Physical activity (PA) public health programming has been widely used in Mexico; however, few studies have documented individual and organizational factors that might be used to evaluate their public health impact. The RE-AIM framework is an evaluation tool that examines individual and organizational factors of public health programs. The purpose of this study was to use the RE-AIM framework to determine the degree to which PA programs in Mexico reported individual and organizational factors and to investigate whether reporting differed by the program’s funding source.Public health programs promoting PA were systematically identified during 2008–2013 and had to have an active program website. Initial searches produced 23 possible programs with 12 meeting inclusion criteria. A coding sheet was developed to capture behavioral, outcome and RE-AIM indicators from program websites.M = 10, SD = 3.1) and programs that were partially or wholly privately or corporately supported .In addition to targeting PA, five (42%) programs also targeted dietary habits and the most commonly reported outcome was change in body composition (58%). Programs reported an average of 11.1 (±3.9) RE-AIM indicator items . On average, 45% reported reach indicators, 34% reported efficacy/effectiveness indicators, 60% reported adoption indicators, 40% reported implementation indicators, and 35% reported maintenance indicators. The proportion of RE-AIM indicators reported did not differ significantly for programs that were government supported  contains supplementary material, which is available to authorized users. Encuesta Nacional de Salud y Nutrición, ENSANUT) reported that 19.4% of Mexican adults are physically inactive, with many more not meeting recommended guidelines. This represents a worrisome upward trajectory of an increase 44% from 2006 to 2012 [Physical inactivity is endemic in Mexico and has become a public health priority. Findings from the National Health and Nutrition Survey , national guidelines or agreements , websites with general health tips or advice, and results of national surveys or programs that did not include physical activity were not considered. Search terms associated with increasing physical activity were used in Spanish to identify programs in the Google search engine: programas (programs), activación física , México, niños (children), adultos (adults), escuelas (schools), ejercicio (exercise), trabajo (work). Journal articles from a companion review of physical activity interventions in Latin American populations that coincided with the development of this manuscript were also searched for possible Mexican programs that met inclusion criteria .Program websites were examined to determine whether programs were administered at the national, state, community or individual level. Code sheets identified the population group focus , any specific behavior change strategies that were used in the program , additional behaviors that might have also been promoted , behavioral target outcomes  and changes in BMI.A RE-AIM coding sheet was developed similar to others that have been used to review research-initiated behavioral interventions . The queAll information was entered into the code sheet. Information that was available was entered as yes if it were present, along with a brief description, or no, not reported on the website. A research assistant attempted to contact website hosts where information was not reported to confirm that it was not available. In cases where it was available, it was also recorded on code sheets. The University of Houston Committee for the Protection of Human Subjects reviewed and approved all procedures and determined that no consent was required for this study as no protected, participant data were collected.Two native Spanish language speaking reviewers independently screened candidate websites to determine eligibility. Disagreements were discussed with the PI and four members of the research team and resolved by consensus. The original search produced 23 possible websites. Eleven websites did not meet inclusion criteria. Twelve programs met the inclusion criteria and were included in the final review.Two reviewers coded each program for the presence or absence (Yes-present or No-absent) of the behavioral, outcome and RE-AIM indicators described above. Reviewers met to discuss any discrepancies in coding; resolution was completed by direct reference to the program website.ReachIs there information on the target population ?Is there demographic and behavioral information available for the target population?Is there information on how the program was marketed or what recruitment strategies were used?Is there information on the demographics and behaviors of the participants?Is there information on how well the program recruited from the target population?Are there sources of information available to assess the initiative’s reach?Efficacy/EffectivenessDid the program include an evaluation?If yes, what were the results?If an evaluation was complete, can you determine how many participants completed it?Can you determine how the organization defined success of the program?Did they use qualitative methods to determine effectiveness?AdoptionWhere did the initiative take place?Describe the program location.Describe who delivered the program (or implemented a policy).Provide any information on why these locations were selected.Could anyone deliver the intervention or were there restrictions? (please describe)If you can determine the proportion of locations that had access to the program and actually delivered it, provide that number.If you can determine the proportion of staff that had access to the program and actually delivered it, provide that number.ImplementationIf you have any information on how closely the program was delivered as intended add it here.Provide any information that is available on the number of sessions, duration of each session, and frequency of sessions.If available, describe the core program content.Provide any qualitative information that is available on challenges or successes with the implementation process.Was there a theoretical framework identified that was used to develop the program?MaintenanceA.If no, reason for discontinuationB.If yes, was the program modified? Specify what was modifiedIs the program still in place? And if so, what information is available on why it was sustained?Was the program institutionalized?Descriptive information was tabulated across programs. Data exploration included frequency counts and percentages across the RE-AIM indicators. Programs were classified as completely government supported versus partially or completely privately or corporately supported. T-tests were calculated to determine whether the extent of RE-AIM indicators reported differed by government versus partial or complete private or corporate support. The data are presented in an additional file [see Additional file n = 3, 25%), local  or both . Five (42%) were government supported, with two (17%) solely privately or corporate supported and five (42%) supported through a combination of government and corporate/private funding.Of the 12 programs that were evaluated, seven (58%) were framed at the national level, with two (17%) of these having additional regional  programs that were affiliated with the national program. Table Targeted behaviors and measured outcomes of the programs are presented in Table Four programs measured behavioral or physiological outcomes, the most common of which was change in body composition, with all four programs using weight (33%), two using BMI (17%), and one (8%) using waist circumference as outcomes that could be measured in the program. Only three (25%) had an outcome of increased physical activity engagement. Two (17%) also had outcomes focused on reducing smoking, and one (8%) on reducing alcohol use. One (8%) program had increasing water and fruit and vegetable consumption as an outcome corresponding with a program target behavior, and another (8%) had improving school environments as an outcome.n = 11, 92%), demographic and/or behavioral information about the target population , marketing and recruitment strategies , inclusion , recruitment efficiency  and other sources of information available . The reporting of efficacy/effectiveness components was 34% across programs on average. Efficacy/effectiveness indicators included whether the program included an evaluation , whether evaluation results were presented , number of participants who completed the evaluation , a program defined measure of success was presented  or the use of qualitative methods  . The proportion of adoption indicators reported across programs was 60%. All (100%) websites identified where the program occurred, with most  providing some description of the location. In contrast, few  provided information on why locations were selected. Level of expertise of the staff that delivered the program was reported in 4 (33%) of the programs. Four (33%) programs reported the proportion of locations that had access to the program and delivered it, and one (8%) program reported the proportion of staff that had access to the program and actually delivered it. The average reporting proportion of implementation indicators across programs was 40%. No studies reported information on delivery as intended. Five websites (42%) reported information on dose  of programs. All (100%) programs described core content, and four (33%) provided a rationale for the program . No programs provided qualitative information on implementation. The average reporting proportion of maintenance indicators across programs was 35%; however, five programs did not report any maintenance indicators, primarily because they were no longer active. Only one (8%) program had been institutionalized.On average, program websites reported on 11.1 ±3.9) of the 27 RE-AIM indicator items, with a range of 3 to 17 indicators reported  from those that were partially or wholly privately or corporately supported . As well, there were no differences by source of support for any of the individual indicators .T-tests suggested that the proportion of RE-AIM indicators that were reported for the programs did not differ significantly for those programs that were government supported , which is also responsible for public health programs, making this an ideal partnership. Public clinics are accessible in the community and have the equipment and trained staffing to coordinate evaluation efforts in conjunction with public health programs.The information collected using the RE-AIM framework has important implications for future research, policy, and practice. This study identified indicators within the RE-AIM framework where reporting from public PA programs might be improved. This information must be used to help guide the development and design of future PA programs in order to be able to include reporting indicators so that it is possible to measure the impact of these programs and how they can be replicated in other settings. Perhaps the biggest area for improvement is in the reporting of indicators for measurement and evaluation of program outcomes. The lack of indicators available in these arenas may be due in part to the overwhelming number of participants in national level programs. In another study evaluating the implementation of programming in the US, program implementers often believed that adding RE-AIM indicators to evaluation plans required special training or expertise, suggesting that simple educational strategies about the importance and ease of measurement might improve reporting in the future . In ordeThe RE-AIM framework can be used as an evaluation tool, it can also be used at the program’s conception to help guide the planning of the program to ensure adoption, successful implementation, and evaluation. Using the RE-AIM framework to guide the design and evaluation of public health programs can lead to the development of policies and standards that can increase the execution and reporting of RE-AIM indicators. This may produce important information on the effectiveness and replicability of these programs, by improving smaller program details like the allocation of program funding and training of program staff.The Mexican government and private organizations have worked together and independently to fund physical activity programs in Mexico to address increasing levels of physical inactivity. While these programs have demonstrated adequate reach and adoption, poor monitoring and evaluation of outcomes has limited our knowledge of the effectiveness of these programs. There is a strong need to improve efforts of evaluating behavioral and health outcomes. Without this knowledge, we are unable to replicate these programs in other settings with sizeable Hispanic populations. Use of the RE-AIM framework to develop and evaluate future programs will increase our understanding of program factors that contribute to effective program with broad reach, successful implementation, and long-term outcomes.


