Social support is one of the interpersonal stimuli that define an individual’s predisposition to engage in health-promoting behaviors and is considered a facilitator in improving health habits. Patients with type 2 diabetes mellitus (T2DM) can benefit from educating supportive families and friends on self-care management including exercise behavior. Multimedia messaging service (MMS) could also be an effective method for delivering targeted educational interventions that focus on physical activity (PA).This study aimed to assess the effectiveness of MMS educational interventions and perceived social support for exercise on level of PA of patients with T2DM.A quasi-experimental pretest-posttest design was conducted to recruit 98 patients with T2DM. The intervention group received MMS education aiming to improve exercise social support and PA level for 2 months, and their counterparts in the control group received the usual routine care. We sent 2 to 3 messages daily for 2 weeks from Saturday to Thursday . These messages were a combination of videos and texts, and the evidence-based content of these messages was reviewed and approved by the advisory committee. We randomly assigned eligible patients in a 1:1 ratio into the intervention or the control groups. Participants completed a survey in 3 periods.P>.05). Yet, there was a small effect size (Cohen d) in friends’ social support (0.389), family practical support (0.271), and moderate activities (0.386). A medium effect size was found in family verbal (0.463) and emotional (0.468) support. Being married increased the likelihood of friends’ support by 2.3 times after intervention (P=.04), whereas rarely doing exercise decreased the likelihood of friends’ support by 28% (P=.03) and family practical support by 28% (P=.01). Being female and married increased the likelihood of doing moderate activities by 1.6 times (P=.002) and 1.5 times (P=.049) in the intervention group. Being a housewife decreased the likelihood of doing moderate activities by 20% (P=.001). Finally, being a female with a higher educational level decreased the likelihood of doing hard activities by 20% (P=.04) and 15% (P=.002), respectively.There were no significant differences in friends’ support, family verbal, practical, or emotional support over time in the intervention group (A theoretically based MMS health education targeting PA levels and social support of family and friends to perform PA seems promising in promoting family and friends’ social support and improving PA levels among patients with T2DM. Actively involving family and friends in educational interventions that target PA can have an impact on health-promoting behaviors in patients with diabetes. The prevalence of type 2 diabetes mellitus (T2DM) is mounting in low- and middle-income countries at a higher rate than that in developed countries due to several factors including unhealthy diet, aging, obesity, and sedentary behaviors -4. A recYet, several self-management educational interventions showed effectiveness in improving overall health for patients with T2DM ,10,11. TSocial support is one of the interpersonal stimuli that define an individual’s predisposition to engage in health-promoting behaviors and is considered a facilitator in improving health habits ,17. SociOne approach that can help in supporting the self-management of patients with T2DM is information and communication technologies, such as mobile technology, which is convenient and useful in accessing a broader population ,24-26 anA pretest-posttest, quasi-experimental design was carried out over 2 months (June-October 2020) at the Family Medicine, Endocrinology, and Diabetes clinics at a leading university hospital  and affiliated outpatient clinics in the North of Jordan.A nonprobability convenience sampling method was used to recruit 100 patients with T2DM at baseline. During the first (1 month after baseline data collection) and the second (2 months after baseline data collection) follow-up period, 1 patient from each group dropped out, totaling 98 (49 in the intervention group and 49 in the control group). Patients were recruited while they were waiting for their appointment in the identified clinics. Inclusion criteria were the capacity to perform PA, the ability to read and write, owning a smartphone, and the ability to walk without a cane. We randomly assigned eligible patients in a 1:1 ratio into the intervention or the control groups. Patients in the intervention group received the MMS educational messages and their counterparts in the control group received the usual routine care.-up was conducted one month after baseline data collection using telephone interviews to fill out the survey at follow-up. The second follow-up was undertaken 2 months after the baseline data assessment using telephone interviews also to fill out the survey for the third time.The recruitment process was initiated and eligible patients with T2DM were voluntarily invited to participate when they attended the clinics based on a previous appointment. Those who agreed to participate were asked to sign an informed consent and complete a survey. Then, they were randomly assigned into two groups based on the sequential order; one in the intervention group and the next in the control group until the final sample size was obtained. The first followA 2-part survey was used in this study. The first part included information about participant’s sociodemographic characteristics  as well as type of medication, previous related behaviors, and blood sugar level. The second part consisted of following two questionnaires as below:Perceived social support scale for exercise behavior ,33. ThisA 7-day physical activity recall questionnaire . PatientParticipants in the MMS group (intervention group) received educational messages based on the Health Promotion Model . We sentAfter 2 weeks of daily educational messages through MMS, the intervention group participants received 2 messages weekly for up to a month and a half. During this time, we stayed in close contact with patients in case of any questions or complaints and to ensure that they are in good health. Participants in the intervention group also kept communicating back with the research team to show satisfaction with being involved in the study.U test and chi-square tests were performed to determine if there was a significant difference between the groups in baseline data. A comparison between baseline data, first, follow-up data, and second follow-up data according to perceived health status scale and exercise social support and PA recall scales was conducted to determine if there was a significant difference between the 3 data sets in these subscales. We also compared baseline data with the second follow-up of the intervention group on exercise social support and PA recall scales to calculate the effect size using the Cohen d value. Finally, logistic regression analysis of social support and PA recall scales with demographics and health status was also performed to determine the variables that significantly affect social support and PA recall scales. The significance level was set at P<.05.SPSS software  was used to analyze the data. Descriptive analysis was first carried out to present the frequencies and percentages of demographics and health status in both groups. The normality of data was also tested, and nonparametric tests were performed whenever the normality assumption was violated. Then, the Mann-Whitney Before data collection, ethical approval was obtained from the Jordan University of Science and Technology institutional review board . Patients with DM who were willing to participate in the study were invited to sign a consent form in Arabic, including a statement informing them that he or she had the right decline participation at any time. The data were treated anonymously and confidentially. Furthermore, a number of considerations were taken into account to ensure the safety of participants. These considerations were printed out and attached to the consent form, including the following:(1) If the patients notice a sudden rise in the level of sugar in the blood after entering the study, they should stop doing physical activities and visit their doctor or call him or her and explain their condition as soon as possible.(2) Keep an eye on your blood sugar levels and check them frequently before and after exercise, especially if you are new to exercise.(3) Do not exercise if your blood sugar levels are too low or too high. If they are lower than 100 mg/dL or higher than 250-300 mg/dL, it may not be safe to work out; so, eat a snack or wait for it to reach a better level before getting started.(4) Stop exercising if you experience dizziness, shortness of breath, disorientation, or pain. (5) When the patient goes out to exercise in the gym or to take a walk or any other outdoor activity, he or she should take at least 15 gm of sugar  in anticipation of a low level of sugar in the blood while the patient is far from home.Sociodemographic characteristics of participants are presented in U test showed no significant difference between the intervention and control groups in age, BMI, cumulative blood sugar level, educational level, and exercise level at baseline , and the majority were nonsmokers (82% in the intervention group and 80% in the control group). Less than half of participants have 6%-9.9% of blood sugar level (40% in the intervention group and 44% in the control group), and they rarely do exercise  in the intervention group. However, there was a significant difference between baseline, first follow-up, and second follow-up in family practical support (P<.003) in the control group. This implies less social support as discussed in P>.05) in the intervention group, but were statistically significant in the control group  between the baseline and second follow-up in doing moderate activities in the intervention group . However, there was no significant difference between baseline and second follow-up in doing moderate activities and challenging activities in the control group ; being married increased the likelihood of doing moderate activities by 1.5 times (P=.049) whereas being a housewife decreased the likelihood of doing moderate activities by 20%, (P=.001). In regard to the coefficients of the hard activities model for patients in the intervention group, being a female decreased the likelihood of doing hard activities by 20% (P=.04), and having a higher educational level decreased the likelihood of doing hard activities by 15% , whereas rarely doing exercise decreased the likelihood of friends’ support by 28% (P=.03). Using coefficients of the family practical support model, rarely doing exercise decreased the likelihood of family practical support by 28%  for exercise behavior over time in the intervention group. One possible reason was that the SMS educational approach was not efficient in influencing patients’ friends and family members to provide social support to the patient. These findings support previous literature that patients with type 2 diabetes receive less social support for PA compared with other aspects such as medication and diet for diabetes management . Thus, tIn measuring the effect of SMS messages on changing exercise behavior among patients with diabetes in the intervention group, we found a significant difference in moderate activities over time with an increase in the mean score between the baseline data and the second follow-up while a decrease in very hard activities. In the control group, we did not find a significant difference in moderate and hard activities, but a decrease in the mean score for very hard activities.Participants in the intervention group improved their behavior in doing moderate activities over time because they practiced walking on public streets, which is considered moderate activity. Similarly, a study conducted in Jordan  reportedAdditional research that investigates knowledge, attitude, and practice is needed to develop and tailor interventions according to individual patients’ sociodemographic characteristics, needs, and context related to PA. These include the patient’s age, BMI, sex, comorbidities, family and friends’ social support, and patient’s willingness to incorporate PA in their daily lives. This can be best accomplished through feasible, efficient, and affordable tools, such as MMS-based education. Finally, health care providers should personalize PA consultations within routine diabetes primary care services and find the best ways to actively involve family members and friends in PA educational programs.This is the first national study that used MMS through mobile phones to deliver educational interventions to patients with T2DM. The quasi-experimental design and the use of valid and reliable scales were strengths of the study. Additionally, the intervention was developed based on the Health Promotion Model. Nevertheless, this study has some limitations. First, the relatively small number of samples, which was mainly due to the COVID-19 pandemic and that the national lockdown that slowed down the process of recruiting patients. Second, using a convenience sample could have affected the generalizability of the findings; yet, we managed to increase the representativeness of the findings by recruiting all eligible patients who approached the included clinics and voluntarily agreed to participate over the period of data collection.The design and implementation of a structured educational program using the Health Promotion Model of PA among patients with T2DM had a positive impact on changes in PA behaviors but not on social support for exercise. Delivering interventions through MMS using cell phones is feasible and cost-effective with a promising impact on adopting healthy lifestyle behaviors, such as PA. Involving family members and friends in PA educational programs for patients with T2DM could yield benefits in social support.


