Opportunistic osteoporosis screening using routine computed tomography images to identify bone loss in gynecologic cancer survivors.

OBJECTIVE: Cancer treatment-induced bone loss is a known side effect of cancer therapy. Computed tomography (CT) bone mineral density screening is a novel tool for identifying bone loss. This study aims to use routine CT images to determine long-term bone mineral density changes and osteoporosis risk among women with gynecologic cancers. METHODS: Bone loss was evaluated in a retrospective cohort of women ≤65 years old with gynecologic cancer who underwent oophorectomy from January 2010 to December 2014. Opportunistic CT-based bone mineral density measurements (Hounsfield units, HU) were performed at baseline and intervals up to 5 years after cancer diagnosis. Osteoporosis risk was categorized by HU. Bivariate and multivariate analyses were performed to compare baseline to follow-up bone mineral density at 1, 3, and 5 years and to identify predictors of bone loss following diagnosis. RESULTS: A total of 185 patients (median age 53 years, range 23-65 years, 78.1% ovarian cancer) were included. Bone mineral density significantly decreased between baseline and 1 year (p<0.001), 3 years (p<0.001), and 5 years (p<0.001). Half with normal bone mineral density at baseline had risk for osteopenia or osteoporosis at 5 years. Four percent had osteoporosis risk at baseline compared with 1 year (7.4%), 3 years (15.7%), and 5 years (18.0%). Pre-treatment bone mineral density was a significant predictor at 1 and 5 years (1 year: p<0.01; 5 years: p<0.01). History of chemotherapy predicted bone loss at 1 year (p=0.03). More lifetime chemotherapy cycles were associated with increased risk of osteoporosis at 1 year (p=0.03) and 5 years (p=0.01). CONCLUSIONS: Women with gynecologic cancers may experience accelerated cancer treatment-induced bone loss. Routine CT imaging is a convenient screening modality to identify those at highest risk for osteoporosis who warrant further evaluation with dual-energy X-ray absorptiometry. Routine bone mineral density assessments 1 year following oophorectomy for cancer treatment may be warranted in this population.

Reported Concerns and Acceptance of Information or Referrals Among Breast Cancer Survivors Seen for Care Planning Visits: Results from the University of Wisconsin Carbone Cancer Center Survivorship Program.

Breast cancer survivors' experience physical and psychosocial concerns following active curative-intent treatment. Survivors' complex needs are often reviewed at survivorship care planning visits (SCP visits). However, little is known about the post-treatment concerns and resource needs addressed within the context of SCP visits. Using discretely collected electronic health record data, we examined characteristics, concerns, and acceptance of education materials and/or referrals among stages 0-3 breast cancer survivors seen for SCP visits. Most survivors reported concerns related to activity (n = 739; 72.7%) and nutrition (n = 677; 66.6%). Survivors of color were more likely to report concerns related to pain/swelling (odds ratio (OR), 4.4; 95% CI, 1.7-11.4) and employment/insurance (2.8; 1.4-5.7) compared to Whites. More than half accepted materials or referrals for concerns related to nutrition, activity/pain, substance use, sexual health, mood, and sleep (padj-value < 0.05). However, not all reported concerns led to acceptance of materials or referrals. Survivors seen for SCP visits report a wide range of concerns at the end of active curative-intent treatment but may not necessarily accept materials or referrals for their concerns within the context of these visits. Our findings highlight the importance of exercise, physical rehabilitation, and nutrition interventions for survivors following active curative-intent treatment. Further study is needed to elucidate the reasons for acceptance vs. non-acceptance of resources addressing reported concerns.

Diagnostic Performance of MRI for Esophageal Carcinoma: A Systematic Review and Meta-Analysis.

