Pulmonary arterial hypertension restricts the ability of patients to perform routine physical activities. As part of pulmonary arterial hypertension treatment, inhaled iloprost can be administered via a nebulizer that tracks inhalation behavior. Pulmonary arterial hypertension treatment is guided by intermittent clinical measurements, such as 6-minute walk distance, assessed during regular physician visits. Continuous digital monitoring of physical activity may facilitate more complete assessment of the impact of pulmonary arterial hypertension on daily life. Physical activity tracking with a wearable has not yet been assessed with simultaneous tracking of pulmonary arterial hypertension medication intake.We aimed to digitally track the physical parameters of patients with pulmonary arterial hypertension who were starting treatment with iloprost using a Breelib nebulizer. The primary objective was to investigate correlations between changes in digital physical activity measures and changes in traditional clinical measures and health-related quality of life over 3 months. Secondary objectives were to evaluate inhalation behavior, adverse events, and changes in heart rate and sleep quality.We conducted a prospective, multicenter observational study of adults with pulmonary arterial hypertension in World Health Organization functional class III who were adding inhaled iloprost to existing pulmonary arterial hypertension therapy. Daily distance walked, step count, number of standing-up events, heart rate, and 6-minute walk distance were digitally captured using smartwatch (Apple Watch Series 2) and smartphone (iPhone 6S) apps during a 3-month observation period (which began when iloprost treatment began). Before and at the end of the observation period (within 2 weeks), we also evaluated 6-minute walk distance, Borg dyspnea, functional class, B-type natriuretic peptide  levels, health-related quality of life (EQ-5D questionnaire), and sleep quality .Of 31 patients, 18 were included in the full analysis . Changes from baseline in traditional and digital 6-minute walk distance were moderately correlated (r=0.57). Physical activity  and clinical measures  changed concordantly from baseline to the end of the observation period. Health-related quality of life showed little change. Total sleep score and resting heart rate slightly decreased. Distance walked and step count showed short-term increases after each iloprost inhalation. No new safety signals were identified .Our results suggest that despite challenges, parallel monitoring of physical activity, heart rate, and iloprost inhalation is feasible in patients with pulmonary arterial hypertension and may complement traditional measures in guiding treatment; however, the sample size of this study limits generalizability.ClinicalTrials.gov NCT03293407; https://clinicaltrials.gov/ct2/show/NCT03293407RR2-10.2196/12144 Remote patient monitoring can play an important role in disease management, supporting the conventional approach of face-to-face visits. In patients with chronic diseases such as left-sided heart failure, remote monitoring has been reported to have beneficial effects—reduced readmissions (possibly due to earlier treatment for symptoms detected before scheduled follow-up visits), reduced mortality, increased quality of life, increased participation in self-management of the disease, and improved knowledge of the disease -4.Pulmonary arterial hypertension is a progressive, life-threatening disease that can lead to right-sided heart failure and death . DyspneaIloprost, a prostacyclin-based inhaled therapy for patients with primary pulmonary hypertension  in WHO functional class III, has shown beneficial effects on 6-minute walk distance and WHO functional class in clinical trials -12. IlopThe primary aim of our study was to track daily physical activity in patients with pulmonary arterial hypertension starting treatment with inhaled iloprost, using a commercially available smartwatch and smartphone, and to investigate the association between changes in digital physical activity measures and changes in traditional clinical measures of disease severity and health-related quality of life over a 12-week period.Secondary aims were to assess acceptance of the smartwatch by patients and the feasibility of measuring 6-minute walk distance digitally and to identify digital measures linked to traditional 6-minute walk distance. Further aims were to digitally monitor heart rate and iloprost inhalation behavior, to explore temporal patterns in activity level and heart rate relative to iloprost inhalation periods, and to evaluate changes in clinical outcome measures, daily physical activity, heart rate, and sleep quality after initiation of inhaled iloprost therapy. The study was not designed to investigate or confirm the effectiveness and safety of iloprost (Ventavis).Additional details are available in a previous publication  and in MAs part of a national, prospective, observational, multicenter, single-arm cohort study  investigating the associations between clinical and device-reported outcomes in patients with pulmonary arterial hypertension  who were adding inhaled iloprost to existing pulmonary arterial hypertension therapy, we collected digital measures of daily physical activity, heart rate, and 6-minute walk distance using smartwatch (Apple Watch Series 2) and smartphone (Apple iPhone 6S) apps (xbird GmbH). The apps continuously captured data from the smartwatch for the purpose of analyzing physical activity and behavior patterns; the 6-minute walk distance app captured data from the smartwatch during the 6-minute walk distance test. Raw sensor data from the smartphone were not used because it was impossible to ascertain whether patients always carried the smartphone with them. Device functionality was reduced to the minimum requirements for the study. To reduce bias, the apps did not provide feedback on physical activity to patients or physicians. A nebulizer  was used to record inhalation behavior ,15,16.The study period consisted of baseline data collection during the period from the initial visit and decision to start iloprost treatment until the actual start of iloprost treatment (≤2 weeks), an observation period of 3 months (±2 weeks) from the start of iloprost treatment, and final data collection at discontinuation of therapy or at the end of the study (whichever was earliest). The decision to start treatment with inhaled iloprost was made at the discretion of the treating physician; the decision was made in advance and independently of inclusion in the study. Follow-up was conducted during routine patient visits to their pulmonary arterial hypertension centers.The study was approved by the central ethics committee of the Justus Liebig University Giessen (AZ153/17) and the ethics committees of all participating sites.In preparation for this study, a survey on acceptance of digital tracking was performed, which indicated that approximately 50% of patients were willing to participate .Patients were enrolled from 7 specialized pulmonary arterial hypertension centers in Germany from February 2018 to July 2019. Patients aged ≥18 years with pulmonary arterial hypertension in WHO functional class III despite treatment were eligible for enrollment if they were willing to wear a smartwatch for the duration of the study, had no previous treatment with inhaled iloprost, and they and their treating physician had decided to initiate treatment with inhaled iloprost using a Breelib nebulizer. Patients were excluded if they were allergic to nickel and methacrylates, or if they were already participating in an investigational program that included an intervention outside of routine clinical practice. All patients who were enrolled provided signed informed consent.Study participants were trained by site personnel or investigators to correctly use the smartphone and smartwatch. Study participants were given training on inhaler use through a patient support program , which is routinely offered to patients.Anamnestic data  were collected by an investigator from medical records, if available, and entered into an electronic case report form that formed part of an electronic data capture system developed and managed by a contract research organization (Institut Dr. Schauerte).Traditional clinical measures  and vital parameters were assessed at the initial and final visit to the study center; data were also recorded in the electronic case report form. Patient-reported outcomes—EuroQol 5-dimension questionnaire (EQ-5D) and Pittsburgh Sleep Quality Index (PSQI)—were documented on paper at the initial and final visits and sent to the contract research organization for analysis. Adverse events, from the periods between the first use of inhaled iloprost to 30 days after the last dose within the study period, were documented in the electronic case report form.Digital measurements of daily physical activity and heart rate were captured continuously by the smartwatch and app. Digital 6-minute walk distance data  were collected at the initial and final visit using the smartwatch and 6-minute walk distance app . Inhalation data  were captured by the nebulizer, transferred to the smartphone using the BreeConnect App (Bayer AG), and then transferred to the contract research organization for analysis.All data collected by the smartwatch were stored pseudonymized on a secure cloud server (xbird GmbH) for further processing. Processed data points for all variables were transferred as pseudonymized data to the electronic data capture system and matched to other collected data after the last visit of the last patient.The primary endpoint was correlation between changes from baseline to the final visit in digital measures of physical activity, traditional clinical measures, and in health-related quality of life. Changes from baseline were evaluated as a first step. The traditional clinical measures included in the primary analysis were the 6-minute walk distance, Borg dyspnea score after the 6-minute walk distance test, WHO functional class, and BNP or NT-proBNP levels. Health-related quality of life was assessed using the EQ-5D. The digital measures were distance walked, number of steps, number of standing-up events, and digital 6-minute walk distance .Secondary endpoints included inhalation behavior  and the mean association between physical activity level (device-based) and time since the last inhalation. The change from baseline to the end of the observation period in sleep quality (PSQI) and heart rate , the association between heart rate and other device-based measures during the whole study period, and the incidence of treatment-emergent adverse events and serious treatment-emergent adverse events were also evaluated as secondary endpoints. Other endpoints included acceptance of the smartwatch by patients, correlation of traditional and digital 6-minute walk distance measurements, and association of digital measures with 6-minute walk distance.Statistical analyses were exploratory and descriptive.Based on a feasibility study conducted in 2018 and ongoing study experience, the final planned sample size was 25 to 50 patients. The minimum number of 25 patients was considered sufficient to obtain reasonably precise correlation coefficients (even with 40% missing data).The safety analysis set included all patients who received at least 1 dose of inhaled iloprost. If a patient withdrew consent without agreeing to further use of their data, they were excluded from the safety analysis set. The full analysis set included all patients from the safety analysis set who had ≥3 days of activity measurements during the baseline period, ≥3 days of activity measurements during the last 2 weeks of the observation period, and data at the initial and final visits for at least 1 of the following clinical outcome measures: 6-minute walk distance, BNP/NT-proBNP levels, and WHO functional