Studies were then compared and evaluated based on delivery success, functional outcomes, and translatability. Delivering JAG1 to harness its ability to control cell fate has the potential to serve as a therapeutic for many diseases.JAG1 is a ligand that activates the NOTCH signaling pathway which plays a crucial role in determining cell fate behavior through cell-to-cell signaling. JAG1-NOTCH signaling is required for mesenchymal stem cell (MSC) differentiation into cardiomyocytes and cranial neural crest (CNC) cells differentiation into osteoblasts, making it a regenerative candidate for clinical therapy to treat craniofacial bone loss and myocardial infarction. However, delivery of soluble JAG1 has been found to inhibit NOTCH signaling due to the requirement of JAG1 presentation in a bound form. For JAG1-NOTCH signaling to occur, JAG1 must be immobilized within a scaffold and the correct orientation between the NOTCH receptor and JAG1 must be achieved. The lack of clinically translatable JAG1 delivery methods has driven the exploration of alternative immobilization approaches. This review discusses the role of JAG1 in disease, the clinical role of JAG1 as a treatment, and summarizes current approaches for JAG1 delivery. An in-depth review was conducted on literature that used both  The NOTCH canonical pathway is involved in determining cellular fate and targeting this pathway can potentially be used as a therapy for diseases that involve JAG1 mutations. Alagille syndrome, for example, is an autosomal dominant disorder that results from nutations in JAG1 and NOTCH2 . Mutatio in vivo . Our lab in vivo . Previou in vivo  and achi in vivo . The use in vivo . ExampleJAGGED1 (JAG1) is one of 5 ligands  that interacts with the NOTCH receptor and therefore plays a key role in NOTCH signaling . MammalsJAG1 is located on chromosome 20, stretching across 36 kb, and has 26 exons ranging in size from 28 to 2,284 bp  Oda et . JAG1 isHeterozygous mutations in JAG1  and/or min vivo.Tetralogy of Fallot (TOF) is a prevalent congenital heart defect with a rate of 3.3 cases per 10,000 live births and it affects normal blood flow through the heart . PulmonaThe role of the NOTCH signaling pathway and JAG1 in different types of cancer development is well established given their involvement in cell proliferation, differentiation, apoptosis, and angiogenesis . It has in vitro and in vivo, JAG1 was upregulated in both in vitro osteogenic differentiation and in vivo tibial bone fracture healing. Moreover, JAG1 activated NOTCH signaling in human alveolar and iliac bone-derived cells resulted in enhanced mineralization in vitro  through NOTCH signaling which can potentially be used as a therapeutic in periodontal defects . AdditioThe clinical roles of JAG1 can also extend to addressing cardiac conditions such as myocardial infarction and improving cardiac development. It has been demonstrated that JAG1-NOTCH signaling promotes the differentiation of MSC into cardiomyocytes which helps improve left ventricular function . DeliverHair loss is another clinical problem JAG1 addresses as a study has shown its therapeutic potential for androgenetic alopecia. The topical application of JAG1 promoted hair regeneration and its effect was enhanced when combined with epidermal growth factor . In anotThe role of JAG1-NOTCH signaling in regulating cell behavior such as differentiation, proliferation, and apoptosis has been widely researched. Delivery of JAG1 requires the protein to be bound or immobilized in a way that the receiving cell’s NOTCH receptor will be cleaved into NICD. Delivering soluble JAG1 actively inhibits NOTCH signaling by occupying the receptor but does not lead to NICD cleavage. Therefore, the immobilization of JAG1 to a delivery scaffold is required and is a significant hurdle to developing JAG1-based therapies. Delivering JAG1 in the correct orientation to signal with the NOTCH receptor at the cell surface is critical for NOTCH signaling . Taking in vitro indirect affinity immobilization method to immobilize JAG1, where surface-bound JAG1 was prepared by incubating the wells of a tissue culture plate with recombinant protein G followed by incubation with JAG1 and the desired cell line as shown in in vitro. It was found that JAG1-treated hDPs exhibited downregulation of genes related to the cell cycle and DNA replication and immobilized JAG1 promoted odonto/osteogenic differentiation in hDPs. caspase 3 and occludin) were upregulated compared to the control groups (no treatment and Fc control). Additionally, endothelial cell differentiation by these biomaterials was confirmed by observing an increase in intermediate (involucrin and CK10) and late (filaggrin) stage differentiation markers. in vitro. The results demonstrated that indirect affinity immobilized JAG1 on the membranes upregulated hPDL NOTCH target gene expression. Recently, The use of protein G is a common method for JAG1 immobilization as it is a protein that binds immunoglobulin G (IgG) of many species. Additionally, commercially produced JAG1 contains a tag protein, such as a Fc fragment that protein G can interact with, which helps orient JAG1. Earlier studies have used an in vitro and upon evaluation, it was found that JAG1 induced differentiation of human MSC into osteoblasts through canonical NOTCH signaling while osteoblastogenesis was inhibited in mouse MSCs demonstrating a major pitfall in the use of mouse models to study bone abnormalities for diseases such as ALGS  were mixed with an equal amount of ethanol. This mixture was then used to coat the wells of a 24-well tissue culture plate. Finally, the A6 macromer was photopolymerized by exposure to ultraviolet light in a nitrogen-purged environment. This study explored direct and indirect immobilization to establish an optimal immobilization strategy that induces NOTCH activation at higher protein concentrations which is required for in vivo therapeutic effects. For direct immobilization, JAG1 was diluted with PBS at various concentrations and was adsorbed to A6, whereas for indirect immobilization, a secondary antibody (anti-Fc antibody) was adsorbed to A6 and the anti-Fc antibody was in turn bound to the Fc portion of JAG1. Upon immobilizing JAG1 and evaluating it in hMSCs, the results demonstrated that JAG1 induced an osteogenic phenotype in hMSCs, with the direct strategy being more effective  comprised of diethylene glycol diacrylate (A) and isobutylamine (6), known as A6 . This poffective .Self-assembled monolayers (SAMs) is another approach that has been used for JAG1 immobilization. SAMs are highly ordered organic substrates obtained by spontaneous organization of alkanethiols on surfaces. Some features that make these surfaces favorable over other substrates for immobilization is that they provide precision of surface control, different functional groups can be exposed on the same surface, and they allow a broad range of surface chemistry modifications . One of Functionalizing self-assembling peptides (SAP) with a peptide mimic of JAG1 has also been used as a therapeutic to deliver JAG1. Another method for JAG1 delivery is functionalizing nanocarriers with JAG1. in vivo, a Matrigel plug assay was performed where the JAG1 containing exosomes were incubated with a Matrigel plug, which was placed in athymic nude mice. The results demonstrated an increase in formation of new vessels on the gel, that JAG1 was the only NOTCH ligand present in the HIF-MSC exosomes, and HIF-1α increased the levels of JAG1 both at the cellular and exosome level . Although this study suggested a novel mechanism for JAG1 delivery, its major limitation was that it did not demonstrate whether angiogenesis induction was from the direct interaction between the MSC-derived exosomes and the NOTCH receptors located on the endothelial cell plasma membrane or if it was due to the transfer of JAG1 from the MSCs to the HUVECs. Therefore, each component of the system that contributes to angiogenesis must be assessed. Additionally, the study did not quantify the concentration of JAG1 present in the exosomes. Therefore, it is unclear how this approach would be clinically translatable. Quantifying JAG1 would provide a better understanding of dosing adjustments required for treatment, therefore making this approach clinically translatable.Nanoparticles can also be functionalized with JAG1 which is what in vitro study, this study served as a proof of concept for the need to immobilize JAG1 and the use of microspheres for JAG1 delivery. Furthermore, these biomaterials would further need to be analyzed for their biological effects in the context of cell differentiation promotion. Finally, the binding capacity and conjugation of JAG1 to these microspheres would need to be scaled for clinical applicability.in vivo. However, further analysis will be needed to be performed on the mechanism of the hair growth promoting effect JAG1 and EGF has as it is unclear if this effect was due to the stimulation of cell proliferation. Moreover, there was no treatment group that was treated with JAG1 alone, without the presence of testosterone. As we know from literature, testosterone promotes hair growth  JAG1 must be immobilized to a delivery scaffold and 2) a correct orientation must be achieved between the NOTCH receptor at the cell surface and the JAG1 ligand of the other cell to ensure cell-to-cell contact. Many approaches have been proposed to address these requirements such as using an indirect affinity immobilization method where the delivery scaffold could be protein G, self-assembled monolayers, synthetic membranes, and nanoparticles. However, these delivery methods come with the limitation of not being clinically-applicable due to its low yield of ligand density which is vital for cell behavior regulation such as differentiation and proliferation. Other delivery scaffolds that have been suggested are dynabeads, self-assembling peptides, nanocarriers, cell-derived exosomes, collagen scaffolds, and microspheres. Some approaches, such as the use of dynabeads alone or encapsulating these dynabeads in PEG-MAL hydrogels, have been proven to be toxic, while other approaches lack the fundamental understanding of how the canonical pathway is activated. Therefore, there is a need to expand upon these delivery methods to make them clinically applicable. The use of PEG-MAL hydrogels to directly immobilize JAG1 without the use of a secondary substrate such as dynabeads can be an approach for future studies.