Background Although CT, endoscopic US, and PET are critical in determining the appropriate management of esophageal carcinoma (squamous cell carcinoma and adenocarcinoma), previous reports show that staging accuracy remains low, particularly for nodal involvement sensitivity. Purpose To perform a systematic review and meta-analysis to determine the diagnostic performance of MRI for multiple staging thresholds in patients with biopsy-proven esophageal carcinoma (differentiation of stage T0 disease from stage T1 or higher disease, differentiation of stage T2 or lower disease from stage T3 or higher disease, and differentiation of stage N0 disease from stage N1 or higher disease [where T refers to tumor stage and N refers to nodal stage]). Materials and Methods Studies of the diagnostic performance of MRI in determining the stage of esophageal carcinoma in patients before esophagectomy and pathologic staging between 2000 and 2019 were searched in PubMed, Scopus, Web of Science, and Cochrane Library by a librarian and radiation oncologist. Pooled diagnostic performance of MRI was calculated with a bivariate random effects model. Bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (version 2) tool. Results Twenty studies with a total of 984 patients were included in the analysis. Pooled accuracy for stage T0 versus stage T1 or higher had a sensitivity of 92% (95% CI: 82, 96) and a specificity of 67% (95% CI: 51, 81). Pooled accuracy for stage T2 or lower versus stage T3 or higher had a sensitivity of 86% (95% CI: 76, 92) and a specificity of 86% (95% CI: 75, 93). Pooled accuracy for stage N0 versus stage N1 or higher had a sensitivity of 71% (95% CI: 60, 80) and a specificity of 72% (95% CI: 64, 79). The concern for applicability was low for the patient selection, index test, and reference test domains, except for 10% of studies (two of 20) that had unclear concern for patient selection applicability. Conclusion MRI has high sensitivity but low specificity for the detection of esophageal carcinoma, which shows promise for determining neoadjuvant therapy response and for detecting locally advanced disease for potential trimodality therapy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Leeflang in this issue.

Postoperative venous thromboembolism in gynecologic oncology patients undergoing minimally invasive surgery: Does modality matter?

OBJECTIVES: Minimally invasive surgery (MIS) is increasingly utilized for gynecologic cancers. While incidence of venous thromboembolism (VTE) after MIS is low, some guidelines recommend extended chemoprophylaxis for these patients undergoing MIS. Our objectives were to determine incidence of postoperative VTE in patients undergoing MIS, evaluate differences in the incidence by MIS modality and assess the need for extended chemoprophylaxis. METHODS: We conducted a retrospective cohort study including all patients undergoing MIS (robot-assisted, multi-port laparoscopy, single-port laparoscopy) for gynecologic cancers between January 2014 and December 2018 at our institution. Demographic and perioperative variables were collected. Patients <18 years, with benign pathology, or on preoperative anticoagulation were excluded. Chi-square, Fisher's exact test, and one-way ANOVA were performed to determine risk factors related to VTE occurrence. RESULTS: We identified 806 patients who underwent MIS with median age 61. Most had Stage I disease (81.5%) and uterine cancer (81.5%). Five VTE events occurred within 90 days following surgery (0.6%). Incidence of 90-day VTE did not differ between MIS modalities (p = 0.6). Patients with longer OR times (p = 0.004) were more likely to experience VTE. Age, smoking status, BMI, type of cancer and stage were not significant risk factors for VTE. CONCLUSIONS: The incidence of postoperative VTE in patients with gynecologic cancers undergoing MIS is low and does not appear to differ by MIS modality. Given the very low incidence of postoperative VTE, extended chemoprophylaxis is unlikely to benefit patients with gynecologic malignancies undergoing MIS procedures.

Lag penalized weighted correlation for time series clustering.

BACKGROUND: The similarity or distance measure used for clustering can generate intuitive and interpretable clusters when it is tailored to the unique characteristics of the data. In time series datasets generated with high-throughput biological assays, measurements such as gene expression levels or protein phosphorylation intensities are collected sequentially over time, and the similarity score should capture this special temporal structure. RESULTS: We propose a clustering similarity measure called Lag Penalized Weighted Correlation (LPWC) to group pairs of time series that exhibit closely-related behaviors over time, even if the timing is not perfectly synchronized. LPWC aligns time series profiles to identify common temporal patterns. It down-weights aligned profiles based on the length of the temporal lags that are introduced. We demonstrate the advantages of LPWC versus existing time series and general clustering algorithms. In a simulated dataset based on the biologically-motivated impulse model, LPWC is the only method to recover the true clusters for almost all simulated genes. LPWC also identifies clusters with distinct temporal patterns in our yeast osmotic stress response and axolotl limb regeneration case studies. CONCLUSIONS: LPWC achieves both of its time series clustering goals. It groups time series with correlated changes over time, even if those patterns occur earlier or later in some of the time series. In addition, it refrains from introducing large shifts in time when searching for temporal patterns by applying a lag penalty. The LPWC R package is available at https://github.com/gitter-lab/LPWC and CRAN under a MIT license.