Carvedilol belongs to a group of medicines termed non-selective beta-adrenergic blocking agents. In the presented approach, a practical and environmentally friendly microextraction method based on the application of ionic liquids (ILs) was followed by fluorescence spectrometry for trace determination of carvedilol in pharmaceutical and biological media.A rapid and simple ionic liquid phase microextraction was utilized for preconcentration and extraction of carvedilol. A hydrophobic ionic liquid (IL) was applied as a microextraction solvent. In order to disperse the IL through the aqueous media and extract the analyte of interest, IL was injected into the sample solution and a proper temperature was applied and then for aggregating the IL-phase, the sample was cooled in an ice water-bath. The aqueous media was centrifuged and IL-phase collected at the bottom of the test tube was introduced to the micro-cell of spectrofluorimeter, in order to determine the concentration of the enriched analyte.−1 and a limit of detection (LOD) of 1.7 μg l−1 were obtained.Main parameters affecting the accuracy and precision of the proposed approach were investigated and optimized values were obtained. A linear response range of 10–250 μg lFinally, the presented method was utilized for trace determination of carvedilol in commercial pharmaceutical preparations and biological media. Carvedilol belongs to a group of medicines termed non-selective beta-adrenergic blocking agents Figure . This drIn order to assay the presence of carvedilol in pharmaceutical and biological samples, some analytical approaches including chromatography -6, spect3, CCl4 and etc. In order to remove these toxic materials from microextraction procedures, ionic liquids (ILs) are the best choice. ILs offer many advantages such as low vapor pressure, tunable solubility, desire thermal stability and etc. , acetone, acetonitrile, methanol, ethanol, HCl, NaOH and sodium hexafluorophosphate (NaPF6) were obtained from Merck . A working solution of NaPF6 (250 mg ml-1) was prepared. For preparing stock solution of carvedilol (1000 mg l−1) , proper amount of this drug was dissolved in methanol and diluted with ultra pure water. Standard solutions were prepared by dilution of the stock solution with ultra pure water. Tablets containing 12.5 mg and 25 mg carvedilol were purchased from a local pharmacy.Analytical-reagent grade of 1-Hexyl-3-methylimidazolium hexafluorophosphate [Hmim][PF6] ionic liquid and 0.7 ml of hexafluorophosphate (NaPF6) (250 mg ml−1) was injected into the aqueous sample solution. After mixing the extractor with sample solution, the resultant solution was transferred into a hot water batch equipped with a thermostat. The temperature of the water batch was fixed at 50°C for 4 min. Under driving the temperature, IL-phase was dissolved and dispersed through the aqueous media. In order to aggregate the IL-phase, the sample was cooled at 0°C for 7 min. In order to collect the enriched phase, sample solution was centrifuged . After removing the aqueous media, the enriched phase was diluted with ethanol to 200 μl and transferred into the micro-cell of the spectrofluorimeter. Finally, quantitation of carvedilol was performed. Schematic diagram of the designed method is shown in Figure In this sample pretreatment method, ten milliliters of sample solution , 2.0 ml of the upper phase (clear condition) was diluted with ultra pure water and 10.0 ml of the obtained sample was utilized for quantitation.In order to prepare human urine samples, ten milliliters of urine were centrifuged . Then, 2.0 ml of the upper clear phase was placed in centrifuge test tube and different amount of carvedilol was added to this and diluted to 10.0 ml. Finally, the defined quantitation procedure was performed.In recent work, a simple and benign sample pretreatment method based on the application of ILs was combined with fluorescence spectrometry for enrichment and determination carvedilol in real samples. Main parameters affecting the accuracy and precision of the proposed approach were investigated and optimized values were obtained.−1) was recorded 2 N− show hydrophobic properties.Based on the results obtained in our previous studies ,19, thre6] was used as an optimum microextraction solvent in all tests.According to these factors, [Hmim][PFThe viscosity of ionic liquids is relatively high; hence their direct transfer into the micro-cell of spectrofluorimeter for analyzing carvedilol is difficult. As a result, enriched-phase was conditioned and diluted. For this goal, some conditioner solvents such as methanol, ethanol, acetonitrile and acetone were evaluated as the diluting solvent. The obtained data showed that reproducible and sensitive signals were obtained in using ethanol as a conditioner agent. Due to the better data stability and ethanol environmental safety (less toxicity), this organic solvent was preferred and used in all experiments.As it was mentioned, in this microextraction procedure, IL was applied as the microextraction phase. In this kind of sample pretreatment method, one of the major parameters affecting the performance is the amount of IL. This parameter has a significant effect on the reproducibility and sensitivity. In order to optimize the amount of extraction solvent, this parameter was tested within the range of 10–100 mg Figure . Stable 6−, significantly reduce the solubility of IL. This act improves the extraction performance of carvedilol and provides better analytical sensitivity. Effect of this parameter was examined in the range of 0–250 mg  solves this problem and fixes the volume of the enrich phase. The effect of ionic strength was studied within the range of 0–40% (w/v) using NaNO3 as an electrolyte. In the studied range, no significant influence on fluorescence signal was observed.One of the most important parameters which affects on the extraction performance is ionic strength of the aqueous media. An increase in ionic strength causes a considerable increase in solubility of IL. As a result, the volume of the settled phase depends on the salt content of the sample solution. This phenomenon has a negative influence on the stability of analytical data. Fortunately, presence of PFa value of carvedilol is 7.97) [In the case of microextraction of molecules like carvedilol, which have ionizable property, pH of the aqueous media reveals a significant role. In order to obtain the highest extraction efficiency, the uncharged condition of carvedilol must be prevalent (pKis 7.97) . The effIn this microextraction procedure, IL-phase is dispersed into the aqueous media under increasing the temperature. The effect of this parameter was evaluated in the range of 25–80°C. Finally, a temperature of 50°C was used as an optimum value. In order to collect the IL-phase after extraction, the sample solution must be cooled. For the recent goal, the aqueous media was placed in ice-water bath and kept at 0°C for 7 min.+, Na+, Mg+, F−, Cl−, NO3−, SO42−, glucose, urea, lactic acid, sucrose, ascorbic acid and fructose as the interfering or quenching agents on the determination of carvedilol (100 μg L−1) was evaluated. No change in signals over than 4.5% was observed.For studying the possible interferences coming form other compounds, which exist in real samples, some ions and compounds were subjected to the recent combined methodology. In this investigation, the effect of 100-fold of K−1. Other analytical figures of merits obtained by the ionic liquid phase microextraction-spectrofluorimetry are shown in Table bl/m. This equation is resulted from the equation showed below:Linear analytical response range was defined by analyzing standard solutions of carvedilol. The obtained results revealed that analytical responses are linear from 10 to 250 μg lm, Sbl, sbl, K, m and Cm show the minimum distinguishable analytical signal, average of blank analytical signal, blank standard deviation, constant value equal with 3 (confidence level of 95%), calibration graph slope and detection limit, respectively. Using this way, a value of 1.7 μg l−1 carvedilol was achieved. In order to determine the relative standard deviation (RSD), four 100 μg l−1 of carvedilol was subjected to the designed methodology and finally a value of 3.8% was obtained.SIn order to show the analytical advantages of the proposed method for the quantitation of carvedilol, some details were compared with reported methods in literature, and these results are shown in Table In order to demonstrate the analytical application of the presented technique, real samples including human urine and human plasma were spiked with different amounts of carvedilol and analyzed. Results of this investigation are shown in Table A rapid, benign and simple ionic liquid phase microextraction was utilized for preconcentration and extraction of carvedilol. The enriched-phase was introduced to spectrofluorimeter for quantitation of carvedilol. No toxic and hazardous material was used in this sample pre-treatment method. In addition, an inexpensive and sensitive analytical instrument was applied for quantitative measurements. Finally, the combined methodology was successfully applied for quantitation of carvedilol in real samples.


