ARID1A expression in HCC, and investigated the mechanisms of ARID1A-mediated tumor suppression.Hepatocellular carcinoma (HCC) is a common malignancy worldwide, which is especially prevalent in Asia. Elucidating the molecular basis of HCC is crucial to develop targeted diagnostic tools and novel therapies. Recent studies have identified AT-rich interactive domain-containing protein 1A (ARID1A) as a broad-spectrum tumor suppressor. We evaluated the clinical implications of decreased in vitro in MHCC-97H and Huh7 HCC cell lines, and in vivo in a xenografted HCC tumor model.Quantitative PCR, western blotting, immunohistochemical analysis of ARID1A mRNA and protein expression was conducted in 64 paired HCC and adjacent non-tumorous tissues. ARID1A function was evaluated ARID1A knockdown promoted HCC cell migration and invasion in vitro, whereas overexpression of ARID1A inhibited migration and invasion. E-cadherin levels were closely correlated with ARID1A expression, suggesting a role in migration and invasion. In addition, ARID1A and E-cadherin (CDH1) expression were found to be regulated in a coordinated fashion in HCC samples. Furthermore, ARID1A knockdown significantly increased HCC tumor growth and lung metastasis in vivo.ARID1A mRNA and protein expression were significantly decreased in HCC tissues, and decreased expression was significantly associated with overall metastasis, including local lymph node and distant metastasis, and poor prognosis. ARID1A served as an important tumor suppressor. Decreased expression of ARID1A was associated with tumor progression, metastasis, and reduced overall survival in mice and humans. ARID1A could represent a promising candidate therapeutic target for HCC.The online version of this article (doi:10.1186/s13046-015-0164-3) contains supplementary material, which is available to authorized users. Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and is especially prevalent in Asia . ExistinAT-rich interactive domain-containing protein 1A (ARID1A) is a key member of the SWI/SNF chromatin-remodeling complex. Also known as BAF250a, SMARCF1, or p270, ARID1A belongs to a family of proteins that contain a highly conserved, ~100 amino acid DNA binding domain termed ARID (AT-rich interacting domain) , 7.ARID1A mutations in a multitude of human cancers including subtypes of ovarian [ARID1A mutations were observed in 10–16.8 % of the studied tumors [ARID1A mutations are insertion/deletion mutations, leading to downregulation of the encoded protein [in vitro, and conducted HCC tumor xenograft studies to determine the biological functions of ARID1A in vivo.Several genome-wide sequencing studies have uncovered frequent  ovarian , 9, endo ovarian , uterine ovarian , gastric ovarian , 13, eso ovarian , breast  ovarian  and tran ovarian . In lived tumors , 18 and d tumors . Further protein , 21. Imm protein . ARID1A  protein . HoweverSixty-four patient-derived paired HCC and adjacent nontumorous tissue samples were collected at the Zhongshan Hospital of Xiamen University. Written informed consent was obtained from all patients, and the study was approved by the Clinical Research Ethics Committee of Zhongshan Hospital of Xiamen University.ACTB) expression. The PCR primers are listed in Additional file Total RNA was isolated using TRIzol® Reagent  according to manufacturers’ instructions. Subsequently, cDNA was generated using the PrimeScript™ RT reagent Kit with gDNA eraser , and quantitative real-time reverse transcription polymerase chain reaction (qPCR) was performed using the Real-Time PCR detection system  with 2× SYBR Green II/ROX qPCR Master Mix (Takara Bio Inc.). Relative mRNA expression was calculated using the delta threshold cycle (ΔΔCT) method and normalized to β-actin . Free-floating section immunostaining was performed using the avidin–biotin–peroxidase complex method . Sections were deparaffinized in xylene, and rehydrated in a graded ethanol series. They were then placed in EDTA antigen retrieval buffer  and incubated at 121 °C for 3 min in an autoclave. Endogenous peroxidase activity was blocked by placing the specimens in 3 % hydrogen peroxide solution for 10 min. Sections were incubated overnight at 4 °C in an anti-human ARID1A antibody . Sections were stained in parallel with non-immune immunoglobulin G as a negative control. Antibody binding was detected using an Elivision plus kit , which uses 3, 3’-diaminobenzidine for visualization. Sections were counterstained with hematoxylin, then dehydrated, and coverslips were mounted onto slide-fixed specimens for microscopy. Slides were examined by 2 investigators in an independent and random manner. Five views per slide with 100 cells/view were evaluated at 400× magnification using a light microscope . Nuclear staining was considered as positive. Immunohistochemical grading was performed using the following scoring system: 0, 0–10 %; 1, 11–29 %; 2, 30–59 %; and 3, > 60 %. Samples had a higher score in HCC than in notumor tissue were defined as ARID1A high. Otherwise, they were be defined as ARID1A low. Hematoxylin-eosin (HE) stain was performed as previous described .2. The short hairpin RNA (shRNA) retroviral plasmid (RNAi-Ready pSIREN-RetroQ), which contains a puromycin resistance gene, was purchased from Clontech. The ARID1A shRNA sequences cloned into this vector are shown in Additional file A panel of human HCC cell lines including MHCC-97H, LM3, SK-Hep1, SMMC-7721, HepG2, and Huh7 were purchased from the Cell Bank of Shanghai, Institutes for Biological Sciences, China. HEK293T and GP2-293 cells were generously gifted by the Medical College of Xiamen University. All clonal cells except SMMC-7721 cells were cultured in Dulbecco’s Modified Eagle’s Medium supplemented with 10 % fetal bovine serum in a humidified incubator at 37 °C and 5 % COTotal protein was extracted from cells in RIPA lysis buffer  and quantified using a Bradford assay. In total, 30 μg of protein was separated using 10 % sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and then transferred to a polyvinylidene difluoride (PVDF) membrane . The membrane was blocked in a 5 % powdered milk solution and incubated in primary antibody overnight at 4 °C. After washing, the membrane was incubated with a horseradish peroxidase–conjugated secondary antibody  at 37 °C for 1 h. Protein bands were visualized using Western Bright ECL  and detected using ImageQuant LAS4000mini . Relative protein levels were calculated based on a glyceraldehyde 3-phosphate dehydrogenase (GAPDH) loading control. Antibodies used included E-cadherin , Vimentin , Fibronectin , GAPDH , and ARID1A .5 cells per well in 200 μL serum-free medium. Next, 0.5 mL of 10 % fetal bovine serum-containing medium was added to the lower chamber as a chemoattractant. Cells were incubated for 24–48 h (depending upon migration capability) at 37 °C. Non-migrating cells on the upper membrane surface were scraped off using cotton swabs. Cells that migrated to the bottom of the membrane were stained with 0.1 % crystal violet for 30 min, followed by washing with water for 30 s to remove residual dye. Four views were examined per transwell and cells/view were counted at 200× magnification. Each experiment was performed in triplicate. The invasion assay was performed in a similar fashion using BD BioCoat™ Matrigel™ Invasion Chambers , except that the upper chambers were precoated with ECMatrix™ gel.Migration of HCC cells was assessed using the 24-well polycarbonate membrane cell migration assay kit  according to the manufacturer’s instructions. Briefly, HCC cell lines were transfected with control and ARID1A shRNAs and were incubated in serum-free medium for 24 h. The cells were then transferred to the upper chamber of a Transwell plate by seeding 2 × 10Cell growth was determined using a Cell Counting Kit-8 (CCK-8) cell viability assay  according to the manufacturer’s instructions as described previously .Cell apoptosis detection was performed with Annexin V/PI (propidiumiodide) double staining . Briefly, 48 h after transfection and 12 h Cisplatin (20 μM) treatment, cells were harvested by 0.25 % trypsin (without EDTA), washed twice with chilled PBS, followed by resuspension in 200 μL of binding buffer. Staining solution containing Annexin V/FITC and PI was added to the cell suspension. After incubation in the dark for 30 min, the cells were analyzed by FACS Gallios flow cytometer .6/0.2 mL of PBS) stably transfected with either control or ARID1A shRNA expression vectors were subcutaneously injected into right flank of each mouse (n =8 mice/group). Tumor growth was monitored once a week using a caliper, and the tumor volume was calculated using the following formula: volume = π/6 × length × width2. We monitored tumor growth over an 8-week period.All animal protocols were approved by the Animal Care and Use Committee of Xiamen University. We purchased male BALB/c nude mice (4–5weeks old) from Shanghai Experimental Animal Center of Chinese Academic of Sciences . Animals were kept under standard pathogen-free conditions and allowed to acclimate for 1 week before use. MHCC-97H cells  was used for all analyses. All values are expressed as mean ± SEM. Correlations of ARID1A expression with clinicopathological characteristics were evaluated with a ARID1A mRNA levels were significantly downregulated in HCC tissues compared with nontumorous tissues   Fig. . In the After surgical resection, patients with tumors with low ARID1A expression showed a significantly worse prognosis compared with those with high ARID1A expression  Fig. . In addiin vitro, we used a panel of HCC cell lines. Western blot analysis indicated relatively high ARID1A expression in Huh7 cells, whereas MHCC-97H cells lacked ARID1A expression  expression in HCC tissue samples . Our results exhibited the tumour growth curve on the time course after tumor cell injection  is one of the crucial events regulating hepatocellular carcinoma, prostate cancer invasion and metastasis , 31, we motility . HoweverIn nature, HCC is an invasive tumor that metastasizes hematogenously and lymphogenously to other organs, even after local recurrence. The most common organs of distant metastases include the lungs, lymph nodes, bone, and brain, with the lung metastasis occurring in 18–60 % of HCC cases . This wabona fide tumor suppressor. Therefore, it will be of interest to determine whether depletion of ARID1A can be therapeutically exploited by targeting downstream and potentially reversible epigenetic consequences of remodeler mutation [Our results,together with previous mutational and functional studies, suggest ARID1A is a mutation .ARID1A is frequently downregulated in hepatocellular carcinoma and is related to the aggressive phenotype of HCCs. We explored comprehensive role of the gene in HCC, which might provide direction for future studies on the molecular mechanisms of ARID1A. ARID1A represents a potential drug candidate for molecular-targeted therapy for HCC.In conclusion, our results have shown that