Imbalanced randomization in clinical trials.

Randomization is a common technique used in clinical trials to eliminate potential bias and confounders in a patient population. Equal allocation to treatment groups is the standard due to its optimal efficiency in many cases. However, in certain scenarios, unequal allocation can improve efficiency. In superiority trials with more than two groups, the optimal randomization is not always a balanced randomization. In noninferiority (NI) trials, additive margin with equal variance is the http://www.statlab.wisc.edu/shiny/SSNI/.

Telemedicine Use across Medical Specialties and Diagnoses.

BACKGROUND: The COVID-19 (coronavirus disease 2019) pandemic rapidly expanded telemedicine scale and scope. As telemedicine becomes routine, understanding how specialty and diagnosis combine with demographics to impact telemedicine use will aid in addressing its current limitations. OBJECTIVES: To analyze the relationship between medical specialty, diagnosis, and telemedicine use, and their interplay with patient demographics in determining telemedicine usage patterns. METHODS: We extracted encounter and patient data of all adults who scheduled outpatient visits from June 1, 2020 to June 30, 2021 from the electronic health record of an integrated academic health system encompassing a broad range of subspecialties. Extracted variables included medical specialty, primary visit diagnosis, visit modality (video, audio, or in-person), and patient age, sex, self-reported race/ethnicity and 2013 rural-urban continuum code. Six specialties (General Surgery, Family Medicine, Gastroenterology, Oncology, General Internal Medicine, and Psychiatry) ranging from the lowest to the highest quartile of telemedicine use (video and audio) were chosen for analysis. Relative proportions of video, audio, and in-person modalities were compared. We examined diagnoses associated with the most and least frequent telemedicine use within each specialty. Finally, we analyzed associations between patient characteristics and telemedicine modality (video vs. audio/in-person, and video/audio vs. in-person) using a mixed-effects logistic regression model. RESULTS: A total of 2,494,296 encounters occurred during the study period, representing 420,876 unique patients (mean age: 44 years, standard deviation: 24 years, 54% female). Medical diagnoses requiring physical examination or minor procedures were more likely to be conducted in-person. Rural patients were more likely than urban patients to use video telemedicine in General Surgery and Gastroenterology and less likely to use video for all other specialties. Within most specialties, male patients and patients of nonwhite race were overall less likely to use video modality and video/audio telemedicine. In Psychiatry, members of several demographic groups used video telemedicine more commonly than expected, while in other specialties, members of these groups tended to use less telemedicine overall. CONCLUSION: Medical diagnoses requiring physical examination or minor procedures are more likely to be conducted in-person. Patient characteristics (age, sex, rural vs. urban, race/ethnicity) affect video and video/audio telemedicine use differently depending on medical specialty. These factors contribute to a unique clinical scenario which impacts perceived usefulness and accessibility of telemedicine to providers and patients, and are likely to impact rates of telemedicine adoption.

A Series of Remote Melatonin Supplement Interventions for Poor Sleep: Protocol for a Feasibility Pilot Study for a Series of Personalized (N-of-1) Trials.

