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Recruitment, randomization, and allocation
PD, Parkinson, Parkinson Support groups).This trial
EVENTS, MOVEMENT DISORDERS, DISORDERS, RECRUITMENT
Subjects will be recruited from the OHSU Movement Disorders Clinic, the OHSU Parkinson Center of Oregon and Movement Disorders clinical program, the Balance Disorders Laboratory, the Oregon Clinical & Translational Research Institute, local neurologists (at Portland Metro area hospitals and clinics), community recruitment (e.g., public talks and distribute study flyers at various community outreach events and locations, such as the Senior Living Centers, Athletic Clubs, Rotary Clubs, Parkinson Support groups).This trial will enroll 80 eligible people with PD who will be randomized at a 1:1 ratio into the experimental group (
PMC10571293
Blinding
Due to the nature of the intervention, participants and physical therapists cannot be blinded to group allocation. However, participants will be blinded to the expected outcomes, unaware of the study hypotheses, and will be explicitly instructed not to discuss their training program with the assessors to maintain assessor blinding. A trained assessor who is blinded to group allocation will be responsible for all outcome assessments. Data analysts and statisticians will also be blinded to group allocation.
PMC10571293
Safety issues
PD, gait impairments
ADVERSE EVENTS
All adverse events, either during physical therapy or during data collection in the home and/or virtually will be recorded and reported. Falls and musculoskeletal strains are the greatest risks for exercise in patients with PD who have balance and gait impairments. An initial home visit by the physical therapist and customized levels of exercise progression and modification will help ensure safety in the home during exercise sessions.
PMC10571293
Home-based, in-person pre- and post-exercise
PD
In the home, the following assessments will be performed: i) the Mini-BESTest, a 14-item test of balance shown to be related to fall risk in people with PD [
PMC10571293
Home-based virtual pre- and post-exercise
Virtually (using home computer, iPAD, or study computer) we will administer: i) an instrumented L-shape mobility test where participants will wear 3 sensors (one Opal sensor on a belt with the sensor placed over the lumbar area and two Opal instrumented socks by APDM Wearable Technologies, a Clario company, placed on both feet) and will be instructed to sit for 30 s, then stand with feet together and look straight ahead for 60 s, walk at least 10 steps before turning 90 degrees, and take at least 5 steps to complete an L-shaped path, turn 180 degrees, walk back and finish an L-shaped path. The participants will perform 5 repetitions of an L-shape path continuously, and end with 30 s of quiet sitting. This instrumented L-shape mobility test can characterize multiple domains of balance (Objective balance and gait outcome measures collected at home with both virtual instrumented L-shape mobility test and daily-life mobility monitoring (7 days), divided by balance domains
PMC10571293
Daily-life monitoring pre- and post-exercise
Participants will wear Opal Instrumented Socks that are made of a thin elastic cloth and have inertial sensors embedded for the measurement of mobility in daily life. When worn, the sensors are located on the dorsum of the foot with the battery above the lateral malleolus, as previously published [
PMC10571293
Data management and monitoring
DISORDERS
Data entry will be handled by the team members. Data will be entered into REDCap and the OHSU Balance Disorders database. Hard copies of these records will be stored inside a locked office in a locked cabinet at OHSU. The de-identified Mobility Lab data will be collected on a password-protected and data-encrypted laptop computer and uploaded after each test session to an OHSU secure server, where the Balance Disorders database is located. The computer that will store the project database will be protected by current network security behind the OHSU firewall. All data will be double-checked for accuracy by a person who is not involved in the day-to-day life of the study.
PMC10571293
Sample size calculation
PMC10571293
Aim 1
PD
REGRESSION, DISORDERS
To estimate power and sample size for relating the instrumented L-shape mobility test collected virtually in the home to the Mini-BESTest in-person, we used the pilot data from 114 people with PD who had measures on the Mini-BESTest and the ISAW – both performed in-person in the Balance Disorders Laboratory. Using multiple linear regression, we used a subset of objective measures to predict the Mini-BESTest total score as well as the four Mini-BESTest domain sub-scores. The subset of objective measures was selected based on bivariate correlations between the objective measures and the Mini-BESTest total score. A correlation at or above 0.4 was retained and included: 1) gait speed, 2) angle of the foot at heel strike, 3) stride length, 4) turning duration, 5) turning velocity, 6) steps during turning, and 7) range of motion of the 1
PMC10571293
Aim II
One of the goals of Aim II is to generate preliminary estimates of the sensitivity of balance measures (Mini-BESTest and ISAW) due to the Tele-ABC program. These estimates ultimately will be used to inform power and sample size computations for a larger clinical trial. We did examine effect sizes detectable by intervention at the planned sample size and related these to effect sizes observed in other similar interventions. In our pilot study, we observed improved dual-task gait speed using the same, wearable mobility sensors after an in-person balance exercise intervention [
PMC10571293
Aim III
One of the goals of Aim III is to generate preliminary estimates of effect size for daily life metrics measured in the home after rehabilitation, for both the groups (experimental and control). These estimates ultimately will be used to inform power and sample size computations for a larger clinical trial. Specifically, we will calculate effect size estimates from 5 main home metrics that are predicted to be the most likely to show improvement after rehabilitation (turn angle, swing variability [coefficient of variation], the angle at heel strike, the angle at heel strike variability [coefficient of variation], and stride length variability [coefficient of variation]). Using paired sample t-tests, we estimate that we will have at least 80% power to detect pre/post differences with moderate effect sizes (Cohen’s d = 0.45) or greater with 40 participants at an alpha level of 0.05.