This study will assess the effects of a self-management and exercise program in comparison to an educational intervention (control program) on symptoms, physical fitness, health-related quality of life, self-management behaviors, self-efficacy, physical activity level and coping strategies.International recommendations suggest exercise and self-management programs, including non-pharmacological treatments, for knee osteoarthritis (KOA) because they can benefit pain relief and improve function and exercise adherence. The implementation of a combined self-management and exercise program termed PLE2NO study is a single-blinded, randomized controlled trial of elderly (aged above 60 yrs old) patients with clinical and radiographic KOA. The patients will be allocated into either an educational group (control) or a self-management and exercise group . All participants will receive a supplement of chondroitin and glucosamine sulfates. This paper describes the protocol that will be used in the PLE2NO program.This PLEThis program has several strengths. First, it involves a combination of self-management and exercise approaches, is available in close proximity to the patients and occurs over a short period of time. The latter two characteristics are crucial for maintaining participant adherence. Exercise components will be implemented using low-cost resources that permit their widespread application. Moreover, the program will provide guidance regarding the effectiveness of using a self-management and exercise program to control KOA symptoms and improve self-efficacy and health-related quality of life.NCT02562833 (09/23/2015) Osteoarthritis (OA) is the most common type of rheumatic disease . OA is pOA is an active disease  that affMost types of interventions that are aimed at managing KOA involve community and primary care . Hence, Patient education, information and self-management support are critical for patient cooperation during treatment. Besides OARSI international recommendations (11), several evidence-based studies of self-management programs have demonstrated that it is effective to empower patients to better manage their own chronic diseases –26.Psychoeducational interventions are growing in popularity in the primary care field . Among tTwo programs have followed the format of the Stanford Model. These include the Arthritis Self-Management Program (ASMP) and the Chronic Disease Self-Management Program (CDSMP) , 32. TheA meta-analysis of the ASMP and the CDSMP  revealedStudies have demonstrated that exercise benefits patients with KOA –46. The Thus, combining aerobic and muscle strengthening exercises into a single program may produce even better outcomes in arthritis patients  than proAlthough important, controlling symptoms is not the only target when treating OA patients. Indeed, an ideal treatment for OA should preserve joint structures, improve quality of life and for drug therapy or supplementation, have a good safety profile . It is pGlcN-S has been shown to exhibit structure-modifying effects, including small to moderate protective effects on minimum joint spaces after 3 years, in KOA patients . This fiCS has also been evaluated in different clinical trials that have sought to document both its symptomatic potential and its structure-modifying effects. A recent study  demonstrA double-randomized placebo-controlled clinical trial with a 2-year follow-up of 605 patients with KOA demonstrated that after adjusting for factors associated with structural disease progression, a dietary supplement that consisted of a combination of GlcN-S and CS resulted in significantly less joint space narrowing than was observed with the placebo, whereas neither CS nor GlcN-S alone was effective . A combiAlthough some interventions have combined patient self-management with an exercise component, we were unable to identify any study that combined these components with GlcN-S and CS supplementation.2NO program (in Portuguese: Free Program of Education and Exercise for Osteoarthritis) for elderly patients with KOA for a duration of three months. The PLE2NO is based on applying the principle of self-efficacy to manage the pathology. When patients gain confidence in taking control of their disease, they are more comfortable exercising and managing OA symptoms and consequently make better decisions about treatment. This allows them to increase their quality of life. To encourage participant’s adherence to and maintenance of the program and to contribute to pain control, all participants will receive a supplement containing CS and GlcN-S.The aim of this study is to design and implement a PLEThe following three hypotheses were therefore formulated. H1, self-reported KOA symptoms  and physical fitness will improve more in the self-management and exercise group than in the control group; H2, self-management skills and self-efficacy will improve more in the self-management and exercise group than in the control group; and H3, health-related quality of life, physical activity levels and coping strategies will improve more in the self-management and exercise group.2NO is a single-blinded, randomized controlled trial with a three-month duration and a six-month follow-up. The participants will be individually randomly assigned to one of two groups: (1) a self-management and exercise group or (2) an educational control group. Both groups will receive supplementation (CS and GlcN-S). Figure 2NO design. It will not be possible to blind the participants because of the nature of the intervention. However, the assessors will be blinded to group allocation.The PLE groups:  a self-mThe sample size was calculated based on the primary outcome (self-reported pain). The analysis were done by the program GPower 3.1 , based oThe recruitment and selection processes will be performed using the following eligibility criteria: (1) an age of 60 years old or older, (2) bilateral or unilateral KOA diagnosed according to the clinical and radiological criteria of the American College of Rheumatology (ACR) , and (3)2NO program. Social networks, newspapers, magazines, contacts with senior universities, health centers, churches and community centers, and the site of the Portuguese League Against Rheumatic Disease will be the main channels used for PLE2NO announcements.To avoid convenience sampling, the participants will be recruited from the Lisbon area, and different marketing strategies will be used to advertise and publicize the PLEAll individuals interested in participating will be invited to an awareness session in which the details of the program will be explained, and the patients will complete an eligibility questionnaire, which is necessary to acquire more detailed information, including whether they have any allergies to components in the supplements. As many sessions as necessary will be performed until the expected sample size is attained. Anyone who is interested and fulfills the eligibility criteria will receive a request for an x-ray examination. The exam requests will be referred to a rheumatologist who will make the final diagnosis according to the ACR clinical and radiological criteria. This is a more specific diagnosis (86 %) than a simple clinical diagnosis (69 %) . If the The randomization process will be performed on the baseline assessment day by the research team leader. The randomization sequence will be a 1:1 allocation to the two treatment arms.Harpagophytum extract and 10 mg of hyaluronic acid. The recommendation is to use two packets per day. The participants themselves will have to complete daily sheets that request information regarding pain levels that are assessed on a visual numeric pain scale [The active treatment group will engage in self-management and exercise (SMEG), and the control group will engage in patient education (EG) only. The SMEG patients will receive a combination program including self-management and exercise that will be delivered on the same days twice per week. Each session will last 90 min. The first 30 min will be allocated for self-management, and the remaining 60 min will be used for exercise. The program will be offered in a group format that encourages interaction and socialization, which can help to counteract feelings of depression and isolation. To avoid any conflict of interest and because we believe that it will help support the participants’ adherence, maintenance and pain control, all participants will receive a supplement that consists of a combination of two main substances: 1500 mg of glucosamine sulfate and 1200 mg of chondroitin sulfate, in addition to two secondary substances: 100 mg of in scale  and a biThe self-management component is based on a program that was developed at Stanford University, the Chronic Disease Self-Management Program (CDSMP) , which aThe exercise component is based on the Fit and Strong Program , ExercisThe exercise session type includes a warm up for the first 5 min, followed by 15 to 20 min of recreation activity and balance exercise, 30 to 40 min of the strengthening exercises, and 10 to 15 min of stretching and relaxation exercises at the end.Specific strength exercises will be performed to recruit specific muscle groups in the lower limbs  and the upper limbs . The strength exercises will use a combination of elastic bands (upper limbs) and cuff weights (lower limbs) or calisthenics, as previously used in other studies , 74 and The prescribed intensity and management of exercise resistance will be primarily guided by answers related to self-reported pain, which will be assessed using a Visual Numeric Pain Scale  before, This component will be overseen by a professional with a master’s degree in Science of Physiotherapy and another individual who is an Exercise and Health master’s student. Both will be from the Faculty of Human Kinetics.To develop exercise self-efficacy and promote the maintenance of the exercise program before the end of the class, a chart with the main exercises for each physical fitness component  will be given to the participants during the last two weeks of the intervention program. The participants will be encouraged to perform the exercises by themselves by following the chart during the last two weeks with supervision from the same professionals that conducted the exercise program. It is expected that they will develop the capacity to perform the exercises by themselves in their homes without supervision by the