Electronic Diary Research Articles

Reduction in acute migraine-specific and non-specific medication use in patients treated with erenumab: post-hoc analyses of episodic and chronic migraine clinical trials

BackgroundIn patients with migraine, overuse of acute medication, including migraine-specific medication (MSM) such as triptans and ergots, can lead to adverse health outcomes, including development of medication overuse headache. Here, we examined the effect of erenumab on reducing acute medication use, in particular MSM, in patients with episodic migraine (EM) and chronic migraine (CM).MethodsThe current post-hoc analyses were based on data from the double-blind treatment phase (DBTP) of two erenumab studies, a pivotal EM (N = 955) and a pivotal CM (N = 667) trial, and their respective extensions. Patients were administered subcutaneous placebo or erenumab (70 or 140 mg) once monthly. Daily acute headache medication use (including MSM and non-MSM) was recorded using an electronic diary during a 4-week pretreatment baseline period until the end of the treatment period. Outcome measures included change in monthly acute headache medication days (HMD) in acute headache medication users at baseline, and changes in monthly MSM days (MSMD) in MSM users at baseline and non-MSMD in non-MSM users at baseline.ResultsIn total, 60 and 78 % of patients (all acute headache medication users) with EM and CM used MSM at baseline, respectively. For acute headache medication users, the change in mean monthly acute HMD over Months 4, 5 and 6 compared with the pre-DBTP was 1.5, 2.5, and 3.0 for placebo, erenumab 70 mg and 140 mg, respectively for the EM study. The respective change in monthly MSMD in MSM users was 0.5, 2.1 and 2.8, and in monthly non-MSMD in non-MSM users was 2.3, 2.6, and 2.7. In the acute headache medication users at baseline, the change in monthly acute HMD at Month 3 compared with pre-DBTP was 3.4, 5.5, and 6.5 for placebo, erenumab 70 mg and 140 mg, respectively for the CM study. The respective change in monthly MSMD in MSM users was 2.1, 4.5, and 5.4, and in monthly non-MSMD in non-MSM users was 5.9, 6.4, and 6.6. Reductions in MSMD versus placebo were sustained in the extension periods of both studies. Erenumab was also associated with a higher proportion of MSM users achieving ≥ 50 %, ≥ 75 and 100 % reduction from baseline in monthly MSMD versus placebo in both EM and CM.ConclusionsIn both EM and CM, treatment with erenumab is associated with a significant and sustained reduction in the use of acute headache medication, in particular MSM.Trial registrationsNCT02456740; NCT02066415; NCT02174861.

Predicting Delay in Goal-Directed Action: An Experience Sampling Approach Uncovering Within-Person Determinants Involved in the Onset of Academic Procrastination Behavior.

Academic procrastination involves the delayed implementation of actions required to fulfill study-related tasks. These behavioral delays are thought to result from momentary failures in self-regulation (i.e., within-person processes). Most previous studies focused on the role of trait-based individual differences in students’ procrastination tendencies. Little is known about the within-person processes involved in the occurrence of procrastination behavior in real-life academic situations. The present study applied an event-based experience sampling approach to investigate whether the onset of task-specific delay behavior can be attributed to unfavorable changes in students’ momentary appraisals of tasks (value, aversiveness, effort, expectations of success), which may indicate failures in self-regulation arise between critical phases of goal-directed action. University students (N = 75) used an electronic diary over eight days to indicate their next days’ intentions to work on academic tasks and their task-specific appraisals (n = 582 academic tasks planned). For each task, a second query requested the next day determined whether students’ task-related appraisals changed and whether they implemented their intention on time or delayed working on the respective task (n = 501 completed task-specific measurements). Students’ general procrastination tendency was assessed at baseline using two established self-report questionnaires. Stepwise two-level logistic regression analyses revealed that within-person changes in task-related appraisals that reflected a devaluation of the study-related tasks increased the risk for an actual delay. The risk to delay decreased when students maintained a positive attitude toward the task. Students’ general procrastination tendency did not predict individual differences in their task-specific delay behavior. We discuss these findings in light of the growing effort to understand the within-person processes that contribute to induce procrastination behavior under real-life academic conditions and illustrate how this knowledge can benefit the design of tasks and instructions that support students’ self-regulation to their best.

