .bcr gene in the knock-in mice might not be sufficiently high for leukemia transformation by p210 BCR::ABL1. In this context, 3’-untranslated region (UTR) is also involved in transcriptional and post-transcriptional regulation [BCR::ABL1 gene, the involvement of microRNA in post-transcriptional regulation through 3’ UTR has been reported [BCR::ABL1 cDNA was largely deleted in the above mice models. Moreover, cDNA lacks introns. Although its significance in leukemogenesis remains to be elucidated, alternative splicing of the BCR::ABL1 gene has been reported to be involved in TKI resistance [ABL1::BCR fusion derived from balanced translocation. Gene transfer of reciprocal ABL1::BCR fusion into murine hematopoietic stem cells enhanced proliferation and stem cell capacity of early progenitors [ABL1::BCR in leukemogenesis. Under these circumstances, the development of a novel platform that permits testing of leukemogenic activities of balanced translocation under intrinsic transcriptional and post-transcriptional regulation is indispensable.One possible explanation for this discrepancy between transgenic models and knock-in models is that promoter activity of the gulation , 31. In reported . Howeversistance . Anothergenitors , suggestBCR and ABL1 gene breakpoints as an initiation event for leukemogenesis. Thus, we induced DSBs at specific breakpoints of BCR and ABL1 genes, using the CRISPR/Cas9 system in a human factor-dependent leukemia cell line. The obtained factor-independent sublines acquired p210 or p190 BCR::ABL1 and their reciprocal fusion genes as a result of balanced translocation, which is cytogenetically identical to the Ph chromosome. Using these sublines, we evaluated the significance of p210 and p190 BCR::ABL1 in signal transduction and transcription profile.In the present study, we sought to investigate the hypothesis that the Ph chromosome is generated by aberrant repair of two simultaneous DSBs at the https://www.benchling.com) (Supplement Table https://sg.idtdna.com). Each single guide RNA (sgRNA) and pSpCas9(BB)-2A-GFP  was amplified by polymerase chain reaction (PCR) and ligated using a NEBuilder HiFi DNA assembly kit . A 293 T cell line was maintained with 10% fetal calf serum (FCS) containing Dulbecco’s modified Eagle’s medium (DMEM) medium. The plasmid was transfected using Lipofectamine 3000 . A TF-1 cell line was purchased from ATCC  and expanded with 10% FCS containing RPMI1640 medium with 2 ng/ml of human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) . The plasmid was transfected using the Neon electroporation system (Thermo Fisher Scientific) with single pulse at 1300 volts for 20 msec. The cells were cultured in the presence of GM-CSF for seven days. Subsequently, 1 × 104 cells were placed in a 24-well plate in the absence of GM-CSF. The number of living cells was counted every seven days after trypan blue staining.Synthesized self-complementary oligomers designed by Benchling software , and complementary DNAs (cDNAs) were generated with SuperScript IV Reverse Transcriptase (Thermo Fisher Scientific). Amplification was performed using the primers listed in Supplement Table Genomic DNA was extracted using a PureLink Genomic DNA Mini Kit (Thermo Fisher Scientific). The sequence of each primer is listed in Supplement Table Genomic DNA was extracted using a QIAamp DNA Blood Mini Kit (QIAGEN). PCR was performed using the fluorescent primers listed in Supplement Table TM BCR Dual Fusion and LSITM ASS-ABL probes  at 37 °C for 50 h. Karyotypic and FISH analyses were performed using a CytoVision system .After 2 h of treatment with 0.1 ug/ml of KaryoMAX COLCEMID Solution (Thermo Fisher Scientific), the cells were exposed to 0.075 mol/l of KCL at 37 °C for 15 min and fixed on slide glasses, using a 3:1 methanol/glacial acetic acid solution three times. After trypsin-Giemsa staining of the air-dried slide samples, 20 metaphases were analyzed for each sample. For FISH analysis, the air-dried slide samples were denatured at 75 °C for 1 min and hybridized with LSISpectral karyotyping (SKY) was performed with a SkyPaint probe mixture . Briefly: after denaturation, each sample was hybridized at 37 °C for 67 hr and counterstained with DAPI I . Karyotyping was performed using a SpectraCube system with SkyView 1.5 .Cells were stained with propidium iodide (PI)  or fluorescein isothiocyanate (FITC) conjugated with Annexin V and PI . Each sample was analyzed using flow cytometry . Data evaluation was performed using FACS Diva software  and FlowJo software .4) were incubated with six concentrations of imatinib, dasatinib, nilotinib, or ponatinib, in triplicate, using a 96-well plate. After 66 hr of incubation, the cells were additionally incubated with alamarBlue  for 6 h [Cells (0.1 × 10 for 6 h . AbsorbaCells were treated with 1 mM of 4-(2-aminoethyl) benzene sulfonyl fluoride HCl  on ice for 10 min, then solubilized in lysis buffer . The lysates were separated on a SDS-polyacrylamide