end of the intervention.2NO’s scientific team. This book contains descriptions and tips for managing KOA in addition to educational and exercise information presented as images. Additionally, the participants will attend three monthly educational sessions that are one hour in length each regarding joint protection strategies, exercise, and self-management techniques. These sessions will be delivered by the coordinator of the PLE2NO project, who is a PhD Professor in the Faculty of Human Kinetics, and an Exercise and Health master’s student from the same institution. Telephone contacts will be established 15 days after each educational session to avoid withdrawals and to maintain closer monitoring.This group will receive a book  publishe2NO team member(s)  who are blinded to group allocation. Each evaluator performs the same test to avoid inter-rater variability. The assessments will be performed on the same day. To avoid overloading the participants, the physical tests and questionnaires will be performed alternately. Additionally, the physical tests involving load-bearing activities will be alternated with those that are performed while seated. The order of those tests and questionnaires were determined previously, in accordance with the statements already mentioned.The assessments will be performed one week prior to the start of the program (baseline), during the week following the final intervention (three months later), and at a 6-month follow-up, and will be done by PLEThe main outcome will be self-reported pain (sub-score of the Knee Injury and Osteoarthritis Outcome Score –KOOS). The secondary outcomes will be: other KOA symptoms, KOA-specific health-related quality of life, self-efficacy, self-management behaviors, a healthier quality of life, a physically active lifestyle, coping strategies, aerobic capacity, functional strength, mobility, flexibility, gait speed, static balance and handgrip. All outcomes and instruments are illustrated in Table This questionnaire collects personal data  and the inclusion and exclusion criteria for participation in the program. It will be available both online and on paper.Bilateral, anterior-posterior knee radiographs will be used to identify OA in the tibiofemoral joint, and sunrise views will be used to identify OA in the patellofemoral compartment. The severity of OA in the tibiofemoral and patellofemoral joint will be measured by a rheumatologist using the K-L grading scale .A questionnaire will be created by the researchers that poses demographic questions, including date of birth, race, sex, marital status, current occupation, occupation before retiring and education level. Body mass index (BMI) will also be calculated as weight (measured in kilograms) over height squared (height measured in meters).A list containing the names of all medications being used and their doses and indications will be requested from the patients before and after the intervention (baseline and post-intervention).This questionnaire includes 5 dimensions to measure KOA-specific health-related quality of life (QOL), knee pain (Pain), other disease-specific symptoms (Other Symptoms), daily living activities (ADL), and sport/recreation functions (Sport/Rec). A score for each of the five dimensions is calculated as the sum of the items that are included, which is then converted to a 0–100 scale in which 0 represents extreme knee problems and 100 represents no knee problems. The KOOS has been validated for use in patients with knee injuries and patients with KOA and is a reliable and responsive self-administered instrument for short-term follow-ups .This 6-item scale contains items taken from several self-efficacy scales that were developed for the Chronic Disease Self-Management study. This is a one to ten scale that includes six questions. The scale was tested on 605 subjects with chronic diseases . The obsThis scale comprises six questions and has an observed range of 0–5. The scale was tested on 1129 subjects with chronic disease, and 51 of these subjects who underwent a test-retest protocol . The meaThis questionnaire includes three questions. The scale was tested on 1130 subjects with chronic disease, and 51 of these subjects underwent a test-retest protocol . The resThe EQ-5D-5L is a generic instrument for measuring health-related quality of life (HRQoL) that allows the generation of an index that represents a status value of the health of an individual. This scale is based on a classification system that describes health along the following five dimensions: mobility, personal care, usual activities, pain/discomfort, and anxiety/depression. Each of these dimensions has five levels of severity. This instrument employs psychometric techniques similar to those of the EQ-5D .The short form of the IPAQ was chosen because it is easy to apply. Its reliability has been verified in many countries and in different populations , 82.The first version of the COPE inventory by Carver, Scheier and Weintraub  was subsThis test is a valid measure of aerobic capacity in older adults , and it This measure is a widely used measure of functional strength. The ICC values for this test reveal good to high test-retest reliability for adults and subjects with osteoarthritis , 88, 89.This is a test of strength, agility and dynamic balance that incorporates multiple activity themes. The time (seconds) taken to rise from a chair, walk 3 m , turn, walk back to the chair and then sit down wearing regular footwear  is assessed .The CSR test is a safe and socially acceptable alternative to traditional floor sit-and-reach tests and is a reasonably accurate and stable measure of hamstring flexibility . The subThe BST is a measure of overall shoulder range of motion. This test involves measuring the distance, using a ruler, between (or overlap in) the middle fingers when they are placed behind the back . After aThis test measures linear walking ability, excluding acceleration and deceleration . This vaThis test will be performed bilaterally. While near a wall, the subject crosses theirs arms over their chest, lifts the preferred leg off the floor without touching the other leg, and holds this position with their eyes open as long as possible. Contact between the legs, the support touching the ground, touching the wall and withdrawing the arms from the chest are considered errors. The evaluator stops recording the time upon the occurrence of any error. The participants will perform two repetitions of the test, and the best result will be recorded .This test evaluates the maximal isometric force exerted by the muscles of the hand and forearm using a dynamometer. Although this study will not examine hand OA, this test has been used in the elderly as an indicator of sarcopenia and/or disability , 97. PriThis scale is often used in clinical research, particularly in musculoskeletal studies . The chaThis scale is used to self-report pain. It combines strong visual cues with an 11-point numeric rating scale. The VNS is highly correlated with the visual analogue scale , is sensitive to changes in pain, and has been demonstrated to be a valid measure .This scale is a perceived exertion scale used with resistance exercise, and its high level of construct validity indicates that the OMNI-RES measures the same properties related to exertion as the Borg RPE scale  during rThe data will be analyzed in a blinded manner. Descriptive statistics will be used to describe subject characteristics. The intervention and control groups will be examined for baseline comparability with respect to demographic and other factors. Kolmogorov-Smirnov tests will be used to test for normality. Univariate analyses of covariance (ANCOVA) will be conducted to compare changes between groups  with adjustments for baseline values. The mean difference within groups will be calculated as Mom 1 (baseline) minus Mom 2 (after intervention program). The effect sizes will be verified using partial eta squared statistics. Repeated measures analyses using linear mixed models will be used to assess the constancy of any effects in the self-management and exercise group over time. Missing data will be assumed to be missing at random. All statistical analyses will be performed using IBM SPSS Statistics 22.0 and MedCalc Statistical Software , and significance will be established at a level of 5 %.It is essential to identify the best approach to treating patients with KOA. Such an approach should consider the individuals’ quality of life, international recommendations for treatment and the availability of health services. Therefore, the combined use of self-management, exercise and supplements (glucosamine and chondroitin sulfate) appears to be a feasible and effective option for treating elderly patients with KOA.There are several strengths to the design and implementation of this study protocol. First and foremost, this program combines the recommendations of international organizations  with a combination of exercise and educational (self-management) programs. The study design is extremely current, ambitious and grounded.Second, the program will be administered in close proximity to the patients. To achieve this goal, the program will take place at four different locations: two senior universities, one church, and one community center. This is necessary because when we consider the age and pathological conditions that we expect to find in the study patients, locomotion may be a barrier. Therefore, if a patient will not be able attend for financial reasons, a van from a church or a team member’s car will provide transportation services. These efforts will minimize the problem of access to the classes.Third, the methodology of the program, in terms of both self-management and exercise, has been planned in extreme detail using simple resources, including paper roles for the self-management component and elastic bands, ankle weights and chairs for the exercise components. Thus, the program can be feasibly disseminated . The exercise program will be administered by highly qualified exercise instructors, two of whom have master’s degrees in Sport Science and the Science of Physiotherapy, and one other instructor who is an Exercise and Health master’s student from the Faculty of Human Kinetics. All of these instructors specialize in exercise, health and fitness group skills. Furthermore, a certified leader of the Chronic Disease Self-Management Program (CDSMP) at Stanford University will administer the self-management program.The program will also have a self-efficacy component for exercise, with a goal that following the end of the program, the patients will continue doing exercises, and they will receive support in this