Baricitinib Rapidly Improves Skin Pain Resulting in Improved Quality of Life for Patients with Atopic Dermatitis: Analyses from BREEZE-AD1, 2, and 7.

IntroductionSkin pain (described as discomfort or soreness) is increasingly recognized as a symptom of atopic dermatitis which impacts patient quality of life. This analysis examined the effect of baricitinib on skin pain in atopic dermatitis in three phase 3 studies (BREEZE-AD1, -AD2, and -AD7).MethodsPatients were randomly assigned 2:1:1:1 to receive once-daily placebo, baricitinib 1 mg, 2 mg, or 4 mg in BREEZE-AD1 (N = 624) and -AD2 (N = 615) and 1:1:1 to receive once-daily placebo, baricitinib 2 mg, or 4 mg, with topical corticosteroids, in BREEZE-AD7 (N = 329) for 16 weeks. Patients recorded their skin pain severity using the Skin Pain Numerical Rating Scale (NRS) via an electronic daily diary. Data were analyzed by study as least squares mean change from baseline in daily scores for the randomly assigned patients using mixed model repeated measures analysis. Analysis of Skin Pain NRS response was done using logistic regression using non-responder imputation.ResultsBaricitinib produced significant percentage change from baseline compared with placebo in patient-reported skin pain severity by day 2 in BREEZE-AD1 (baricitinib 4 mg − 11.9%, p < 0.001; baricitinib 2 mg − 6.4%, p = 0.016; baricitinib 1 mg − 6.2%, p = 0.016), -AD2 (baricitinib 4 mg − 12.6%, p < 0.001; baricitinib 2 mg − 5.6%, p = 0.036; baricitinib 1 mg − 6.9%, p = 0.011), and -AD7 (baricitinib 4 mg − 6.9%, p = 0.04; baricitinib 2 mg − 7.9%, p = 0.018). A greater proportion of patients treated with baricitinib reported at least a 4-point reduction in Skin Pain NRS score at week 16 (Skin Pain NRS responders) in BREEZE-AD1 (baricitinib 4 mg 25.3%, p < 0.001), -AD2 (baricitinib 4 mg 20.0%, p < 0.001; baricitinib 2 mg 19.0%, p < 0.001), and -AD7 (baricitinib 4 mg 48.8%, p < 0.001; baricitinib 2 mg 45.2%, p = 0.004) compared to placebo. A significantly higher proportion of Skin Pain NRS responders also achieved at least a 4-point improvement in Dermatology Life Quality Index at week 16 when compared with Skin Pain NRS non-responders in BREEZE-AD1 (89.2%, p < 0.0001), -AD2 (92.5%, p < 0.0001), and -AD7 (88.3%, p < 0.0001).ConclusionBaricitinib improved patient-reported skin pain severity as early as day 2.ClinicalTrials.gov identifiersBREEZE-AD1, NCT03334396; BREEZE-AD2, NCT03334422; BREEZE-AD7, NCT03733301.

Seizure Diaries and Forecasting With Wearables: Epilepsy Monitoring Outside the Clinic.