Saúde Não Tem Preço (SNTP)] for access to diabetes treatment medicines in Brazil.In 2011, private pharmacies associated to the Brazilian Ministry of Health provided patients with two types of insulin (regular human insulin and isophane insulin or NPH) and three oral antidiabetic medications (5 mg glibenclamide and 500 and 850 mg metformin) free of charge. The aim was to evaluate the impact of the “Health Has No Price” Program [This longitudinal and observational study is based on the number of units of oral hypoglycemic agents, insulin and insulin analogues supplied in 55,000 private pharmacies from February 1, 2010 to January 31, 2012. The number of tablets  and international units  supplied in the first 12 months of the SNTP Program were compared with the number of tablets and international units supplied in the 12 months prior to its implementation.The insulins in the SNTP program had the highest percentage change in the number of international units supplied; regular human insulin increased by 97.8 % and isophane insulin (NPH) by 78.0 %. Among the oral hypoglycemic agents, 5 mg glibenclamide increased by 65.9 %, and 500 and 850 mg metformin increased by 46.8 and 39.9 %, respectively, in the number of tablets dispensed in the first year of the SNTP Program. Among the hypoglycemic agents not available in SNTP, 4 mg glimepiride had the highest percentage increase in units supplied (19.2 %) in the same period. Among the insulin analogues, which were not available in the SNTP Program, insulin glulisine showed the greatest increase in units dispensed (34.2 %).The SNTP Program contributed to increased access to medicines for the treatment of diabetes in Brazil. According to the World Health Organization (WHO), access to essential medications is one of the five indicators of progress in securing the right to health . AlthougAccording to Cameron et al. , even whAlthough the Brazilian Public Health System [Sistema Único de Saúde (SUS)] has the duty to provide medications for the treatment of diabetes that are included in the national list of essential medicines , 8, BahiTo increase access to medications in Brazil, in 2006 the state began to subsidize approximately 90 % of the cost of drugs used for the treatment of diabetes and hypertension through a co-payment system associated with the Ministry of Health that covered medications purchased from private pharmacies . In FebrWe performed a longitudinal observational study of the access to antidiabetic medications in Brazil after the implementation of the SNTP Program. Data were collected from 55,000 pharmacies, representing approximately 76 % of private pharmacy establishments in the country, from February 1, 2010 to January 31, 2012 [The number of supplied units of all medicines for the treatment of diabetes in the SNTP Program increased in the first 12 months of the SNTP Program compared with the 12 months prior to the implementation of the program. The percentage of variation ranged from 39.9 to 97.8 %. Four sulfonylureas , one biguanide (metformin) and three fixed-dose combinations marketed in Brazil were included in the analysis of oral antidiabetic medications. The number of tablets supplied in the SNTP program increased from 39.9 to 65.9 % in the first year of the program. No other oral antidiabetic medication showed a comparable increase in the number of units supplied. The number of tablets dispensed (none in the SNTP Program) of the three fixed-dose combinations analyzed decreased after implementation of the SNTP Program  showed an increase in the number of international units dispensed Table .Table 2NThis is the first study describing the impact of the SNTP Program on the access to antidiabetics in Brazil. The results confirmed a significant expansion of access to the diabetes treatment medications included in the SNTP Program, especially compared with other medications of the same therapeutic classes that are available in the Brazilian market. The analysis of the percentage change in the number of oral antidiabetic tablets and the number of international units of insulin supplied, whether as single agents or fixed-dose combinations, indicates that access expansion was greater for medicines included in the SNTP Program.It was further observed that a lack of some fixed-dose combinations in the SNTP Program may result in the prescription of two individual medicines. The four fixed-dose combinations analyzed and formulated with active ingredients of single agents can be obtained at no cost in associated pharmacies. These combinations exhibited a decrease in the number of units dispensed after the start of the SNTP Program. This result may indicate a preference for the prescription of medicines available through the program.The implementation of the SNTP Program, through an agreement between private pharmacies and the Ministry of Health, increased the access to medicines for the treatment of diabetes in Brazil. Also, the number of associated pharmacies increased from 14,003 in December 2010 to 22,470 establishments in July 2013, covering 3664 cities [The initiative by the Ministry of Health to subsidize the purchase of medications in private pharmacies began in 2006 through a co-payment system in which the government was responsible for approximately 90 % of the cost of some antidiabetic and antihypertensive medicines. From 2011, the government began to pay the full cost of medications included in the SNTP program . The conMortality due to diabetes declined in Brazil over the 15 years between 1996 and 2011, minimally in men but considerably in women . HoweverThe number of dispensed units of oral antidiabetic medications included in the SNTP Program was eight times higher than the growth in the pharmaceutical market in Brazil during the same period (12.7 %). The highest percentage increase in oral antidiabetics was observed for 5 mg glibenclamide (65.9 %). The highest variation in the number of tablets was for 500 mg metformin, with an increase of over 135 million tablets compared with the 12 months preceding the implementation of the SNTP Program.The insulin medications included in the SNTP Program showed the greatest significant changes in the number of international units dispensed. The increase was 97.8 % for regular human insulin and 78.0 % for isophane insulin (NPH). Among the antidiabetic medications not included in the SNTP program, only insulin glulisine significantly increased (34.2 %), but this increase was still less than the growth observed for the insulin types included in the program.Despite the observed increase in the number of international units of insulin analogues dispensed, health technology assessments conducted by the National Technology Implementation Commission  for SUS in 2013, recommended against the inclusion of the fast-acting insulin analogues  for the treatment of type 1 diabetes  and the It is important to note that a limitation of the results of this study did not include medicines used in hospital or dispensed for free at pharmacies of the Brazilian Public Health System, which according to Gialdi , represeThe results of this study reveal that the SNTP Program has significantly contributed to an increase in access to medications for the treatment of diabetes, indicating that this public health policy has achieved its goal.