endeavor, including access to the materials that were used in the program, a chart with a description of all of the exercises that they performed in class and a brief explanation about how these exercises should be performed.With the exception of the knee radiographs for the OA diagnoses, all measurements will be obtained at the same place at baseline immediately after the end of the program and at the 6-month follow-up. Therefore, to support the project, the staff team includes one secretary who is responsible for the administrative work and four health professionals who will conduct the tests and questionnaires. To avoid inter-rater error, the same health professionals will lead the applications of the three assessments, i.e., the baseline, post-intervention and follow-up assessments.Participant adherence to the exercise program is one of the main challenges, mainly because the participants are elderly and susceptible to other health problems. Therefore, motivational cues, intragroup social interactions, frequent telephone calls and the quality of the professors are the main strategies that have been selected to prevent the occurrence of dropouts.One possible constraint to the success of the program is the extensive exclusion criteria, but these criteria are required to maintain the quality of the study. In this study, all adverse events will be documented and reported from screening until study completion.Our study is based on the premise that elderly patients with KOA need an appropriate treatment regimen that is accessible and achievable, given their condition. Therefore, the study treatment regimen was designed to develop their self-efficacy to manage their own condition. The concepts of autonomy, self-management and self-efficacy are therefore essential. Moreover, once the program ends, the participants are expected to continue the treatment using self-management skills and by performing the exercises on their own, which should consequently assist them in coping better with pain and KOA symptoms.The findings of this study will contribute to clinical trial reference data for elderly individuals with KOA by adding information regarding the effectiveness of combining a self-management strategy with an exercise program.The format of the sessions, the study duration and the weekly frequency of the program are organized in a manner that ensures that this proposal is executable not only for this project but also for future implementations by communities.This study is a randomized controlled trial (RCT) that uses a self-management and exercise intervention strategy along with glucosamine and chondroitin sulfate supplementation. The protocol was specially designed according to a carefully controlled methodology. The projected results will enable the implementation of a new combination treatment for elderly patients with KOA.2NO, (in Portuguese: Free Program of Education and Exercise for Osteoarthritis); SMEG, self-management and exercise group; SYSADOA, symptomatic slow-acting drugs for osteoarthritis; TKR, total knee replacement6 MWT, six-minute walking test; ACR, American College of Rheumatology; ASMP, The arthritis self-management program; BMI, body mass index; BST, back scratch test; CDSMP, chronic disease self-management program; CS, chondroitin sulfate; CSR, chair site and reach; EG, education control group; EQ-5D-5 L, EuroQuol five-dimension five-level; EULAR, European League Against Rheumatism; FRSTST, five repetitions sit to stand test; GlcN-S, glucosamine sulfate; IPAQ, international physical activity questionnaire; KOA, knee osteoarthritis; KOOS, knee injury and osteoarthritis outcome score; NSAIDs, nonsteroidal anti-inflammatory drugs; OA, osteoarthritis; OARSI, Osteoarthritis Research Society International; PGIC, patient’s global impression of change; PLE


Internet-based health programs have been shown to be effective in reducing risk for cardiovascular disease. However, their rates of enrollment and engagement remain low. It is currently unclear whether rewards from established loyalty programs can serve as a conditioned stimulus to improve the use of a freely available Internet-based program.The objectives of the study were to (1) examine enrollment rates and levels of engagement with the My Health eSupport program between a Conditioned Reward group and a Control group, and (2) investigate the influence of loyalty rewards and participant characteristics on levels of enrollment and program engagement.The study sample  consisted of individuals who were offered enrollment in an Internet-based health intervention  after completing the Heart&Stroke Risk Assessment on the Heart and Stroke Foundation website. My Health eSupport programs provided encouragement and tips for lifestyle change. This is a free, self-guided, fully automated program that proactively delivers tailored email messages at 2-week intervals based on the participant’s stage of motivational “readiness” and priority for lifestyle change. Participants in the Conditioned Reward group were offered a single exposure of 20 loyalty reward points from the Air Miles loyalty program for completing the Heart&Stroke Risk Assessment (10 reward points) and enrolling in the Internet-based program (10 reward points). Meanwhile, no rewards were given to the Control group participants. All data were collected between February 1, 2011 and February 10, 2012.P<.001) more likely to join the My Health eSupport program when presented with loyalty rewards controlling for gender, age, education, ethnicity, employment, and number of modifiable risk factors. However, ongoing engagement level was low in both groups and it was not influenced by loyalty rewards. Instead, individuals were more likely to engage with the My Health eSupport program if they were greater than 60 years of age , were female , or had one or more modifiable risk factors .In total, 51.38%  of individuals in the Conditioned Reward group and 48.62%  of individuals in the Control group completed the Heart&Stroke Risk Assessment. Subsequently, significantly more individuals from the Conditioned Reward group  enrolled in the My Health eSupport program than Controls . Regression analyses indicated that individuals were 27.9 times (95% CI 26.4-29.4; Our findings suggest that a single exposure of loyalty rewards may be used to encourage individuals to enroll in an Internet-based preventative health program, but additional strategies are required to maintain engagement level. Future studies need to examine the schedules of loyalty reward reinforcement on the long-term engagement level of Internet-based health programs. Cardiovascular diseases (CVDs) are the number one cause of death globally. It is estimated that the number of people who die from CVDs will reach 23.3 million by 2030 . StudiesThe wide adoption of Internet usage presents an incredible opportunity for delivering preventive health initiatives at a population level. In 2012, approximately 83% of Canadians had personal access to the Internet: 85% of whom live in metropolitan areas and 75% in rural areas ,5, psychExternal rewards such as financial and loyalty rewards have been used as a strategy to increase the enrollment and engagement of behavioral interventions ,14. The This was an observational study and the data was collected by the Heart and Stroke Foundation of Canada (HSFC) between February 1, 2011 and February 10, 2012. The HSFC is a non-profit public organization that aims to empower Canadians to live healthy lives free of heart disease and stroke by raising awareness of the key risk factors and encouraging and supporting them to play an active role in managing their health. Study participants were 18 years or older and provided consent for the study. All personal identifiers were removed prior to retrieving the records from the HSFC database. This study was approved by the University Health Network Ethics Board.The study sample consisted of individuals who were invited to participate in an Internet-based heart health program  after completing their Heart&Stroke Risk Assessment on the HSFC website. A total of 142,726 individuals completed the Heart&Stroke Risk Assessment and were included in our analyses. This sample was comprised of two groups: Conditioned Reward vs Control. Participants in the Conditioned Reward group were recruited from the Air Miles loyalty program using a standardized recruitment email. The email described the opportunity to receive a non-cash, uniform reward of up to 20 Air Miles reward points for enrolling in the My Health eSupport HSFC program. Specifically, participants were assured of immediately receiving 10 Air Miles reward points for completing the Heart&Stroke Risk Assessment and another 10 Air Miles for enrolling in My Health eSupport. No additional rewards were given after enrollment. The Heart&Stroke Risk Assessment was a free e-tool on the HSFC website that first enabled individuals to assess their lifestyle in regard to CVD risk. It then offered enrollment to the My Health eSupport program. Enrollment in the My Health eSupport program required the participants to first complete the Heart&Stroke Risk Assessment and create a log-in ID on the HSFC website. Air Miles participants accessed the Heart&Stroke Risk Assessment and claimed the reward using a unique Web link embedded in the recruitment email. Air Miles participants who completed the Heart&Stroke Risk Assessment were assigned to the Conditioned Reward group. Participants in the Control group accessed the Heart&Stroke Risk Assessment on the HSFC website without using the unique Web link provided by the Air Miles loyalty program. Control participants did not receive any rewards for completing either program.The My Health eSupport program was a free, self-guided, fully automated healthy lifestyle program that proactively delivered tailored email messages at 2-week intervals. The emails contained information on heart healthy living with links to the HSFC website. The initial email from My Health eSupport was delivered to the participants following enrollment. The email guided participants to report their stage of motivational “readiness” to adhere to Health Canada guidelines for diet , exercise (planned exercise and daily activity), and smoke-free living. Readiness for change was operationally defined for each behavior according to the conventional algorithm of Prochaska’s Transtheoretical Model  , and body mass index . Modifiable CVD risk factors were defined as the following: physical activity level , smoking status (Yes or No), excess alcohol consumption , and whether participants consumed high fat foods (3 or more times per week), fruits and vegetable (5 or more servings per day), and food with high