Gestational diabetes mellitus (GDM) is a risk factor for the development of type 2 diabetes. Metformin and lifestyle change through a Diabetes Prevention Program (DPP) are equally effective in preventing diabetes in patients with a GDM history, so women can choose a strategy based on their preferences. This study aims to test whether shared decision making (SDM) can help women with a history of GDM increase adoption of evidence-based strategies and lose weight to lower their risk of incident diabetes in real-world settings.n = 155 from UCLA Health and n = 155 from Intermountain Healthcare). The primary outcome is the proportion of participants who lose ≥5% body weight at 12 months. Secondary outcomes include uptake of DPP and/or metformin and other patient-reported outcomes such as patient activation and health-related quality of life. Rates of GDM in a subsequent pregnancy will be an exploratory outcome. A descriptive analysis of costs related to SDM implementation will also be conducted.This pragmatic randomized controlled trial (RCT) will test the effectiveness of SDM for diabetes prevention among 310 overweight/obese women with a history of GDM and prediabetes from two large health care systems (This is the first RCT to examine the effectiveness of SDM on weight loss, lifestyle change and/or metformin use, and other patient-reported outcomes in participants with a GDM history at risk of developing diabetes.ClinicalTrials.gov, NCT03766256. A hisThere is strong evidence from the Diabetes Prevention Program (DPP) trial supporting the efficacy of lifestyle change or metformin use among women with a GDM history since either option reduces incident T2DM by about 50% –9. AmongSince women with a history of GDM face a “preference-sensitive” decision with two evidence-based alternatives to prevent T2DM , SDM is This is the first study testing the effectiveness of SDM for diabetes prevention in women with a history of GDM.2.2.1.This multicenter randomized controlled trial (RCT) tests whether SDM can increase weight loss and adoption of evidence-based strategies to lower the risk of incident T2DM in women with a history of GDM and prediabetes at high risk of developing T2DM. Participants will be randomized to the SDM intervention versus control and the primary outcome will be the proportion of participants with ≥5% weight loss at 12 months . Seconda2.2.This RCT will take place within two large health care systems with locations across California, Utah, Nebraska, and Idaho.2.3.Our eligibility criteria are summarized in 2.4.2.4.1.Women who meet eligibility criteria based on our screening of electronic health record (EHR) data will receive an invitation letter. We will replicate our successful recruitment approach from prior work in SDM for diabetes prevention –38, firs2.5.2.5.1.Healthwise®, the health education nonprofit with whom we contracted. The clinician will present a 100-person chart based on data from the DPP trial which demonstrates the relative benefits of metformin and ILI in the form of a DPP for T2DM prevention among women with a history of GDM  with their patient. Our study team’s interactions with the control group are meant to supplement that information.2.5.3.We will use approaches recommended by the NIH Behavior Change Consortium to ensure that the SDM intervention is being delivered and received as intended . These i2.5.4.We will provide each participant with a $35 gift card after their baseline visit, a $15 gift card after their 6-month telephone follow-up, and $35 gift cards after their 12 month and 24 month follow ups.2.6.We will collect data on individual participant-level outcomes and measure implementation-related costs to conduct a cost analysis of the program.2.6.1.We will collect data at baseline, 6 months (by telephone), 12 months, and 24 months  for participants in both the intervention and control arms of the evaluation. A baseline questionnaire was developed to ask participants about their risk awareness of T2DM and experience with preventative measures, as well as to assess patient activation and lifestyle choices around nutrition/physical activity. At the initial visit, the intervention participants will meet with pharmacists or registered nurses while the control participants will meet with research assistants. At 6 months, all participants will receive a telephone call from a research assistant to assess uptake of lifestyle change (yes/no) and/or uptake of metformin (yes/no). Attendance of a minimum of 9 of 16 weekly lifestyle change sessions will be the threshold for uptake of lifestyle change for both groups, as this reflects the CDC’s standard for DPP recognition from 2011 to 2020. Since some patients will not be able to tolerate metformin at the goal total daily dose of 2000 mg, we will encourage patients to take the maximum dose that they can tolerate and will count any metformin dose toward the yes/no outcome of “taking metformin.” We will backfill with EHR data on medication reconciliation as needed, since nurses and medical assistants at both systems verify and document current medications at each ambulatory and inpatient visit. At the 12-month and 24-month follow-ups, all participants will conduct an in-person or virtual follow-up visit with research assistants for weight measurement and follow-up surveys. The primary outcome (proportion of participants with ≥5% weight loss at 12 months) will be determined from weights recorded at study-related visits, but we will backfill missing weights from the EHR. We will include a variable in our analysis indicating whether weight was measured based on the patient’s home scale provided by the study or backfilled from the EHR. Additional outcomes are shown in 2.7.2.7.1.Hypothesis: The intervention will result in a greater proportion of participants achieving ≥ 5% weight loss at 12 months as compared to patients receiving usual care.For the primary analysis, we will use logistic regression to compare the proportion of participants with ≥5% weight loss between the two study arms at 12 months. The model will include indicator variables for study arm, SDM provider type (UCLA pharmacist vs. Intermountain registered nurse), and pre-selected baseline patient characteristics such as age and race/ethnicity. Given potential differences in intervention effectiveness across sites, we will conduct preliminary analyses within each site. Effect estimates for the intervention and relevant baseline covariates, if any, from the two models will be compared. Those with relatively large differences indicate potential interaction effects with site . We will not draw final conclusions from these preliminary analyses, but in the formal analysis which combines data from the two sites, we can test interaction effects between site and intervention, and between site and other covariates as indicated by the preliminary analyses.We used data from prior work in SDM for diabetes prevention to estimate the effect size of the proposed intervention –38, in w2.7.2.Hypotheses: The intervention will result in: 1) a greater proportion of participants achieving ≥ 5% weight loss at 24 months, 2) increased uptake of lifestyle change and/or metformin at 6 months, 3) better patient-reported outcomes , 4) annual follow-up screening for progression to T2DM.1c level or an oral glucose tolerance test. The model will include the same set of predictors outlined above for the logistic regression and also adjust for baseline patient-reported outcomes.We will use the same analytic plan as described above for the primary outcome to compare intervention and usual care in terms of the rates of ≥5% weight loss at 24 months, uptake of lifestyle change and/or metformin use at 6 months, and rates of screening for T2DM. Linear regression will be used to examine patient-reported outcomes at 6, 12, and 24 months, and we will be able to measure whether patients attended a minimum of 9 of 16 weekly lifestyle change sessions even if there was a delay in enrollment. Annual follow-up screening for progression to T2DM will include any ADA-recommended screening test for the detection of T2DM, including measuring fasting plasma glucose or HbA2.7.3.Hypothesis: The intervention will result in lower rates of GDM in a subsequent pregnancy.We will use the same analytic plan as described above for the primary outcome to compare the rates of GDM in a subsequent pregnancy. GDM diagnosis will be based on ICD10 codes or positive 1-step or 2-step oral glucose tolerance test. The analysis will be restricted to participants who are not pregnant at baseline or at the 6 month follow up and who are no >3 months pregnant as the 12 month follow up. This analysis will be adjusted for baseline covariates that show differential distributions between the two groups. However, this will be an exploratory outcome, and our study is not powered to assess its significance.2.7.4.We will not test a hypothesis with this aim, but will rather conduct a descriptive analysis of costs related to implementation of the intervention . We will2.8.2.8.1.Study data will be examined and summarized by descriptive statistics including median, mean, and standard deviation for quantitative variables and by frequencies and proportions for categorical ones. All variables of interest will be summarized for the whole sample, by clinic sites, and by study arms. We will control for baseline covariates and use either logistic or linear regression models, depending on the type of outcome variable. Graphic displays, such as boxplots and histograms, will be used to inspect skewness and normality for quantitative variables and to identify possible outliers. All randomized subjects will be included and the intention to treat principle will be applied.Missing data will be handled using multiple imputation techniques that assume data are missing at random . Analysi2.9.Potential adverse events include musculoskeletal injuries as a consequence of supervised physical activity, lactic acidosis, and loss of confidentiality of prediabetes diagnosis due to a data breach. Every adverse event will be documented, including events that are reported to the study team and/or research associates through means other than those described above. A report will be generated for each event, including a description of the event, when and how it was reported, as well as any official chart records or documentation to corroborate the event and determine its attribution. Any serious adverse events as described above will be reported within 7 days to the outside Data and Safety Monitoring Plan monitor, and to the UCLA or Intermountain IRB as well as the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) program officer. Additionally, safety reports will be submitted to our Data and Safety Monitor every 6 months throughout the study period. Any action resulting in a temporary or permanent suspension of this study  will be immediately reported to the appropriate NIDDK program official.ClinicalTrials.gov .Institutional Review Board (IRB) approval has been obtained from the UCLA Office of Human Research Protection Program  and from the Intermountain Healthcare IRB . This trial is registered at 3.This study protocol describes the planned methodology of the Gestational diabetes Risk Attenuation for New Diabetes (GRAND) study, a multi-center RCT that evaluates whether SDM can help women with a history of GDM and prediabetes increase weight loss and adoption of evidence-based strategies to lower their risk of incident diabetes. We will compare the proportion of participants (intervention vs. control) achieving ≥5% weight loss and taking up lifestyle change and/or metformin in a real-world setting. We will also assess whether SDM may result in lower rates of GDM in a subsequent pregnancy and estimate the costs related to implementing SDM intervention to help healthcare practices assess the resources they will need to implement a similar program.Given the increased lifetime risk of incident T2DM in women with a GDM history, engaging this population in evidence-based strategies for diabetes prevention is critical. This study presents a unique opportunity to address a vital area of unmet need in diabetes prevention for women with history of GDM, leveraging our health system infrastructure and our collaborative, multidisciplinary team with a strong record of accomplishment in diabetes prevention.4.This study addresses a major unmet need and would be the first to evaluate SDM for diabetes prevention for women with a history of GDM. Our results will provide critical evidence as to whether close collaboration between patients and healthcare providers in a real-world clinical setting helps women with a GDM history make informed, timely, and effective decisions to reduce their risk of T2DM. This work will provide pragmatic, effective and sustainable approaches to increase evidence-based diabetes prevention strategies for women with a history of GDM that can be readily adopted in other health systems.