It is a major challenge in clinical epilepsy to diagnose and treat a disease characterized by infrequent seizures based on patient or caregiver reports and limited duration clinical testing. The poor reliability of self-reported seizure diaries for many people with epilepsy is well-established, but these records remain necessary in clinical care and therapeutic studies. A number of wearable devices have emerged, which may be capable of detecting seizures, recording seizure data, and alerting caregivers. Developments in non-invasive wearable sensors to measure accelerometry, photoplethysmography (PPG), electrodermal activity (EDA), electromyography (EMG), and other signals outside of the traditional clinical environment may be able to identify seizure-related changes. Non-invasive scalp electroencephalography (EEG) and minimally invasive subscalp EEG may allow direct measurement of seizure activity. However, significant network and computational infrastructure is needed for continuous, secure transmission of data. The large volume of data acquired by these devices necessitates computer-assisted review and detection to reduce the burden on human reviewers. Furthermore, user acceptability of such devices must be a paramount consideration to ensure adherence with long-term device use. Such devices can identify tonic–clonic seizures, but identification of other seizure semiologies with non-EEG wearables is an ongoing challenge. Identification of electrographic seizures with subscalp EEG systems has recently been demonstrated over long (>6 month) durations, and this shows promise for accurate, objective seizure records. While the ability to detect and forecast seizures from ambulatory intracranial EEG is established, invasive devices may not be acceptable for many individuals with epilepsy. Recent studies show promising results for probabilistic forecasts of seizure risk from long-term wearable devices and electronic diaries of self-reported seizures. There may also be predictive value in individuals' symptoms, mood, and cognitive performance. However, seizure forecasting requires perpetual use of a device for monitoring, increasing the importance of the system's acceptability to users. Furthermore, long-term studies with concurrent EEG confirmation are lacking currently. This review describes the current evidence and challenges in the use of minimally and non-invasive devices for long-term epilepsy monitoring, the essential components in remote monitoring systems, and explores the feasibility to detect and forecast impending seizures via long-term use of these systems.

Determining the Evolution of Headache Among Regular Users of a Daily Electronic Diary via a Smartphone App: Observational Study.

BackgroundSmartphone-based apps represent a major development in health care management. Specifically in headache care, the use of electronic headache diaries via apps has become increasingly popular. In contrast to the soaring volume of available data, scientific use of these data resources is sparse.ObjectiveIn this analysis, we aimed to assess changes in headache and migraine frequency, headache and migraine intensity, and use of acute medication among people who showed daily use of the headache diary as implemented in the freely available basic version of the German commercial app, M-sense.MethodsThe basic version of M-sense comprises an electronic headache diary, documentation of lifestyle factors with a possible impact on headaches, and evaluation of headache patterns. This analysis included all M-sense users who had entered data into the app on a daily basis for at least 7 months.ResultsWe analyzed data from 1545 users. Mean MHD decreased from 9.42 (SD 5.81) at baseline to 6.39 (SD 5.09) after 6 months (P<.001; 95% CI 2.80-3.25). MMD, AMD, and migraine intensity were also significantly reduced. Similar results were found in 985 users with episodic migraine and in 126 users with chronic migraine.ConclusionsAmong regular users of an electronic headache diary, headache and migraine frequency, in addition to other headache characteristics, improved over time. The use of an electronic headache diary may support standard headache care.

An Open-Label, Phase II Study Of The JAK1 Inhibitor INCB039110 In Patients With Myelofibrosis

An Open-Label, Phase II Study Of The JAK1 Inhibitor INCB039110 In Patients With Myelofibrosis

Impact of Galcanezumab on Total Pain Burden: A Post Hoc Analysis of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study in Patients with Episodic Cluster Headache.

PurposeIn a phase 3 study, galcanezumab significantly reduced the frequency of episodic cluster headache attacks across weeks 1–3 (primary endpoint) compared with placebo. However, multiple pain dimensions may contribute to the total burden of episodic cluster headache pain. This post hoc analysis assessed the impact of galcanezumab on the total pain burden of episodic cluster headache using a composite measure.Patients and MethodsPatients with episodic cluster headache were randomized 1:1 to galcanezumab 300 mg or placebo once monthly for 8 weeks. Mean weekly total pain burden was calculated (daily cluster headache attack frequency × average duration × average pain severity summed over 7 days) using data collected in an electronic patient-reported outcomes diary. Change from baseline in weekly total pain burden across weeks 1–3 was compared between galcanezumab and placebo. To explore construct validity, mean weekly total pain burden scores were stratified by Patient Global Impression of Improvement (PGI-I) responses at the week 4 clinic visit.ResultsThe reduction from baseline in mean weekly total pain burden was significantly greater with galcanezumab (N=49) than with placebo (N=57): the least squares mean difference was −11.18 severity-weighted hours (p=0.035). Median weekly total pain burden decreased as PGI-I ratings improved, from 33.6 to 5.0 severity-weighted hours for patients who felt “very much worse” and “very much better,” respectively.ConclusionGalcanezumab significantly reduced mean weekly total pain burden compared with placebo in patients with episodic cluster headache. The composite pain measure demonstrated construct validity. Total pain burden may provide a holistic measure of the pain of episodic cluster headache.Clinical TrialsClinicalTrials.gov, NCT02397473.