salt content (3 or more times per week).t tests were used to compare characteristic differences between the Conditioned Reward and Control groups. Statistical significance can be influenced by a large sample size [V (post chi-square statistic) and Cohen’s d (post independent t test) to determine the strength of these statistically significant results. A weak, moderate, and strong association (effect size) for Cramer’s V was defined as <0.2, 0.2-0.6, and >0.6, respectively [d was defined as ≤0.2, 0.5, and ≥0.8, respectively [Chi-square and independent ple size ; therefoectively . Meanwhiectively . Binary ectively ,18, all A total of 73,327 individuals in the Conditioned Reward group and 69,399 individuals in the Control group completed the Heart&Stroke Risk Assessment. Baseline characteristics of the participants are presented in P<.001). Factors influencing enrollment are presented in Enrollment in the My Health eSupport program was higher in the Conditioned Reward group  than the Controls . Loyalty rewards provision was the strongest predictor for enrollment in the My Health eSupport program  and it was not a significant predictor for ongoing engagement (P=.66). Meanwhile, age, gender, and numbers of modifiable risk factors were significant predictors of ongoing engagement  of individuals in the Conditioned Reward group and 8.49% (240/2826) of the Controls assessed their readiness for change and selected a priority area for lifestyle change. Out of these participants, 20.98% (1013/4829) in the Conditioned Reward group and 24.17% (58/240) in the Control group completed the second assessment at week 6. In our regression analyses, loyalty rewards strategy was negatively associated with initial engagement  studies that has been conducted to examine the effects of loyalty rewards on enrollment and engagement with an Internet-based intervention.Internet-based interventions hold great potential for delivering preventive health initiatives at a population level. A single exposure of loyalty rewards can increase enrollment but additional strategies are required to maintain engagement level. This study has significant design implications for incorporating loyalty rewards as an effective enrollment strategy for future Internet-based interventions. More research is needed that explores the long-term effects of using loyalty rewards to reinforce engagement level and the associated efficacy of Internet-based health programs.


Reaching individuals who can benefit from evidence-based health promotion and disability prevention programs is a goal of federal, state, and local agencies as well as researchers, providers, community agencies, and other stakeholders. Implementation effectiveness at the organizational level must be achieved in order to reach these individuals and sustain the program. This mixed methods study examined eight organizations within two states that successfully implemented the Chronic Disease Self-Management Program (CDSMP) and sustained it from 4 to 10 years. There were two types of organizations: aging services and health care. Internal and external implementation factors and influences were explored. Additional examination of state activities  was conducted. The examination found agreement among the eight organizations regarding why they had adopted the CDSMP – citing the alignment between the program and their organizations’ mission and purpose to improve health status and promote better self-care, and the demonstrated value (benefits) of the program. Organizations were also alike in that they described the importance of an internal champion and supportive senior leader. Organizations differed in how they experienced and valued peer support and collaborative networks. Organizations also differed in how they filled their CDSMP workshops. Internal drivers and capability were more often discussed as facilitating successful implementation than external factors. However, state activities and external support enabled successful adoption – particularly funding and training. The primary challenges identified by this set of organizations included difficulty in recruiting participants (filling workshops) and irregular or insufficient funding sources. These challenges were identified as significant and represented barriers to sustaining the program. Reaching individuals who can benefit from evidence-based health promotion (EBHP) and disability prevention programs is an important goal for public health. Stakeholders for successful EBHP program dissemination and implementation include: the individual/consumer, program manager or champion within an organization, the organizational executive, a purveyor or external agent such as the state department of health or of aging, funding organizations, national program centers maintaining fidelity-monitoring, federal agencies, and policymakers. Decisions made at each level can change the landscape for effective implementation.human capability and systems [emphasis added] that support the practitioner/worker implementing the program  is an evidence-based program for adults with chronic disease to encourage these individuals to better manage and maintain their health status. The development of the CDSMP evolved from knowledge and practice experience gained from the Arthritis Self-Management Program One estimate puts a dollar value of potential medical care cost savings at over $4.2 billion – savings that could be realized from better health management if just 10% of persons with chronic conditions participated in the CDSMP , 17. In The CDSMP follows a 6-week, 2.5 h/week group format and is guided by a tightly scripted protocol that is delivered by certified instructors. Each week, the workshop focuses on a specific self-care management and educational topic. Instructors (two instructors are required for every workshop) follow guidelines and participants set a goal each week to pursue. Participants report on progress they have made, week by week, to the other participants in the group. The format includes facilitated interaction and group sharing. Participants often encourage each other and offer insights into the way they have managed their own conditions.Dissemination of the CDSMP was fostered through a collaborative initiative  funded under the American Reinvestment and Recovery Act (ARRA). Two-year grants (2010–2012) totaling $27 million were awarded to 45 states. A program evaluation of this national dissemination initiative for CDSMP was conducted in 2012–2013 . This prGiven the multiple program components and requirements for both instructors and organizational sponsors of CDSMP, the need for specific marketing or referral methods to attract participants into the program, and the specific funding needed to sustain it, this EBHP program can be considered a complex innovation. Embedding the program and sustaining it requires ongoing commitment by the organization to continue to invest in the training, materials, and outreach to keep the workshops filled and facilitated by instructors who meet the protocol requirements.The ARRA-funded national dissemination and implementation effort for CDSMP provides an opportunity to study the experiences of organizations and a dataset, which can be mined. This study uses that dataset as a starting point to identify a set of organizations that effectively implemented and sustained the CDSMP. To be considered successful, the organizations had to have offered at least four workshops in the 2-year timeframe, with a completion rate of 65% or higher. All organizations had to continue to offer the program at the time of the interviews (2013).Key informant interviews with organizational managers responsible for the program provided qualitative data. Using a set of internal and external factors that previously have been identified in the literature as important facilitators, this study examined commonalities and differences among two different types of organizations implementing the CDSMP. It focused on common internal facilitators and also explored the type and perceived value of external support provided by a key state agent – the department charged with dissemination of the program.“What affected implementation success of the evidence-based CDSMP among eight organizations located in two states – examining a defined set of implementation factors ?”The research question was:The purpose of this article is to offer insight on implementation of CDSMP from the organizational perspective. Understanding more about what factors or influences positively support organizations on the CDSMP implementation “journey” from adoption to sustainability can help identify what needs to be enhanced, what barriers exist, how some organizations have overcome these barriers, and what lessons they have learned. Such insight can help enhance external supports, such as policy, technical assistance, public health marketing, or fidelity-monitoring as well as clarify internal organizational elements that were important. This knowledge may help increase the likelihood that organizations will effectively implement and sustain the program.This mixed methods study examined implementation of CDSMP by eight organizations located in two states (identified as State #1 and State #2) and the support offered by their state agency to facilitate dissemination and implementation. The two states remain unnamed to protect the identity of the respondents. There were two types of organizations included in this sample: aging services organizations (ASOs), including three area agencies on aging and one other aging services provider, and health care organizations (HCOs), including three hospital/clinic systems and one health care center.The ARRA dataset (secondary data) and results from an electronic survey (primary data) were used to conduct several iterations of review in order to select the study sample of organizations. The ARRA dataset provided information, by state, on the number and type of organizations that participated in CDSMP implementation from 2010 to 2012 through the ARRA network. States were selected that had participated in a previous national EBHP initiative (from 2006 to 2007). This was done in order to maximize the likelihood that the state had invested time and resources to create structures or processes that fostered dissemination and implementation of these EBHP programs.There were 24 states that participated in both the prior EBHP initiative and the ARRA grant. The pool was further narrowed to seven states that had at least six ASOs and HCOs. The ARRA dataset was then used to find organizations that met a set of criteria indicating implementation effectiveness for CDSMP. These criteria were: the organization offered at