Electronic diaries in the management of haemophilia gene therapy: Perspective of an expert group from the German, Austrian and Swiss Society on Thrombosis and Haemostasis (GTH).

INTRODUCTION: Gene therapy (GT) is becoming a realistic treatment option for patients with haemophilia. Outside clinical trials, the complexity and potential complications of GT will pose unprecedented challenges to haemophilia care centres. AIM: To explore the potential use of electronic tools to improve the delivery of GT under real-world conditions. METHODS: Considering the hub-and-spoke model, the GTH working group on GT considered the entire patient pathway and reached consensus on requirements for an integrative software tool to secure documenting and sharing information between treaters, pharmacies and patients. RESULTS: Six steps of the gene therapy process were identified, each requiring completion of the previous step as a prerequisite for entry. The responsibilities of GT dosing and follow-up treatment centres, read/write access rules, and the minimum data set were outlined. Data contributed by patients through mobile devices was also considered. CONCLUSION: Important information needs to be shared between patients and treatment centres in a real-world GT hub-and-spoke model. Collecting and sharing this information in well-organised electronic applications will not only improve patient care but also enable national and international data collection in clinical registries.

Feasibility of a hybrid clinical trial for respiratory virus detection in toddlers during the influenza season.

BACKGROUND: Traditional clinical trials are conducted at investigator sites. Participants must visit healthcare facilities several times for the trial procedures. Decentralized clinical trials offer an interesting alternative. They use telemedicine and other technological solutions (apps, monitoring devices or web platforms) to decrease the number of visits to study sites, minimise the impact on daily routine, and decrease geographical barriers for participants. Not much information is available on the use of decentralization in randomized clinical trials with vaccines. METHODS: A hybrid clinical trial may be assisted by parental recording of symptoms using electronic log diaries in combination with home collected nasal swabs. During two influenza seasons, children aged 12 to 35 months with a history of recurrent acute respiratory infections were recruited in 12 primary health centers of the Valencia Region in Spain. Parents completed a symptom diary through an ad hoc mobile app that subsequently assessed whether it was an acute respiratory infection and requested collection of a nasal swab. Feasibility was measured using the percentage of returned electronic diaries and the validity of nasal swabs collected during the influenza season. Respiratory viruses were detected by real-time PCR. RESULTS: Ninety-nine toddlers were enrolled. Parents completed 10,476 electronic diaries out of the 10,804 requested (97%). The mobile app detected 188 potential acute respiratory infections (ARIs) and requested a nasal swab. In 173 (92%) ARI episodes a swab was taken. 165 (95.4%) of these swabs were collected at home and 144 (87.3%) of them were considered valid for laboratory testing. Overall, 152 (81%) of the ARIs detected in the study had its corresponding valid sample collected. CONCLUSIONS: Hybrid procedures used in this clinical trial with the influenza vaccine in toddlers were considered adequate, as we diagnosed most of the ARI cases on time, and had a valid swab in 81% of the cases. Hybrid clinical trials improve participant adherence to the study procedures and could improve recruitment and quality of life of the participants and the research team by decreasing the number of visits to the investigator site. This report emphasises that the conduct of hybrid CTs is a valid alternative to traditional CTs with vaccines. This hybrid CT achieved high adherence of participant to the study procedures. TRIAL REGISTRATION: 2019-001186-33 (EudraCT).

Natural history of generalized motor seizures: A retrospective analysis.

PURPOSE: This study aims to characterize the natural history of generalized motor seizures through longitudinal stratification of patient-reported clinical seizures into high, medium and low rates of generalized motor seizures (also known as generalized tonic-clonic seizures or GTCs). METHODS: From 2007 to 2018, 1.4 million seizures were recorded by 12,402 SeizureTracker.com users that met inclusion/exclusion criteria. The number of GTCs per year since the first seizure diary entry was calculated for each user and categorized as: Low (0 GTCs/year), Medium (1-2 GTCs/year), or High (>3 GTCs/year) GTC rates. RESULTS: Kaplan-Meier survival curves for the time until exiting the initial category were computed. There was a global difference between risk groups (p < 0.01). Further pairwise log rank tests revealed a difference between each pair of risk groups (p < 0.01). At 3 years, 40.8% of people initially presenting with high GTC rates remained in their initial category, while 77.3% of people initially presenting with low GTC rates remained in their initial category. CONCLUSION: A patient with a low rate of GTCs is likely to remain at low risk for future GTCs, whereas higher GTC rate patients (at least one GTC/year) may leave their initial risk stratification. Thus, yearly re-assessment may be prudent when considering risk of further GTCs. Given the association between higher yearly rates of GTCs with increased SUDEP risk and morbidity in epilepsy, further validation of these findings is important for prognostication.