BACKGROUND: Poor sleep, defined as short-duration or poor-quality sleep, is a frequently reported condition with many deleterious effects including poorer cognitive functioning, increased accidents, and poorer health. Melatonin has been shown to be an efficacious treatment to manage symptoms of poor sleep. However, the treatment effects of melatonin on sleep can vary greatly between participants. Personalized, or N-of-1, trial designs represent a method for identifying the best treatment for individual participants. Although using N-of-1 trials of melatonin to treat poor sleep is possible, the feasibility, acceptability, and effectiveness of N-of-1 trials using melatonin are unknown. Using the National Institutes of Health Stage Model for Behavioral Intervention Development, a stage IB (intervention refinement, modification, and adaptation and pilot testing) design appeared to be needed to address these feasibility questions. OBJECTIVE: This trial series evaluates the feasibility, acceptability, and effectiveness of a series of personalized interventions for remote delivery of melatonin dose (3 and 0.5 mg) versus placebo supplements for self-reported poor sleep among 60 participants. The goal of this study is to provide valuable information about implementing remote N-of-1 randomized controlled trials to improve poor sleep. METHODS: Participants will complete a 2-week baseline followed by six 2-week alternating intervention periods of 3 mg of melatonin, 0.5 mg of melatonin, and placebo. Participants will be randomly assigned to 2 intervention orders. The feasibility and acceptability of the personalized trial approach will be determined with participants' ratings of usability and satisfaction with the remote, personalized intervention delivery system. The effectiveness of the intervention will be measured using participants' self-reported sleep quality and duration and Fitbit tracker-measured sleep duration and efficiency. Additional measures will include ecological momentary assessment measures of fatigue, stress, pain, mood, concentration, and confidence as well as measures of participant adherence to the intervention, use of the Fitbit tracker, and survey data collection. RESULTS: As of the submission of this protocol, recruitment for this National Institutes of Health stage IB personalized trial series is approximately 78.3% complete (47/60). We expect recruitment and data collection to be finalized by June 2023. CONCLUSIONS: Evaluating the feasibility, acceptability, and effectiveness of a series of personalized interventions of melatonin will address the longer term aim of this program of research-is integrating N-of-1 trials useful patient care? The personalized trial series results will be published in a peer-reviewed journal and will follow the CONSORT (Consolidated Standards of Reporting Trials) extension for N-of-1 trials (CENT 2015) reporting guidelines. This trial series was approved by the Northwell Health institutional review board. TRIAL REGISTRATION: ClinicalTrials.gov NCT05349188; https://www.clinicaltrials.gov/study/NCT05349188. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45313.

Patterns of Health Portal Use by Regular Portal Users Among Patients With Cancer: Results From the UWCCC Survivorship Program.

PURPOSE: We sought to evaluate the patterns of portal usage among patients with cancer who regularly log in to the portal. These data will inform approaches to facilitate portal use among patients with cancer. PATIENTS AND METHODS: We conducted a retrospective analysis of patient portal usage by patients with cancer at the University of Wisconsin Carbone Cancer Center. Our analysis focuses on patterns of portal use by regular users (≥ 2 portal logins/year, > 3 months) receiving ongoing oncology care between January 1, 2017, and December 31, 2019. Demographics, cancer characteristics, number of oncology visits per month, and portal usage data were extracted. Regular portal users were grouped and compared on the basis of their frequency of use. A linear mixed-effects model was used to determine if the frequency of oncology visits influenced the number of logins. RESULTS: We identified 2076 regular portal users. The median number of portal logins/year was 72 for the entire cohort. Age and race were associated with frequency of portal logins. There was no difference in frequency of portal login on the basis of cancer type or stage. Each additional oncology office visit in a month increased the frequency of portal logins by 3.05 ± 0.11 (SE) within the same month. Messages and test result functionalities were used by 98.7% and 98.9% of the regular users, respectively. Regular users who logged in to portal more frequently used all five studied portal functionalities. CONCLUSION: Patients with cancer who use portals regularly use it more in proximity to an oncology office visit and use multiple available portal functionalities. These findings can direct strategic planning to facilitate portal utilization among those not engaged with this tool.

Protocol of a feasibility study of a virtual personalized (N-of-1) trial for increasing low-intensity physical activity in older adults via habit formation.