class. Patients identified as screening failures after enrollment (included by mistake) were excluded from the full analysis set.Measurements per day were normalized, for an assumed 18 hours (6 AM to midnight) of activity per day if parts of the observational time period of that day were missing, based on the percentage of time spent wearing the smartwatch. If the watch was worn for less than 10% of a given day, data for that day were treated as missing.Device-measured daily physical activity at baseline was calculated as the median of ≤14 daily assessments before the first intake of inhaled iloprost. Device-measured daily physical activity at the end of the observation period was calculated as the median of daily assessments in the last 14 days of the observation period.Pearson correlations were calculated for complete, pairwise observations of traditional and digital measures included in the primary analysis. Missing data for these parameters were not imputed.Regression analyses were performed with change from baseline in a traditional clinical measure as the dependent variable and changes from baseline in digital measures  as independent variables.We screened and enrolled 31 patients; 30 patients were included in the safety analysis set, and 18 patients were included in the full analysis set . Most paThe most common iloprost dose at the start and end of the observation period was 2.5 μg; 3 patients changed doses . The medThe median observation period in the full analysis set was 91.5 days . Participants wore the smartwatch between 30 and 113 days overall , for a mean time ranging from 4.8 hours per day to 11.5 hours per day . During the baseline period, 12 of the 18 patients (67%) wore the smartwatch for less than 7 days, and 6 of the 18 patients (33%) wore their smartwatch for at least 7 days. During the end of the observation period, almost three-quarters of the patients  wore the smartwatch every day, and all patients  wore it for at least 7 days. . The numThe median increase in traditional 6-minute walk distance was 26 m . AlthougBorg dyspnea index increased from baseline in 7/18 patients (39%), remained stable in 6/18 patients (33%), and decreased in 3/18 patients (17%) . WHO funDigital measures of daily physical activity  increased from baseline to the end of the observation period .Changes from baseline in traditional 6-minute walk distance and digital 6-minute walk distance were moderately correlated . The numThe median average heart rate at rest was 75.9 beats per minute (IQR 70.4 to 88.5) at baseline and 76.5 beats per minute (IQR 69.5 to 85.4) at the final visit. From baseline to the final visit, the average heart rate at rest showed a median decrease of −1.3 beats per minute (IQR −8.0 to 3.5).Heart rates measured during the 6-minute walk distance test were slightly higher at the last visit compared with those at the baseline visit . The medThe study design enabled parallel digital tracking of iloprost inhalation, heart rate, and physical activity. An analysis of patients stratified by the median duration of iloprost inhalation and treatment month suggested that the average heart rate during iloprost inhalation showed a slight increase with duration of inhalation . Owing tDistance walked  showed a short-term increase in activity shortly after inhalation and a long-term increase in activity over the entire observation period A. A simiFor each iloprost inhalation session per day, 12 intervals (of 15 minutes) beginning at the end of the inhalation session were defined, and the distance walked per interval was recorded. The corresponding intervals for each inhalation per day were averaged for each patient  The resulting 12 average values for each patient each day were then averaged over all patients. Complete and incomplete inhalations were included. Approximately 3700 inhalations were excluded from the analysis because the watch was not worn over the entire period of 3 hours after the end of inhalation. Some of the 3-hour intervals were overlapping. The coverage for the first analyzed 15-minute interval of each inhalation could be less than 100%, which occurred about 40 times. Within 1 day, the intervals after the inhalations were not distributed equally over the day.r=0.86) and at the final visit (r=0.87). Further details of these and other additional analyses are presented in In regression analyses, the change from baseline in traditional 6-minute walk distance was associated with changes in digital outcomes . Absolute measurements of traditional and digital 6-minute walk distance were strongly correlated but not congruent at baseline  and for the end of the observation period . Although correlations between changes in digital and traditional clinical outcome measures were few, the overall directions of those changes were generally concordant. The results also demonstrated the feasibility of continuously measuring multiple digital parameters  in parallel with different devices and matching the data. We were able to detect short-term increases in physical activity after each iloprost inhalation session with fine granularity. The results also highlighted some important challenges and limitations that should be considered for future digital studies in patients with pulmonary arterial hypertension.Recruitment was limited by a lack of available patients, which resulted in a small study population. This could be partly due to the rarity of pulmonary arterial hypertension , the wilAlthough there was general agreement between changes in digital and traditional parameters from baseline, parallel digital and traditional measurements of 6-minute walk distance were not congruent. The proprietary digital 6-minute walk distance algorithm was based on step count and the step length of healthy individuals, which in general is not valid for patients with pulmonary arterial hypertension. Substitution of the healthy step length with a patient’s individualized step length could provide better estimation of distance. The current series of Apple devices includes individual and repeated measurement of step length, which may be used in future studies to better estimate distance. This feature may also enable researchers to characterize other changes in health status  more precisely. Alternatively, measurement of distance by GPS may be suitable if the 6-minute walk distance test can be performed outdoors. Wi-Fi could be a potential alternative to GPS for 6-minute walk distance tests conducted indoors. However, measurement of 6-minute walk distance by GPS or Wi-Fi would require precise location tracking. A feasibility survey suggested that precise tracking on a long-term basis would not be accepted by patients ; such trPrevious digital studies -22 with The number of standing-up events is difficult to interpret. In a recent study with patients with pulmonary arterial hypertension, sit-to-stand test results (the number of sit-to-stand movements that patients were able to complete in 30 seconds) were associated with quadriceps muscle strength, which in turn was associated with 6-minute walk distance . An offiThe physical activity level may also be influenced by factors other than the severity of pulmonary arterial hypertension . Nevertheless, daily activity has been linked to prognosis in patients with pulmonary hypertension .The abovementioned limitations provide examples of some of the many criteria that must be fulfilled to ensure a successful digital study. The criteria can be broadly categorized into 6 themes, collectively referred to as the digital real-world evidence matrix: patient , indication , biomarker , type of sensor or device , quality , and endpoint . These themes were addressed in the design of the VENTASTEP study, which combined digital and traditional monitoring to provide new insights into the real-life treatment of patients with pulmonary arterial hypertension.There was an increase of 26 m for traditional investigator-measured 6-minute walk distance from baseline after addition of inhaled iloprost to oral pulmonary arterial hypertension therapy, which is consistent with the results of previous clinical trials ,11. The 6-Minute walk distance assessed during an office visit may be affected by daily fluctuations in physical function and may not accurately capture long-term changes in symptoms and physical function. Furthermore, the 6-minute walk distance test reflects maximal activity, whereas daily physical activity parameters provide an average of overall activity. Digital monitoring provides new insights into patient activity, with a more complete picture of the patient’s health status than traditional 6-minute walk distance alone. For example, the digital data showed that physical activity increased shortly after each iloprost inhalation session. This sheds light on the day-to-day experiences of patients with pulmonary arterial hypertension taking inhaled iloprost and may be helpful information for patients or physicians considering iloprost therapy.The increase in heart rate during the 6-minute walk distance test was marginally greater at the final visit compared with that the baseline visit, and heart rate recovery time after the 6-minute walk distance test increased. A previous study  showed sDespite increases in daily physical activity over the course of the study, the EQ-5D weighted index showed little change. The EQ-5D score has produced mixed results in key clinical trials of pulmonary arterial hypertension therapies , showingSleep disturbance in patients with pulmonary arterial hypertension has been associated with symptom severity, psychological state, and health-related quality of life . PSQI scThe strengths of this study include its continuous, parallel, digital measurement of inhalation behavior, heart rate, and physical activity over a long observation period. The limitations of this study include its small sample size, insufficient BNP or NT-proBNP data, and the fact that the digital 6-minute walk distance algorithm was based on the step length of healthy individuals rather than that of patients with pulmonary arterial hypertension. A substantial proportion of the study population took concomitant beta-blockers, which should be considered when interpreting the heart rate data.Further research is warranted to assess the association of iloprost inhalation behavior with changes in digital physical activity measures, traditional clinical measures, and health-related quality of life. The relationship between daily physical activity and traditional 6-minute walk distance requires further exploration. In addition, studies with longer-term follow-up are needed to determine if clinical outcomes  are better predicted by the change in traditional 6-minute walk distance or the change in digital 6-minute walk distance over time.The recruitment difficulties in this study (which focused on a rare disease) suggest that digital monitoring studies may be more feasible in indications with large patient populations, such as heart failure. In addition, most patients were older adults; recruitment may be higher among populations of younger patients who are more familiar with digital technology. Refinement of the digital 6-minute walk distance algorithm for the target patient population is also needed.Although generalizability is limited because of the small sample size and other limitations, the study demonstrated the general feasibility of performing digital assessments with a commercially available smartwatch and smartphone in patients with pulmonary arterial hypertension. Digital measures of daily physical activity and traditional clinical measures showed concordant changes from baseline after addition of inhaled iloprost to oral pulmonary arterial hypertension therapies. However, the data indicate that activity tracking algorithms validated for healthy people require adaptation for patients with pulmonary arterial hypertension. Further investigations are therefore necessary.