Due to random pose changes in the workpieces on the production line, demand for online 3D modeling has increased and many researchers have focused on it. However, online 3D modeling has not been entirely determined due to the occlusion of uncertain dynamic objects that disturb the modeling process. In this study, we propose an online 3D modeling method under uncertain dynamic occlusion based on a binocular camera. Firstly, focusing on uncertain dynamic objects, a novel dynamic object segmentation method based on motion consistency constraints is proposed, which achieves segmentation by random sampling and poses hypotheses clustering without any prior knowledge about objects. Then, in order to better register the incomplete point cloud of each frame, an optimization method based on local constraints of overlapping view regions and a global loop closure is introduced. It establishes constraints in covisibility regions between adjacent frames to optimize the registration of each frame, and it also establishes them between the global closed-loop frames to jointly optimize the entire 3D model. Finally, a confirmatory experimental workspace is designed and built to verify and evaluate our method. Our method achieves online 3D modeling under uncertain dynamic occlusion and acquires an entire 3D model. The pose measurement results further reflect the effectiveness. With the increasing demands for intelligent manufacturing and industrial automation, digital three-dimensional (3D) models of workpieces hold increasingly important status in production processes ,2, such 3D modeling applied in factories can be performed offline or online ,5. OffliCommon online 3D modeling methods can be divided into two categories. One is to arrange multiple depth sensors around the workpiece, and register point clouds collected from multiple perspectives ,7,9,10. Recently, many researchers have started to focus on the occlusion problems of dynamic objects to find some ways to segment dynamic objects. Existing methods can be classified into three categories: optical flow-based, point cloud clustering-based, and learning-based methods. A traditional segmentation method is optical flow , where tIn this paper, aiming at the uncertain dynamic occlusion problem, an online 3D modeling method based on a single binocular camera is proposed. This method does not rely on prior information about objects, and can only achieve the robust segmentation of feature points and corresponding point clouds (2D-3D) by analyzing the motion patterns of adjacent frames. Through exploring the distribution of pose hypotheses calculated using 2D-3D point pairs that are obtained by multiple random sampling, 2D-3D point pairs corresponding to dense regions of the pose distribution are chosen as the segmentation results. Initial poses between adjacent frames can be acquired from these 2D-3D point pairs. On this basis, considering the incomplete point cloud of the occluded target object obtained after segmentation, an optimization method based on local constraints of covisibility regions and global loop closure is proposed to optimize the local registration and the entire 3D model. Furthermore, we design and build an experimental workspace to verify the feasibility and effectiveness of our method.Aimed at the task of 3D modeling under uncertain dynamic occlusion, we propose an online 3D modeling method, as shown in Model for Dynamic Objects Segmentation. Given two consecutive images, the feature point correspondences This model combines the complexity of segmentation, the number of inliers and the motion consistency of the object, where The best segmentation Cluster Analysis. A pose hypothesis can be obtained by one sampling in point correspondences, where one sampling represents sampling the smallest set of point pairs that are sufficient to compute a pose hypothesis. The pose hypotheses calculated from point pairs sampled on the same object must coincide in the pose parameter space. Based on this idea, cluster analysis can be achieved (1) by finding the dense regions in pose hypotheses and object segmentation can be acquired.(1) Pose Hypothesis Calculation. To compute the pose hypothesis ht-point  method aht-point  method tradation . In thisradation  is adopt(2) Pose Hypotheses Clustering. Based on these pose hypotheses, the clustering algorithm is carried out. Euclidean distance in the Lie algebra coordinate system is adopted to measure the distance between two pose hypotheses.Algorithm 1. Pose Estimation for Each Cluster Region Input: feature points Output: rigid body pose ,1  carry out multiple sampling in 2  3  cluster 2,…,N by  4  obtain cluster centers 5  sort all regions in descending order according to if there is only one cluster center, that is, 6  7    8    return 9    end if10  11 reject the region Considering that the number of objects in the scene is unknown, the cluster method proposed in  is introel (ORK) . We sortrithm in  is used Notation. We take the coordinate system of object Constraints and Factor Graph Establishment. After object segmentation, the 2D-3D corresponding point pairs and initial pose of each object can be obtained. Due to which object is the target object is unknown, all objects need to be estimated. Moreover, only using these initial poses cannot register the point clouds well because the point cloud of each frame is incomplete caused by occlusion. Therefore, an optimization method based on local constraints and global loop closure is introduced to acquire accurate poses.(1) Reprojection Constraints. For a spatial 3D point For a 3D point Here, Here, (2) Object Motion Constraints. On the basis of object motion For all points on object (3) Smoothness Constraints. Taking into account the smoothness of the motion of the objects That is to say, the moving speed of dynamic objects between adjacent frames is roughly the same.All of the above constraints are added to the factor graph. The variables that need to be optimized are Then, (14) can be solved using the Levenberg-Marquardt method  to optimHere, we not only establish the above constraint relationships between adjacent frames, but also establish constraints between closed-loop frames with covisibility regions, so as to further optimize relevant variables. After optimization, 3D models and object poses can be acquired at last.Our method was verified on an experimental workspace built by ourselves. We modeled three objects under uncertain dynamic occlusion in the workspace and used the modeling results to estimate poses. The three objects were a complex surface part (As shown in The vision system mainly included two high-resolution Basler cameras acA1920-50 gm (2.3 million pixels) and an auxiliary texture device. Two cameras were symmetrically arranged with a large baseline. The purpose was to improve the accuracy of depth measurements. By adjusting the focal length, the two cameras could focus on the central axis of the turntable. The auxiliary texture device was installed between two cameras. It needed to be simultaneous with the camera to provide the texture when some untextured objects were measured. After the cameras and the auxiliary texture device were installed and fixed, the calibration of the intrinsic and extrinsic parameters of the two cameras was performed. The stereo calibration method  was adopIn our experiment, the camera was fixed and the target object was rotated by a positioner during modeling. To test the effectiveness of the proposed method, we kept the tool moving between the target object and the camera so that the target object was occluded throughout the whole process. The auxiliary texture was utilized to obtain the corresponding points of the left and right images. The resolution of captured images was Dynamic object segmentation can be implemented by the algorithm described in In order to present the clustering process more graphically, we chose the translation vector of the pose transformation to represent the pose hypothesis. The 3D pose parameter space is displayed in the 3D Cartesian coordinate system. The translations of the camera and objects have a real scale. The intermediate results of the segmentation of In our experiment, dynamic object segmentation is only performed at the beginning and when the number of points on the objects is less than a certain threshold. In other frames, the points on each object are separately tracked.After object segmentation, the initial pose of each object can be acquired. Then, the factor graph optimization described in In We also tested the running time of optimization. The experiments were performed on an Intel Core i7-8700 3.2 GHz desktop with 24 GB RAM. For three objects In order to evaluate the registration accuracy of the incomplete point cloud of each frame in the case of uncertain dynamic occlusion, we compared it with three methods. One was an incremental open-loop registering method. The method in  was utilThe pose measurement results for the target object were also evaluated. The initial entire 3D model was first acquired. Then, the target object was driven by the turntable to perform pre-defined relative pose transformations. After each pose transformation, the 3D model was acquired again at this transformed position and was registered with the initial entire 3D model to estimate the relative pose transformation. The pre-defined pose transformations could be regarded as ground truths of the pose transformations between two positions. Here, we provide three pre-defined relative pose transformations In order to more vividly show the registration results of the incremental open-loop registering method, ICP, and our method, we demonstrate the results of the In this paper, we propose a segmentation method based on motion consistency constraints without any prior knowledge, which only achieves robust segmentation by analyzing the motion patterns of adjacent frames. The demonstration experiment of the clustering process fully reflects that pose hypotheses calculated from point pairs sampled on the same object must coincide in the pose parameter space. The number of clustering centers represents the number of possible dynamic objects with an inconsistent motion. Our method does not require object samples for training compared with deep learning-based methods, and it is insensitive to the size and motion of moving objects compared with the point cloud clustering-based and optical-flow-based methods. It can meet the needs of 3D modeling under uncertain dynamic occlusion. The experiments also further emphasize the importance of dynamic object segmentation. ICP and other methods are difficult to register point clouds without segmenting dynamic objects. For the registering of incomplete point clouds, we propose an optimization method based on local constraints and global loop closure constraints. Aimed at the task of 3D modeling under uncertain dynamic occlusion, we propose an online 3D modeling method for pose measurements under uncertain dynamic occlusion. Firstly, in order to solve the uncertain dynamic object occlusion problem, we propose a dynamic object segmentation method based on motion consistency constraint without any prior knowledge about the objects, which segments the objects by random sampling and pose hypotheses clustering. Then, the initial pose and 2D-3D point pairs of each object between two adjacent frames can be obtained. After that, because the incomplete point cloud of the target object of each frame needs to be registered and inspired by the constraint relationships of the covisibility regions, an optimization method based on local constraints of overlapping view regions and global loop closure is introduced to optimize the registration of adjacent frames and the entire 3D model. Furthermore, constraints between global closed-loop frames are also established to refine the results. Finally, based on the proposed framework and method, we design and build a confirmatory experimental workspace. The experiments are carefully carried out in this workspace to test and verify the performance of our method. For the modeling results of three objects, our method outperforms three other classical methods. The 3D model is utilized to measure the poses, and the poses are further compared with the ground truths. The performance of our method meets the expected requirements. In this paper, we mainly focus on improving the optimization speed and solving the object reflection problem. Optimization will slow down as the number of points increases. Graphics Processing Unit (GPU) acceleration and the filter-based method are considered to address this problem. Reflection is also a challenging problem in computer vision. At present, traditional methods cannot solve this problem well. We intend to introduce a learning-based technique to deal with this.