The Internet is an optimal setting to provide massive access to tobacco treatments. To evaluate open-access Web-based smoking cessation programs in a real-world setting, adherence and retention data should be taken into account as much as abstinence rate.The objective was to analyze the usage and effectiveness of a fully automated, open-access, Web-based smoking cessation program by comparing interactive versus noninteractive versions.Participants were randomly assigned either to the interactive or noninteractive version of the program, both with identical content divided into 4 interdependent modules. At baseline, we collected demographic, psychological, and smoking characteristics of the smokers self-enrolled in the Web-based program of Universidad Nacional de Educación a Distancia  in Madrid, Spain. The following questionnaires were administered: the anxiety and depression subscales from the Symptom Checklist-90-Revised, the 4-item Perceived Stress Scale, and the Heaviness of Smoking Index. At 3 months, we analyzed dropout rates, module completion, user satisfaction, follow-up response rate, and self-assessed smoking abstinence.P<.001), as did smoking 30 minutes  or 1 hour after waking  compared to smoking within the first 5 minutes after waking.A total of 23,213 smokers were registered, 50.06%  women and 49.94%  men, with a mean age of 39.5 years (SD 10.3). Of these, 46.10%  were married and 34.43%  were single, 46.03%  had university education, and 78.73%  were employed. Participants smoked an average of 19.4 cigarettes per day (SD 10.3). Of the 11,861 smokers randomly assigned to the interactive version, 2720 (22.93%) completed the first module, 1052 (8.87%) the second, 624 (5.26%) the third, and 355 (2.99%) the fourth. Completion data was not available for the noninteractive version . The 3-month follow-up questionnaire was completed by 1085 of 23,213 enrolled smokers (4.67%). Among them, 406 (37.42%) self-reported not smoking. No difference between groups was found. Assuming missing respondents continued to smoke, the abstinence rate was 1.74% , in which 22,678 were missing respondents. Among follow-up respondents, completing the 4 modules of the intervention increased the chances of smoking cessation (OR 1.95, 95% CI 1.27-2.97, The findings suggest that the UNED Web-based smoking cessation program was very accessible, but a high level of attrition was confirmed. This could be related to the ease of enrollment, its free character, and the absence of direct contact with professionals. It is concluded that, in practice, the greater the accessibility to the program, the lower the adherence and retention. Professional support from health services and the payment of a reimbursable fee could prevent high rates of attrition. The World Health Organization  states tSmokers are aware of the harmful effects of tobacco consumption: 70% would like to quit smoking and half try to quit each year, mostly without professional help -11. BetwA problem of this magnitude requires treatments that are both effective and accessible to prevent millions of deaths worldwide -16, espePrior work has shown that interactive Web-based interventions for smoking cessation can be more effective than static websites and that there is a relationship between dose of intervention and its effect -31. In rConcerning the usage of open-access eHealth programs, some studies have shown massive enrollment of users followed by a high level of dropout in the initial phase of treatment, without second visits to the website. The proportion of dropouts and nonusers decreases during treatment and subsequent follow-up in logarithmic progression. However, users who are registered in these open and public websites can benefit just as much from treatment as the participants in clinical studies, in which there is greater control over the recruitment of subjects and their behavior in the program ,33-35. LThe aim of this paper is to describe the demographic, consumption, and psychological characteristics of 23,213 participants self-enrolled in the UNED Web-based smoking cessation program, to analyze the usage and effectiveness of the program, and the differences between 2 versions: an interactive automated control on the progress of the user and another without control or interactivity. We also examine if the participants’ adherence to treatment is related to the effectiveness of the intervention, and which user characteristics predict abstinence.The hypotheses tested were (1) the interactive and tailored version of the program will yield higher quit rates than the static version, (2) usage of the modules of the intervention will drop drastically from the first module, (3) exposure to the content of the program will improve quit rates, and (4) the participants with higher education or lower physical dependence are more likely to achieve abstinence. Additionally, independent variables predicting module completion  and follow-up response  were analyzed.The study was a service open to all comers. The Bioethical Committee of the UNED approved the study. Registration of this trial was not required. Before starting the experiment, informed consent was obtained from the participants.Participants confirmed via the Web the following requirements before they could start the intervention: not undergoing other treatments to quit smoking, being older than 18 years, wishing to cease tobacco consumption in the next 30 days, smoking at least 2 cigarettes per day, having Internet access and an email address, and accepting the treatment conditions. Participants were informed that they had to complete a follow-up questionnaire 3 months after the beginning of the intervention.At baseline, we collected demographic, psychological, and smoking characteristics data from the self-enrolled participants on the open-access UNED Web-based smoking cessation program  from OctTwo days after filling out the baseline questionnaire, the user received a link by email to register in the program. Once the link was activated, the smoker accessed a randomly assigned version of the program and the baseline questionnaire. The obligation to fill out the 61-item self-administered questionnaire and the 2-day delay in treatment access aimed to prevent the enrollment of impulsive smokers who had no intention of following the treatment.At 3 months, participants were automatically reminded by email to complete a questionnaire about satisfaction with the program along with smoking and psychological variables. There was no live contact with the users to remind them to fill out the follow-up form.Participants self-reported their age, sex, nationality, marital status, education, and employment status. Psychological measurement instruments previously used online ,37,38 weThe participants’ self-reported on when they started smoking, physician’s advice on smoking cessation, motivation to quit smoking, living with smokers, and expectations of treatment success. Physical dependence on nicotine was measured with the Heaviness of Smoking Index (HSI) . The HSITo analyze utilization of the program, at 3 months we studied dropout rates, module completion, satisfaction with the program, and follow-up response rate. The participants could leave the program formally through the program menu option so that they were registered as a dropout. Module completion data was obtained automatically from the module questionnaire. Only when all the questions from each module were correctly answered was the smoker allowed to advance to the next module and module completion registered by the program. That information was only accessible from the interactive version. Satisfaction with the program was rated by the participants on a 5-level scale from 0=not at all satisfied to 4=extremely satisfied.The follow-up response rate was calculated from the number of participants who completed the 3-month follow-up assessment. There was no contact by phone or by other means to reach the missing respondents.The effectiveness of the program was measured by self-reported smoking status by using complete case and intention-to-treat analyses (ITT) at 3 months after registration. However, in cases of high dropout rates or very small follow-up response rate, ITT analysis could underestimate the effect of the program on the participants who were using it and who had been exposed to the intervention . BecauseThe content of the UNED Web-based smoking cessation program is divided into 4 consecutive modules. The intervention followed the Clinical Guidelines for the Treatment of Smoking  and is bThe program randomly assigned the users to either interactive or noninteractive versions of the program, both with the same therapeutic content. In the interactive format, the user had to follow a particular sequence of treatment in such a way that the modules were presented from first to fourth. Each module incorporated an evaluation form, which, if not answered correctly, prevented progress in the treatment sequence in order to guarantee that users had received the contents gradually, according to its own progress, and that users who had completed the last module had been exposed to all the content. An algorithm also allowed or prevented advancing to the next module depending on the time that had elapsed since the start of the module. In addition, another algorithm reminded the users through email that a week had passed and they had not completed the respective module. Greater exposure to the treatment was the aim. The previously completed modules were available to the user for review.In the noninteractive version, users received identical content to that in the interactive version through a link to a single static Portable Document Format (PDF) file. Participants decided by themselves either to follow the normal sequence of modules or to skip some content. In this version, the program could control neither the behavior nor