Parental Engagement of a Prototype Electronic Diary in an Ambulatory Setting Following Adenotonsillectomy in Children: A Prospective Cohort Study

Adenotonsillectomy is performed in children on an outpatient basis, and pain is managed by parents. A pain diary would facilitate pain management in the ambulatory setting. Our objective was to evaluate the parental response rate and the compliance of a prototype electronic pain diary (e-diary) with cloud storage in children aged 2–12 years recovering from adenotonsillectomy and to compare the e-diary with a paper diary (p-diary). Parents recorded pain scores twice daily in a pain diary for 2 weeks post-operation. Parents were given the choice of an e-diary or p-diary with picture message. A total of 208 patients were recruited, of which 35 parents (16.8%) chose the e-diary. Most parents (98%) chose to be contacted by text message. Eighty-one families (47%) returned p-diaries to us by mail. However, the response rate increased to 77% and was similar to that of the e-diary (80%) when we included data texted to the research phone from 53 families. The proportion of diaries with Complete (e-diary:0.37 vs. p-diary:0.4) and Incomplete (e-diary:0.43 vs. p-diary:0.38) data entries were similar. E-diaries provide a means to follow patients in real time after discharge. Our findings suggest that a smartphone-based medical health application coupled with a cloud would meet the needs of families and health care providers alike.

Temporomandibular disorders and dietary changes: A cross-sectional survey.

Advice about a 'soft diet' may be useful in the short-term alleviation of temporomandibular disorders (TMD) but may contradict the long-term aims of multi-dimensional approaches if a poor nutritional state is caused or exacerbated. The changes patients with TMD make to their diet, because of their condition or its management, have not previously been explored. To explore the relationship and trends between TMD, TMD interventions and diet using self-report measures. Registrants of the Temporomandibular Joint Association (TMJA) were invited to participate. After completing a screening questionnaire to check for eligibility, participants completed a questionnaire exploring demographics, TMD interventions and dietary habits, as well as jaw functional limitation scale (JFLS) score, graded chronic pain scale score, self-assessed limitation of opening and patient health questionnaire 4 (PHQ-4). This was followed by a validated 3-day electronic diet diary. Descriptive and inferential statistics were used to explore the data for trends and differences in the dietary intake of those participating according to various strata including demographic variables; experience of surgery; other interventions for TMD; duration of TMD; and limitation of mouth opening. Eighty-five registrants of the TMJA completed the questionnaire, of which 42 (49%) completed the 3-day diet diary. Most participants (66/85 [77.6%]) reported modifying their diet due to their TMD. The most common modification was to cut food into smaller pieces (61/85 [71.8%]) followed by boiling until soft (36/85 [42.4%]) and mashing (34/85 [40%]). Higher JFLS scores were associated with participants reduced enjoyment of food (t(83)=2.78, p=.007), limitations in the foods they can eat (t(83)=2.99, p=.004), necessity for modified food preparation (t(83)=3.38, p=.001) and self-reported weight change (F(2, 82)=9.31, p=.0002). This study suggests a significant proportion of patients with TMD make alterations to their diet which may impact the nutritional value of their diet. However, self-reported symptoms and interventions for TMD made little difference to nutritional intake as measured by a 3-day diary. Patients reporting self-assessed limited opening had more pain as measured by validated tools, suggesting patients' self-reporting of opening is a useful proxy for clinical measurement in monitoring TMD.

Factors That Influence the Use of Electronic Diaries in Health Care: Scoping Review.