Taxation on sugar-sweetened beverages (SSBs) has been adopted in more than 40 countries but remained under discussion in Vietnam. This study aimed to estimate the health impacts of different SSBs tax plans currently under discussion to provide an evidence base to inform decision-making about a SSBs tax policy in Vietnam.Five tax scenarios were modelled, representing three levels of price increase: 5%, 11% and 19–20%. Scenarios of the highest price increase were assessed across three different tax designs: ad valorem, volume-based specific tax & sugar-based specific tax. We modelled SSBs consumption in each tax scenario; how this reduction in consumption translates to a reduction in total energy intake and how this relationship in turn translates to an average change in body weight and obesity status among adults by applying the calorie-to weight conversion factor. Changes in type 2 diabetes burden were then calculated based on the change in average BMI of the modelled cohort. A Monte Carlo simulation approach was applied on the conversion factor of weight change and diabetes risk reduction for the sensitivity analysis. We found that the taxation that involved a 5% price increase gave relatively small impacts while increasing SSBs’ price up to 20% appeared to impact substantially on overweight and obesity rates (reduction of 12.7% and 12.4% respectively) saving 27 million USD for direct medical cost. The greatest reduction was observed for overweight and obesity class I. The decline in overweight and obesity rates was slightly higher for women than men.This study supports the SSB tax policy in pursuit of public health benefits, especially where the tax increase involves around a 20% price increase. The health benefit and revenue gains were evident across all three tax designs with the specific tax based on sugar density achieving greatest effects. In 2016 it was estimated that globally almost half of adults and one fifth of children aged 5–19 were overweight or obese . Low andIncreasing taxes on SSBs has been strongly encouraged to reduce the SSB consumption as part of a comprehensive, evidence-based approach to improving diets and reducing the burden of diet-related NCDs , 6. So fIn Vietnam, while the rising trend of NCD burden has been observed in the last decade, Vietnam has shown limited progress towards achieving the diet-related non-communicable disease (NCD) targets for 2020 . A rapidTo date, limited efforts have been made to limit trends in overweight and obesity. SSBs were considered for inclusion in the list of goods subjected to a special consumption tax (or excise tax) under Vietnam’s Law on Excise Tax in 2008 but it was not materialized. In 2017, the Ministry of Finance again proposed an ad-valorem tax at 10% applied on SSBs . In thisAs the study employed a multiple stage modelling approach, there are two time-horizons applied, starting with the 3-year horizon for weight change projection (short-term impact) and a lifetime horizon for the prediction of diabetes mellitus prevalence (long-term impact). For the first projected outcome regarding weight change and obesity status, the time horizon of our model was set at 3 years from the point of SSBs tax implementation based on the average time to obtain expected weight change . For theIn Vietnam, currently the excise tax is imposed on the ex-factory before-tax price (or factory price). The government tax strategy until 2030, No508/QĐ-TTg 2022, indicated that an excise specific tax component (as fixed amount of tax placed on a product quantity such as volume or sugar content) could be considered for some products so as to have a mixed ad valorem/specific tax system. This step was designed to cover two transitions: (i) tax to price and (ii) price to consumption. In combination, the impact of tax policy placed on SSBs’ retail price is estimated, giving a prediction of reduction in SSBs consumption after imposing SSBs tax.Step 1a:The transition from tax to retail price:This study used the findings from the TaxSim simulation model on sugar-sweetened beverages carried out by Health Bridge Canada in Vietnam  to obtaiStep 1b:The transition from price to consumptionThe model employed the own-price elasticity of SSBs from Linh Luong et al 2020 which estimated price elasticities using Vietnam Household Living Standard Survey 2016 . The ownWe used average sugar content in each SSBs category multiplied by the average change in SSB consumption to estimate the change in the amount of sugar consumed from SSBs. The energy content in kilojoules (kJ) was calculated based on grams of sugar content. Then, the changes in caloric intake from SSBs were summed to give the net change in energy intake. To reduce model complexity, we assumed that no significant changes in other sources of energy intake happened. The sugar content in carbonates, juices, RTD coffee and tea, and sports and energy drinks are 11gr, 7gr, 9gr and 16 gr per 100ml respectively. One gram of sugar is equivalent to 4 kcal or 16.7kJ .Step 3a: Body weightFor children under 6, the change in weight for young children aged between 2 and 5 years was calculated based on the coefficients for change in weight per change in energy intake according to Long et al. . For boyA Monte-Carlo simulation was applied at this stage to simulate the reduction of energy intake from SSBs to the average body weight change. In each simulation, the parameters are drawn from a normal distribution  with theStep 3b: BMI index & obesity statusAt this stage, the dataset of the National Survey on Non-communicable diseases risk factors (STEP) 2015 was used to develop a cohort simulation for further estimation for adult population aged 18 and above. Assuming there is no significant change in the height of all cohort participants, the BMI change was estimated based on the change in body weight after 3 years. The change in average BMI index was estimated for age and sex-specific groups of the STEP 2015 cohort and generalized to Vietnamese population aged 18–69. For children, the model was only able to estimate the projection of average weight change without further estimation to their BMI because children tend to experience rapid growth in their height which limits the validity of a BMI projection.svyset command for complex survey data to extrapolate the estimation of overweight and obesity prevalence for Vietnamese population.The prevalence of overweight and obesity was estimated using the threshold of Western Pacific Region of WHO for Asian population in which 23 ≤ BMI <25 is classified as overweight; 25≤BMI<30 as obesity class I and BMI≥30 as obesity class II . While oThe findings in Asia Pacific Cohort Studies Collaboration 2005  showed tProbabilistic sensitivity analysis was performed using Monte Carlo simulation. The calorie-to-weight conversion factor was drawn using normal distribution, the relative risk of diabetes from BMI reduction is obtained from beta distribution. All simulations were carried out using the 95% confident interval and averaging from 10,000 iterations. The probabilistic analysis was later branched out into two models in which the Monte Carlo simulation employed two different sets of parameters. Model 1 performed the probabilistic analysis on weight change only while model 2 performed the extended probabilistic analysis on weight change and the risk reduction of diabetes because the risk reduction of diabetes based on BMI changes was highly sensitive to the calculation of diabetes’s burden. Additionally, one-way deterministic sensitivity analysis was carried out on the price elasticity at -1.0 and -0.8 . Findings of deterministic sensitivity analysis was included in th, 2021). This paper uses data from the Vietnam 2015 STEPS survey, implemented by Vietnam Ministry of Health with the support of the World Health Organization. The deposited data covers 3,856 respondents aged 18–69 that was fully anonymized and, hence, the need for consent was waived by the ethics committee.The study was approved by the Ethical Review Board for Biomedical Research Hanoi University of Public Health  for the direct medical cost of diabetes treatment. Model 2 provided a similar estimate to model 1 for the change in diabetes burden. The number of avoided diabetes cases was slightly higher than model 1, ranging from 20,386 to 81,455 cases. The saving in health care cost estimated in model 2 is also greater, ranging from 156.1–623.6 billion VND .Overall, the results indicated that projected SSB consumption levels reduced in relation to the application of higher tax rates. The Ministry of Finance-proposed option of 10% ad valorem  was predicted to bring down the total SSB consumption by 171.3 million litres, equivalent to the reduction of 2.6 litres per capita per annum. And the reduction was expected to be four times higher in response to an average price increase of 19–20% in three highest tax plans (scenario 3 to 5). The reduction in total amount of consumption would be 9.8. 10.2 and 10.5 litres per capita per year in scenario 3, 4 and 5, respectively. Although scenario 3 with 19% price increase has less impact on the SSB consumption compared to scenario 4 & 5 of 20% price increase, the reduction in sugar intake from SSBs was almost equal at 3.1–3.3 gram/day/person in all three tax options. This could be explained by the effect of tax design on consumption behaviours including an industry response (through product reformulation) because the sugar-based specific tax has more power to reduce the consumption of high sugar-content products and promote the switch to lower sugar-content lines.Reflecting the similar pattern of reduction in the amount of sugar consumed, the change in diet related NCD burden is predicted to show the most benefits when a sufficient level in price increase is reached. There is a clear difference in the prevalence of overweight and obesity class I when applying a price increase from 5% to 11% and up to 19–20% see  above. AIn comparison with previous simulation studies on SSB tax, the study results show consistent direction and compared to some countries, are close in magnitude of policy impacts on obesity status. At price increase of 20%, other simulation work on SSB tax reported the reduction in overweight and obesity prevalence varying from around 1% up to 3.8% such as in Thailand , IrelandThe study’s findings, consistent with previous work, suggest a tax on SSBs has the potential to reduce rates of over-weight/obesity and attain positive health effects in Vietnam. By taxing SSBs, the benefit could be observed not only in the health of the general population but also in the revenue gain and saving of healthcare cost for the government. The study focused on examining two determinants for developing SSB tax policy which are how and how much SSBs should be taxed.Firstly, about the tax design, across three tiers of price increase, the impacts on consumption, health and economic outcomes would grow in line with the level of price increase. While 5% price increase would bring some benefits, increasing price up to 20% could bring a sizeable impact on the overweight and obesity rate. WHO recommends at least 20%, which is a good starting point for any country considering a tax , 38. LawSecondly, at the same price increase, the comparison of