PMC10571293
Statistical analysis
PMC10571293
Aim I
REGRESSION
To determine if a virtual, balance assessment (instrumented L-shape mobility test) using wearable sensors can predict a gold-standard, clinical in-person assessment of balance (Mini-BESTest), we will use multiple linear regression. We will fit linear regression models with the total Mini-BESTest score, in addition to the four Mini-BESTest domain sub-scores. To determine the optimal set of predictors, we will employ three separate analytic approached to select predictors: 1) assess predictors based on their individual contribution to total R
PMC10571293
Aim II
The primary outcome, Mini-BESTest score, and its subscores, pre and post-exercise will be compared between the two groups. Secondary outcomes described in Tables
PMC10571293
Aim III
To determine if daily-life mobility changes after interventions, our main analysis will be the paired t-tests to compare the values in each metric described in Table Missing data: We will first assess the missing data frequency and patterns for both primary outcomes. If ≤ 5% of observations are missing the primary outcome, then multiple imputation methods will not be of benefit and we will perform analysis without imputation. If > 5% of observations are missing outcomes, we will perform multiple imputations as necessary to address the missing-ness. For all analyses, level of significance will be set at
PMC10571293
Discussion
PD, balance deficits, deficit in balance dysfunction, balance impairments
Telerehabilitation is now commonly used for patients with PD, but there are several unknown aspects of its efficacy, both for the assessment and treatment of balance deficits in people with PD. In addition, studies on balance telerehabilitation (separate from virtual reality) for people with PD are scarce. For telerehabilitation to be effective, both assessment and treatment should be able to be completed virtually. The TelePD Trial targets both virtual assessment and treatment for balance problems in people with PD.Regarding assessment, no virtual comprehensive balance assessment has been conducted pre and post-telerehabilitation in people with PD [Regarding treatment, effective balance rehabilitation requires precise targeting of the impaired domain in order to ultimately treat the underlying deficit in balance dysfunction [The TelePD trial is designed to determine the usefulness of using wearable sensor-based measures of balance and gait remotely to assess balance, the feasibility and efficacy of balance telerehabilitation in people with PD, and the translation of balance improvements after telerehabilitation to daily-life mobility. The successful implementation of the TelePD Trial will shed further light on balance telerehabilitation interventions for people with PD. The long-term goal of this project is to develop an effective, virtual balance assessment and evidence-based treatment that can be used in any older adult with balance impairments.
PMC10571293
Acknowledgements
Not applicable.
PMC10571293
Authors’ contributions
KTS, WL, MM
CSB, JLW, KTS, MS, PCK, SC, WL, TGDLH, FBH, MM, LAK contributed to the development of the study design. CSB and LAK drafted the manuscript. CSB, JLW, KTS, MS, PCK, SC, WL, TGDLH, FBH, MM, LAK revised the manuscript. LAK and MM obtained funding support. CSB, JLW, KTS, MS, PCK, SC, WL, TGDLH, FBH, MM, LAK read and approved the final manuscript.
PMC10571293
Funding
R01HD107074
This study is funded by NIH (R01HD107074 and UL1TR002369).
PMC10571293
Availability of data and materials
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. The final results of this study will be published in peer-reviewed journals.
PMC10571293
Declarations
PMC10571293
Ethics approval and consent to participate
The study was approved by the Institutional Review Board at Oregon Health & Science University (OHSU) (eIRB #24453). The trial has been prospectively registered at the Clinical Trials Registry (NCT05680597). Each participant will sign the informed consent form before inclusion in the study.
PMC10571293
Consent for publication
As the study includes images of the participants, we ensure a consent for publication was obtained from the participants.
PMC10571293
Competing interests
KTS, WL, MM
CSB, JLW, KTS, MS, PCK, SC, WL, TGDLH, MM, and LAK declare that they have no conflicts of interest relevant to the content of this manuscript. OHSU and FBH have significant financial interest in APDM, a Clario company, that may have a commercial interest in the results of this research and technology.  This potential conflict has been reviewed and managed by OHSU.