the progress of the user or the modules’ completion.r) was used to relate the quantitative variables and the chi-square test (χ2) for the categorical variables. The relation between categorical and quantitative variables was calculated with the Student t test.An alpha level of .05 was used for the statistical tests. Pearson correlation coefficient , small, medium, and large effect sizes are .10, .30, and .50, respectively [Given the large sample size of the study, some very small differences could be statistically significant; therefore, we calculated the strength of relationship or effect size through Cohen’s ectively ,49.With a small sample size, a lack of statistical significance does not necessarily mean the absence of differences, but rather low statistical power of the test. The statistical power depends on the number of subjects, the significance level, and the effect size. In our study, the large number of participants in the sample allowed us to detect small effect sizes in differences of means, correlations, and chi-square tests.r, and between 785 and 1362 subjects (depending on the degrees of freedom) in the case of the chi-square test. The sample size required to detect medium effect sizes with a statistical power of alpha=.8 and an alpha=.5 is 64 for mean difference, 85 for Pearson’s r, and between 87 and 151 subjects (depending on the degrees of freedom) in the case of the chi-square test [The sample size required to detect small effect sizes with a statistical power of alpha=.8 and an alpha=.5 is 393 for mean difference, 783 for Pearson’s are test .t tests. The forward stepwise method was used to test variables for entry into the model one by one. After each entry, variables that were already in the model were tested for possible removal based on the significance of likelihood ratio.Logistic regression analysis was used to examine the relationship between smoking cessation and predictor variables. Additionally, we examined completion of the program and the 3-month follow-up response as dependent variables. We calculated adjusted odds ratio (OR) for every predictor variable to understand its effect on the dependent variable. Following the recommendations of Hosmer and Lemeshow , the iniThe Consolidated Standards of Reporting Trials (CONSORT) flow diagram with the number of participants randomly assigned to each group, participants who completed each module of the treatment in the interactive group, and participants analyzed for the outcome is shown in P=.79) or any baseline variable. The mean age of participants was 39.5 years (SD 10.3) and most were of Spanish nationality , married , with university education , and employed .Demographic characteristics at baseline are presented in Program users’ mean daily tobacco consumption was 19.3 cigarettes (SD 10.3). Most participants smoked within the first half hour upon waking up. According to the HSI , nicotinAdditional analysis showed that the number of cigarettes smoked per day increased in males, with age, with lower educational level, and in the case of separated people and widowers, with medium effect sizes for age and education and small effect sizes for sex and marital status .d=.11); in women, small effect sizes were observed in the depression subscale and the PSS-4 in relation to cigarettes smoked .Mean scores on anxiety, depression, and stress were not clinically significant. Groups did not differ significantly on any score. Additional analysis showed a significant relation between cigarette consumption and the psychological variables, but with a very small effect size . The rel21=75.9, P<.001; Cramer’s V=0.057, P<.001), with very small effect size.Of the 23,213 self-enrolled smokers, 1326 (5.71%) formally dropped out of the program. There were statistically significant differences between the interactive and noninteractive groups. The interactive group had higher dropout rates than the noninteractive  completed the first module, 1052 (8.87%) the second, 624 (5.26%) the third, and 355 (2.99%) the fourth . CompletP<.001), aged between 40 and 47 years  or older than 48 years , having university education , and “some,” “pretty much,” and “complete” expectations of success  increased the chances of respondents completing all the intervention modules. Being male , smoking between 16 and 20  or more than 20 cigarettes per day , and a higher level of stress  decreased chances  with very small effect size.At 3 months, 1085 (4.67%) of the 23,213 smokers enrolled in the program completed a follow-up questionnaire about smoking status and satisfaction with the program. The 2 groups differed in the proportion of assessments: in the interactive group, 390 (3.29%) of 11,902 participants completed the follow-up questionnaire, whereas 695 of 11,861 (5.84%) did so in the noninteractive (χP<.001); aged between 32 and 39 years , between 40 and 47 years , or older than 47 years ; having a higher level of education ; smoking between 16 and 20  or more than 20 cigarettes per day ; and having “pretty much”  or “complete” expectations  of success in the and noninteractive group  increased the chances of completing the follow-up questionnaire. Being male decreased chances   . There w24=25.4, P<.001; Cramer’s V=0.153, P<.001) such that users of the interactive version showed higher proportions of very satisfied and extremely satisfied. Older people were more satisfied , as were completers , abstainers , and participants with positive expectations .User satisfaction was reported at 3-month follow-up (n=1085). The participants rated their satisfaction from not at all satisfied to extremely satisfied. Among them, 11.15% (121/1085) were not at all satisfied, 19.26% (209/1085) were slightly satisfied, 34.10% (370/1085) were somewhat satisfied, 25.81% (280/1085) were very satisfied, and 9.67% (105/1085) were extremely satisfied. There were differences in satisfaction in terms of the version of the program  of the participants did not report outcome information, we conducted both ITT analysis and follow-up respondent analysis.21=26.7, P<.001; Cramer’s V=0.034, P<.001) with a very small effect size.Assuming the missing respondents continued to smoke, the abstinence rate was 1.74% , in which 22,678 were missing respondents. There was a significant difference in abstinence rates between groups (χP=.03) and complete expectations of success  increased the chances of quitting smoking. Smoking between 16 and 20 cigarettes per day  or more than 20 cigarettes per day , and using the interactive version of the program  decreased chances of quitting .Considering only the participants who responded to the follow-up questionnaire (n=1085), the abstinence rate was 37.42% (406/1085), whereas 62.58% (679/1085) self-reported as continuing to smoke. There was no significant difference in self-reported abstinence rates between groups (χP=.003) or 1 hour  of waking increased their chances of quitting compared to those who had their first cigarette earlier. There was no significant effect of the other variables included in the regression model, version of the program, age, sex, first cigarette of the day, number of cigarettes smoked, level of dependence on nicotine, expectations, physician advice, depression, and marital status.Logistic regression analyses revealed that smokers who had their first cigarette of the day after 30 minutes . To study the effect of module completion on abstinence (exposure to treatment), we conducted a secondary analysis with the participants who answered the follow-up questionnaire in the interactive version (n=375). Only module completion had a significant effect on smoking cessation . There was no significant effect of other variables included in the regression model, age, sex, first cigarette of the day, number of cigarettes smoked, level of dependence on nicotine, expectations, physician advice, depression, and marital status.The abstinence rate among the participants who completed the intervention was 46.47% (165/355) versus 35.49%  among noncompleters  significantly reduced both the average number of cigarettes smoked daily (from 17.9 to14) and the level of physical dependence on nicotine with medium effect sizes of .45 and .53, respectively .The aim of this paper was to describe the characteristics of participants self-enrolled in the UNED Web-based smoking cessation program and to analyze the program’s usage and effectiveness and the differences between its 2 versions: interactive and noninteractive. We also examined if participants’ exposure to treatment was related to its effectiveness and which user characteristics predicted abstinence. Additionally, independent variables predicting module completion  were analyzed.From October 2009 to May 2010, 23,213 users self-enrolled in the UNED Web-based smoking cessation program, which was free of charge and fully automated. There were no differences in the demographic, psychological, and smoking characteristics between the 2 versions of the program.The demographic and smoking characteristics of the study participants are similar to those reported in other Internet smoking cessation programs ,32,51-55The proportion of users with university education (46%) versus other categories is noteworthy, confirming once again the existence of a digital divide in the specific field of eHealth. In Spain, the percentage of people with higher education in 2009 was 16.29% versus 20.22% with primary education. However, that same year, the percentage of Internet users with higher education was 28.34% versus 7.85% with primary education according to the Instituto Nacional de Estadística  ,58. TherConcerning scores of psychological scales, the results do not differ from those obtained in other studies in the general population ,63. In sThe registration of smokers in the program was high, with 23,213 participants self-enrolled in 8 months. This may be because of the characteristics of Web-based