gel under reducing conditions and transferred to a nitro-cellulose membrane. The membrane was incubated overnight at 4 °C with the primary antibodies listed in Supplement Table INHβB as an internal control.Triplicated samples with SYBR Green PCR Master Mix (Thermo Fisher Scientific) were amplified through 40 cycles (at 95 °C for 15 sec and 60 °C for 1 min), using the primers listed in Supplement Table https://www.ncbi.nlm.nih.gov/assembly/GCF_000001405.39), using hisat2 (v.2.2.1). Reads were counted and normalized using featureCount (v.2.0.0). The total number of reads and gene lengths among samples were corrected, using transcripts per million (TPM). Differentially expressed genes among samples were analyzed using a DEseq2 package (v.1.30.1) [Total RNA was extracted from the triplicated samples using a RNeasy Plus Mini Kit (QIAGEN). The library preparation and sequencing were entrusted to Bioengineering Lab . RNA concentration and quality were evaluated with a Quantus Fluorometer, using the QuantiFluor RNA system , and a 5200 Fragment Analyzer System, using an Agilent HS RNA Kit . A sequence library was prepared, using an MGIEasy RNA Directional Library Prep Set . Library concentration and quality were evaluated with a Qubit 3.0 Fluorometer, using a dsDNA HS Assay Kit (Thermo Fisher Scientific), and with a Fragment Analyzer, using a dsDNA 915 Reagent Kit (Agilent Technologies). Construction of cDNA was performed using an MGIEasy Circularization Kit (MGI Tech). The DNA nanoballs generated with a DNBSEQ-G400RS High-throughput Sequencing Kit (MGI Tech) were sequenced using DNBSEQ-G400 (2 × 100 bp). Adaptor sequences, indexes, and primer regions were removed, using Cutadapt (v.1.9.91). Read sequences with low-quality scores (<20) and short read lengths (<40 bp) were removed, using Sickle (v.1.33). The read sequences were aligned to the human reference genome  . Princip.1.30.1) . A heatm.1.30.1) , respectBCR::ABL1 fusion gene is generated between exon e13 of the BCR gene and exon a2 of the ABL1 gene. To generate e13a2 type fusion, we transfected two sgRNAs targeting intron 13 of the BCR gene and intron 1 of the ABL1 gene  were accumulated in the sub-G0/G1 phase, while two GM- sublines showed almost similar distributions to those of the parental cells cultured in the presence of GM-CSF (GM + ) Fig. . In an aCCND2, CCND3, and MAPKAPK3) and cell survival (LITAF and BCL2L11) were commonly upregulated in the GM + parental cells and the two GM- sublines  were upregulated in the p210 BCR::ABL1 subline , differed substantially from diverse large indels observed at the cleavage sites of genome editing with CRISPR/Cas9. These differences may be attributed to re-cleavage of the repair site by CRISPR/Cas9. In its usual repairing process by non-homologous end joining, a repair site might be repeatedly cleaved until massive indel is acquired [The genomic sequences at the acquired . In contacquired .BCR::ABL1 sublines, we compared the gene expression profile of the BCR::ABL1 sublines and parental cells with that of 59 myeloid leukemia cell lines, including 13 Ph-positive cell lines (https://sites.broadinstitute.org/ccle/) and 10 CML patients’ samples  [RAPGEF2, a member of the RAS subfamily of GTPases that function in signal transduction [HOXB2, SOX5, and KLF1, transcription factors, and GAGE antigens, a family of cell surface antigens originally identified in melanoma cells. Of note, in these 16 genes, the gene expression profile of Ph-positive myeloid leukemia cell lines , by perin HL-60 , an acuthomolog) , RAPGEF2sduction , HOXB2, ing CD93 , MPL [71PL [RARB , and MECB [MECOM , were upBcr::Abl1 and BCR::ABL1 fusions in the murine Ba/F3 line and in human hematopoietic stem cells purified from cord blood cells, respectively, using the same strategy. Since we have had no success in these two cellular systems, we speculated that TF-1 could have some advantages in generating the BCR::ABL1 fusion with this strategy.Based on our success in TF-1, we have also attempted to generate the BCR and ABL1 genes by the CRISPR/Cas9 system generate a balanced translocation that mimics the Ph chromosome in a human factor-dependent leukemia cell line, indicating that simultaneous DSBs at the BCR and ABL1 breakpoints could be initiation events in Ph+ leukemia oncogenesis. Although the utility of the simultaneous introduction of the DSBs by the CRISPR/Cas9 system for the generation of BCR::ABL1 fusion is limited to TF-1 cells thus far, our strategy may provide a novel platform for functional evaluation of the oncogenic activities of BCR::ABL1 in the near future. (4421/4500 words).In summary, we demonstrated that double cleavages at the breakpoints of Supplemental Figure LegendsSupplemental Fig 1Supplemental Fig 2Supplemental Fig 3Supplemental Fig 4Supplemental Fig 5Supplemental Fig 6Supplemental Fig 7Supplement Table 1Supplement Table 2Supplement Table 3Supplement Table 4Supplement Table 5Supplement Table 6Supplement Table 7