PMC10571293
References
PMC10571293
Background
This is the first clinical trial to investigate the effectiveness of maggot debridement therapy (MDT) for full-thickness burn injuries in comparison to conventional silver dressings.
PMC10510148
Methods
burns, necrosis
SECONDARY, NECROSIS
Thirty-one cases with full-thickness (grade III based on ICD-10 classifications version 2019) burns were assigned into larval therapy (15 cases) and conventional treatment (16 cases) groups. Participants in the MDT group have received loose larvae on days 0, 2, 4, and 6, while controls received a conventional regimen comprised of sharp debridement, silver sulfadiazine, antibiotic therapy, and offloading every day. The primary and secondary outcomes were defined as the time to debridement (from admission to skin autograft) and time to healing (from admission to complete healing post-skin autograft). Patients in two groups were also compared in terms of necrosis resolution, granulation, and granulation/necrosis (g/n) ratio during study time periods.
PMC10510148
Results
necrosis
NECROSIS
Participants who received larvae had significantly decreased necrosis on days 2 (
PMC10510148
Conclusions
burns
Our findings revealed that MDT has a favorable superiority over conventional regimen for the treatment of grade-III burns, and thus further clinical trials with larger sample size are warranted to confirm these results.
PMC10510148
Supplementary Information
The online version contains supplementary material available at 10.1186/s12916-023-03063-7.
PMC10510148
Keywords
PMC10510148
Background
diabetic ulcers, Burns, traumatic injuries, burn injuries, burns, injuries
DIABETIC ULCERS, BED SORES
Burns are considered as one of the commonly occurring traumatic injuries worldwide, leading to life-long disabilities and adverse health, social, and economic consequences [Based on their severity, burn injuries are classified into different grades, where burns that entirely affect the uppermost skin layer are classified as grade I, while deep partial-thickness burns are considered as grade II [In recent years, biological therapies have attracted great attention in treating burn wounds and are widely studied for potential clinical use [In addition to their beneficial effects in treating diabetic ulcers and bed sores, there are several case reports demonstrating that MDT can also improve the healing process in burn injuries [
PMC10510148
Methods
PMC10510148
Patients and study design
Burns, bleeding, phobia, gangrene, pain, burns
SLOUGH, MAY, BLEEDING, GANGRENE
This open randomized controlled trial was carried out at Shahid Motahari Burns Hospital, Tehran, Iran, from November 2018 to May 2020. Participants were 31 cases with at least one full-thickness (grade III based on ICD-10 classifications) burn that referred to Shahid Motahari Burns Hospital related to Iran University of Medical Sciences, Tehran, Iran. The flow of participants is shown in Fig. Flow of participants enrolled in this study. The present study was conducted based on CONSORT guidelines for reporting clinical trialsAll the cases in the larvae group were informed about the methodology and study purposes and enrolled as volunteers, with a signed consent letter. Patients who had phobia or other serious per-exiting conditions including the presence of gangrene, severe pain, refractory to treatment, and immunocompromised patients (e.g., HIV/AIDS) and those who have been receiving steroids and anti-coagulants that might affect the results were excluded from the study. Furthermore, probable bleeding because of larvae therapy and causing slough burns were also considered as exclusion criteria. All the procedures were in accordance with the Helsinki Declaration regarding human research and were reviewed and approved by the Medical Ethics Board of Tehran University of Medical Sciences, Tehran, Iran (with code no. IR.TUMS.VCR.REC.1396.4691) [
PMC10510148
Interventions
burns, necrosis
NECROSIS
As mentioned earlier, eligible participants were those who had full-thickness (grade-III based on ICD-10 classifications version 2019) burns based on the pathological examinations and expert opinions irrespective of the size and necrosis rate of wounds. The larvae group and controls were 15 and 16 patients with full-thickness (grade-III) burns, respectively. In the intervention group, each patient has received loose larvae 3–4 times (5–10 larvae/cm
PMC10510148
Data collection and outcome measurements
burns, Necrosis, necrotic
NECROSIS, NECROTIC
Demographics of patients including age, sex, and baseline data on burn mechanisms (exposure source), site of burning, and necrotic and granulation tissues were collected at admission to the hospital and summarized in Table Demographics and clinical data of burn patients in both treatment armsOf special note, to further minimize interpretation bias, the results were also adjusted to the would size.The primary outcome in this study was considered as time to debridement that was defined as the time in which burns were cosmetically clean and participants were ready to receive transplantation (skin autograft). Digital photographs were taken during every 2 days, when old larvae dressings were replaced with new ones, and are presented for each patient in Additional file Necrosis and granulation changes between and within groups received larvae or conventional therapy. Necrosis was significantly decreased in patients who received larvae on days 2 and 4 compared to baseline and conventional treatment groups. The larvae group had significantly improved granulation throughout the interventional duration. Error bars represent the standard deviation for the bar charts and the standard error of the mean for scatter plots. * shows statistical differences between groups, *