least four workshops within the 2 years of the ARRA initiative, had at least a 65% completion rate, and continued to offer the workshop in 2013. In addition, the CDSMP program manager within the organization had to have institutional memory of the implementation process. Institutional memory is defined as knowledge of the organization’s motivation, climate, and/or steps to beginning the program by virtue of being employed by the organization during the timeframe when this occurred.The qualitative data source was comprised of 10 semi-structured interviews conducted by telephone by the investigator. The two types of key informants were: (1) state representatives who were the responsible managers for the CDSMP in their state, and (2) organizational representatives who were the managers of the CDSMP within their implementing organizations.Two semi-structured interview protocols were designed with questions probing a set of pre-defined implementation factors, drawing from the work of Durlak and DuPre, Fixsen, Greenhalgh, and Damschroder –3, 20. TMany of the items on the interview protocol had adjectival responses scaled (best to worst) with a corresponding weight from +2 to −2. This five-point scale is consistent with the scale used by Damschroder .Training in interview techniques was not required as the investigator was a seasoned interviewer, having conducted more than 100 interviews over 20 years of experience in health services evaluation – of both health services professionals as well as laypersons. Key informants provided verbal and written consent. The questions were provided to each key informant at least 1 week prior to the scheduled interview. Each interview took about an hour to conduct. Interviews were recorded and transcribed. The study was submitted to the University of North Carolina Institutional Review Board and determined to be exempt.Drivers of CDSMP dissemination and implementation in the state.Type and level of assistance provided to implementing organizations in the state.Peer support and communication – whether and how this was fostered within the state.Factors probed in the state representative interviews were:Drivers for adoption within organization – the “will” to do this.Program fit.Ease of use of the protocol.Value.External support (particularly state agency support and peer networking).Factors probed in the organizational interviews included:State agency representatives were interviewed first (April/May 2013). This allowed the investigator to ask questions about the external context in which the implementing organizations had been operating. It provided a picture of the state’s activities in fostering CDSMP from the state’s perspective, prior to hearing from the organizations. The aging services division was the entity responsible for CDSMP dissemination within State #1. Two representatives from this agency participated in the key informant interview, including the program coordinator who had been in that role for 3 years and the director of the division. One representative from State #2 participated in the key informant interview. This individual had served as the program coordinator since 2007 and was from the department of public health.Organizational representatives were interviewed second. There were eight organizational key informants (one per organization) who participated in interviews between June and August, 2013. All had been involved in the implementation of CDSMP for their organizations for at least 3 years and all were CDSMP Master Trainers.The results from the state key informant interviews provide context and background to the organizational data and therefore are offered first.The technical assistance and dissemination support to implementing organizations from State #1 focused on building the capacity and infrastructure for CDSMP. Drivers for the state included interest in helping elders to stay active and healthy-support for CDSMP and other EBHP programs were included in the State Plan. The state began offering “mini-grants” to aging services providers interested in CDSMP through a competitive application process. The state tapped into the existing network of Area Agencies on Aging. The primary support provided to implementing organizations were start-up grants (to cover workshop direct costs), Master Trainer and Peer Leader training sessions, and the CDSMP workbooks, which were to be given or loaned to participants. This state focused on having a corps of Master Trainers trained by Stanford University. The Master Trainers would then train workshop leaders.Drivers for CDSMP came from the public health department in State #2. The attraction was the evidence base and the defined purpose/focus for this program, which emphasized personal engagement in one’s own health. This state contracted with external agencies to provide technical assistance and support to implementing CDSMP organizations. Through these agencies, the state provided training, workshop materials, marketing support, and fidelity-monitoring. The state also required implementing organizations to participate in peer collaboration and information sharing. Initially, this state paid for the license cost of each funded organization under ARRA. With state support the number of Master Trainers grew substantially.We had programs that encouraged health and wellness of seniors – but before 2006 people were not aware of CDSMP. We did not have this evidence-based program. There was only 1 Master Trainer in the whole state. We needed to build capacity and infrastructure. We started with natural partners who had an interest.We included this kind of focus in our State Plan. There were major goals around empowering older people to stay active and healthy.We had several organizations that were committed to evidence-based programing and knew about CDSMP. In fact our first training session was led by one of them. We created partnerships with these organizations and partnered with them very closely.We found interest among organizations that had already had a successful track record of offering the program. It then grew very organically from one organization to another. As it [funding] was made available [for implementing organizations] we worked with organizations all over the state – rural, metro, etc.Comments by these state representatives about early dissemination efforts included:One of these states contracted separately with a consultant agency to identify data elements for tracking and monitoring the program. Each funded CDSMP provider organization was required to submit data to the state office on these elements. In 2010, this state adopted a name for CDSMP to be used consistently statewide – this name was branded. In that same year, the state purchased a multi-organizational license for CDSMP for their state. This meant that many organizations that with their own single-organization licenses through Stanford switched to operate under the state’s license.When asked about how information sharing was fostered among CDSMP implementing organizations, these state representatives described their role as conveners and facilitators – providing forums for these organizations to gather and communicate. This included regional meetings, newsletters, and electronic list-serves.Since the ARRA funding ended, one state has focused on supporting the Master Trainers and ensuring fidelity-monitoring. This state also includes a calendar of workshop offerings on their government website as well as all the forms that CDSMP providers need. With the ARRA funding ended, the other state does not pay license costs for CDSMP providers, nor does it compensate organizations for training costs. The state representative explained that it has a philosophy of local authority and control and also that program sustainability requires embedding at the organizational level. Each organization is expected to create its own business plan to address CDSMP . The state still provides some funding support to the external agency providing technical assistance and peer collaboration facilitation and marketing assistance. This state also maintains policy support for CDSMP .I think that an across-the-board issue in implementation is staff turnover and agency redirection as a result … Any time [senior] management changes there is a question – will they see the value?There is a very high investment upfront to become a CDSMP provider organization – heavy staff or volunteer training and certification, etc. That is also an ongoing issue – keeping the volunteers certified and active. They have many reasons why they might drop out including their own health issues.One thing I’ve seen is if the organization doesn’t truly have the buy-in of the higher level administration, it will struggle when the funding ends. Grants are good for start-up, but a sustainability plan is needed.The state representatives offered the following insights about organizational implementation of CDSMP and sustainability:The results from the electronic survey showed that most of the eight organizations (75%) had begun offering CDSMP between 2006 and 2009 (one began before 2006 and one started in 2010). All of the organizations had offered at least four CDSMP workshops in the 2-year time period. The range in number of workshops offered spanned from a low of 5 to a high of 21 in this time period. All eight organizations had an overall completion rateI was the champion for the program and then I influenced others. I think the evidence-based nature and availability of the training was what attracted me to CDSMP.The examination found agreement among the eight organizations on why the organization had adopted the CDSMP – citing alignment between the program and the organization’s purpose related to improving health and promoting better self-care. Many organizations had begun implementing the program prior to the ARRA grant funding in 2010 – thus the grant facilitated the work that this set of organizations had already begun (it was not the reason that they adopted the program). Informants frequently discussed the organizational leadership and internal champion for the program. This strong champion for the program (sometimes it was the respondent) was instrumental in getting their organization to adopt and implement CDSMP. For example, this comment was offered:From the beginning and continuing through the time of the interviews – organizational respondents said that CDSMP was seen as a good fit. Even so, CDSMP was often discussed as being somewhat unusual compared to the organization’s other services. The structured protocol of CDSMP was what set this program apart from the organizations’ usual health education and wellness services.This program is a great fit – it fits extremely well. However I would also say that  – in some ways it was new. It was outside the norm (the group workshop with a structured protocol) of what we typically did, how we typically provided education.The program fits well with the organization. This is because the core concept of CDSMP is one of promoting the individual’s self-management.Really this is a perfect fit with our organization. All of our volunteers are 55 and older and this program is designed around the idea of peer leaders. That fit perfectly.Figure Implementation of CDSMP requires a number of components . Despite this complexity, the program was often described by informants as relatively easy to adopt. This was true even though many of these organizations had not had any prior experience implementing an EBHP program.All informants mentioned that the heavily scripted workshop sessions, well-developed content of CDSMP, and required training assisted in implementation. This ease of use was noted by both experienced informants  and by informants who said they had never used evidence-based protocols. Figure Even though we had never done an evidence-based class, I would say the protocol was very easy to follow. The guidelines were very clear.I would say the protocol was very easy because of the partnership we had. When we first started we were under another license-holder’s license … they provided us with technical support and trainings, and the manuals. That made it easy.This was somewhat easy in that it was scripted and heavily directed.This program is of extremely high value. It has proven results. It also attracts volunteers …As we go down the health care reform path, I think this kind of program will be even more valued.Comments about value focused on the participants and benefits they received from the program. Respondents talked about seeing participants make progress on their personal health goals and maintain a commitment to a healthier lifestyle. Respondents also discussed program value in terms of alignment with the future direction for the organization – many mentioned health care reform and the growing awareness of the need to achieve better population health management, prevent disability or decline Figure . CommentOne objective of this research was to assess the importance of external support to the organizations implementing CDSMP. The support from the state agency disseminating CDSMP was particularly probed, as the state department responsible for CDSMP dissemination was considered a key purveyor of the program.Most of the informants indicated that their state agency had assisted with: funding, marketing, training, fidelity-monitoring, supplies, and peer networking. However, the way that these informants valued this support differed from “very helpful” to “neutral.” One reason given for the lukewarm rating given by a respondent was that the support from the state had diminished over time.In addition to the support provided by the state, organizations named other sources of external support including: Stanford University , local organizations such as libraries, senior housing facilities, senior centers and hospitals , and the county health department (helped with peer leader training).The peer collaboration is not growing. It was initially high, but as the program grew, it became minimal.We have had modest peer collaboration.There is extensive peer collaboration … We meet monthly via conference calls and share information and strategies … We’ve worked at making this CDSMP operate consistently across the state. We are doing fidelity monitoring the same way across the state and have set up a method to do that, as a peer group. We communicate regularly.Respondents differed in how they experienced or perceived the level of peer support/collaboration their organizations received. Several remarked they did not receive much of this type of external support. A few said that there was extensive support and collaboration with similar organizations. This may indicate differences in the type or level of support offered – or it may be a function of the individual’s or organization’s commitment to and efforts around engaging in peer networks and collaborative activities. Comments included:A graphic depiction of the ratings from all eight organizations on the level and helpfulness of external support  is shown in Figure Organizational key informants were asked about their implementation challenges. There was substantial consistency among this set of eight respondents about the challenges they faced in implementing CDSMP and in sustaining the program.Recruiting participants and filling workshops was the number one challenge described by five of the eight organizational informants. Seven of the eight organizational informants said that it took “very significant effort” (−2) or “significant effort” (−1) to fill the workshops. Stanford fidelity guidelines recommend that class size be from 8 to 16 participants to optimize peer support and problem-solving. Six of the eight organizational representatives said that they have had to cancel a class at some point in time due to insufficient registration. These findings are consistent with other studies , 21.The lack of demand for CDSMP was seen as being an effect of at least two things. First, very few individuals with chronic disease self-identify as needing the program – that is the individual hearing or reading about CDSMP does not interpret the program as being relevant for them. Marketing to consumers directly was challenging. This group of organizational managers instead often sought out other collaborative agencies, such as seniors center managers, senior housing facility managers, case managers, or health coaches to describe and promote the program as well as encourage participation among their clientele. Second, there was a lack of awareness on the part of physicians and other clinical providers about CDSMP and its’ benefit. The organizational informants said that they rarely had direct referrals from physicians to the CDSMP workshops .Informants described extensive efforts to market the program and educate adults about the benefits of the program. The four aging service organizations more often described their “sales” and “outreach” efforts – going to senior centers, retirement housing facilities, doctor’s offices and putting up fliers, including information in newsletters, and networking with local social services agencies. The four HCOs more often described their internal health system connections as sources of referrals, including physicians working in the health system and health coaches.Getting the workshops/classes filled is difficult – getting the number of participants we need to hold the class. They need it, but they don’t understand that – it has to be sold.It takes significant effort – marketing and recruitment to fill the workshops.We have a system of referrals within the clinic. If a provider wants to refer he or she can click on the classes we are offering through our electronic system – then we get the referral and follow-up.A side-by-side comparison across the eight organizations of ratings on the “Demand/Recruitment” factor is shown in Figure Many of the key informants also discussed challenges with funding the CDSMP. The ASOs and HCOs differed in where they obtained funds to support the program. However, they were alike in commenting that funds received did not cover full costs.Three of the aging services providers had partial funding of their CDSMP through Older American Act Title III-D funds. Donations and small fees as well as supplemental state grant funds were other sources of revenue to cover costs. One organization was covering the costs entirely out of their core operational budget – which also relies heavily on grants.Three of the HCOs talked about the lack of external funding and hospital budget issues. These organizations discussed the shorter-term focus of their organizations where community health education is not seen as core – more of a community benefit. Therefore CDSMP and other health promotion, disease prevention programs are vulnerable to budget cuts. Despite this, one HCO respondent saw the potential for CDSMP. She said it was becoming more relevant for where the health care system is going in terms of accountability for population health. Despite their lack of current external funding, there was some optimism around the growing awareness and support for this type of program among the health care organizational respondents.Without additional funding we can’t do this on an ongoing basis … I only expect to do 1 or 2 [workshops] this year. This is down from the 18 workshops we did in 2011 and 2012.Hospitals are under a lot of budget restrictions. They are less able to provide this kind of community benefit now. We’ve had some reductions in staff in community health education. I don’t think this is self-sustaining – not so far.I think there is some potential demand for this – under ACOs there is a commitment to population health and every member within their population. There is a basic level of service to be provided. CDSMP could be part of that.Organizational informants reflected on lessons learned. They used various strategies to address implementation challenges or enhance their programs.Have a strong program champion internally.Build and maintain support at all levels internally especially senior administration and managers or clinical professionals who can serve as referral sources internally.Pursue a variety of ways to extend reach and improve visibility of CDSMP in order to build external referral sources and tap into collaborative resources .Recruit, train, and retain strong workshop leaders (staff or volunteers).Conduct ongoing marketing and outreach to make target population groups  aware of the program.Measure results. Present a “return on investment” or value proposition to key stakeholders.Strategies and advice included:A study of eight organizations, purposively selected because of long-term successful experience with CDSMP, revealed that internal drivers and capability were more often discussed as facilitating successful implementation than external factors.Program-to-organization fit.Organizational leadership.Training and well-developed materials.Common facilitating factors for adoption and successful implementation of the CDSMP included:These factors are consistent with other studies examining program implementation and sustainability. For example, a review of 19 empirical studies of health-related programs found the following factors to be important to the organizations : program champion, program fit with organizational mission, perceived value/benefits to clients, and support of