Background: Personalized interventions that can be delivered remotely are needed to increase physical activity (PA) in older adults to reduce risk of CV disease and mortality. Prior research indicates that Behavioral Change Techniques (BCTs) (e.g., goal setting, self-monitoring, behavioral repetition) can instill a habit for increasing daily walking. However, past interventions relied on between-subject randomized clinical trials, which can only only be informative about response of the hypothetical average person. Personalized trial designs can identify the benefits of an intervention for a specific individual although extended periods are required for collecting frequent measurements within-subject. Advances in remote, virtual technologies (e.g., text messaging, activity trackers), integrated with automatic platforms, can meet these requirements because they capacitate delivery of BCT interventions, and collection of data during daily life without personal contact. This Stage I-b trial is designed test whether a virtual, personalized intervention is feasible and acceptable to older adults, can elicit participant adherence and exhibit preliminary evidence for efficacy. Methods: A series of up to 60 single-arm, personalized trials, involving no personal contact, will recruit adults, 45-75 years of age, to wear an activity tracker during a 2-week baseline and a 10-week intervention. Five BCT prompts to execute a walking plan will be delivered on a daily basis during the intervention phase. Participants will rate satisfaction with personalized trial components and whether automaticity of the walking plan can be achieved. Step-counts, adherence to the walking plan and self-monitoring of step-count will also be recorded.

The effect of a multi-component behavior change technique intervention on medication adherence among individuals on primary prevention statin therapy: a dose-finding protocol.

BACKGROUND: In the USA, the primary cause of death and morbidity continues to be cardiovascular disease (CVD). Numerous trials have shown that statin medication reduces the likelihood of CVD events; it is a cornerstone of CVD prevention. However, studies have also indicated that up to 60% of the estimated 26.8 million Americans prescribed primary prevention statin treatment are nonadherent during the first year. Multi-component behavioral change technique (BCT) therapies have shown moderate promise in improving medication adherence as well as other positive health behaviors (such as physical activity). However, no research has looked at the duration of multi-component BCT intervention needed to result in a clinically significant improvement in statin adherence behaviors. This study aims to determine the necessary dose of a multi-component BCT intervention (defined as duration in weeks) to promote adherence to statin medication among those on primary prevention statin treatment by utilizing the modified time-to-event continuous reassessment method (TiTE-CRM). METHODS AND DESIGN: The study will utilize the modified TiTE-CRM in 42 participants, recruited in 14 cohorts of 3 participants each. The goal of this analysis is to identify the minimum effective dose (MED) of a multi-behavior change technique (BCT) intervention required to increase adherence to statins by 20% between baseline and follow-up periods. Using the TiTE-CRM method, the dose of the behavior intervention in weeks will be assigned to each cohort based on the performance of the prior cohort. At the end of the study, the intervention dose that has been found to be associated with a 20% increase in statin adherence among 80% of participants assigned to that dose will be identified as the MED. DISCUSSION: If successful, the current trial will provide additional guidance to researchers and clinicians seeking to increase statin medication adherence using a BCT intervention by identifying the dose (i.e., the duration) of an intervention required to meaningfully increase adherence. TRIAL REGISTRATION: ClinicalTrials.gov NCT05273736. Registered on March 10, 2022. https://www. CLINICALTRIALS: gov/ct2/show/NCT05273736.

Testing Behavior Change Techniques to Increase Physical Activity in Middle-Aged and Older Adults: Protocol for a Randomized Personalized Trial Series.