PMC10510148
Rearing fly eggs and preparing larvae
We used
PMC10510148
Dressing and debridement
MACERATION, STERILE
Before applying the maggots, the wounds were cleansed by saline, and then zinc oxide was used on the healthy skin around the wounds (to protect the skin from irritation or maceration from the proteolytic wound drainage and maggot secretions). Dressings were prepared by cutting an opening in the sterile gauze as the shape of the wound. The sterile gauze was then employed over the barrier-protected periwound skin. This was done to restrict the larvae to the wound bed and to create a space for their activity. In detail, 5 to 10 maggots/1cm
PMC10510148
Bacterial sampling
burns
Since bacterial contamination is a common feature of grade-III burns, therefore we investigated whether MDT could affect bacterial load of burn wounds [
PMC10510148
Statistical analysis
All the analyses were performed by Prism 8.1 and STATA version 14 softwares. The normal distribution of data was checked using Kolmogorov–Smirnov test. Significant levels were considered as confidence interval of 95% (CI 95%) and
PMC10510148
Discussion
high-grade burn injuries, necrotic, infection, burns, necrosis burns, necrosis
INFECTION, NECROTIC, NECROSIS
This study is the first clinical trial to compares the therapeutic potency of maggot debridement therapy (MDT) for full-thickness (grade-III) burn injuries versus conventional treatment regimen. We found that patients who received maggots had significantly improved granulation and decreased necrosis within the same timeline compared to the conventional treatment group. As it is summarized in Table On the other hand, these maggots can also scavenge microbial infection from the affected surface. In addition, To minimize the bias, we also performed a subgroup analysis for patients who had > 50 necrosis at the baseline, to investigate whether MDT or conventional treatment could be more potent in high necrosis burns. Of particular note, we found that MDT had a significant superiority to conventional regimen in treating high necrotic wounds. We defined a novel index of granulation/necrosis (g/n) to elucidate the efficacy of MDT in comparison to routine treatment for grade-III burns. As shown in Fig. Bacterial contamination of high-grade burn injuries is also another matter of importance which affect the treatment length, as well as the final outcome [
PMC10510148
Strengths and limitations
high-grade burns, burn injuries, diabetic leg ulcers
Although several case reports have been reported, however, this is the first trial that has investigated the therapeutic potential of Larvae for burn injuries in regard to conventional therapeutic regimen. The findings of this study is a proof of concept that in addition to their benefits for diabetic leg ulcers, larvae can also improve the healing process in burn wounds and have the potential to be used as an effective alternative or complementary for high-grade burns [
PMC10510148
Conclusions
burns, necrotic, necrosis
NECROTIC, NECROSIS
Our results showed that patients with grade-III burns who received larval therapy had remarkably improved granulation and decreased necrosis within 6 days of intervention compared to baseline and conventional regimen group. Moreover, treatment with Larvae had a significant superiority in high necrotic (> 50%) burns over conventional treatment. Additionally, maggot therapy was able to remove microbial contamination from burn comparable to that seen in the conventional group who have been given antibacterial agents. In summary, the findings of this study provide the basis for the application of larvae in treating grade-III burn wounds. However, further randomized clinical trials with larger sample size should be done to shed light on the different aspects of the MDT in treating grade-III burn wounds, as well as grades I and  II.
PMC10510148
Acknowledgements
Burns
This study was supported by grants from Tehran University of Medical Sciences, Tehran, Iran, and Iran University of Medical Sciences, Tehran, Iran. The authors would like to appreciate Burn Research Center, Iran University of Medical Sciences, Tehran, Iran; participants in this study; and all the staff in Shahid Motahari Burns Hospital.
PMC10510148
Authors’ contributions
J.G.H. carried out the experiments and wrote the first draft of the manuscript; K.A., M.B., and R.H. provided consultations and contributed to the writing of the manuscript. S.M. contributed to the study methodology and statistical analysis of the data. Z.S.A. and R.S.K. contributed to the experimental works. J.R. conceptualized the work and M.D. provided the clinical consultations and study conceptualization. All the authors read and approved the final manuscript.
PMC10510148
Funding
The present study was funded by Tehran University of Medical Sciences (grant number# 97012737483).
PMC10510148
Availability of data and materials
The data that support the findings of this study would be available upon a reasonable request and editorial office permission.