three tax designs has also shown some small differences in health benefits which the specific tax based on sugar density was predicted to be most effective on reducing sugar consumption from SSBs. The single tier based specific tax or ad valorem is familiar and straightforward for tax administration agency. The tax design based on sugar content is highly appraised for incentivizing industry to reformulation SSB products and have already been in practice in at least eight countries.Last but not least, the policy implications should consider the alternatives to sugar-sweetened beverages, especially “diet” drinks—beverages with artificial sweeteners to have less sugar or sugar free—which consumers may substitute for SSBs. The United Kingdom has showcased an example on the surge of diet drinks following the implementation of SSB tax. An obvious shift of the market share for diet drinks from 44% in 2011 to 61% in 2021 was reported . A 2021 Model limitations should not be ignored for further interpretation and implications. Firstly, the model outcomes are likely to offer a lower bound estimate of tax effects because only diabetes is modelled as a disease outcome and the body weight change was assumed from reduction in SSB consumption only, not accounting for reformulation of products to contain less sugar. Preliminary findings from Vietnam STEPS 2021 suggests that obesity burden is increasing rapidly compared to the 2015 figure  . Given tAdditionally, model projection was also truncated within the cohort aged 18–69 so there may be substantially higher impacts when extended the modelled group to the whole population. Given the concern on childhood obesity in Vietnam during current time, further attempts on estimating SSB tax impact on childhood obesity explicitly is highly recommended. Additionally, one of the key parameters of calorie-to-weight conversion factor which originated from studies among Caucasian ethnicities might not provide a close approximation for Vietnamese population. Further, the assumption on the pass-on rate needs testing in the real world, but any reduction in this would likely have proportional impacts on health and cost consequences of an intervention.Otherwise, this study presents another drawback that should be addressed in further studies if resources allow. The study did not provide estimates differentiated by potentially correlators such as socio-economic status (SES) or rural/urban residency. This is important not just in terms of estimating potential health effects where gradients related to SES may exist but also in terms of the distribution of the tax. International experiences showed that the acceptability of SSB taxes among both public and policymakers is greatly influenced by evidence related to the perceived equity of the tax burden , 44, andThe study findings appear to offer strong support for the implementation of a SSB tax, which will slow the increase rate of obesity burden and further reduce this burden if the policy is taken strongly. This is highly likely to benefit population health improvement through its contribution to a healthy food environment while generating considerable government revenue. The implementation of a SSB tax policy should be facilitated as multisector initiative , 47. TheS1 File(DOCX)Click here for additional data file.S2 File(DOCX)Click here for additional data file.S3 File(DOCX)Click here for additional data file.


Plasmodium vivax cases represent more than 50% of a diminishing malaria case load in Vietnam. Safe and effective radical cure strategies could support malaria elimination by 2030. This study investigated the operational feasibility of introducing point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing into malaria case management practices. A prospective interventional study was conducted at nine district hospitals and commune health stations in Binh Phuoc and Gia Lai provinces in Vietnam over the period of October 2020 to October 2021. The STANDARD™ G6PD Test  was incorporated to inform P. vivax case management. Case management data and patient and health care provider (HCP) perspectives, as well as detailed cost data were collected. The G6PD test results were interpreted correctly by HCP and the treatment algorithm was adhered to for the majority of patients. One HCP consistently ran the test incorrectly, which was identified during the monitoring and resulted in provision of refresher training and updating of training materials and patient retesting. There was wide acceptability of the intervention among patients and HCP albeit with opportunities to improve the counseling materials. Increasing the number of facilities to which the test was deployed and decreases in the malaria cases resulted in higher per patient cost for incorporating G6PD testing into the system. Commodity costs can be reduced by using the 10-unit kits compared to the 25 unit kits, particularly when the case loads are low. These results demonstrate intervention feasibility while also highlighting specific challenges for a country approaching malaria elimination. Plasmodium vivax is the second-most predominant malaria parasite globally and accounts for 39% of cases in the World Health Organization’s (WHO) Southeast Asia region [P. vivax can form hypnozoites which are dormant parasite stages in the liver that cause relapses of infection weeks to years after the primary infections. Curing a patient of P. vivax requires the administration of a combination therapy that treats both blood-stage and liver-stage parasites [P. vivax cases requires addressing G6PD deficiency and ensuring patients with normal G6PD enzyme activity levels complete a multi-day regimen with PQ or receive a single day regimen of TQ [a region . P. vivaarasites ,3. Liverarasites ,5. Safe en of TQ .P. vivax [P. vivax cases represented over half of all cases [P. vivax and can halt onward transmission of parasites. The Malaria National Strategic Plan for 2021–2025 emphasized the necessity of providing a safe radical cure for P. vivax patients [In Vietnam, malaria continues to be a persistent public health problem despite declining caseloads. In 2019, nearly 4700 malaria cases were reported, of which 32.2% were P. vivax . In 2021ll cases . In aligP. vivax infection was limited in Vietnam. National guidelines for managing P. vivax cases states that all patients with P. vivax malaria older than 6 months should be given chloroquine for 3 days and a 14-day course of PQ unless they have G6PD deficiency or they are pregnant [P. vivax, or being exposed to the risks with minimal benefits.There have been numerous studies of G6PD deficiency in Vietnam involving multiple ethnic groups, multiple provinces, and multiple G6PD test types. Modeling based on surveys done by the Malaria Atlas Project predict a G6PD deficiency prevalence of 8.9% ,11. Untipregnant . In the Point-of-care (POC) diagnostics for G6PD deficiency are now available and have the potential to expand access to safe radical cures as well as enable significant progress towards malaria control and elimination goals. Integrating a point of care G6PD test in routine case management may help mitigate the risks of providing radical cure in Vietnam. Realizing the potential of point of care G6PD tests to do so will require a clear understanding of the challenges and transitions that routine malaria case management will need to undergo to adopt them successfully. Vietnam represents a country approaching elimination, which presents unique training, implementation, and cost implications in the incorporation of a new commodity into current malaria treatment and elimination strategies. This paper aims to demonstrate the first instance of using G6PD testing as part of malaria treatment and elimination strategies in Vietnam.P. vivax malaria as part of routine care. Operational feasibility was defined across multiple dimensions including:The primary goal of this study was to assess the operational feasibility of integrating point-of-care G6PD testing into the management of P. vivax diagnostic and treatment algorithm and degree to which patients are treated according to the revised algorithm that incorporates G6PD screening  method. The G6PD test used in the study includes a set of high and low control reagents that can be used for QA and quality control purposes. Each facility was instructed to run the controls once per month, document the results, and report any abnormalities along with any other device malfunctions.WCG Institutional Review Board (20202625) and the NIMPE ethics committee  approved this study. Written informed consent was obtained for all participants. Minors under 18 provided assent and written informed consent was obtained from parents/legal guardians.P. vivax malaria. The STANDARD™ G6PD test has now been evaluated in multiple clinical studies [The STANDARD G6PD Test  is an enzymatic colorimetric assay intended for the quantitative measurement of G6PD activity and total hemoglobin (T-Hb) concentration in finger-prick or venous whole blood. The STANDARD G6PD Test provides a numeric measurement of G6PD activity normalized by hemoglobin. This value can then be used in a semi-quantitative manner to classify individuals as G6PD normal, intermediate, or deficient according to established thresholds provided by the manufacturer. This classification can be used to inform clinical decision-making, particularly as it relates to priority applications, including informing treatments for  studies ,15,16,17The disposable components of the test can be ordered in a kit containing test devices along with the required extraction buffer tubes and sample collectors. At the time of the study implementation, the test devices were only available in a 25-unit kit but since then, the manufacturer also offers a 10-unit kit.P. vivax cases loads. The high-risk populations in these areas are forest goers, and farmers working on coffee, pepper, or cashew nut farms.A prospective interventional study was conducted at nine district hospitals and commune health stations in Binh Phuoc and Gia Lai provinces in Vietnam , midline (January 2021), and endline (October 2021). A standardized proficiency instrument was used to measure changes in proficiency and perceptions over time. Key informant interviews and focus group discussions were held with a subset of HCPs and P. vivax patients to explore the acceptability of G6PD testing, G6PD counseling, and PQ adherence messages, as well as barriers to seeking and completing treatment.Data were collected from October 2020 to October 2021. Data sources included augmented routine data on the test results and treatments provided to Cost data were collected throughout the intervention period to estimate the incremental financial costs to NIMPE of introducing and sustaining POC quantitative G6PD testing in routine care. These costs included the cost of the products and the costs associated with training and quality control activities. Economic costs to patients were not considered. The adoption of a QA method included the use of control reagents that support the STANDARD G6PD test. Each facility was instructed to run the controls once per month, document the results, and report any abnormalities along with any other device malfunctions. This QA method was assessed