BACKGROUND: Being physically active is critical to successful aging, but most middle-aged and older adults do not move enough. Research has shown that even small increases in activity can have a significant impact on risk reduction and improve quality of life. Some behavior change techniques (BCTs) can increase activity, but prior studies on their effectiveness have primarily tested them in between-subjects trials and in aggregate. These design approaches, while robust, fail to identify those BCTs most influential for a given individual. In contrast, a personalized, or N-of-1, trial design can assess a person's response to each specific intervention. OBJECTIVE: This study is designed to test the feasibility, acceptability, and preliminary effectiveness of a remotely delivered personalized behavioral intervention to increase low-intensity physical activity (ie, walking) in adults aged 45 to 75 years. METHODS: The intervention will be administered over 10 weeks, starting with a 2-week baseline period followed by 4 BCTs (goal-setting, self-monitoring, feedback, and action planning) delivered one at a time, each for 2 weeks. In total, 60 participants will be randomized post baseline to 1 of 24 intervention sequences. Physical activity will be continuously measured by a wearable activity tracker, and intervention components and outcome measures will be delivered and collected by email, SMS text messages, and surveys. The effect of the overall intervention on step counts relative to baseline will be examined using generalized linear mixed models with an autoregressive model that accounts for possible autocorrelation and linear trends for daily steps across time. Participant satisfaction with the study components and attitudes and opinions toward personalized trials will be measured at the intervention's conclusion. RESULTS: Pooled change in daily step count will be reported between baseline and individual BCTs and baseline versus overall intervention. Self-efficacy scores will be compared between baseline and individual BCTs and between baseline and the overall intervention. Mean and SD will be reported for survey measures (participant satisfaction with study components and attitudes and opinions toward personalized trials). CONCLUSIONS: Assessing the feasibility and acceptability of delivering a personalized, remote physical activity intervention for middle-aged and older adults will inform what steps will be needed to scale up to a fully powered and within-subjects experimental design remotely. Examining the effect of each BCT in isolation will allow for their unique impact to be assessed and support design of future behavioral interventions. In using a personalized trial design, the heterogeneity of individual responses for each BCT can be quantified and inform later National Institutes of Health stages of intervention development trials. TRIAL REGISTRATION: clinicaltrials.gov NCT04967313; https://clinicaltrials.gov/ct2/show/NCT04967313. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/43418.

The effect of a multi-component behavior change technique intervention on physical activity among individuals on primary prevention statin therapy: A dose-finding trial protocol.

BACKGROUND: Statin therapy is a mainstay of cardiovascular disease (CVD) prevention, but research shows that statin therapy alone is insufficient for preventing incident CVD and mortality. Combining statin medication with increased physical activity (PA) can lower mortality risk more than either statin or PA alone. However, PA levels often remain the same and may even decline following statin prescription. Additional information is needed to identify how to increase PA among statin users and determine the minimal length of an intervention (i.e., intervention dose) necessary to increase PA. OBJECTIVE: The study aims to identify the required dose of a behavior change technique (BCT) intervention to increase PA among individuals on primary prevention statin therapy who have an elevated risk for cardiovascular disease (CVD). METHODS: The study will utilize the modified time-to-event continual reassessment method (TiTE-CRM) in 42 participants. We expect insights relating to dose-efficacy models and BCTs (Behavior Change Techniques) to improve PA in adults at risk for CVD. This trial will also examine potential mechanisms of action (MoAs) for interventions to increase PA, identify any effect a PA intervention may have on medication adherence, and determine whether participants respond uniformly to their respective behavioral interventions. ETHICS AND DISSEMINATION: This trial was approved by the Northwell Health Institutional Review Board (IRB) and all participants will complete informed consent. The trial results will be published in a peer-reviewed journal. All publications resulting from this series of personalized trials will follow the CONSORT reporting guidelines. REGISTRATION DETAILS: This trial is registered on www. CLINICALTRIALS: gov (Number NCT05273723).

Protocol for randomized personalized trial for stress management compared to standard of care.

Stress is a significant public health burden in the United States, with most Americans reporting unhealthy levels of stress. Stress management techniques include various evidence-based treatments shown to be effective but with heterogeneous treatment responses, indicating a lack of uniform benefits for all individuals. Designed to assess a participant's response to a specific intervention, personalized (N-of-1) trials provide guidance for which treatment (s) work (s) best for the individual. Prior studies examining the effects of mindfulness meditation, yoga, and walking for stress reduction found all three interventions to be associated with significant reductions in self-reported measures of stress. Delivering these treatments using a personalized trial approach has the potential to assist clinicians in identifying the best stress management techniques for individuals with persistently high stress while fostering treatment decisions that consider their personal condition/barriers. This trial will evaluate a personalized approach compared to standard of care for three interventions (guided mindfulness meditation; guided yoga; and guided brisk walking) to manage perceived stress. Participants will respond to daily surveys and wear a Fitbit device for 18 weeks. After a 2-week baseline period, participants in the personalized trial groups will receive 12 weeks of interventions in randomized order, while participants in the standard-of-care group will have access to all interventions for self-directed stress management. After intervention, all participants will undergo 2 weeks of observation, followed by two additional weeks of the stress management intervention of their choosing while continuing outcome measurement. At study completion, all participants will be sent a satisfaction survey. The primary analysis will compare perceived stress levels between the personalized and standard of care arms. The results of this trial will provide further support for the use of personalized designs for managing stress. Clinical Trial Registration: clinicaltrials.gov, NCT05408832. Protocol version: 9/14/2022, 21-0968-MRB.