PMC10510148
Declarations
PMC10510148
Ethics approval and consent to participate
The patients who participated in this study were informed about the methodology and study purposes and enrolled as volunteers, with a signed consent letter. All the procedures were in accordance to the Helsinki Declaration regarding human research and were reviewed and approved by the Medical Ethics Board of Tehran University of Medical Sciences, Tehran, Iran (with code no. IR.TUMS.VCR.REC.1396.4691). This study has also been registered in Iranian registry of clinical trials and received a clinical trial code (IRCT ID: IRCT20170531034272N2).
PMC10510148
Consent for publication
A consent letter was taken from the participants for the publication of relevant data presented in this paper.
PMC10510148
Competing interests
The authors declare that they have no competing interests.
PMC10510148
References
PMC10510148
Background
The use of health technologies and gamification to promote physical activity has increasingly been examined, representing an opportunistic method for harnessing social support inherent within existing social ties. However, these prior studies have yielded mixed findings and lacked long-term follow-up periods. Thus, a pilot cluster randomized controlled trial was conducted to gauge the feasibility and preliminary efficacy of a digital gamification-based physical activity promotion approach among teams of insufficiently active adults with existing social ties.
PMC10623775
Methods
Teams (
PMC10623775
Results
TECH had a lower mean number of days of Fitbit self-monitoring versus TECH + Gamification during the intervention (adjusted difference: -.30; 95% CI, -.54 to -.07;
PMC10623775
Conclusions
A gamified physical activity intervention targeting teams of adults with existing social ties was feasible and facilitated favorable, clinically meaningful additive physical activity effects while in place but did not drive enhanced, long-term physical activity participation. Future investigations should explore optimal team dynamics and more direct ways of leveraging social support (training teams; gamifying social support).
PMC10623775
Trial registration
Clinicaltrials.gov (
PMC10623775
Supplementary Information
The online version contains supplementary material available at 10.1186/s12966-023-01530-1.
PMC10623775
Keywords
PMC10623775
Background
The 2018 Physical Activity (PA) Guidelines for Americans recommend achieving 150 min or more per week of moderate-intensity equivalent PA – which translates to approximately 7,000–8,000 steps or more per day [Ecological models [Gamification [Thus, the purpose of this cluster pilot RCT was to evaluate the feasibility (treatment adherence and satisfaction) and preliminary efficacy of an e/mHealth gamification approach designed to harness the influence of existing social ties for increasing steps and moderate-to-vigorous physical activity (MVPA) among insufficiently physically active adults.
PMC10623775
Methods
PMC10623775
Study design
word of mouth
RECRUITMENT, BLIND
A 12-week (April-July 2018), parallel-group, pilot cluster RCT for promoting PA called Columbia Moves was conducted. Participants were recruited (January-April 2018) from the Greater Columbia, South Carolina, U.S.A. area via flyers, e-mails sent via listservs, and word of mouth. Interested individuals were encouraged to form a self-selected team of 3–8 persons comprised of members in their existing social circle (e.g., friends, family members, co-workers). Individuals applied through a study recruitment website and were screened for eligibility by phone. Then, they were invited to an in-person orientation and informed consent was obtained. Following the orientation session, individuals’ PA status was measured via the ActiGraph GT9X Link accelerometer (ActiGraph, Pensacola, FL), serving both as confirmation of eligibility and a baseline measure. Additional baseline assessments occurred at a subsequent visit. Treatment assignment was then communicated to each eligible team of individuals via email and an in-person kickoff meeting was administered to introduce them to their respective intervention. Assessments were conducted immediately after the 12-week intervention and at 40 weeks post-intervention. The assessor was not blind to group allocation, but assessment instructions were standardized, the PA measures were device-based, and survey items were administered online via LimeSurvey, minimizing the risk of assessor bias. Incentives were offered for completing these two assessment periods (drawing for a $50 gift card for one participant per study arm and a $20 gift card for 1 participant per team at 12 weeks, as well as a drawing for 1 $200 gift card, 4 $100 gift cards, and 5 t-shirts valued at $25 across both arms, and $25 gift cards for up to 2 participants per team at 52 weeks). The study was approved by the Institutional Review Board at the University of South Carolina.
PMC10623775
Participants
Individuals were eligible if they were between ages 18 and 65 years, were insufficiently physically active (i.e., had an average daily baseline step count of < 7500 [
PMC10623775
Randomization
Teams were randomly assigned to either a 12-week standard technology-delivered PA intervention (TECH) or the same intervention plus a step competition and PA challenge game (TECH + Gamification) by the lead statistician, using a computer-based random number generator in a 1:1 ratio, stratified by team size.