The Scleroderma Patient-centered Intervention Network (SPIN) developed an online self-management program (SPIN-SELF) designed to improve disease-management self-efficacy in people with systemic sclerosis . The aim of this study was to evaluate feasibility aspects for conducting a full-scale randomized controlled trial (RCT) of the SPIN-SELF Program.This feasibility trial was embedded in the SPIN Cohort and utilized the cohort multiple RCT design. In this design, at the time of cohort enrollment, cohort participants consent to be assessed for trial eligibility and randomized prior to being informed about the trial. Participants in the intervention arm are informed and provide consent, but not the control group. Forty English-speaking SPIN Cohort participants from Canada, the USA, or the UK with low disease-management self-efficacy  who were interested in using an online self-management program were randomized (3:2 ratio) to be offered the SPIN-SELF Program or usual care for 3 months. Program usage was examined via automated usage logs. User satisfaction was assessed with semi-structured interviews. Trial personnel time requirements and implementation challenges were logged.Of 40 SPIN Cohort participants randomized, 26 were allocated to SPIN-SELF and 14 to usual care. Automated eligibility and randomization procedures via the SPIN Cohort platform functioned properly, except that two participants with SEMCD scores > 7  were included, which was caused by a system programming error that rounded SEMCD scores. Of 26 SPIN Cohort participants offered the SPIN-SELF Program, only 9 (35%) consented to use the program. Usage logs showed that use of the SPIN-SELF Program was low: 2 of 9 users (22%) logged into the program only once (median = 3), and 4 of 9 (44%) accessed none or only 1 of the 9 program’s modules (median = 2).The results of this study will lead to substantial changes for the planned full-scale RCT of the SPIN-SELF Program that we will incorporate into a planned additional feasibility trial with progression to a full-scale trial. These changes include transitioning to a conventional RCT design with pre-randomization consent and supplementing the online self-help with peer-facilitated videoconference-based groups to enhance engagement.clinicaltrials.gov, NCT03914781. Registered 16 April 2019. What uncertainties existed regarding the feasibility?What are the key feasibility findings?An online, self-guided, self-management intervention to support self-efficacy for disease management in people with systemic sclerosis (SSc) was developed (SPIN-SELF Program). The planned full-scale randomized controlled trial (RCT) would be conducted using the novel cohort multiple RCT (cmRCT) design. In the cmRCT design, compared with conventional parallel-group RCT designs, randomization to the intervention or control arm is conducted prior to obtaining consent for the intervention, thus declining participation happens post-randomization. Uptake of the intervention offer has been low in previous studies with the cmRCT design. Thus, prior to testing for effectiveness in a full-scale RCT, we sought to (1) evaluate the offer uptake of the intervention as well as other aspects of feasibility of the planned trial methodology, and (2) assess whether the online intervention is user-friendly and acceptable to trial participants.What are the implications of the feasibility findings for the design of the main study?Forty participants were enrolled in the SPIN-SELF feasibility trial, and the randomization feature embedded in the Cohort platform functioned properly. Participants were able to easily connect to and use the online SPIN-SELF Program and found the program easy to use. Two key problems related to the feasibility of conducting a full-scale RCT of the SPIN-SELF Program were identified: (1) of 26 participants offered to try the SPIN-SELF Program, only 9 (35%) consented to use it, and (2) usage logs showed that use of the SPIN-SELF Program was low: 2 of 9 users (22%) logged into the program only once (median = 3), and 4 participants (44%) accessed none or only 1 of the 9 available modules in the program (median = 2).The design of the main study needs to be adapted to improve enrollment in the SPIN-SELF Program as well as usage of the program among trial participants. Changes will include a transition from the cmRCT design to a conventional parallel-group RCT design and peer-facilitated online groups to support engagement with the SPIN-SELF Program will be organized in addition to the online self-guided program.Self-management programs are designed to support people with chronic medical conditions to improve their self-efficacy to manage their condition, maintain life roles, and cope with negative emotions. They are typically delivered in group formats and emphasize the development of problem-solving skills and effective collaboration with health care providers –3. GenerN = 267) tested a SSc internet-based self-management program but reported that it did not improve self-efficacy or other outcomes [Rare diseases are defined as conditions that affect fewer than 1 in 2000 people. Cumulatively, 4–6% of people may have a rare disease . Systemioutcomes .The Scleroderma Patient-centered Intervention Network (SPIN) is an international collaboration of researchers, clinicians, patient advocates, and people with SSc that develops, tests, and disseminates tools to support people living with SSc . PatientThe aim of the SPIN-SELF feasibility trial was to inform necessary adjustments to the program and trial procedures prior to conducting a full-scale RCT by assessing trial procedures, required resources and management, scientific aspects, and participant acceptability of procedures and program content.The SPIN-SELF Feasibility Trial was a parallel, two-arm feasibility cohort multiple RCT (cmRCT) conducted using the SPIN Cohort to identify and enroll eligible participants and ascertain outcomes. In the cmRCT design , particihttps://www.spinsclero.com/en/cohort/sites) during regular medical visits, and written informed consent is obtained. Participants consent to (1) their data being used for observational studies; (2) their data being used to assess intervention trial eligibility and, if eligible, that they will be randomized; (3) if eligible and randomized to the intervention arm of a trial, to be contacted and offered access to the intervention; and (4) if eligible and randomized to the usual care arm of a trial, to not be notified about the trial but to use their regularly collected cohort data to evaluate trial outcomes. A medical data form is completed by the treating physician and submitted online to enroll participants. Approximately 1300-1500 active participants from 7 countries and 50 sites complete assessments in any 3-month period.The SPIN Cohort  has collTrial eligibility assessments occurred automatically via the online SPIN Cohort platform during participants’ regular SPIN Cohort assessments. Eligible participants were those who completed cohort measures in English, had low disease management self-efficacy  ), and inWe used simple randomization of participants with a 3:2 ratio to an offer to use the SPIN-SELF Program for 3 months versus usual care. A 3:2 ratio was used to attempt to enroll enough participants who would be offered the intervention to assess usage. Eligible participants were identified and randomized automatically as they completed regular SPIN Cohort assessments using a feature in the SPIN Cohort platform, which provides immediate centralized randomization and, thus, complete allocation sequence concealment.Participants randomized to be offered the program received an automated email invitation including a link to the SPIN-SELF Program website and the consent form. At initial login, using their SPIN Cohort username and password, they were prompted to provide written consent to participate in testing the SPIN-SELF Program by verifying agreement with consent elements and providing their email address as electronic signature. Consented participants were automatically directed to the SPIN-SELF Program introduction page. Participants who logged out without consenting were returned to the consent page upon subsequent logins. Participants who accepted the offer could use the web link to enter the secure intervention site for 3 months.SPIN personnel also contacted participants by phone, usually within 48 hours of sending the invitation email, to describe the study, review the consent form, and answer questions. A maximum of 5 attempts were made to contact participants within 10 days of sending the invitation email. If not successfully contacted, a sixth attempt was made approximately 20 days post-invite. Email and phone technical support were available to help participants with the consent process and use of the intervention site.Participants assigned to usual care were not notified about the trial and completed their regular SPIN Cohort assessments as normal. Thus, participants offered the intervention were not blind to their status, whereas participants assigned to usual care were blind to their trial participation and assignment. This replicates actual practice, where patients are not typically advised about treatments that are not options and may reduce risk of disappointment bias , 25.The SPIN-SELF Program was designed based on key tenets of self-management skills that have been incorporated in successful self-management programs for chronic diseases, including problem solving, decision making, resource utilization, forming a patient–health care provider partnership, and taking action . Input oUpon first use, instructions on how to navigate the program are provided in a website tour video. Participants are introduced to the concept of self-management by a physician with expertise in SSc and a patient sharing her experience with self-management. The program utilizes an engaging and easy-to-navigate web interface, and language of the modules is at an appropriate level for understanding based on input from members of SPIN’s Patient Advisory Board. Pages can be bookmarked, text can be enlarged, and captions for each video are available for download. There are 9 modules, and after the program introduction, users are directed to a 9-item quiz designed to guide them to modules most relevant to their symptoms and disease-management challenges. Based on the quiz score, links to the 3 most relevant modules appear on top, with links to the other 6 modules available below. The 9 modules target (1) coping with pain; (2) skin care, finger ulcers, and Raynaud’s; (3) sleep problems; (4) fatigue; (5) gastrointestinal symptoms; (6) itch; (7) managing emotions and stress; (8) coping with body image concerns due to disfigurement; and (9) effective communication with healthcare providers. Each module includes an educational component that provides background information on the topic and teaching of skills, as well as a goal-setting component.In addition to the modules, the SPIN-SELF Program includes tools to support key self-management strategies, including education on goal setting, fillable goal-setting forms, and worksheets to help users integrate newly learned skills and techniques into daily routines. The online goal form encourages users to choose a number of days per week and total weeks