A Series of Personalized Virtual Light Therapy Interventions for Fatigue: Feasibility Randomized Crossover Trial for N-of-1 Treatment.

BACKGROUND: Fatigue is one of the most common symptoms treated in primary care and can lead to deficits in mental health and functioning. Light therapy can be an effective treatment for symptoms of fatigue; however, the feasibility, scalability, and individual-level heterogeneity of light therapy for fatigue are unknown. OBJECTIVE: This study aimed to evaluate the feasibility, acceptability, and effectiveness of a series of personalized (N-of-1) interventions for the virtual delivery of bright light (BL) therapy and dim light (DL) therapy versus usual care (UC) treatment for fatigue in 60 participants. METHODS: Participants completed satisfaction surveys comprising the System Usability Scale (SUS) and items assessing satisfaction with the components of the personalized trial. Symptoms of fatigue were measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) daily, PROMIS weekly, and ecological momentary assessment (EMA) questionnaires delivered 3 times daily. Comparisons of fatigue between the BL, DL, and UC treatment periods were conducted using generalized linear mixed model analyses between participants and generalized least squares analyses within individual participants. RESULTS: Participants rated the usability of the personalized trial as acceptable (average SUS score=78.9, SD 15.6), and 92% (49/53) of those who completed satisfaction surveys stated that they would recommend the trial to others. The levels of fatigue symptoms measured using the PROMIS daily fatigue measure were lower or improved in the BL (B=-1.63, 95% CI -2.63 to -0.63) and DL (B=-1.44, 95% CI -2.50 to -0.38) periods relative to UC. The treatment effects of BL and DL on the PROMIS daily measure varied among participants. Similar findings were demonstrated for the PROMIS weekly and EMA measures of fatigue symptoms. CONCLUSIONS: The participant scores on the SUS and satisfaction surveys suggest that personalized N-of-1 trials of light therapy for fatigue symptoms are both feasible and acceptable. Both interventions produced significant (P<.05) reductions in participant-reported PROMIS and EMA fatigue symptoms relative to UC. However, the heterogeneity of these treatment effects across participants indicated that the effect of light therapy was not uniform. This heterogeneity along with high ratings of usability and satisfaction support the use of personalized N-of-1 research designs in evaluating the effect of light therapy on fatigue for each patient. Furthermore, the results of this trial provide additional support for the use of a series of personalized N-of-1 research trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04707846; https://clinicaltrials.gov/ct2/show/NCT04707846.

Feasibility Test of Personalized (N-of-1) Trials for Increasing Middle-Aged and Older Adults' Physical Activity.

Purpose: To test the feasibility of a remotely-delivered intervention to increase low-intensity physical activity (walking) in middle-aged and older adults. Design: This study used a Personalized (N-of-1) trial design. Setting: This study took place at a major healthcare system from November 2021 to February 2022. Subjects: Sixty adults (45-75 years, 92% female, 80% white) were recruited. Intervention: A 10-week study comprising a 2-week baseline, followed by four 2-week periods where 4 Behavior Change Techniques (BCTs) - self-monitoring, goal setting, action planning and feedback - were delivered one at a time in random order. Measures: Activity was measured by a Fitbit, and intervention components delivered by email/text. Average daily steps were compared between baseline and intervention. Participants completed satisfaction items derived from the System Usability Scale and reported attitudes and opinions about personalized trials. Results: Participants rated personalized trial components as feasible and acceptable. Changes in steps between baseline and intervention were not significant, but a large heterogeneity of treatment effects existed, suggesting some participants significantly increased walking while others significantly decreased. Conclusions: Our intervention was well-accepted but use of BCTs delivered individually did not result in a significant increase in steps. Feasibility and heterogeneity of treatment effects support adopting a personalized trial approach to optimize intervention results.