BackgroundA large number of people suffer from psychosocial or physical problems. Adequate strategies to alleviate needs are scarce or lacking. Symptom variation can offer insights into personal profiles of coping and resilience (detailed functional analyses). Hence, diaries are used to report mood and behavior occurring in daily life. To reduce inaccuracies, biases, and noncompliance with paper diaries, a shift to electronic diaries has occurred. Although these diaries are increasingly used in health care, information is lacking about what determines their use.ObjectiveThe aim of this study was to map the existing empirical knowledge and gaps concerning factors that influence the use of electronic diaries, defined as repeated recording of psychosocial or physical data lasting at least one week using a smartphone or a computer, in health care.MethodsA scoping review of the literature published between January 2000 and December 2018 was conducted using queries in PubMed and PsycInfo databases. English or Dutch publications based on empirical data about factors that influence the use of electronic diaries for psychosocial or physical purposes in health care were included. Both databases were screened, and findings were summarized using a directed content analysis organized by the Consolidated Framework for Implementation Research (CFIR).ResultsOut of 3170 articles, 22 studies were selected for qualitative synthesis. Eleven themes were determined in the CFIR categories of intervention, user characteristics, and process. No information was found for the CFIR categories inner (eg, organizational resources, innovation climate) and outer (eg, external policies and incentives, pressure from competitors) settings. Reminders, attractive designs, tailored and clear data visualizations (intervention), smartphone experience, and intrinsic motivation to change behavior (user characteristics) could influence the use of electronic diaries. During the implementation process, attention should be paid to both theoretical and practical training.ConclusionsDesign aspects, user characteristics, and training and instructions determine the use of electronic diaries in health care. It is remarkable that there were no empirical data about factors related to embedding electronic diaries in daily clinical practice. More research is needed to better understand influencing factors for optimal electronic diary use.

Can reactogenicity predict immunogenicity after COVID-19 vaccination?

Background/AimsThis study aimed to assess the association between local and systemic reactogenicity and humoral immunogenicity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination.MethodsAdverse events were prospectively evaluated using an electronic diary in 135 healthy adults who received a SARS-CoV-2 vaccine (AZD1222, AstraZeneca/Oxford, n = 42; or BNT162b2, Pfizer/BioNTech, n = 93). We semi-quantitatively measured anti-S1 immunoglobulin G (IgG) using an enzyme-linked immunosorbent assay at baseline, 3 weeks after the first dose of AZD1222 or BNT162b2, and 2 weeks after the second dose of BNT162b2. We evaluated the association between the maximum grade of local or systemic adverse events and the anti-S1 IgG optical density using multivariate linear regression with adjustment for age, sex, and use of antipyretics.ResultsThe median age of the 135 vaccinees was 30 years (36 years in the AZD1222 group and 29 years in the BNT162b2 group) and 25.9% were male (9.5% in the AZD1222 group and 33.3% in the BNT162b2 group). Local and systemic adverse events were generally comparable after the first dose of AZD1222 and the second dose of BNT162b2. The grades of local and systemic adverse events were not significantly associated with anti-S1 IgG levels in the AZD1222 or BNT162b2 group.ConclusionsLocal and systemic reactogenicity may not be associated with humoral immunogenicity after SARS-CoV-2 vaccination.

DOP84 Early treatment responses within 14 days of intravenous vedolizumab induction therapy for Crohn’s Disease: Post hoc analysis of patient-reported outcomes from the VISIBLE 2 study