to work on a goal, to reflect on why achieving the goal is important to them, and to write their reason in a text box. For each goal, users can input weekly progress, receive e-mail reminders to facilitate successful completion, and share goals and progress with friends and family. Worksheets are specifically tailored to each module and can be saved and printed for later use. The program incorporates social modeling through educational videos of people with SSc who describe their challenges and coping strategies, and of health professionals who teach key self-management techniques.Feasibility outcomes included:  proportiTo assess user acceptability and satisfaction, semi-structured interviews were conducted with consenting participants in the intervention arm, at 3 months post-randomization, using 27 items of the Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT) , which aMeasures of disease-management self-efficacy and functional health outcomes that will be used to evaluate the program in the full-scale trial were reported, although no hypothesis tests were conducted, consistent with the feasibility trial design , 29. Outnot confident at all) to 10  scale. The total score is the mean of all items. The SEMCD was previously validated for SSc through the SPIN Cohort [The 6-item SEMCD  measuresN Cohort .T-scores standardized from the general US population . Higher scores indicate greater physical function and social role and activity participation but worse anxiety, depression, fatigue, sleep disturbance, pain interference, and pain intensity. The PROMIS-29 version 2.0 has been validated for SSc [The 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29) profile version 2.0  assesses for SSc , 33.Guidance on the appropriate sample size for feasibility trials varies, with rules-of-thumb suggesting 12 to 30 participants or more per trial arm , 35. In Descriptive statistics were used to characterize the sample and feasibility outcomes, including personnel and time resources required, participant eligibility, recruitment numbers, percentages of participants who responded to follow-up measures, and frequency of logins and time spent using the program. The presence of floor or ceiling effects on outcome measures was assessed. Qualitative information on participant experiences was recorded.Feasibility outcomes were evaluated qualitatively, and no quantitative cut-offs for progression to full-scale trial  were pre-specified.Enrollment began on July 6, 2019 and was completed on July 27, 2019. Of 40 participants, 26 (65%) were allocated to the intervention arm and 14 (35%) to the usual care arm  met trial eligibility criteria. One error in the automated eligibility assessment process was identified. Two enrolled participants had SEMCD scores > 7 (7.2 and 7.3) and, thus, were randomized despite not meeting eligibility criteria. This occurred because of a system programming error that rounded scores rather than including decimal places. A review of participant characteristics and assessment scores showed that all other eligible and ineligible cohort participants were correctly classified.Total time spent by SPIN personnel on calls, including leaving voicemails, and emails with the 26 participants randomized to the intervention arm was 228 min (8.8 min per participant). Participants who attempted to log in were able to do so easily, so no troubleshooting outside of the protocol calls was needed. One participant reported difficulties using the program on their smartphone but was able to successfully use it on a computer without assistance.Study personnel spent an additional 99 min on other tasks, including reviewing the randomization process, tracking enrollment and consent progress, and managing call logs. Mean time per day was less than 5 min. This did not include team meetings to review project progress and administration. One technical issue was identified on the first day of enrollment when intervention participants did not appear on the SPIN Cohort platform’s management page. Time spent to resolve this issue by information technology personnel was 35 min. No other challenges were reported by study personnel.Usage data from the SPIN-SELF platform and SPIN Cohort data were successfully linked 100% of the time. Of the 26 participants randomized to intervention, 15 (58%) did not log in to the consent page; 2 (8%) logged in but did not consent, and 9 (35%) consented. Of the 9 who consented, 2 (22%) logged in only once, 2 (22%) logged in twice, and the other 5 logged in 3 to 7 times .N = 6, 67%) accessed the fatigue module, 4 (44%) accessed the gastrointestinal symptoms module, and 3 participants (33%) accessed modules on sleep and pain. The modules addressing body image concerns, itch, and skin care were accessed by 2 participants each (22%), and the modules on effective communication with healthcare providers and managing emotions were accessed by 1 of the 9 participants (11%). Two participants (22%) created one or two goals, others did not use this feature.After consent, 6 of 9 participants (67%) watched the expert introduction video, and 3 of these also watched the patient introduction (33%). Four participants (44%) used the website tour. All 9 participants completed the quiz to identify the modules most relevant to them. One participant (11%) did not access any module in the SPIN-SELF Program, and 3 participants (33%) accessed 1 of the 9 modules. Other participants accessed between 3 and 9 modules . Of the different modules, most participants . See PEMAT interview responses in Table Of the 40 participants, 35 (87.5%) completed their 3-month follow-up cohort assessments, including 23 in the intervention arm (88.5%) and 12 in the control arm (85.7%). Table Forty SPIN Cohort participants were successfully enrolled in the SPIN-SELF feasibility trial, and the randomization feature embedded in the Cohort platform functioned properly. However, the automated eligibility procedure allowed for two ineligible participants to be enrolled. This was caused by a system programming error that rounded down the participants’ mean scores on the SEMCD Scale. This system error will be fixed to ensure that only eligible participants are randomized for the full-scale trial. Overall, the required trial personnel resources for the trial were low and mainly spent on follow-up calls made to enrolled participants. Participants were able to easily connect to and use the program, thus required technical support was minimal. Although only 5 trial participants in the SPIN-SELF arm completed the semi-structured interview, overall, they reported high satisfaction with the trial procedures as well as the SPIN-SELF Program (average score 8.4/10). They found the program easy to use and said they would recommend it to other people with SSc. One participant suggested that there is a lot of information and would have liked more guidance on what to focus on. The satisfaction estimate should be interpreted with caution, as it might be biased and possibly overestimates satisfaction, as patients who participated in the interview might rate the program more favorably than the ones not participating. The majority of the feasibility trial participants in both arms completed the 3-months follow-up assessment (87.5%). Two major problems related to the feasibility of conducting a full-scale RCT of the SPIN-SELF Program were identified, however. These include (1) the low consent rate among participants who were offered the SPIN-SELF Program (35%) and (2) the low usage of the program among consented participants.N = 466; consent rate 61%), which similarly enrolled participants through the SPIN Cohort [In the cmRCT design, compared with conventional parallel-group RCT designs, randomization to the intervention or control arm is conducted prior to obtaining consent for the intervention, thus decisions to accept or decline participation in the intervention arm happen post-randomization . AlthougN Cohort . AlthougN Cohort  suggest N Cohort , 40. SPIN Cohort , this apWe plan to make two major changes to the design of the planned SPIN-SELF Trial, which we will test in an additional feasibility trial with progression to a full-scale trial. First, rather than utilizing the cmRCT design, we will conduct a conventional parallel-groups RCT, utilizing the SPIN Cohort as well as external enrollment procedures to enroll participants. Thus, eligible SPIN Cohort participants, based on their regular assessments, will be contacted and asked to consent to participate in the SPIN-SELF Trial prior to enrollment and randomization. We will additionally increase our recruitment efforts by advertising the trial through social media (Twitter and Facebook) posts to generate interest in the trial from both SPIN Cohort and non-Cohort individuals with SSc.N = 249; 92% logged in at least once; mean logins 25.4, SD 1.7) [N = 172) [Second, we will move from an individual self-guided program to a group-based program in which participants use the online SPIN-SELF Program as the curriculum in an interactive program. Low usage of self-guided, online psychological programs, as we encountered in our study, is a well-known problem across settings , 43. Whi SD 1.7) . RecentlN = 172) , 49. SPIN = 172) . Thus, tThe present study has limitations that should be considered in interpreting its results. First, the SPIN Cohort constitutes a convenience sample of SSc patients receiving treatment at a SPIN recruiting center, and patients at these centers may differ from those in other settings. Additionally, SSc patients in the SPIN Cohort complete questionnaires online, which may further limit the generalizability of findings, as all participants already have Internet access and are comfortable using it in a research setting. Third, we were only able to include English-speaking SPIN Cohort participants in this study. French-speaking patients were not included because there was a limited number of French-speaking SPIN Cohort participants at the start of this study, and we wanted to be able to assess feasibility aspects but be able to maximize the number of French participants eligible for the subsequent full-scale trial. At this moment, the SPIN-SELF Program is not yet available in Spanish, meaning we cannot include Spanish-speaking Cohort patients in the trial. Finally, we did not attempt to assess the reasons for not accessing the intervention in non-consenting participants, which might have given us additional insights into reasons for the low uptake.In sum, the SPIN-SELF feasibility trial identified major problems, including low uptake of the intervention offer among participants randomized to intervention and low usage among those who did consent to try the intervention. This will lead to substantial changes that we will incorporate into a planned additional feasibility trial with progression to a full-scale trial. These changes include a transition from the cmRCT design to a conventional RCT design and a change in the mode of delivery to include additional peer-facilitated videoconference-based groups to the online program. The full-scale RCT will provide information on effectiveness of the SPIN-SELF Program. After the trial, it will be made available through patient organizations around the world to support people in their efforts to cope with living with SSc.