PMC10623775
Intervention
PMC10623775
Common intervention components
Each study arm’s PA intervention was rooted in the social cognitive theory (SCT) [
PMC10623775
Outcome measures
The TECH + Gamification group also engaged with custom-designed gamification elements underpinned by the SCT [Teams also participated in a weekly PA challenge game called the Shoe Mascot Game, which was supported by the incoming Fitbit data. Each team had a virtual shoe mascot avatar. The object of the game was to keep their shoe mascot on a virtual walking trail (highest level of the game) and away from three lower levels of the game represented by sedentary objects by achieving two weekly PA challenges that were presented at the start of each week on the study website. Each PA challenge had a corresponding point value. Some challenges were team-based (e.g., your team must collectively accumulate more steps this week versus the prior week), and others were more individual oriented (e.g., one team member will be randomly selected to see if they achieved their personal step goal for the week). During some weeks, teams could pick their challenge from options. If the challenges were met, then the team would not lose points, and their shoe mascot stayed on the walking trail. If the challenges were not fulfilled, then the team would lose points and fall to lower levels, with only one chance to return to the walking trail by achieving a bonus challenge. Team rankings for the game were displayed on the leaderboard, and the team that retained the most points by the end of the 12-week intervention won the game. Winning teams of the step competition and Shoe Mascot Game received a congratulatory message on the website that was visible to all other teams.
PMC10623775
Treatment adherence
Mean total number of days per week that participants self-monitored their PA, mean proportion of participants who self-monitored PA at least one day per week, and mean proportion who self-monitored PA all 7 days per week using their Fitbit, were calculated for both the 12-week intervention period and 40-week post-intervention period. An accumulated step count of 500 or more on any given day represented a valid day of self-monitoring [
PMC10623775
Treatment satisfaction
At the end of the intervention, participants were asked via online questions about their satisfaction with the program and willingness to recommend it to family, friends, or co-workers using a 5-point Likert-type scale, with lower scores reflecting strong dissatisfaction and unlikeliness to recommend it and vice versa.
PMC10623775
ActiGraph accelerometer-measured steps and MVPA
Daily steps and MVPA minutes were measured using the ActiGraph at baseline, 12 weeks, and 52 weeks. Participants were instructed to wear the device during all waking hours (except when showering or swimming) for 7 consecutive days on their non-dominant hip using a provided waistband and pouch. Data were sampled at a frequency of 90 Hz. Using ActiLife 6 software (version 6.13.3), raw accelerometer data were processed into 60-s epochs and subsequently scored using the Troiano 2008 adult cut points for classifying MVPA [
PMC10623775
Fitbit-measured steps and active minutes
Data were considered valid if an accumulated daily step count of 500 or more was achieved on 3 or more days for a given week [
PMC10623775
Social support for exercise
Perceived social support from family and friends combined for exercise (SSE) was measured online using the valid and reliable 13-item Sallis Social Support Scale for Exercise [
PMC10623775
Sociodemographic characteristics
Sociodemographic characteristics were reported at baseline using an online questionnaire.
PMC10623775
Body weight and height
Weight was measured at baseline to the nearest 0.1 kg in street clothes, without shoes, using a calibrated digital scale (Tanita BWB 800, Arlington Heights, IL). Height was measured at baseline to the nearest 0.1 cm using a standard stadiometer. BMI was calculated as weight (kg) per height (m
PMC10623775
Statistical analyses
SECONDARY
Descriptive statistics were calculated for baseline demographic measures, retention rates, and all outcomes. The generalized linear model with logit link was used for investigating the predictors for non-completers at 12 weeks and 52 weeks. Primary outcomes were treatment adherence, study retention, treatment satisfaction, and change in ActiGraph-measured daily steps from baseline to 12 weeks. Changes in ActiGraph-measured daily steps from baseline to 52 weeks, ActiGraph-measured daily MVPA minutes from baseline to 12 weeks and baseline to 52 weeks, SSE from baseline to 12 weeks and baseline to 52 weeks, and Fitbit-measured daily steps and active minutes aggregated across the 12-week intervention period and 40-week post-intervention period were secondary outcomes.For the missing ActiGraph accelerometer data, the generalized estimating equation model (GEE) [For the SSE data, the missing data were not in a monotonic pattern and thus assumed to be missing at random (MAR). Multiple imputations were conducted for the missing values based on the Markov Chain Monte Carlo method. The final results from the imputed data were based on 10 imputed data sets [Missing Fitbit step data and corresponding active minutes data were not in a monotonic pattern and thus assumed to be missing at random (MAR), and the aforementioned methods were applied. Two-sample A two-sample
PMC10623775
Treatment adherence
Based on the two-sample Figure  Percentage of Fitbit wear indicates the percentage of participants who wore the Fitbit for at least 1 day in that week. Any day during which a participant logged 500 or more steps on the Fitbit was regarded as a valid day and constituted wearing the tracker for that dayFigure  Percentage of Fitbit wear indicates the percentage of participants who wore the Fitbit all 7 days in that week. Any day during which a participant logged 500 or more steps on the Fitbit was regarded as a valid day and constituted wearing the tracker for that dayBased on the two-sample Figure Percentage of log-ins indicates the percentage of participants who logged in to the website at least 1 time in that week during the 12-week intervention
PMC10623775
Treatment satisfaction
Most TECH + Gamification (96%) and TECH (92%) participants agreed or strongly agreed that they would recommend the program to a friend, family member, or co-worker, and 91% and 90% indicated they were satisfied with their respective program.