Abstract Background Vedolizumab (VDZ), an anti-a4β7 integrin antibody that selectively blocks lymphocyte trafficking to the gut, is approved for the treatment of adult patients with moderate-to-severe Crohn’s disease (CD). This post hoc analysis of data from the VISIBLE 2 trial evaluated early patient-reported outcomes assessed within the first 14 days of VDZ induction. Methods VISIBLE 2 (NCT02611817; EudraCT 2015-000481-58) was a phase 3, multicentre, placebo-controlled study, evaluating the efficacy and safety of subcutaneous VDZ for maintenance treatment in patients with moderately to severely active CD. Efficacy was assessed based on CD Activity Index (CDAI). Patients received induction treatment with intravenous (IV) VDZ 300 mg open-label at Weeks 0 and 2. For this analysis, responses to VDZ were assessed using CDAI sub-scores for patient-reported abdominal pain (AP) and stool frequency (SF) collected daily via electronic diary in the first 14 days of VDZ treatment (Day 1 to 15) in all patients receiving ≥1 VDZ dose at induction. Descriptive statistics were used. Results The analysis included 611 patients (mean [SD] age 37.6 [13.4] years; CD duration 9.0 [8.1] years); 323 (53%) were male; 228 (37%) had severe disease (CDAI &amp;gt;330) at baseline; and 350 (57%) were anti-TNF-experienced. In the first 14 days of VDZ IV induction, the rate of patients with daily SF≤3 increased from 30% at baseline (Day 1) to 47.7% on Day 15. Increases were similar in both anti-TNF-naïve vs. anti-TNF-experienced patients and in patients with severe vs. moderate disease (Figure 1). Mean baseline SF was reduced from 6.4 to 5.0 at Day 15 in patients with severe disease and from 4.3 to 3.5 in patients with moderate disease. Overall, the proportion of patients rating AP as severe/moderate declined from baseline to Day 15 of induction (from 14.6% to 8.2% for severe AP and from 60.7% to 40.6% for moderate AP). Similar Day 1-to-15 reductions were reported in both anti-TNF-naïve (severe AP: 14.2% to 9.2%; moderate AP: 62.6% to 44.6%) and anti-TNF-experienced patients (severe AP: 14.8% to 7.4%; moderate AP: 59.3% to 37.7%), respectively. Although a minority of patients (6.3%) in the sub-group with moderate AP at baseline had worse pain at Day 15, there were early improvements in AP ratings for most patients reporting severe or moderate AP at baseline (Figure 2). Conclusion This post hoc analysis of daily patient-reported SF and AP in the VISIBLE 2 CD study indicates an early onset of response to VDZ IV induction within the first 14 days of treatment.

Technology During Pandemics: Ecological Momentary Assessment as an Assessment Tool for Real Time Monitoring

Background: Ecological Momentary Assessment (EMA), a term coined in 1994 by Stone and Schiffman, is a modality by which participants can record their symptoms, triggers and thoughts in real time. This data is recorded electronically through the use of smartphones, tablets, and smartwatches as subjects live their daily lives. EMA can be thought of as an electronic diary by which a subject can respond to alerts by entering their observations several times throughout the day. These assessments involve different discrete methodologies such as interpersonal interaction diaries, ambulatory physiological monitoring, and collection of medication compliance data. EMA was developed to counteract the recall bias and inter-evaluator discrepancies that can occur during regularly scheduled outpatient appointments. Methods: A literature review was done using EMA as the search criteria. Results: Davidson et al discussed the use of EMA in suicidality through the use of paper journals, personal digital assistants and cellphones. The paper outlined two sampling schemes; event-based sampling which asks participants to respond to questions each time they experienced a behavior and time-based sampling which asks for responses at a set period of time. Bell et al, 2017 reviewed the application of EMA in treatment of psychotic disorders and reviewed current literature. Schueller et al, 2017 analyzed the use of EMA for depression and anxiety providing mechanisms, study designs and therapeutic measures that can be incorporated for design of an EMA for depression and anxiety. Smith et al 2019 reviewed EMA in the assessment of eating disorders (ED) by looking at realms of type, frequency and temporal sequencing of ED symptoms in natural environment. The use of EMA for child and adolescent patients using mobile based utilization was researched by Heron et al., 2017. Using these modalities children and adolescents may have improved reporting of pain, treatment adherence, sleep and disease symptoms. Raugh et al 2019 studied EMA for psychophysiological assessments. EMA was used for monitoring of EKG, Blood pressure, EEG, electroculography, electromyography and other variables. Conclusions: There are multiple advantages and disadvantages to EMA. Advantages include participants avoiding recall bias and providing real time assessments. Treatment is not dependent on respondent’s bias and immediate interventions can be enacted. EMA also allows a remote alert to providers and can be used for research. Disadvantages of EMA include it being dependent on equipment, technology and network connectivity. There is a risk of attrition as well as possible redundancy. There is a need for detailed study modeling. EMA requires motivation on the part of the participant to respond and participate regularly. Additionally, encryption is necessary to safeguard such sensitive data. More research is required investigating the benefits of this method.