The COVID-19 pandemic has propelled patient-facing research to shift to digital and telehealth strategies. If these strategies are not adapted for minority patients of lower socioeconomic status, health inequality will further increase. Patient-centered models of care can successfully improve access and experience for minority patients.This study aims to present the development process and preliminary acceptability of altering in-person onboarding procedures into internet-based, remote procedures for a mobile health  intervention in a population with limited digital literacy.We actively recruited safety-net patients  into a randomized controlled trial of text messaging support for physical activity. Because of the COVID-19 pandemic, we modified the in-person recruitment and onboarding procedures to internet-based, remote processes with human support. We conducted a preliminary evaluation of how the composition of the recruited cohort might have changed from the pre–COVID-19 period to the COVID-19 enrollment period. First, we analyzed the digital profiles of patients (n=32) who had participated in previous in-person onboarding sessions prior to the COVID-19 pandemic. Next, we documented all changes made to our onboarding processes to account for remote recruitment, especially those needed to support patients who were not very familiar with downloading apps onto their mobile phones on their own. Finally, we used the new study procedures to recruit patients (n=11) during the COVID-19 social distancing period. These patients were also asked about their experience enrolling into a fully digitized mHealth intervention.P=.49).Recruitment across both pre–COVID-19 and COVID-19 periods (N=43) demonstrated relatively high rates of smartphone ownership but lower self-reported digital literacy, with 32.6% (14/43) of all patients reporting they needed help with using their smartphone and installing apps. Significant changes were made to the onboarding procedures, including facilitating app download via Zoom video call and/or a standard phone call and implementing brief, one-on-one staff-patient interactions to provide technical assistance personalized to each patient’s digital literacy skills. Comparing recruitment during pre–COVID-19 and COVID-19 periods, the proportion of patients with digital literacy barriers reduced from 34.4% (11/32) in the pre–COVID-19 cohort to 27.3% (3/11) in the COVID-19 cohort. Differences in digital literacy scores between both cohorts were not significant (Patients of lower socioeconomic status have high interest in using digital platforms to manage their health, but they may require additional upfront human support to gain access. One-on-one staff-patient partnerships allowed us to provide unique technical assistance personalized to each patient’s digital literacy skills, with simple strategies to troubleshoot patient barriers upfront. These additional remote onboarding strategies can mitigate but not eliminate digital barriers for patients without extensive technology experience.Clinicaltrials.gov NCT0349025, https://clinicaltrials.gov/ct2/show/NCT03490253 The COVID-19 pandemic has drastically changed how health care is delivered, resulting in an increasing shift to digital and telehealth approaches. The pandemic has also substantially altered patient-facing research, relying on similar digital outreach and implementation strategies . Many ofDespite the ubiquitous integration of technological innovations into health care, it is important to recognize the inequitable access to digital health tools among marginalized populations. Notably, previous studies show that reduced access to sufficient internet or data plans and low computer use remain barriers to participation in digital strategies among racial or ethnic minorities with low socioeconomic status (SES) -5. AdditAs patient-facing research transforms into digitized clinical trials, it is important to adopt patient-centered models to ensure recruitment of diverse populations and equitable access to digital health tools for all. Patient-centeredness is defined as “care that is respectful of and responsive to individual patient preferences, needs, and values” and provides patients with the “tools and support they need”  to engagThrough our experience of recruiting English and Spanish speakers of lower SES into clinical research in a public health care delivery system, we developed practical guidelines for internet-based remote recruitment of populations who have access to technology but face digital literacy barriers to self-enroll into mobile health  interventions. This paper explains the development process and preliminary acceptability of altering our study procedures from previous in-person sessions to internet-based remote visits for the recruitment of patients with diabetes and depression into an mHealth intervention. We also conducted a preliminary examination of how the composition of recruited patients might have changed from pre–COVID-19 to COVID-19 enrollment periods.The data herein are part of a larger randomized controlled trial (RCT). The Diabetes and Depression Text Messaging Intervention (DIAMANTE) study (NCT03490253) is testing a smartphone-based mHealth intervention  , aiming However, social distancing due to the COVID-19 pandemic necessitated the transition to remote recruitment strategies, without the ability to troubleshoot onboarding issues in-person . To be as efficient as possible in addressing any challenges our target population might encounter in providing consent to participate via DocuSign (rather than via pen-and-paper), completing the online Qualtrics baseline enrollment assessments, and downloading the smartphone application remotely, we significantly altered our study procedures for the screening and recruitment of eligible patients.Patient-centeredness has traditionally been used to improve health equity within research and operational programs. In the context of mHealth, patient-centeredness is rooted in active collaboration between patients and research staff . PatientThe adaptation of previous in-person study procedures to remote practices took place from March to April 2020. As an initial step, we analyzed the digital profiles—including digital literacy and device or broadband access—of patients who participated in our previous pre–COVID-19 in-person sessions (hereafter referred to as the pre–COVID-19 cohort). Following the analysis, research staff met to discuss personal experiences encountered during previous in-person onboarding sessions. Analysis and feedback allowed us to address the most relevant barriers to and facilitators of an internet-based remote visit. The results led us to alter our study procedures to orient patients to download the digital health application being studied via an internet-based remote visit . The project coordinator conducted several educational meetings to introduce and share the rough outlines of the new study procedures with the entire research team. Several amendments were made to these outlines based on onboarding research staff’s feedback and internal piloting efforts.The final versions were then used to enroll eligible patients (n=11) into a complete, digitized version of the clinical trial during the period of social distancing in the context of the COVID-19 pandemic (hereafter referred to as the COVID-19 cohort), from April 2020 to September 2020. Finally, the enrolled patients who were able to attend a remote onboarding visit were asked about our new remote recruitment processes, and their feedback was both audio-recorded and documented with detailed field notes.Using the online Qualtrics surveys conducted during the usability testing phase and the RCT phase of the DIAMANTE study, we collected several measures to conduct a preliminary examination of how the composition of the recruited sample might have changed from the pre–COVID-19 to the COVID-19 enrollment period.First, we measured the participants’ SES using the MacArthur Scale. This scale captures the cumulative influences of social hierarchy  and has been shown to better predict health and wellbeing -23. The very or somewhat difficult on both questions was considered to have limited digital literacy.We also measured the patients’ digital literacy. Digital literacy, defined as “the ability to use emerging information and communication technologies to find, access, create, download and communicate information” . NotablyFinally, semi-structured interviews were conducted to explore the acceptability of remote onboarding procedures. Questions were based around downloading the app and the experience during and after completion of an internet-based remote session for clinical research.P<.05.Given the small sample size, nonparametric, paired-sample, one-sided Fisher exact test was performed using SPSS  software to capture differences in digital literacy scores between the pre–COVID-19 and COVID-19 cohorts. We considered a difference to be statistically significant at To explore acceptability of the new onboarding procedures, we categorized enrolled participant feedback about the remote onboarding procedures from our field notes and audio-recorded interviews. RH read the interviews in their entirety, using the semistructured format of the interview guides to code for the categories represented in the interview guide as follows: (1) overall experience with an internet-based remote session and (2) difference and benefits or drawbacks of an internet-based remote visit in comparison to a patient-facing visit.In all, 35 of the 43 (81.4%) participants filled out the MacArthur Scale, including all RCT participants. Overall, our sample self-identified as having low SES . Specifically, the self-reported mean score for patients in the pre–COVID-19 cohort was 4.79 (SD 2.11), whereas the mean score for those in the COVID-19 cohort was 4.36 (SD 2.77).P=.49).After implementing these procedures, we then compared the digital access and literacy among participants in the pre–COVID-19 cohort with those in the COVID-19 cohort . Althougto see the hospital's commitment to the community.” In addition, 7 of 11 (64%) patients classified time efficiency and the convenience of not having to travel outside their home as a major benefit to participating in research via remote visits.Finally, we summarized patient experiences with the new remote onboarding procedures. In all, 8 of 11 (73%) patients in the COVID-19 cohort had never participated in a remote visit for research in the past, but all 11 (100%) patients stated that they enjoyed participating in remote visits for research. One patient, for example, expressed that staff taking the time to offer technological assistance allowed them “When discussing how this research study fit into their overall needs for digital health care at our safety-net health care setting, the patients remained supportive of these remote approaches during the COVID-19 pandemic and beyond:It's still important to have someone guide patients for things that are confusing in this remote session. I felt safe doing this.The technology for video conferencing is overdue, and we should have been doing it for a longer time, but now we have been forced to adapt…[it] feels wonderful to be included in all… Video conferencing can be used to reach out to populations or cultures that have a harder time going to their appointments.Despite these positive comments, 3 of 11 (27%) patients stated that they would still prefer an in-person patient-facing session in the future, given the simplicity of steps involved.With the speedy uptake of digital and telehealth strategies propelled by the COVID-19 pandemic, it is a high priority to proactively reform current practices to ensure equitable access among vulnerable populations, including