stakeholders .values of the organization  and the organization – particularly the fit with the purpose or nization , 4. ThisThe managers responsible for CDSMP discussed both their own leadership as internal champions of the program, and the leadership from their supervisors, department directors, or senior executives – who demonstrated their support for CDSMP adoption and the implementation process. These administrators remained committed to offering the program even with limited funding.most frequently mentioned as facilitating implementation . Organizational respondents particularly noted the importance of having skilled, committed staff and supportive senior leadership  to support organizational performance and implementation effectiveness .External support also facilitated implementation among these eight organizations. Key external supports described as “very helpful” by these eight organizations were: (1) funding, (2) training and workshop materials, and (3) fidelity-monitoring. The value of peer support and collaboration varied among this set of respondents – for some organizations this type of support had been (and continued to be) very important. Other organizations had not participated and/or did not rely on peer support very much. These findings are consistent with other research identifying key supports for implementation, including the perceived benefits of using the EB program and collaborative technical assistance or program supports that are matched or tailored to the organization . This exCommon barriers and threats to sustainability included difficulties in recruiting participants, and lack of funding for the program – including lack of participant health insurance coverage for this type of EBHP program. It is likely that these challenges are linked.Recruiting participants to the workshops was a key challenge among the organizations in this study. Seven of the eight organizations said that getting participants into the workshops was the number one challenge. Organizations said that there is low awareness of the program among both the lay public and physicians – a key referral source.The need for better marketing and distribution systems for public health programs has been identified elsewhere. In a study of 32 community-based prevention programs only modest penetration occurred in the marketplace, which limited impact. The researchers called for more effective approaches that “employ a reinforcing combination of both high-risk (targeting) and population-wide strategies” Since many people with chronic conditions have Medicare as their primary insurance, the fact that CDSMP is not covered by Medicare is an impediment.While the focus or mission of health care and ASOs may be to assist individuals to improve or maintain health, they are reimbursed largely for addressing problems (after-the-fact), not preventing them. HCOs’ reimbursement comes primarily from illness care/treatment not prevention . For socIt is the author’s opinion, that without a regular source of funding or payment for service, the “value” of CDSMP has to be demonstrated one person and one provider at a time. The lack of payment for EBHP programs such as CDSMP may be interpreted by the lay public or by physicians as a signal that the program does not provide sufficient value in terms of health status improvement or effect. Given these forces at work, participation remains low and each referral/registration to a CDSMP workshop is hard-won. Organizations expend extra effort to get the program costs covered for those who do elect to participate. Without demand, there is little pressure to pay for these programs. Thus, the cycle perpetuates.This issue goes beyond what the single manager within an implementing organization can address alone or even what a program coordinator at the state level can solve. It calls for a systems approach – where the stakeholders are aware of common overall objectives, their roles and boundaries in producing results, and the accountability of component parts to one another –31.It is also important that policy and technical assistance is informed by and supportive of practice in the field. The Centers for Medicaid and Medicare Services (CMS) has commissioned studies of EBHP programs that include CDSMP, but notes challenges, particularly how to directly fund community-based wellness and prevention programs for this and other programs . CMS calMeanwhile the infrastructure to support CDSMP may be eroding. The infrastructure investment under ARRA facilitated regional and local training, grew state, and organizational expertise on how to run these programs, fostered fidelity-monitoring peer collaboration and shared learning, produced Master Trainers and peer workshop leaders in every state, and engaged implementing organizations to commit to and market the program. As evidenced by the response from these eight organizations in just two states, these external supporting and infrastructure components seem to be shrinking.The primary limitation of this study is due to there being a single investigator. A second researcher to review and confirm the categorization and coding of comments and to interpret the findings would add strength to this examination. This limitation was addressed into some degree by: (1) conversations with experts in the field who are familiar with CDSMP and its implementation history and challenges, (2) careful crafting of the key informant interview instruments, (3) feedback from the national dataset program manager familiar with organizations implementing this program and with state agents, and (4) review of published studies about CDSMP, particularly recent program evaluations to identify important external factors. Other limitations include the small sample size of organizations and the exclusive focus on “successful” implementing organizations. This research would be strengthened by examining additional organizations of many types, located within other states, and having variable success in implementation – using the same interview protocol including the scaled response options.Reflecting on the lessons learned from these eight successful CDSMP organizations, recommendations related to enhancing internal and external supports are offered.internal capability to support effective implementation include:Identify an internal program champion who has the ability to help drive adoption and ensure senior level buy-in and commitment to the program;Make the case that the program is a good fit with the organization’s mission and purpose;Clearly identify the value of the program in terms that make sense to key stakeholders – e.g., to the participant, organization, funders, and policymakers. Measure and report this value consistently and repeatedly to enhance demand and solidify the foundation of support – which will help raise awareness of the value and benefits of CDSMP in the local area and should help in referrals to the program.Supportive elements for adoption and early implementation efforts that drove these organizations were very consistent, especially organizational leadership and the perceived value and fit of CDSMP with the mission and purpose of the organizations. Advice by this set of successful organizations included clarifying the benefit of the program using both participant and organizational metrics. Thus recommendations to enhance external supports include:Enhance supportive policy at the federal and state level for CDSMP and programs like it that focus on improving prevention and self-management behaviors of individuals with chronic conditions and engaging individuals in their own care through fostering organizational readiness;Maintain support for training and fidelity-monitoring as a funded external support that appears to be key to both implementation and sustainability;Improve visibility/public awareness of the program through national campaigns or other methods to lessen the burden on each organization to make this program known;Accelerate efforts to make benefit changes to the Medicare program to include CDSMP as a defined benefit for persons with chronic conditions to reduce the barriers around funding the program and to embed it in the fabric of the organizations that have done the hard work of adopting and implementing it.External supports were also clearly important for adoption and early implementation efforts among these organizations. Training and fidelity-monitoring were especially noted, as was funding to get the program up and running. Organizations noted that they could have also used help building awareness of the program. Therefore, recommendations for program sustainability in terms of Reaching individuals who can benefit from EBHP and disability prevention programs is an important public health goal. As health care and social support “systems” within the U.S. move haltingly forward toward more accountability for producing outcomes in health status among defined population (patient/client) groups, programs like CDSMP will become more relevant as a strategy for population health management. At that time, perhaps the program will be seen as a fundamental service of these organizations, with funding allocated through internal budgeting processes.Until that time, organizations willing to adopt such programs must be supported effectively. Key external supports, such as training, materials, and funding provide the bedrock for dissemination and implementation .Chronic disease represents one of the top public health issues domestically and globally. Stronger public policy to ensure there is an infrastructure to support EBHP programs that have demonstrated effectiveness with chronic disease populations should be a public health priority.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.This paper is included in the Research Topic, “Evidence-Based Programming for Older Adults.” This Research Topic received partial funding from multiple government and private organizations/agencies; however, the views, findings, and conclusions in these articles are those of the authors and do not necessarily represent the official position of these organizations/agencies. All papers published in the Research Topic received peer review from members of the Frontiers in Public Health  panel of Review Editors. Because this Research Topic represents work closely associated with a nationwide evidence-based movement in the US, many of the authors and/or Review Editors may have worked together previously in some fashion. Review Editors were purposively selected based on their expertise with evaluation and/or evidence-based programming for older adults. Review Editors were independent of named authors on any given article published in this volume.