Digital tools for epilepsy: Opportunities and barriers.

This review and commentary presents and discusses the major categories of digital tools that are currently available to epilepsy patients. This review synthesizes the breadth of resources that may be used to create a comprehensive self-management platform. The manuscript organizes the discussion into the following topics: self-management education programs, electronic diaries for self-monitoring, and automated wearables for seizure detection. Despite being available for many years, these tools are utilized by only a small fraction of epilepsy patients. To directly address this, the discussion section will opine on some of the possible barriers, including a lack of historical precedent or prescribing infrastructure, a lack of financial incentives, concerns about data privacy or liability, and uncertainty about the supporting evidence for these solutions.

Privacy Issues in Smartphone Applications: An Analysis of Headache/Migraine Applications.

BACKGROUND: Headache diaries are a mainstay of migraine management. While many commercial smartphone applications (apps) have been developed for people with migraine, little is known about how well these apps protect patient information and whether they are secure to use. OBJECTIVE: We sought to assess whether there are privacy issues surrounding apps so that physicians and patients could better understand what medical information patients are providing to the app companies, and the potential privacy implications of how the app companies (and other third parties) might use that information. METHODS: We conducted a systematic search of the most popular "headache" and "migraine" apps and developed a database of the types of data the apps requested for input by the user and whether the apps had clear privacy policies. We also examined the content of the privacy policies. RESULTS: Twenty-nine apps were examined (14 diary apps, 15 relaxation apps). Of the diary applications, 79% (11/14) had visible privacy policies. Of the diary apps with privacy policies, all (11/11) stated whether or not the app collects and stores information remotely. A total of 55% (6/11) stated that some user data were used to serve targeted advertisements. A total of 11/15 (73%) of the relaxation apps had privacy policies. CONCLUSIONS: Headache apps shared information with third parties, posing privacy risks partly because there are few legal protections against the sale or disclosure of data from medical apps to third parties.

Ecological Momentary Assessment Methodology in Chronic Pain Research: A Systematic Review.

Self-reported pain intensity assessments are central to chronic pain research. Ecological momentary assessment (EMA) methodologies are uniquely positioned to collect these data, and are indeed being used in the field. However, EMA protocols are complex, and many decisions are necessary in the design of EMA research studies. A systematic literature review identified 105 articles drawing from 62 quantitative EMA research projects examining pain intensity in adult chronic pain patients. Study characteristics were tabulated to summarize and describe the use of EMA, with an emphasis placed on various dimensions of decision-making involved in executing EMA methodologies. Most identified studies considered within-person relationships between pain and other variables, and a few examined interventions on chronic pain. There was a trend toward the use of smartphones as EMA data collection devices more recently, and completion rates were not reported in nearly one third of studies. Pain intensity items varied widely with respect to number of scale points, anchor labels, and length of reporting period; most used numeric rating scales. Recommendations are provided for reporting to improve reproducibility, comparability, and interpretation of results, and for opportunities to clarify the importance of design decisions. PERSPECTIVE: Studies that use EMA methodologies to assess pain intensity are heterogeneous. Aspects of protocol design, including data input modality and pain item construction, have the potential to influence the data collected. Thorough reporting on design features and completion rates therefore facilitates reproducibility, comparability, and interpretation of study results.

'I Got it off my Chest': An Examination of how Research Participation Improved the Mental Health of Women Engaging in Transactional Sex.

Ecologic momentary assessment (EMA) is a form of close-ended diary writing. While it has been shown that participating in a study that incorporates EMA improves mental health of participants, no study to date has examined the pathways through which benefits may occur. For 4-weeks, twice-daily EMAs and weekly interviews captured mood, daily activities and HIV risk behavior of 25 women who engage in transactional sex. Qualitative analysis of exit interviews was performed to examine how participation impacted women's mental health. The majority of participants felt that EMAs heightened awareness of emotions and behavior. Most reported experiencing catharsis from the interviews; specifically, from having a non-judgmental, trusting listener. Participants felt responsible for completing tasks, a sense of accomplishment for completing the study, and altruism. This study demonstrates there are direct benefits associated with participation in an EMA and interview study.