those who might have access to technology and broadband but face additional digital literacy barriers. Prior to the COVID-19 pandemic, the majority of health care systems did not provide training for populations with limited digital literacy to ensure adoption of the available digital health tools, including mHealth interventions and telehealth or telemedicine -31. To aFurthermore, we started data collection to evaluate whether patients of lower SES and limited digital literacy were still able to participate in mHealth research in the midst of direct economic and health consequences of the COVID-19 pandemic. Our findings indicate that one-on-one staff-patient partnerships can be effective in providing technical assistance to populations who have limited digital literacy skills and are interested in gaining access to digital health tools. We were able to enroll a sample similar to our pre–COVID-19 cohort during the COVID-19 social distancing period by using a new onboarding procedure. Specifically, although, there was a nonsignificant reduction in patients with limited digital literacy enrolling into our study during the COVID-19 pandemic, both cohorts had challenges with digital literacy. The COVID-19 cohort had unique challenges in trying to use both our DIAMANTE app as well as Zoom (many participants were using these apps for the first time) without the assistance of in-person support . Our findings demonstrate that with adequate attention and support, it is possible to reach patients with limited digital literacy by using remote strategies. This finding is consistent with the previous literature that shows that patients of lower SES have high interest in using digital platforms to manage their health, but they may require additional upfront human support to gain access and have an overall better user-experience ,33. At tAlthough our rate of recruitment has slowed down overall given the pandemic, we know that patients are able to enroll into the study and successfully download a smartphone app through visual and verbal coaching from research assistants. Patients showed willingness to participate in the development of procedures, provided feedback on how to improve user-experience, and ultimately, showed acceptability of internet-based remote sessions for research.Previous research reveals gaps in accessibility to telehealth, telemedicine, and remote strategies within vulnerable populations, particularly those with lower technical abilities, older age, and limited English proficiency—these issues are particularly acute in the context of the COVID-19 pandemic ,35. OtheThe COVID-19 pandemic has emphasized that we must identify clear strategies for engaging patients with limited digital literacy to extend health care services (and access to research studies) outside of in-person care. Engagement strategies in clinical settings are necessary in order to prevent further growth of health disparities. In addition, ensuring engagement in digital and remote research will ensure an inclusive knowledge base.Responses to expanding the use of technology in care have included policy changes to expand reimbursement for telemedicine, and efforts to expand access to the internet. In addition to these priorities, our findings indicate the need for additional research and practice to address digital literacy barriers and ensure equitable access to digital health care interventions in the near and long term. Researchers who focus on digital health interventions should prioritize better reporting of digital literacy capabilities of their enrolled participants, incorporate service design frameworks within their trial protocols, and thoroughly explain the steps needed to enroll in digital health interventions. Implementation techniques across digital health trials should be leveraged to facilitate the translation of research findings into clinical practice. For example, health care systems could implement brief screenings prior to remote visits to know whether a patient is ready to try a video visit or needs additional support or training. The guidelines we have developed can benefit clinicians and clinical researchers working with vulnerable patients with limited digital literacy to ensure that digital advancements in health care do not lead to increased health disparities. Moving forward, we must dedicate attention and practical resources to those with lower levels of digital literacy as we continue to rapidly expand access to digital health tools; otherwise, we risk increasing existing health disparities for both telemedicine uptake as well as broader health care and research interventions.


Atrial fibrillation (AF) is the most common cardiac arrhythmia in the adult population. AF is associated with a poor quality of life (QoL) and, in many patients, current medical treatments are inadequate in alleviating AF symptoms . Patients often present with symptom preoccupation in terms of symptom fear, avoidance, and control behaviors. Internet-delivered cognitive behavior therapy is effective for treating other somatic disorders but has never been evaluated in patients with AF.The aim of this study is to evaluate the efficacy and feasibility of AF-specific internet-delivered cognitive behavior therapy.We conducted an uncontrolled pilot study in which 19 patients with symptomatic paroxysmal AF underwent internet-delivered cognitive behavior therapy. Participants completed self-assessments at pretreatment, posttreatment, and at a 6-month follow-up along with handheld electrocardiogram measurements with symptom registration. The treatment lasted 10 weeks and included exposure to physical sensations, reduction in avoidance behavior, and behavioral activation.d=0.80; P<.001), and in symptom preoccupation  at posttreatment; the results were maintained at the 6-month follow-up. Treatment satisfaction and adherence rates were also high. We observed an increased AF burden, measured by electrocardiogram, at the 6-month follow-up, but a significant decrease was observed in the overestimation of AF symptoms at posttreatment and 6-month follow-up. Exploratory mediation analysis showed that a reduction in symptom preoccupation mediated the effects of internet-delivered cognitive behavior therapy on AF-specific QoL.We observed large within-group improvements in the primary outcome, AF-specific QoL (Cohen This study presents preliminary evidence for the potential efficacy and feasibility of a novel approach in treating patients with symptomatic AF with internet-delivered cognitive behavior therapy.ClinicalTrials.gov NCT02694276; https://clinicaltrials.gov/ct2/show/NCT02694276 Atrial fibrillation (AF) is the most common cardiac arrhythmia, with a prevalence of approximately 3% in the general adult population . AF is cAF burden can be defined as either objective AF episodes, measured and confirmed by an electrocardiogram (ECG), or subjectively perceived AF symptoms measured by self-report . When coWe have defined symptom preoccupation in AF as the fear of experiencing and triggering AF episodes, hypervigilance toward cardiac symptoms, persistent worry about complications , and avoidance of physical and social activities . SymptomCognitive behavior therapy (CBT), with an emphasis on exposure, aims to break the cycle of avoidance behavior, symptom fear, and disability through systematic contact with a stimulus that evokes conditioned aversive responses while abstaining from avoidance and safety behaviors . ExposurOne development in the effort to bridge the gap between the demand and availability of CBT  has beenThe purpose of this study is to evaluate the efficacy and feasibility of internet-delivered AF-specific CBT, primarily based on exposure exercises in preparation for a forthcoming randomized controlled trial (RCT). Additional objectives of the study are to investigate changes over time in the objectively measured AF burden and in the participants’ potential overestimation of their AF symptoms as well as to explore whether symptom preoccupation was a potential mediator of treatment effect on AF-specific QoL.d=0.65, in the primary outcome measure of disease-specific QoL between pre- and posttreatment assessments. However, only 19 participants were recruited because of a slow recruitment rate. An interim analysis after 14 participants had been recruited showed significant improvements on the main outcome measure; therefore, we judged the discontinuation of recruitment to be justifiable.This is an uncontrolled pilot study with a pretest-posttest design and a 6-month follow-up. We aimed to recruit 30 participants to achieve a power of 80% for detecting a moderate improvement, as indicated by an effect size of Cohen The participants were referred by cardiologists in Stockholm, Sweden. To be eligible for this study, participants had to have (1) paroxysmal AF as defined above and (2) receive optimal medical care according to the current clinical guidelines . The folAF-specific treatment satisfaction (two items) measures satisfaction with the current medical treatment and is not included in the total score; thus, it was not analyzed in this study.The primary outcome was the Atrial Fibrillation Effect on Quality-of-Life (AFEQT), which is an AF-specific measure of QoL that evaluates the following parameters: AF symptoms, impairment in social and physical activities, medical treatment concerns, and AF-specific treatment satisfaction . The scaSecondary outcome measures included the Symptoms Checklist, Frequency, and Severity Scale (SCL), which is a disease-specific checklist used to measure AF-related symptoms on two subscales - symptom severity and symptom frequency . The UniThe 4-item Perceived Stress Scale (PSS-4) was used to assess stress sensitivity, , the 7-idid not affect me at all) to 3 (affected me very negatively) [The Client Satisfaction Questionnaire (CSQ-8) was used to measure satisfaction with the CBT treatment . At postatively) . Other mTo assess the objective AF burden, participants were asked to perform a 30-second intermittent handheld ECG  registration at home, four times daily, and while experiencing cardiac symptoms over 2 weeks at pre-and posttreatment and at 6-month follow-up. The participants were instructed to push a symptom indicator button on the device when they perceived that they had AF symptoms, both during the regular four daily measurements and while experiencing cardiac symptoms. A more detailed technical description of the device is available elsewhere .The AF-specific exposure-based internet-CBT treatment was delivered completely via the internet through a tailored and secure web-based platform. The treatment was therapist-guided, lasted for 10 weeks, and included 5 interactive treatment modules with weekly homework assignments to be completed during the first 5 weeks. The modules were downloadable as PDF files and comprised between 13 and 16 pages (A4) of text, and a total of 68 pages. After the fifth module, participants continued to work with the treatment content for the remaining 5 weeks and sent weekly reports about their exposure exercises to their treating psychologist. Participants were encouraged to work with the treatment for approximately 30-60 minutes per day.The treatment protocol was based on an AF-specific CBT protocol that was previously evaluated in a face-to-face pilot study  and an eEducationPathophysiology of atrial fibrillation (AF).The role of anxiety and behavior on symptoms and quality of life.Brief training in self-observation.Interoceptive exposureExposure to physical sensations similar to AF symptoms.Exposure in vivoGradual exposure to avoided situations or activities that patients fear may trigger AF symptoms or where symptoms are unwanted.Combining in vivo exposure with interoceptive exposure.Behavioral