programs, which do not require transportation or schedules and, in the case of the UNED, were free of charge and open-access. In addition, the university press office announced the launch of the program to the mass media.The number of users who completed the 4 modules in the program confirmed the law of attrition proposed by Eysenbach , accordiBecause a high number of participants enrolled over the course of 8 months , the UNED Web-based smoking cessation program was shown to be very accessible. No extra measures were used, except email reminders, to persuade the participants to continue using the program and respond to the follow-up questionnaire. The study confirmed that the easier it is to enroll or to leave the program, the higher the nonusage rate and the rate of those lost to follow-up will be, as Eysenbach  proposedIn addition, the regression model showed that the strongest predictors of completing the program were positive expectations of success and being older than 40 years. This could be explained by older participants having an increased perception of the harmful effects of smoking on health compared to younger people, and by positive expectations being related to a high level of self-efficacy, both causing greater use of the application. Similar results were obtained by Zbikowski et al  and WangThe ITT abstinence rate was 1.71%. This result is difficult to interpret. ITT analysis is feasible when we know the outcome of every participant, regardless of whether they have completed the program or not. If the lack of data on the outcome is very high, ITT analysis is not feasible because considering every participant lost to follow-up as one without successful treatment will produce results that rely on unverifiable assumptions ,69. ThatIf we consider the data from the participants who actually reported their smoking status at follow-up , the cessation rate was 37.42%. This result is in the range of other studies that analyzed cessation rates in participants who answered a 3-month follow-up by phone or through the Web. Cobb et al  found a Despite the results of previous work ,29,30,52We consider the interactivity because this is the main experimental manipulation. Nevertheless, the interactive version includes several components: the regular programmed progression across the modules, the evaluation at the end of each module, and the necessity of interaction with the Web application to follow the programmed steps. Knowing the effect of the interactivity will be necessary to explore these variables.The regression analysis showed that completion of the treatment  increased the chances of smoking cessation, which confirms our third hypothesis. However, contrary to our fourth hypothesis, we could not confirm the effect of education and physical dependence on smoking abstinence. There was no significant effect of any demographic variables on abstinence. Education affected the adherence to the program, but did not improve smoking cessation. Anxiety, depression, and stress did not affect abstinence either. This result is consistent with prior studies that have failed to demonstrate the effect of incorporating mood management components in the intervention ,71.First, the information obtained at baseline was not confirmed by other means. Second, self-reported abstinence was not validated chemically. In a program with more than 23,000 participants from any part of the world, data verification is not viable. Some studies confirmed the validity of self-reported abstinence when compared with chemical verification, becoming the standard method in Web-based studies ,72,73. AThe large number of enrollees in the program is encouraging in terms of accessibility and confirms the feasibility of delivering Web-based programs for smoking cessation to smokers that do not have access to conventional face-to-face programs. It would be very difficult to reach 23,213 smokers through a face-to-face intervention setting. This study showed that completion of the program  improves the chances of cessation. However, high rates of nonusage and loss to follow-up were confirmed. To increase the program’s usage and follow-up completion, some professional involvement could be implemented in such a way as to ensure a self-obligation toward both the program and the professional . For exaTo summarize, the main findings of this research are to disconfirm the general belief that anxiety, depression, and stress are associated with cigarette consumption ,65 and cThe results of our study suggest that future research is needed to determine (1) the factors that will reduce the high rates of attrition in public Web-based programs for smoking cessation, (2) the real proportion of nonsmokers among those lost to follow-up, and (3) the long-term abstinence rate in the UNED Web-based smoking cessation program.


It results from either a microdeletion of or a deleterious sequence variant in the gene EHMT1. Sequence analysis characterized it as an intragenic tandem duplication leading to a frame shift with a premature stop codon in EHMT1.We report on a 3-year-old girl with characteristic symptoms of Kleefstra syndrome. Array comparative genomic hybridization analysis revealed a 145 kilobases duplication spanning exons 2 to 10 of EHMT1 resulting in Kleefstra syndrome.This is the first description of an intragenic duplication of  EHMT1 loss [EHMT1 gene  [EHMT1 [EHMT1 gene have been reported [Kleefstra syndrome  is a clinically well described genetic disorder characterized by the phenotypical core features of psychomotoric retardation/intellectual disability (ID), muscular hypotonia and characteristic facial dysmorphisms. The underlying cause of KS is - in approximately 75% - a microdeletion in the chromosomal region 9q34 leading to either a partial or an entire EHMT1 encodes for a methyltransferase specific for lysine-9 of histone H3 and is a component of the transcription factor E2F6, which can repress gene transcription [cription . E2F6-mecription .EHMT1 gene. The submicroscopic duplication in EHMT1 was detected by array comparative genomic hybridization (aCGH). Transcript analysis revealed a tandem duplication leading to a frame shift and a premature stop codon, suggesting haploinsufficiency as the underlying cause of KS [Here, we describe for the first time a patient with the typical symptoms of KS carrying a 145 kilobases (kb) intragenic duplication in the se of KS ,8.rd and the 10th centile. Apgar scores were 9/9/9.The patient is the third child of healthy non-consanguinous parents. She has two healthy older brothers. Her mother had an intellectually disabled half-brother. Her father’s paternal uncle died directly after birth for unknown reasons. Prenatal ultrasound demonstrated a fetal constitutional growth delay, a polyhydramnion and a single umbilical artery. The girl was born spontaneously at 39 weeks gestation. Her birth length, her birth weight and her head circumference were between the 3Developmental delay was first noted at 3 months of age. The girl showed marked muscular hypotonia. At 2 years of age she could sit without support but was still not able to crawl or walk at the age of 3 years.She tended to be very quiet and did not react to sounds. A hearing test was anamnestically normal. The girl began to vocalize and starts teeth grinding when she was one year old but she could not speak at the age of 3 years.She displayed autistic features with stereotypic movements and the vocalization of clicking voices with her tongue. At 3 years of age she attended a special nursery.Cranial MRIs at the age of 2 and 3 years, respectively, revealed unspecific bilateral T2-hyperintense white matter changes in the occipital region. An electroencephalogram at the age of 3 years was normal.Echocardiography demonstrated a haemodynamically irrelevant patent foramen ovale and a mild peripheral pulmonary stenosis. Myocardial function was normal.At 2 11/12 years of age the patient displayed the following facial features ; GRCh37/hg19; ISCN 2013; Figure EHMT1 . There were several possibilities regarding the localization and the orientation of the duplication but one of the two RNA transcripts shown in Figure EHTM1 gene) and B (exon 2 adjacent to exon 11 of the coding EHTM1 gene), respectively, were performed. Primers for the PCR product of exon 10 adjacent to exon 11 and the PCR product spanning exons 2 to 10, respectively, were used as positive controls for the primer function (data not shown). A PCR product was only obtained for A . The duplication within EHMT1 resulted in a frameshift and a premature stop codon in the additionally inserted exon 2 of the EHMT1 transcript in our patient ; intron 10: 49,07% TIRs). The adjacent introns 2, 9 and 11, respectively, have lower amounts of repetitive elements. In intron 1 especially the amount of Alu elements that belong to the short interspersed elements was higher than in intron 2 . The high rate of repetitive elements - especially Alu elements - in the breakpoint regions of the duplication in our patient provides a plausible explanation for the localization of the duplication. Likely, there will be further KS patients with deletions or duplications leading to haploinsufficiency of EHMT1 with chromosomal breakpoints in one or both of the affected introns reported here.A possible explanation for the location of the duplication in our patient could be the existence of repetitive DNA elements in rrations . Accordirrations  both, inOur patient displayed the typical phenotype of KS -4,11;  according to the manufacturer’s instructions. cDNA was obtained using the Superscript II Kit .Genome-wide copy number scans were performed with the patient’s and her parents’ lymphocyte DNA using an Agilent SurePrint G3 Human CGH Microarray Kit 4 × 180 K and was read using an Agilent Microarray Scanner G256BA and G5761A, respectively, along with Agilent Feature Extraction Software V9.1  according to the manufacturer’s instructions. The results were analyzed using Agilent Cytogenomics 2.0 and 2.5 software, respectively. Array CGH data was confirmed by quantitative real time PCR (qPCR).EHMT1 gene by designing specific primers for exon 6 to 17 of the EHMT1 gene (ENST00000460843). PCRs were performed to amplify the possible transcripts of the EHMT1 gene in our patient. The obtained PCR products were directly sequenced on the ABI 3500xL Genetic Analyzer . Their sequence was compared with the sequence of normal EHMT1 coding transcript (ENST00000460843). All primer sequences and PCR conditions are available on request.qPCR was used to narrow down the C-terminal breakpoint in the Metaphase chromosome spreads of blood samples of the patient’s parents were prepared from phytohemagglutinin (PHA)-stimulated peripheral blood cultures using standard protocols. 10 and 11, respectively, GTG-banded metaphases were analyzed.Written informed consent was obtained from the parents of the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