through monitoring visits, costing data, and interviews with the HCP who implemented it.Analysis population for the primary outcome included all patients who met the selection criteria and consented to their de-identified data being used in the study. Patient characteristics were presented using descriptive summary statistics. The distribution of G6PD test results was described according to the test instructions for use.HCP assessments were conducted post-training (baseline) and at midline and endline sessions using standardized questionnaires what included questions about the G6PD test label, the testing procedure, and how to interpret the test results. HCPs were also asked to demonstrate the use of the test using control reagents. The questionnaires included a total of 26 questions. Participants who scored 85% or above (minimum of 22 questions correct) and were able to run the test with control reagents were considered proficient in the use of the test.All quantitative analyses were carried out using Excel software. Continuous variables were described by their mean, standard deviation, median, quartiles 1 and 3, extreme values (minimum and maximum), and the number of missing data. Categorical variables were described by the total and percentage of each response and the number of missing data. Missing data were not included in the calculation of percentages. Given the sample size, the analysis was descriptive, and no statistical tests were performed.Qualitative data from semi-structured interviews and focus group discussions were collected as part of in-person site visits and thus collected on-site (except for the endline data collection which was conducted online via Zoom software), recorded, and then later transcribed for analysis. The data were analyzed according to recurrent themes, participant type, and facility type.P. vivax cases is assumed to be uniform across health facilities, as a simplifying assumption.An analysis of the financial costs of introducing G6PD testing at nine study facilities was conducted by examining the study G6PD diagnostic commodity and training costs, using the procurement costs incurred by the study. Exchange rates from the date of procurement of the commodities were used to calculate prices in US dollars. In addition, these costs were also analyzed using prices more likely to be incurred when commodities are procured via Global Fund procurement channels costs. We also evaluated the cost implications of procuring kits with smaller units: for the study, the units were procured as 25-unit kits. Since then, a 10-unit kit was made available by SD Biosensor and this analysis explores the implication of using 10-unit kits. Training costs for the training-of-trainers and the health facility-level trainings were estimated and annualized assuming training takes place every two years and the G6PD analyzers have a five-year lifespan. Training of health care workers was considered at the aggregate, annualized, and annualized per health facility level. The financial costs analysis at the nine study facilities was extended via a two-way sensitivity analysis to 25 scenarios representing differing malaria caseloads and differing number of health facilities with G6PD analyzers and trained users. These scenario costs were considered at a total health system financial cost level and a per patient level to illustrate financial costs for a health system to adopt G6PD testing. The estimated costs were multiplied by the number of malaria cases and health facilities accordingly. It was assumed that for every 100 facilities, at least one training-of-trainers will take place, that each facility would need to train two health care workers every two years, a 20% G6PD commodity buffer is needed, and the controls will be run five times per year at the facility. The distribution of This study was conducted during acute periods of the COVID-19 pandemic which impacted the study in multiple ways. First, given the difference between previous rates of care-seeking, it is likely that lower than expected number of cases enrolled into the study due to lockdowns and reduced care-seeking. This was confirmed by anecdotal reports from the facility staff. Additionally, in order to comply with health guidance around regarding travel and large gatherings, some study activities were conducted remotely. All training sessions and the mid-term survey data collection were conducted in person at the selected districts. End-term assessment data collection was done online via Zoom software at each selected district hospital or commune health station.P. vivax confirmed patients were enrolled in the study along with 31 health care workers. This includes a subset of 6 patients and 24 HCP who participated in the qualitative data collection.Between October 2020 and October 2021, 27 P. vivax patients who were treated at the study facilities during that period, with the exception of a single patient at la MRơn commune health station, who was not enrolled in the study as the HCPs were focused on conducting COVID-19 prevention and control activities.In total, there were 20 cases in Binh Phuoc Province and 7 cases in Gia Lai Province, see Most of the 27 patients were from ethnic minorities, including the S’tiêng (33.33%), the Gia Rai (22.22%), and a small number of people who were Khmer, M’nong, and Muong. Notably, most of the patients were recruited from two commune health stations in Binh Phuoc province with 10 patients treated at Đắk Ơ and 9 patients treated at Bu Gia Map facilities.P. vivax patients were screened for G6PD deficiency prior to treatment prescription. Ten patients in the Đắk Ơ commune health station were incorrectly tested by a single user, who had set the G6PD test set in control mode, which is used for testing control reagents, rather than testing mode, which is used for testing patient samples. Among the 17 patients that were tested correctly, 13 tested G6PD normal and 4 tested as G6PD deficient; all of them received the correct PQ treatment based on their G6PD classification. The G6PD deficient cases constituted two M’nong males, one Gia Rai male, and one S’tiêng female. No participants tested G6PD intermediate. Of the four patients who correctly tested G6PD deficient, none of them received the 8-weekly treatment. As per national treatment guidelines, 8-weekly treatment can be provided only in health facilities capable of blood transfusion and these participants declined referral to this facility and thus were not provided any radical cure.The 10 patients in Đắk Ơ commune health station that were incorrectly tested in control mode, rather than testing mode originally tested G6PD normal and received the standard dose of PQ. This was identified when NIMPE conducted a monitoring visit and checked the results stored in the analyzer and discovered the error. The patients were asked to come back and test again. Four patients were unable to be contacted again and six patients retook the test, of which two of them were confirmed G6PD normal and four of them tested as G6PD deficient. The details of this retesting are outlined in Thus, out of a total of 27 patients, 19 (70%) received the correct treatment based on their G6PD status, 4 or 15% of patients incorrectly received the standard dose of PQ, and it is unknown whether 4 (15%) received the correct or incorrect treatment, as their original test result may be invalid and they did not return for any follow-up. HCPs were retrained and training materials were updated after this event to clarify that clinical specimens should not be run in control mode.HCP proficiency was assessed three times over the course of the study. In total, 31 HCPs from 9 health facilities in Binh Phuoc and Gia Lai provinces participated in the training including 3 managers from NIMPE, 13 doctors, 6 laboratory technicians, and 9 other care-giving health staff. At the midline assessment, 27 HCP were present, with 5 absences from the initial training and 1 additional doctor participating. At the endline assessment, 28 HCP participated, with 3 doctors absent from the original cohort. Nearly all participants (30/31) passed the proficiency test immediately after the training, with fewer participants (20/27) passing at the midline assessment and proficiency scores improving (25/28) again at the end of the study period . While fThe key diagnostic test commodity costs in the study include the costs of the G6PD analyzer, the batteries for the analyzer, the test devices, and the G6PD control kit. The training of trainers (TOT) for the study cost USD 3120, or USD 1320 on an annualized basis, unless using Global Fund procurement prices for G6PD diagnostic commodities, in which case the annualized cost of the training-of the trainers is estimated to be USD 1143. The training of health care workers in the nine study facilities cost USD 3518 or USD 1759 on an annualized basis. This latter figure is estimated to be USD 1693 using Global Fund procurement prices for G6PD diagnostic commodities used as part of the training. Per facility training costs were estimated to be USD 195 with four health care workers trained per facility. A complete table of TOT costs can be found in the To understand how deployment strategies in different malaria burden contexts impact, the financial costs of adopting G6PD tests sensitivity analyses were conducted on total and per patient financial costs based on varying caseloads (from 400 to 3200 cases) and health facilities (from 100 to 500) offering G6PD testing. In a scenario with a moderate malaria burden of 3200 cases and 500 health facilities offering G6PD testing, the estimated total financial cost to the health system to adopt G6PD testing is USD 164,741, or USD 51 per patient. In a scenario that reflects a context of malaria elimination, with 400 cases and 100 facilities, the estimated total financial cost to the health system to adopt G6PD testing is USD 32,929, or USD 82 per patient.To better understand which categories are driving the costs of different scenarios, the total costs of six scenarios were broken down by cost category . CommodiWhen considering total financial costs to the health system, as seen in P. vivax cases and number of health facilities with a G6PD analyzer, the quantity of G6PD devices per box also has an impact on total financial costs to the health system due to costs associated with unused G6PD devices that expire. Aside from the number of Qualitative data were collected through focus groups and interviews as part of the midline and endpoint data collection and key themes are presented below. A total of 7 interviews and 13 focus group discussions were conducted at two time points with a total of 24 HCP and 6 patients.The majority of HCPs reported that they had some knowledge regarding G6PD deficiency and the associated risks. Most were able to explain that risk of G6PD deficiency stems from red blood cell destruction and leading to hemolysis. All HCPs agreed that the risks associated with G6PD deficiency should be prioritized in their facilities. All HCPs noted that they would have to transfer the patients to a higher-level facility if they had G6PD deficiency and needed a blood transfusion as none of the local health facilities offered that service. Only one participant, a doctor, described treating a G6PD deficient patient with side effects from primaquine including fatigue, darker color urine, and less amount of urine.P. vivax malaria back then. His condition was good but after the first dose of primaquine, then the second dose. The urine was less and darker in color. That was when I stopped giving that medicine to the patient…From our experience, when such symptoms appear…We stop using primaquine and give infusion for patients.” .