An R Shiny App for a Chronic Lower Back Pain Study, Personalized N-of-1 Trial.

The call for personalized medicine highlights the need for personalized (N-of-1) trials to find what treatment works best for individual patients. Conventional (between-subject) randomized controlled trials (RCT) yield effects for the 'average patient,' but a personalized trial administers all treatments within-subject, so benefits or harms to the individual patient can be identified. The design and analysis of personalized trials involve different strategies from the conventional RCT. These include how to adjust for any carryover effects from one intervention to another, how to handle missing data, and how to provide patients with insight into their data. In addition, a comprehensible report about trial results should be created for each patient and their clinician to facilitate their decision-making. This article describes strategies to address these design and analytic issues, and introduces an R shiny app to facilitate their solution, to explain the use of each of the design and statistical strategies. To illustrate, we also provide a concrete example of a personalized trial series designed to increase activity (i.e., walking steps) in patients with chronic lower back pain (CLBP).

A NOVEL FRAMEWORK TO ESTIMATE MULTIDIMENSIONAL MINIMUM EFFECTIVE DOSES USING ASYMMETRIC POSTERIOR GAIN AND ϵ-TAPERING.

In this article we address the problem of estimating minimum effective doses in dose-finding clinical trials of multidimensional treatment. We are motivated by a behavioral intervention trial where we introduce sedentary breaks to subjects with a goal to reduce their glucose level monitored over 8 hours. Each sedentary break regimen is defined by two elements: break frequency and break duration. The trial aims to identify minimum combinations of frequency and duration that shift mean glucose, that is, the minimum effective dose (MED) combinations. The means of glucose reduction associated with the dose combinations are only partially ordered. To circumvent constrained estimation due to partial ordering, we propose estimating the MED by maximizing a weighted product of combinationwise posterior gains. The estimation adopts an asymmetric gain function, indexed by a decision parameter ϵ, which defines the relative gains of a true negative decision and a true positive decision. We also introduce an adaptive ϵ-tapering algorithm to be used in conjunction with the estimation method. Simulation studies show that using asymmetric gain with a carefully chosen ϵ is critical to keeping false discoveries low, while ϵ-tapering adds to the probability of identifying truly effective doses (i.e., true positives). Under an ensemble of scenarios for the sedentary break study, ϵ-tapering yields consistently high true positive rates across scenarios and achieves about 90% true positive rate, compared to 68% by a nonadaptive design with comparable false discovery rate.

Series of virtual light therapy interventions for fatigue: a feasibility pilot study protocol for a series of personalised (N-of-1) trials.

INTRODUCTION: Fatigue is one of the most commonly recorded patient symptoms that can result in deficits in aspects of psychomotor functioning, cognition, work performance and mood. Research shows that bright light and dim light therapy may be an efficacious way to reduce symptoms of fatigue. Still, the feasibility, scalability, individual treatment effects and adverse event heterogeneity of these treatments are unknown. METHODS AND ANALYSIS: The current study evaluates the feasibility, acceptability and effectiveness of a series of personalised (N-of-1) interventions for virtual delivery of bright light therapy and dim light therapy versus usual care treatment for fatigue in 60 participants. We hypothesise that this study will provide valuable information about implementing virtual, N-of-1 randomised controlled trials (RCTs) for fatigue. It will also offer results about determining participants' ratings of usability and satisfaction with the virtual, personalised intervention delivery system; evaluating participants' improvement of fatigue symptoms; and, in the long term, identify ways to integrate N-of-1 light therapy trials into patient care. ETHICS AND DISSEMINATION: This trial was approved by the Northwell Health Institutional Review Board. The trial results will be published in a peer-reviewed journal. All publications resulting from this series of personalised trials will follow the Consolidated Standards of Reporting Trials extension for N-of-1 trials CENT 2015 reporting guidelines. REGISTRATION DETAILS: This trial is registered in www. CLINICALTRIALS: gov (number NCT04707846). TRIAL REGISTRATION NUMBER: NCT04707846.