activationIdentifying life areas impaired by AF-related disability or symptom fear.Set behavioral goals and gradually take steps toward them.Relapse preventionPrevention of relapse into control or avoidance behaviors by identifying risk situations.The treatment was delivered by two clinical psychologists (BL and JS) with thorough training in exposure-based CBT and experience in treating AF. The participants had continuous contact with an assigned therapist throughout the 10-week treatment period. The role of the therapist was to guide the patient through the treatment and provide feedback on the homework assignments. To progress to the next treatment module, the participants had to complete their weekly home assignments  and report it to the therapist. In addition to reporting the weekly homework assignments, participants could send questions to their therapist via an asynchronous messaging system. Participants received feedback on their reports and questions within two working days. If a participant had technical problems with the platform or did not respond for more than a week, a phone call was made. No treatment interventions were administered over the phone. The treating psychologists could also consult the study cardiologists (FB and HS) at any point throughout the treatment if there were questions regarding the participants’ physical health.Cardiologists within tertiary care were informed about the study via email and lectures and referred participants to the study. The referring cardiologists signed a health form where they confirmed fulfillment of the inclusion criteria, meaning that they confirmed the AF diagnosis and the classification of EHRA class ≥IIb; ; certifid) were calculated by dividing the estimated pairwise differences between the three time points by the model-implied standard deviation at pretreatment. Effect sizes were categorized according to Cohen recommendations, with small, medium, and large effect sizes corresponding to d=0.20, 0.50, and 0.80, respectively [All analyses were performed using R . Pretreaectively . To accoectively , 95% CIsThe ECG measurements were used to analyze the change in AF burden from pretreatment to posttreatment and 6-month follow-up as well as to investigate changes in AF symptom overestimation . Finally, we performed exploratory mediation analyses to investigate whether changes in symptom preoccupation were a potential mediator of the treatment effect on QoL. We included the three subscales of CAQ  as the indicators of symptom preoccupation, and we also included PSS-4 as a competing mediator. PSS-4 measures stress sensitivity, which was not targeted by the CBT intervention, and by including it that as a competing mediator, we could control for nonspecific improvements. The study comprised 19 participants (12 women and seven men), who were recruited and treated between January 2016 and January 2018. During the analysis of the ECG data that were obtained after inclusion, we discovered that two participants had persistent AF at the pretreatment assessment, which means that they, in retrospect, did not fulfill the inclusion criteria of paroxysmal AF at the pretreatment assessment; however, both the participants and their treating physician had reported paroxysmal AF during the inclusion process and were also assessed by the research team as such. Therefore, we decided to keep these two participants in the analysis.In total, 16 out of 19 participants (84%) were considered as treatment completers after completing at least four modules of the treatment and thus commenced work with exposure exercises. The noncompleters (n=3) completed 2-3 modules. The mean number of messages that participants sent and received from their treating psychologist were 12.0  and 15.7 , respectively. The psychologist spent a weekly mean of 9.5 minutes  per patient.P values of slope estimates and effect sizes (d) with 95% bootstrap CIs. Participants showed significant improvements in AF-specific QoL, as measured by AFEQT, with large within-group effect sizes posttreatment (d=0.80) and at 6-month follow-up (d=0.72) as compared with baseline, whereas there was no significant difference between posttreatment and 6-month follow-up. The total AFEQT score corresponded to moderate AF severity at baseline; however, at posttreatment and follow-up, the total AFEQT score corresponded to mild AF severity. We observed large effect sizes posttreatment (d=1.43) and at 6-month follow-up (d=1.52) in the reduction of cardiac anxiety (CAQ). All three subscales of CAQ  showed a significant improvement posttreatment and at 6-month follow-up. We observed moderately sized pre- to posttreatment improvements in depression (PHQ-9), general anxiety (GAD-7), perceived stress (PSS-4), and general QoL (WHODAS). Furthermore, we observed a medium-sized improvement in self-reported AF symptom severity and a small improvement in AF symptom frequency  and general AF symptoms (AFFS) from pre- to posttreatment. We observed a medium effect size in the reduction of cardiac-specific health care visits posttreatment and a further reduction with a large effect size at 6-month follow-up.P=.02). In the AF overestimation analysis, 2175 observations, of which 143 (6.6%) were symptom indications, were included. We excluded 14 recordings where patients were in sinus rhythm but had an irregular pulse due to premature ventricular contractions, which may cause symptoms similar to those of AF, from the analysis. We observed statistically significant decreases in overestimation proportions at both posttreatment  and 6-month follow-up , compared with the pretreatment assessment. A total of 2243 ECG recordings were documented. Of these, 2189 (97.6%) could be classified as sinus rhythm or AF, 36 (1.6%) could not be classified, and 18 (0.8%) were considered artifacts. One participant contributed only pretreatment observations. The AF burden increased from pretreatment to the 6-month follow-up , and the lowest number of observations was 15 during the eighth week. In the single mediator analysis, all the tested mediators had statistically significant ab-products, thereby indicating that they all explained some part of the improvement during treatment on the AFEQT-S. In the multiple mediator analysis, where the mediators competed with each other in explaining the change in AFEQT-S, the CAQ fear subscale and PSS-4 ab-products were substantially lower than that in the single mediator analysis, and the former was no longer significant. The ab-products for the CAQ attention and avoidance subscales were of equal size, statistically significant, and more than three times larger than the other two mediators in the multiple mediator model. At posttreatment, participants scored an average of 24.9 (SD 4.9) out of 32 points on treatment satisfaction as measured by the CSQ-8, and 18 out of 19 participants reported that they were satisfied with the treatment and that it had helped them to deal more effectively with their AF symptoms.At follow-up, 2 of 17 participants had made minor changes in their cardiac medication. None of the patients had undergone invasive cardiac procedures between posttreatment and follow-up. At follow-up, one participant reported deterioration in cardiac health due to more frequent AF episodes. The ECG recording at follow-up indicated a progression to persistent AF in one additional patient.At posttreatment, four participants reported an adverse event from participating in the study. The adverse events described were stress because of the study (n=3) and an increased cardiac attention (n=1). Three of the adverse events were given a low severity rating, both when the effect occurred and on residual discomfort, corresponding to a rating of 1 on a scale of 0-3. One event was rated as having the highest severity (3/3) at the time of occurrence and a (2/3) moderate severity rating for the residual comfort. At the six-month follow-up, no current or residual adverse events from participating in the study were reported.To the best of our knowledge, this is the first study to investigate the efficacy and feasibility of internet-delivered, exposure-based CBT for symptom preoccupation in patients with symptomatic paroxysmal AF. We observed a large improvement in the primary outcome measure of AFEQT that measured AF-specific QoL and self-reported AF symptoms and a large reduction in symptom fear, avoidance behaviors, and hypervigilance as measured by the CAQ. These effects remained large-6 months after the treatment. We also observed small to medium significant effects on the other outcome measures at posttreatment, which were sustained or improved at the 6-month follow-up. Furthermore, the participants’ high adherence to and satisfaction with the treatment, limited reports of adverse events, and perception of being able to deal more effectively with their AF symptoms indicate that exposure-based internet-CBT is a feasible treatment option for the target population.The results suggest that the AF-specific exposure-based internet-CBT had effects in patients with paroxysmal AF that are comparable with the effects of exposure-based internet-CBT in other somatic functional disorders ,44-47. OWe observed a significant increase in the objectively measured AF burden at the 6-month follow-up, which is not unexpected because AF is known to be a progressive disease . InteresThe mediation analyses showed that a reduction in symptom preoccupation mediated the effect of exposure-based internet-CBT on AF-specific QoL and self-reported AF symptoms. These results are in line with the previous mediation analyses by our group of exposure-based CBT, where we have found that a reduction in avoidance behavior mediates improvement in other chronic health conditions -53.The results of this study should be interpreted with the following limitations kept in mind. Importantly, we did not use a control group, which limits the causal inference that can be drawn from the results. Without a control group, we cannot control for the passage of time, the effect of attention from a caregiver, and expectancy of improvement. More than half of the participants had a previous experience of psychological treatment; thus, it is possible that psychological treatment was more suitable for the referred participants than the average patient with AF. The referral by clinical cardiologists could have contributed to a positive expectancy effect dependent on the caregivers’ attitude toward CBT. It is also possible that patients who were generally less prone to respond to treatment were referred to the study, hence contributing to a selection bias. The sample also had disproportionately more women and the subjects were younger than the general AF population , furtherThis is the first study in which patients with symptomatic paroxysmal AF were treated with therapist-guided exposure-based internet-CBT. Despite already receiving optimal medical therapy at baseline, we observed large improvements in AF-specific QoL and symptom preoccupation that were sustained at the 6-month follow-up. Our study highlights avoidance behavior and hypervigilance as potentially important psychological factors contributing to symptom severity and low QoL in patients with AF. However, the psychological aspects of AF appear to be underrecognized in the current medical literature and clinical practice.We conclude that symptom preoccupation is an important target for treatment and that the treatment may be both feasible and clinically effective for the target population. AF-specific CBT delivered via the internet has the potential to reduce health care utilization and improve the well-being of a large group of patients, when current treatment methods have limited effectiveness. These results need to be confirmed in RCTs.