Analyzing Change Processes Resulting from a Smartphone Maintenance Intervention Based on Acceptance and Commitment Therapy for Women with Chronic Widespread Pain.

PURPOSE: This study investigated change processes resulting from a randomized controlled trial smartphone-delivered maintenance intervention with daily electronic diaries and personalized written feedback based on acceptance and commitment therapy (ACT) following a rehabilitation program for patients with chronic widespread pain. METHOD: This study included 48 women who during a 5-week period completed electronic diaries three times daily, totaling 3372 entries. In response to the completed diaries, they received daily feedback from a therapist for 4 weeks (excluding weekends), totaling 799 feedback messages. To analyze the change processes, we explored the associations between feedback and daily ratings of participants' physical activities, positive emotions, pain fear and avoidance, pain acceptance, and self-management. Commitment to physical activities and the participants' evaluation of feedback were also analyzed. Multilevel models were used in the statistical analyses. RESULTS: Participants' average pain fear and avoidance decreased over the intervention period (mean -0.019, P = 0.05). Self-management, pain acceptance, and positive feelings increased (mean -0.030, P < 0.01; mean -0.015, P < 0.01; and mean -0.011, P = 0.01, respectively). Participants' performance of physical activities decreased slightly over time, but the level of commitment was high and they evaluated the feedback as supportive for staying sufficiently active. No correlation between diary contents and feedback messages was found, even though most of the participants evaluated the feedback as supportive. CONCLUSION: No support was found for an association between diary content and feedback based on ACT. However, diary measures were consistent with the ACT model and may have influenced positively the change processes.

Individual variation in temporal relationships between stress and functional somatic symptoms.

OBJECTIVE: Medically unexplained or functional somatic symptoms (FSSs) constitute a major health problem because of their high prevalence and the suffering and disability they cause. Psychosocial stress is widely believed to be a precipitating or perpetuating factor, yet there is little empirical evidence to support this notion. Prior studies mainly focused on comparing groups, which has resulted in the obscuring of temporal complexity and individual differences. The aim of this study is to elucidate the relationship between stress and FSSs over time within individual patients. METHODS: Twenty patients (17 females, ages 29-59) with multiple, persistent FSSs were included in the study. They used electronic diaries to report stress and FSSs twice daily over the course of 12 weeks. For each individual data set, Vector autoregressive (VAR) modelling was used to investigate possible associations between daily average stress and FSSs scores. RESULTS: In six subjects (30%), an increase in stress was followed by an increase in one or more FSSs. In three subjects (15%), an increase in FSSs was followed by an increase in stress. Additionally, negative and mixed associations were found. Only two subjects (10%) showed no cross-lagged association between stress and FSSs in either direction. We did not find specific types of symptoms to be more stress-related than others. CONCLUSION: Although stress does not seem to be a universal predictor of FSSs, an increase in stress precedes an increase in symptoms in some individuals. Identifying these individuals using time-series analysis might contribute to a more patient-tailored treatment.

Temporal trends in symptom experience predict the accuracy of recall PROs.

OBJECTIVE: Patient-reported outcome measures with reporting periods of a week or more are often used to evaluate the change of symptoms over time, but the accuracy of recall in the context of change is not well understood. This study examined whether temporal trends in symptoms that occur during the reporting period impact the accuracy of 7-day recall reports. METHODS: Women with premenstrual symptoms (n=95) completed daily reports of anger, depression, fatigue, and pain intensity for 4weeks, as well as 7-day recall reports at the end of each week. Latent class growth analysis was used to categorize recall periods based on the direction and rate of change in the daily reports. Agreement (level differences and correlations) between 7-day recall and aggregated daily scores was compared for recall periods with different temporal trends. RESULTS: Recall periods with positive, negative, and flat temporal trends were identified and they varied in accordance with weeks of the menstrual cycle. Replicating previous research, 7-day recall scores were consistently higher than aggregated daily scores, but this level difference was more pronounced for recall periods involving positive and negative trends compared with flat trends. Moreover, correlations between 7-day recall and aggregated daily scores were lower in the presence of positive and negative trends compared with flat trends. These findings were largely consistent for anger, depression, fatigue, and pain intensity. CONCLUSION: Temporal trends in symptoms can influence the accuracy of recall reports and this should be considered in research designs involving change.