PMC10623775
Fitbit-based PA outcomes
Figure  Fitbit derived mean number of daily stepsFigure  Fitbit derived mean number of daily active minutes
PMC10623775
Discussion
RECRUITMENT
This study assessed the feasibility and preliminary efficacy of a socialincentive-based gamification approach for improving PA. The findings suggest that the addition of a step competition and weekly PA challenge game to an e/mHealth PA intervention among teams of insufficiently active adults with existing social ties is feasible and acceptable. While in place, this gamification intervention facilitated positive, clinically meaningful differences in Fitbit-measured daily steps and active minutes versus an identical program without gamification. However, once withdrawn, it did not result in increases in ActiGraph-measured daily steps, MVPA, and social support over and above what was observed with the traditional e/mHealth treatment alone.This is the first e/mHealth gamification PA study among teams of adults with existing social ties to measure participants’ PA using both research grade and commercial accelerometers over one year via an RCT, yielding valuable insights about both the short- and long-term effects of team-based gamification among adults. Metrics regarding adherence to self-monitoring PA using the Fitbit were high for both study arms during the intervention but slightly declined thereafter. A more favorable, self-monitoring profile was observed for TECH + Gamification versus TECH, suggesting that the gamified elements had the desired effect of creating a heightened culture of accountability [Consistent with prior studies, [The game-based strategies did not confer an added benefit in Fitbit-measured PA during the post-intervention period. Relatedly, similar, modest increases in ActiGraph-measured daily steps and MVPA were captured immediately after intervention removal in both study arms, and these improvements slightly declined to a similar degree; however, they remained above baseline by 1 year, perhaps due to factors related to being part of a team [It is possible that the gamified approach served largely as an extrinsically oriented motivating factor that had a positive effect while in place but inability to drive sustained PA participation once removed. This factor in combination with the lack of an enhanced gamification effect on social support may have stifled the chance to develop intrinsic motivation which is a strong predictor of PA adherence [Further, future research should explore whether novel “booster” gamification doses (e.g., additional challenges) should be implemented during a maintenance phase [In the current study, it was not possible to disentangle the effects of the team competition and weekly challenge game on the outcomes, which reflects one limitation. Another limitation is the predominantly female and highly educated sample, reducing the generalizability of the findings. However, this study has several strengths, including the following: 40-week post-intervention period; two device-based PA measures; use of an RCT to isolate the efficacy of a custom gamification approach delivered through technologies, enhancing scalability potential; measurement of social support; high retention; and recruitment of teams with varying combinations of existing social ties (friends; family; co-workers).
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Conclusions
Augmenting a theory-based e/mHealth PA promotion program with gamification elements designed to tap into social support within existing social ties was feasible and resulted in a positive, clinically meaningful additive PA effect while in place but did not enhance PA once withdrawn. Given the support inherent within existing social ties, increasing ubiquitousness of health-promoting technologies, and heightened commercial and scientific interest in gamification, continued exploration of methods that capitalize on the combination of these three factors for affecting PA and overall well-being is warranted.
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Acknowledgements
The authors would like to thank the wider research team – Katherine Wallace for her support of intervention delivery, and Matt McGrievy and Andrew Hester for their technology expertise and support. The authors would also like to thank the Columbia Moves participants for volunteering in the study.
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Authors’ contributions
SE
CMM conceived the experiment. CMM, BTM, and SE designed the experiment. CMM, DJS, and AB carried out the experiment. CMM and KB organized the data. BC, CY, and BA analyzed the data. All authors were involved in writing the paper and had final approval of the submitted version.
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Funding
This publication presents independent research funded by the University of South Carolina Office of the Vice President for Research Advanced Support for Innovative Research Excellence initiative (ASPIRE-I).
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Availability of data and materials
The data sets analyzed during the current study are available from the corresponding author upon reasonable request.
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Declarations
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Ethics approval and consent to participate
This study protocol received a favorable ethical decision by the University of South Carolina’s Institutional Review Board and participants provided informed consent to take part in the study.