The need for oil spill monitoring systems has long been of concern in an attempt to contain damage with a rapid response time. When it comes to oil thickness estimation, few reliable methods capable of accurately measuring the thickness of thick oil slick (in mm) on top of the sea surface have been advanced. In this article, we provide accurate estimates of oil slick thicknesses using nadir-looking wide-band radar sensors by incorporating both C- and X-frequency bands operating over calm ocean when the weather conditions are suitable for cleaning operations and the wind speed is very low (<3 m/s). We develop Maximum-Likelihood dual- and multi-frequency statistical signal processing algorithms to estimate the thicknesses of spilled oil. The estimators use Minimum-Euclidean-Distance classification problem, in pre-defined multidimensional constellation sets, on radar reflectivity values. Furthermore, to be able to use the algorithms in oil-spill scenarios, we devise and assess the accuracy of a practical iterative procedure to use the proposed 2D and 3D estimators for accurate and reliable thickness estimations in oil-spill scenarios under noisy conditions. Results on simulated and in-lab experimental data show that M-Scan 4D estimators outperform lower-order estimators even when the iterative procedure is applied. This work is a proof that using radar measurements taken from nadir-looking systems, thick oil slick thicknesses up to 10 mm can be accurately estimated. To the best of our knowledge, the radar active sensor has not yet been used to estimate the oil slick thickness. Oil-spill detection: this provides information about the location of oil slicks, and how large the spread area is. It is necessary information to allow oil spill mapping for both tactical and strategic countermeasures.Oil-thickness estimation: the thickness distribution of spilled oil is critical information for spill-containment because it allows an estimation of the total volume spilled, so that adequate tools can be used in clean-up operations.Oil-classification: knowledge about oil type is helpful to estimate the environmental damage and appropriate response.Oil spills are regrettably common, and have socio-economic implications on communities and disastrous consequences on the marine ecosystem and maritime life ,2. They Among the three key pieces of required information, oil type is the least critical one at early stages of the spill. With respect to spill detection, multiple techniques using various technologies and sensors were developed, with the most recent being based on satellite and airborne remote sensing ,7. HowevOil spills can have varying thicknesses, ranging from less than a micrometer  , althougut 10 mm . Since mut 10 mm , this agThe challenges of remotely measuring oil slick thickness are examined in details by Fingas . Visual Using nadir-looking wide-band radar sensors by joint incorporation of C- and X-frequency bands, maximum-likelihood single (1D), dual- (2D), and multi-frequency (3D and 4D), statistical signal processing algorithms are developed to estimate the thicknesses of spilled oil slicks. The estimators use the Minimum-Euclidean-Distance classification problem on radar reflectivity values in pre-defined multidimensional constellation sets. The active radar sensor has not been used to estimate the oil slick thickness so far.An advanced practical procedure to use the proposed 2D and 3D estimators for accurate and reliable thickness estimations in oil-spill scenarios under noisy conditions is devised, and its accuracy is tested.The performance of the suggested algorithms is tested using simulated and in-lab experimental data. Results show accurate estimates of oil slick thicknesses from 1 to 10 mm.The proposed work is a proof of concept and helps take the oil spill-related research work one step forward towards the development of operational tools for oil-spill intervention.To complete the functionalities for an effective contingency plan, it is crucial to provide the oil slick thickness. Therefore, this new work aims at the thickness estimation of thick oil slicks which persist over long time after the spill. The targeted range of thicknesses is between 1 and 10 mm. This full range is not yet covered by the available techniques in the literature. We propose to use single and dual frequencies to estimate a specific thickness value (3 mm) using radar observations . Then, wThe remaining of this article is organized as follows: Once a spill occurs, the oil will spread quickly on the water surface. Many components of heavy oils, such as crude oil which belongs to 35% of the products spilled, will not evaporate at all even over long periods of time and at high temperatures . Moreoven for the each medium in the multi-layer structure is The refractive index k and q for consistency with the following sections). It is given by:c is the speed of light. The phase shift E is conserved. Using the continuity property at these interfaces, the reflectivity (power reflection coefficient) for the three-layer structure [The propagation of EM waves through the second layer (oil) in the multi-layer structure will introduce a phase shift tructure  is givenThe reflectivity The reflectivity shown in Equation  actuallySince frequencies from the L-band (1–2 GHz) will not change the reflectivity value over the 1–10 mm thickness range by more than 1 dB, they are not considered to be relevant for the proposed approach. Instead, we will use frequencies from the C-band (4–8 GHz) and X-band (8–12 GHz) at increments of 1 GHz for better understanding of the reflectivity behavior at each EM wave frequency. eglected . The relw=35 ppt . For easOn the other hand, referring to , the perq is the index within the plausible discretized range K-frequency estimators, the constellation set will span 1, 2, and K-dimensions, respectively.The oil slick thickness is denoted by Equation . It is eLet q that maximizes The estimator should choose the best index If all the events of having a thickness Equation  reduces Defining The constellation set for 1D estimator is simply composed of 1D line that represents reflectivity values at each thickness in When using dual frequencies In However, it is also very important to be aware that the frequency pairs might change with the targeted thickness (which is unknown for us). For example, if the actual oil slick thickness is 1 mm, even though the constellation corresponding to Q1. When the oil thickness is unknown, how to select the pair of frequencies?Q2. What is the frequency pair that should be selected for the maximum likelihood 2D estimator to estimate a specific oil thickness?This leads to the following two questions:In fact, for each pair of frequencies, we can draw a corresponding constellation set to be used for thickness estimations. Currently we only presented sets without looking at specific thickness values. Q1 is answered in K frequencies, the constellation set will be in K dimensions, and Equation  GHz, instead of doing the optimization for each thickness value, we will fix the selected frequency values irrespective of the oil thickness. These values are selected more or less uniformly from the range of frequencies, i.e., In this section, we evaluate the performance of 4D Minimum-Euclidean-Distance estimators using M = 1). The actual thickness is again 3 mm. The single-frequency (1D) estimator uses M = 1), the 1D estimator provides very bad estimations (At single scan (Next, we study the performance of same estimators when having multiple scans as shown in Previously, we developed an experimental setup to collect radar reflectivity measurements from an oil-spill lab experiment similar to the one conducted by Daling et al. to get calm-sea conditions for very low wind speeds with no wave action . The expOil-spill monitoring systems must provide valuable information about oil slicks to contain their damage. The estimation of slick thickness is very critical so that adequate tools can be used in the contingency plan. For effective oil spill clean-up operations, it is crucial to get the thickness measurements greater than Simulated and in-laboratory experimental results showed high accuracy in estimation. This work is a proof that by processing radar power reflectivity values, taken from nadir-looking systems under weather conditions suitable for cleaning operations, thick oil slick thicknesses up to 10 mm can be accurately estimated. As a future perspective of the presented work, drones would be very convenient platforms for the implementation of the proposed approach. With the proof-of-concept and the performance validation of proposed algorithms on simulated and in-lab experimental data, it is possible to take this work to another implementable level where real drones are used with mounted radar to collect reflectivity measurements for post-processing. Although having nadir-looking radar on drones would produce a smaller radar cross section compared to side-looking systems such as airborne systems, their low cost compared to dedicated aircrafts allows for multiple drones to operate simultaneously. This enables high spatial resolution, quick intervention, wide coverage due to parallelization in scanning, and real-time data collection. Another possible limitation of this approach is its applicability under various meteorological conditions since the developed estimators target calm sea conditions. However, bad weather conditions will not even allow to apply a contingency plan procedure on site. The proposed work is a proof of concept and helps take the oil spill-related research work one step forward towards the development of operational tools for oil-spill intervention.