“There was a patient with All interviewees received training in October 2020. Overall, the interviewees agreed that the content and the length of the training were acceptable. Some participants recommended refresher training every 3 months, as they did not have many opportunities to perform the test due to the low volume of malaria patients. While most healthcare workers did not have difficulties using the test, one participant at Đắk Ơ commune health station ran ten patient specimens in control mode instead of sample mode, demonstrating some confusion between control and test procedures. Additionally, some of the participants thought the test was difficult to perform because of the following reasons: (1) having few patients and thus few opportunities to use the test, causing users to forget the steps required; (2) forgetting how to turn on and set up the devices; (3) having patients that refuse the test or hesitate to cooperate; and (4) not taking sufficient blood sample from the finger prick. Overall, HCPs’ willingness to use the G6PD test was high.Most of the interviewees were satisfied with the QA testing, and the support and supervision they received from higher levels. The reasons provided included that the monthly control test reminder helped them remember the test procedure because sometimes there were too few patients for them to perform the test enough to remember the steps and that the supervision helped them answer questions and gain more hands-on experience. Some people suggested continuing to receive support such as training and providing them with more training materials.HCPs in the study explained the purpose and benefits of the test to the patients and reported that while the time needed to run the test took 5–20 min, the time for consultation and explanation required more time, between 30 and 60 min in total. For patients with G6PD deficiency, some HCPs advised them to go to a higher level to get treatment, as the national treatment algorithm recommends treating deficient patients in locations where blood transfusion is available. Further, some HCPs reported that it was difficult for patients to understand the results of the test.HCPs at hospitals and malaria program managers from district hospitals reported that the most appropriate staff to run the G6PD test are laboratory technicians because they are trained properly and have experience with similar assays. Others indicated that all cadres of HCPs  would be able to do it if trained. Although some people were against the idea of choosing commune health stations to conduct the test, most of the interviewees agreed to this, given that most malaria patients would go to the commune health stations for treatment first instead of the district hospitals. There was recognition that putting the test at lower-level facilities would serve to increase access to the test.Some patients noted some difficulties in accessing diagnosis and treatment for malaria, including the distance from their location to the commune health station and language barriers. In general, patients took from 5 to 20 min to travel to and from the health facility to get treatment, and they spent about 30 to 60 min at the health facility. Regarding the advice they received from HCPs, one patient did not remember anything that the HCP said. Other patients recalled advice about drug treatment , the importance of bed nets when sleeping, and healthy diets. One patient remembered being counseled not to take primaquine if they have G6PD deficiency. One patient did not understand the counseling from doctors, while the others said that it was understandable, and the doctors were willing to answer their questions. Most patients reported receiving the materials but did not read them. For G6PD deficient patients specifically, they were not aware of their condition prior to testing. All patients expressed reluctance to go to the district health centers for G6PD testing and radical cure treatment due primarily to the time required to travel.Quality control (QC) tests results were recorded for 176 instances out of a total expected of 216 instances . Some facilities did the test more than once per month because errors occurred, or the results were out of range, and they re-ran the QC test while some health facilities were not able to run the control tests due to other required COVID-19 prevention and control tasks at the same time.P. vivax malaria management in Vietnam. Previously, the study sites in Binh Phuoc and Gia Lai Provinces recorded a fairly high number of P. vivax cases, at 159 cases in 2018 and 348 cases in 2019. However, during the study period, the number of cases decreased sharply, possibly reflecting the progression of the country towards elimination combined with the effects of the COVID-19 lock down measures during the study. Of the small number of patients, the majority of cases were male with only two females recruited. Albeit in the small sample size of this study (n = 27), the majority of those recruited represented ethnic minorities, who are more likely to be G6PD deficient, and disproportionately vulnerable to malaria infection.11 Indeed, the four G6PD deficient cases identified when the test was conducted correctly were of M’nong, Gia Rai, and S’tiêng origin.This study aimed to demonstrate the feasibility integrating POC G6PD testing into The main results of the study demonstrate that testing is feasible and that patients, when tested correctly, receive the correct classification and subsequent treatment. The issue with a single user performing the test incorrectly in control mode demonstrates that particularly in an environment with low case volumes and few or fragmented users, adequate training and ongoing supervision are critical. In this case, the supervision systems established and carried about by NIMPE were largely successful in identifying and remedying problems. In this particular case, training materials were updated to emphasize that clinical specimens should not be run in control mode. However, the issue also demonstrates that even where training and supervision are conducted, user errors still occur, and follow-up of patients who receive radical cure treatment to monitor for adverse effects is still warranted. This can be achieved through both active follow-up and patient counseling, to educate patients on symptom monitoring.The high scores for HCP proficiency post-training suggest that the training content is effective and that HCP at the commune level can learn how to use the moderately complex test. However, as the study progressed, proficiency scores declined and more HCPs failed the test, further reinforcing the need for ongoing training and supervision. User acceptability as well as proficiency for the STANDARD G6PD test has also been demonstrated in multiple settings across multiple end users ,22,23,24P. vivax caseloads where inclusion of G6PD testing was shown to be cost effective [The total costs of G6PD test integration are driven primarily by the number of health facilities that deploy G6PD tests. These data also show that per patient costs of adopting G6PD diagnostics increase as the number of malaria cases decreases; that is, per patient costs are expected to increase as a country moves towards an elimination scenario. Further, the use of the smaller kit, with 10 as opposed to 25 tests per box, can have a significant impact on reducing wastage and associated costs in percentage terms. While the savings in absolute monetary terms may not seem significant relative to overall malaria budgets, the perception that there is less waste and more efficiency may be important for promoting adoption among key decision-makers. This study did not investigate cost effectiveness of inclusion of G6PD testing. This has been investigated in settings with higher ffective ,23,24. WQualitative data show that knowledge of G6PD deficiency is strong among the target cadre of HCPs and their willingness to use the test was high. Infrequent use of the test among these workers was both cited and demonstrated to be a common challenge, pointing to the need for refresher training and ongoing supervision. The QA system of monthly QC testing could be one way to provide reinforcement regarding the test procedures but the proposed system of monthly testing in an elimination setting may result in more tests being used for QC than for patients. The frequency of QC testing and ways it supports QA will vary widely from setting to setting and country to country, based in part on national clinical laboratory guidelines. Interviewees reflected an ongoing debate about whether G6PD testing should be conducted by higher skilled clinicians and laboratory staff or front-line health care workers such as those at commune health stations, reflecting a potential tradeoff between ensuring quality testing or ensuring broad access. Again, with appropriate supervision, these results suggest that the test can be placed at the commune health station to ensure access to the test is available where patients seek care. Additionally, feedback from patients indicates that patient counselling processes can be improved, particularly among those who test G6PD deficient, to understand their options for treatment.P. vivax case management also prepares the program for adoption of TQ which also may support elimination strategies.There are some limitations to this study; specifically, the low numbers of patients enrolled may limit the generalizability of findings. However, since the study, NIMPE scaled up the use of the STANDARD G6PD Test across the country. In 2022, the test was adopted in 33 health facilities. Since then, the Global Fund has approved NIMPE’s proposal to further scale the use of the G6PD test. The test will be expanded to 220 health facilities, including 3 institutes, 21 provincial centers, 71 district health centers, and 125 commune health stations. This rollout covers all high burden communes classified as having moderate risk of reintroduction or endemic malaria. NIMPE also developed additional training resources such as videos and job-aids and tools to support the broader intervention including materials for treatment adherence and pharmacovigilance. Establishment of quantitative G6PD testing to support This study shows the feasibility of using G6PD tests, both HCP and patient experiences, and demonstrates the associated costs of and changes to health system training and supervision systems that may be required to successfully integrate point of care G6PD testing into malaria case management. The experience in Vietnam, along with the tools and resources developed during implementation, provide a valuable example to other malaria control programs that may be considering expanding access to radical cure through G6PD testing, particularly other countries