Studies of Internet-delivered psychotherapies suggest that clients report development of a therapeutic alliance in the Internet environment. Because a majority of the interventions studied to date have been therapist-assisted to some degree, it remains unclear whether a therapeutic alliance can develop within the context of an Internet-delivered self-guided intervention with no therapist support, and whether this has consequences for program outcomes.This study reports findings of a secondary analysis of data from 90 participants with mild-to-moderate depression, anxiety, and/or stress who used a fully automated mobile phone and Web-based cognitive behavior therapy (CBT) intervention called “myCompass” in a recent randomized controlled trial (RCT).Symptoms, functioning, and positive well-being were assessed at baseline and post-intervention using the Depression, Anxiety and Stress Scale (DASS), the Work and Social Adjustment Scale (WSAS), and the Mental Health Continuum-Short Form (MHC-SF). Therapeutic alliance was measured at post-intervention using the Agnew Relationship Measure (ARM), and this was supplemented with qualitative data obtained from 16 participant interviews. Extent of participant engagement with the program was also assessed.r values between .32-.38, P≤.002). The alliance (ARM) subscales measuring perceived empowerment  and perceived freedom to self-disclose  also correlated significantly in a positive direction with self-monitoring frequency.Mean ratings on the ARM subscales were above the neutral midpoints, and the interviewees provided rich detail of a meaningful and collaborative therapeutic relationship with the myCompass program. Whereas scores on the ARM subscales did not correlate with treatment outcomes, participants’ ratings of the quality of their emotional connection with the program correlated significantly and positively with program logins, frequency of self-monitoring, and number of treatment modules completed : 12610000625077; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=335772&isReview=true (Archived by WebCite at http://www.webcitation.org/6efAc5xj4). Internet delivered psychotherapy for common mental health problems can assist with reducing the problem of unmet treatment need by overcoming barriers to access , and offering advantages of user-privacy and 24-hour availability . In the Much of the variance in outcomes of face-to-face psychotherapy has been attributed to the therapeutic alliance, defined as a non-specific treatment factor reflecting the extent of collaboration, purposeful action, and emotional connection between a client and therapist . ConsideA tendency for humans to respond socially to computing technology in the same way as they respond to other humans has been well documented , and antThe majority of evidence relating to the therapeutic alliance in Internet-delivered interventions derives from studies of interventions that are therapist-assisted to some extent. The nature of the client-therapist interaction varies widely between existing programs, in terms of frequency , nature , modality ), and timeliness  -25. NeveBeating the Blues, a Web-based cognitive behavior therapy (CBT) intervention for depression and anxiety. The ARM assesses 5 dimensions of the client-therapist relationship: bond, partnership, confidence, openness, and client initiative. On average, participants’ perception of the strength of their alliance with the program was positive, although ratings of the alliance were lower than those noted for face-to-face cognitive behavioral therapy (CBT). These pilot data are tentative, however, and require replication in a larger and more rigorously designed study.To the best of our knowledge, only one study has examined whether a therapeutic alliance can develop in a completely automated and self-guided Internet-delivered intervention without therapist input. Ormrod et al  used theIn a recently completed randomized controlled trial (RCT), we reported significant symptom and functional outcome gains for people with mild-to-moderate depression, anxiety, and stress who used a fully automated mobile phone and Web intervention with no therapist input, known as “myCompass”   and at 20 weeks. The design and recruitment procedures for the myCompass RCT have previously been reported in greater detail .Quantitative data for this secondary analysis was derived from participants randomly allocated to receive the myCompass intervention. This was supplemented by qualitative data provided by a purposively selected sample that completed the post-intervention questionnaire and agreed, via email, to participate in a semi-structured telephone interview with one of the authors (MAB). A sampling to saturation recruitment method was used in which data collection continued until no new themes emerged from the interviews .The RCT was approved by the Human Research Ethics Committee of the University of New South Wales, Sydney, Australia (HREC 10019) and registered with the Australian and New Zealand Clinical Trials Registry (ACTRN 12610000625077). The CONSORT-EHEALTH checklist is provided as myCompass is a fully automated public health CBT-based intervention for the treatment of mild-to-moderate depression, anxiety, and stress . The proThe myCompass program assesses users’ self-reported symptoms on registration and then provides 24/7 access to a personalized intervention that includes real-time, self-monitoring of moods and behaviors , and interactive, evidence-based psychotherapeutic modules (via tablet and computer). In addition, users can schedule SMS text message (short message service) or email reminders to facilitate self-monitoring, receive and print graphical feedback about their self-monitoring alongside contextual information on their phone or computer (to monitor change and assist identification of triggers), and elect to receive helpful facts, mental health care tips or motivational statements by text message or email. Registering to use the program is free, and users are not billed for the text messages they receive. A detailed description of the myCompass intervention is provided in Proudfoot et al .Participants in the RCT completed standardized and validated measures of mental health symptoms, work and social functioning, and positive psychological well-being at baseline, post-intervention, and follow-up, and the therapeutic alliance at post-intervention.The Depression, Anxiety and Stress Scales (DASS) is widely used to measure the extent to which a person experienced symptoms of depression, anxiety, and stress over the previous week . Total sThe Work and Social Adjustment Scale (WSAS) assesses the impact of mental health problems on daily functioning in 5 domains: work, social leisure activities, private leisure activities, home-management, and personal relationships . Scores The Mental Health Continuum-Short Form (MHC-SF) measures positive mental health defined as the presence of positive feelings , and positive functioning in individual life  and community life  . Total sThe Agnew Relationship Measure (ARM) uses 28 items to measure 5 elements of the client-therapist relationship: the affective element (bond), extent of mutual collaboration and engagement (partnership), perceived professional competence (confidence), perceived freedom to disclose personal concerns (openness), and empowerment (client initiative) . SubscalParticipant engagement with the myCompass program was measured using the following 3 indices: (1) number of program interactions , (2) number of modules completed, and (3) frequency of self-monitoring .Participant interviews were semi-structured and asked about the non-specific or “common” treatment factors identified in previous studies as contributing to development, persistence, and quality of the therapeutic alliance in face-to-face psychotherapy . The intQuantitative analyses were conducted using SPSS version 21, and used data derived from participants who returned a post-intervention questionnaire. Internal consistency of the modified ARM subscales was tested using Cronbach’s alpha, and subscale means were examined to determine alliance strength. In line with previous studies of Internet-delivered therapies ,23, resiInterview transcripts were audio recorded, transcribed, and analyzed independently by 2 of the authors (MRB and MAB) using a word processing package (MS Word). Thematic analysis of responses was used to identify the main themes and subcategories, while at the same time a thorough search was conducted for divergent views to enable a richer description of therapeutic alliance features . A 95% lOf the 231 RCT participants allocated to the myCompass intervention, 126  returned post-intervention questionnaires . On closCronbach’s alpha coefficients for the ARM subscales ranged from .3 (client initiative) to .86 (confidence), and were slightly higher than those reported in Ormrod et al  Table 2Table 2. As in previous studies , we founParticipant scores on the ARM subscales did not correlate with residual gain scores on the symptom, functioning, and positive well-being outcome measures .r=.26, P=.02) and openness  subscales were correlated significantly in a positive direction with self-monitoring frequency . Thematic analysis elicited 8 themes that described participants’ relationship with the myCompass intervention .Themes and subcategoriesEmpathy and acceptance1. Felt supported and understood2. Did not feel judged3. Able to be oneselfWorking in partnership1. Collaboration2. Motivated goal attainment Confidence and reassurance1. Respect for program content2. Positive regard for skills and techniques3. Expectations about program effectivenessOpenness1. Personal disclosure (client)2. Privacy and/or confidentiality encouraged honestyClient initiative1. Able to set one’s own agenda and/or goals2. Flexibility to use the program in a structured and/or self-guided mannerAvailability1. Convenience 2. 