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Consent for publication
Not applicable.
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Competing interests
The authors declare that they have no competing interests.
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References
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Supplementary Information
thrombosis, fatigue, IVH, PNH, hemolysis
THROMBOSIS, HEMOLYSIS, PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH), PNH
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by uncontrolled terminal complement activation leading to intravascular hemolysis (IVH), thrombosis, and impairments in quality of life (QoL). The aim of this study was to identify the clinical drivers of improvement in patient-reported outcomes (PROs) in patients with PNH receiving the complement component 5 (C5) inhibitors eculizumab and ravulizumab.This Improvements in absolute mean LDH levels were significantly associated with improvements in mean FACIT-F score (These findings suggest that LDH levels are an important determinant of fatigue and QoL outcomes in patients with PNH. The online version contains supplementary material available at 10.1007/s00277-023-05483-0.
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Keywords
Open Access funding enabled and organized by Projekt DEAL.
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Introduction
Cancer, IVH, PNH, organ damage, hemolysis, Fatigue
HEMATOLOGICAL DISORDER, THROMBOEMBOLIC EVENT, CHRONIC ILLNESS, PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH), HEMOLYSIS, PNH, CANCER
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, hematological disorder characterized by uncontrolled terminal complement pathway activation leading to intravascular hemolysis (IVH), as indicated by elevated lactate dehydrogenase (LDH) levels, thromboembolic events, and organ damage [Eculizumab is a first-generation C5 inhibitor and the first disease-specific treatment to be approved for patients with PNH, offering terminal complement inhibition through a biweekly intravenous dosing regimen [Improvements observed in PROs following C5 inhibitor treatment for PNH in studies 301 and 302 have been reported using the Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-F) and the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire–Core 30 (EORTC QLQ-C30) [Data collected from a cohort of complement inhibitor-naive patients with PNH in study 301 were used for this
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Methods
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Study design
Details of study 301 have been described previously [
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PROs
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FACIT-F
Fatigue
Fatigue was assessed at baseline and days 8, 29, 71, 127, and 183 (26 weeks) of C5 inhibitor treatment using the FACIT-F scale version 4 [
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EORTC QLQ-C30
nausea/vomiting, dyspnea, fatigue, diarrhea, pain, constipation, insomnia
APPETITE LOSS
QoL at baseline and days 8, 29, 71, 127, and 183 (26 weeks) of C5 inhibitor treatment was measured using the EORTC QLQ-C30 version 3.0. The EORTC QLQ-C30 contains 30 items covering: five function subscales (physical, role, emotional, cognitive, social); nine symptom subscales/items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties); and a global health (GH) status/QoL subscale [
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Associations between variables of interest and PROs
bone marrow disorders, hemolysis, MDS
MYELODYSPLASTIC SYNDROME, HEMOLYSIS, BONE MARROW DISORDER, APLASTIC ANEMIA
Variables of interest included demographic characteristics (age, sex, and body mass index), baseline and ΔBL LDH levels, baseline and ΔBL Hb levels, concomitant bone marrow disorders (aplastic anemia [AA] and myelodysplastic syndrome [MDS]), transfusion, and hematological parameters (platelet and neutrophil counts, and ratio of reticulocytes to erythrocytes [%]). Baseline LDH level was defined as the average of all available assessments before the first infusion of the study drug. For all other parameters, baseline was defined as the last available assessment before the first study drug infusion. The main laboratory variables of interest in the current analyses were Hb and LDH levels (indicators of the rate of hemolysis). Associations between mean ΔBL PRO score and laboratory variables were assessed up to 26 weeks (day 183), including absolute mean LDH level, absolute mean Hb level, mean LDH response at day 183, mean ΔBL Hb level, and mean ΔBL LDH level at day 183.
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Statistical analyses
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Regression analysis
REGRESSION, REGRESSION
Regression analyses were performed using clinical and PRO data collected in study 301 to identify significant predictors for ΔBL FACIT-F score and EORTC QLQ-C30 GH score. Patient clinical and demographic characteristics were analyzed as covariates in the regression analyses. Covariates included for the full models of both PROs were baseline and ΔBL LDH levels, baseline and ΔBL Hb levels, baseline FACIT-F and EORTC QLQ-C30 GH scores, age, sex (male/female), concomitant AA or MDS (yes/no), transfusion (yes/no), treatment group (eculizumab/ravulizumab), reticulocytes/erythrocytes ratio (baseline, defined as high [≥ 2.3%], normal [0.2–2.3%], and low [≤ 0.2%]), ΔBL platelet count, ΔBL neutrophil count, and body mass index. Generalized linear regression models were fit for each outcome and set of covariates. These were conducted using the
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