24/7 accessInteractivity1. Interactive exercises2. Home tasks3. Text message and/or email reminders and promptsResponsiveness1. Program matched symptom needs2. Personalized feedback3. Graphical reporting of symptomsInterviewees commented that they felt accepted and supported by the myCompass program, and a majority felt that it offered a safe and non-judgmental context within which to deal with their difficulties.The program was good, you could tell that it was made with an empathic voice, with no ulterior motives and that it was purely to help you. And you could tell that the authors had no judgment.Female, 28 yearsOne participant reported that she did not feel the program understood or accepted her.It’s just a computer...it doesn’t need to understand me...If it was a therapist it would be different.Female, 27 yearsAll interviewees felt that they collaborated flexibly with the myCompass program to set and work towards achieving their treatment goals. For a majority of users, the automated alerts and reminders contributed to this partnership and were viewed as important motivators of goal achievement and prompts for staying on track.When prompted, I responded to guidance to talk to a friend. I hadn’t realized how low I was at that timeFemale, 48 yearsOverwhelmingly, interviewees expressed confidence in and respect for program content, and experienced this as reassuring. Furthermore, a majority were optimistic that the quality of the skills taught and advice provided improved their capacity to manage future mental health problems. Several interviewees reported that they were at first skeptical about the usefulness of the program, but noted rising confidence with increased program use.The more modules I did, the more confident I felt in the information. It was becoming more and more helpful, especially the home tasksFemale, 41 yearsOne interviewee reported decreasing confidence in the program over time due to frustration caused by the compulsory home tasks.Interviewees generally appreciated the privacy afforded to them by the program, and the opportunity to openly and honestly share their problem feelings and behaviors. Indeed, for some interviewees, the level of comfort they felt in interacting with the program was greater than they had experienced in the face-to-face context, including with friends and family.It’s very easy when you’re feeling down to put on a brave face and tell everybody you’re fine...but with the computer I was comfortable being honest...Instead of trying to pretend that everything was fine, I could actually say it wasn’t...I felt more in control of thingsFemale, 47 yearsSome interviewees commented on the flexibility of the program in offering a structured , yet at the same time self-guided  intervention. The capacity to choose how they used the program was generally viewed as empowering by the interviewees.There’s a little quiz that you do when you start, and I was a bit surprised at some of the areas that it recommended for me to look at. Then I thought I’ll take a couple of those, and another one I was quite interested in as well, but ignore some of the ones that I thought weren’t so relevant...I felt quite able to make decisions about which ones I was going to look at.Female, 42 yearsThe linear structure of the program’s modules was viewed negatively by a minority of interviewees who would have liked greater control over the speed with which they progressed through the interactive tasks.A majority of interviewees accessed myCompass from both an Internet-enabled mobile phone and desktop computer; 3 interviewees chose not to access the program on their phone.The availability of myCompass 24/7, and the option of using myCompass when and where needed from a mobile device were viewed as major program advantages by all interviewees. Nevertheless, some interviewees felt that myCompass was more easily used on desktop computers than mobile phones because of the larger screen size and more reliable Internet connectivity.I liked the flexibility. And having it available on my mobile phone, just having the convenience there, meant that I could carry it around with me, I could update it on a needs basis, and it’s something I could do at a time and location of my choosing rather than being stuck at a deskMale, 37 yearsA majority of users commented on the usefulness of the interactive elements of the myCompass program, especially the in-task activities and the homework tasks. Several interviewees also appreciated being able to graph their self-monitoring data alongside contextual information.myCompass helped me make changes...Noting my responses and reactions to certain situations and identifying those particular triggers that I wanted to monitor...There were things that I thought might be an issue for me, and it (the graphs) confirmed that they wereFemale, 31 yearsOne interviewee commented that the feedback graphs provided tangible evidence that she was underestimating the extent of her symptoms.It (the graphs) identified that perhaps when I was convincing myself that I was fine, that perhaps really I wasn’t.Female, 47 yearsSome users reported that the feedback provided to them when they logged into the program about their self-monitoring and module progress put extra pressure on them.Sometimes I would log in and there were lots of red marks. I felt pressured...like I’d missed my school workFemale, 39 yearsMany users made comments about the capacity of the myCompass program to respond appropriately to their unique symptom needs, but views were mixed in this regard. On the one hand, there were users who felt the program recognized and appropriately responded to their personal symptom experience.If I was having low days, it would...acknowledge that I’m having a low day and (that) it’s ok to have a low day and have you considered speaking to somebody. Instead of just going, you know what, I can’t help youFemale, 41 yearsConversely, some users commented that the program responded in ways that did not reflect an appreciation of their needs and left them feeling confused and misunderstood.I tracked how I was feeling and then I’d get a message come up that says...perhaps you’re really struggling at the moment and you need to talk to somebody. And I’d think that I didn’t feel that I was that badFemale, 46 yearsThis secondary analysis of data from a large RCT explored the extent and nature of the therapeutic alliance in the fully automated, mobile phone and Web-based intervention, myCompass. Consistent with Ormrod et al  and otheWe also examined whether therapeutic alliance features were associated with treatment gains and program engagement. Consistent with previous studies of Internet-delivered interventions across a range of disorders ,22,26, wOn the other hand, components of the therapeutic alliance did show significant and positive associations with participants’ level of engagement with the myCompass intervention. Most notably, ratings of perceived emotional connection with the program correlated positively with program logins, frequency of self-monitoring, and the number of psychoeducational modules completed, suggesting that users may engage with an Internet intervention to the extent that they experience a collaborative partnership that is working well, just as in face-to-face therapy . EngagemBecause the ARM and other popular measures of the therapeutic alliance  were orSome limitations must be considered in interpreting these findings. As we have discussed previously , dropoutFrom a measurement point of view, we remain uncertain as to whether the psychometric adequacy of the ARM is affected when scale items are adapted along the lines reported here . Until reliability and validity of the modified ARM is demonstrated and/or alternative measures of the human-computer alliance are developed, our conclusions must be considered tentative. In addition, therapeutic alliance data were collected at only one time point . Previous researchers have discussed the importance of measuring therapeutic alliance variables at various stages of the therapeutic process , and theThis study is among the first to provide quantitative and qualitative support for the existence of a positive therapeutic alliance with a fully automated, mobile phone and Web-based psychotherapy intervention involving no therapist assistance. Although it appears that a strong alliance contributes less proximally to therapy outcomes in a fully automated, Internet-delivered intervention compared with face-to-face psychotherapy, our data suggest that the ability to connect meaningfully and work collaboratively may be similarly important for client engagement across both contexts. Client engagement is vital for therapeutic success, yet effective translation of non-specific alliance components of face-to-face therapies into the Internet environment is not easily achieved . For the