Improved everyday executive functioning following profound reduction in seizure frequency with fenfluramine: Analysis from a phase 3 long-term extension study in children/young adults with Dravet syndrome

ObjectiveIndividuals with Dravet syndrome (DS) experience frequent pharmacoresistant seizures beginning in infancy. Most exhibit poor neurodevelopmental outcomes including motor function difficulties, behavior problems, and cognitive impairment. Cognitive deficits in children with DS have been associated with seizure frequency and antiseizure medication (ASM) use.Recent research in children and young adults with DS has begun to examine the role of executive functions (EFs), as these include higher-order cognitive functions and may mediate the relationship between risk factors and cognitive impairment. Current conceptualizations, however, of EFs involve the broader self-regulation of cognitive, behavioral, and emotional domains. We explored relationships between reduction in convulsive seizure frequency and everyday EFs in a subset of children and young adults with DS treated with adjunctive fenfluramine for 1 year. MethodsThis is a post-hoc analysis of data from children and young adults with Dravet syndrome aged 5–18 years who participated in a phase 3 randomized, placebo-controlled clinical trial (core study) followed by completion of at least 1 year of fenfluramine treatment in an open-label extension (OLE) study. Eligible children and young adults started the OLE study at 0.2 mg/kg/day fenfluramine and were titrated to optimal seizure control and tolerability (maximum daily dose: 26 mg/day). Parents/caregivers documented convulsive seizure frequency per 28 days (i.e., monthly convulsive seizure frequency [MCSF]) by electronic diary. A parent/caregiver for each child also completed the Behavior Rating Inventory of Executive Function (BRIEF®) parent form, a questionnaire capturing parents’/caregivers’ perceptions of everyday EF that was included as a safety measure to assess treatment-related adverse effects on EF during the trial. Ratings on BRIEF® were mapped to the current edition, the BRIEF®2 parent form, and were used to calculate T-scores for the Behavior Regulation Index (BRI), Emotion Regulation Index (ERI), Cognitive Regulation Index (CRI), and Global Executive Composite (GEC). Change in BRIEF®2 T-scores from baseline in the core study to Year 1 of the OLE study was calculated. Spearman’s rho correlation coefficients assessed associations between change in BRIEF®2 indexes/composite T-scores and percentage change in MCSF. Children and young adults were divided into 2 groups based on percentage of MCSF reduction achieved from pre-randomization baseline in the core study to Year 1 of the OLE study: <50% and ≥50% MCSF reduction. Changes in the distribution of BRIEF®2 indexes/composite T-scores were compared between MCSF reduction groups using Mann-Whitney U tests. The proportions of children and young adults in these groups who showed clinically meaningful improvement in everyday EF, defined as Reliable Change Index (RCI) values ≥95% certainty relative to a reference population of neurotypically developing healthy volunteers, were then assessed by cross-tabulations and Somers’ D tests (p ≤ 0.05). When there was a significant meaningful improvement in an index score, post-hoc analyses using the same statistical methods were conducted to evaluate the individual BRIEF®2 scales composing that index. Supplemental analyses examined the proportions of patients in MCSF reduction groups <25% and ≥75% who achieved clinically meaningful improvement or worsening in everyday EF using RCI values ≥95% certainty and ≥80% certainty, respectively, relative to the reference population. ResultsAt the time of analysis, 58 children and young adults (mean age: 11 ± 4 years) had reached OLE Year 1 of fenfluramine treatment with a 75% median percentage reduction in seizure frequency from pre-randomization baseline. Overall, there was a significant correlation between change in MCSF and change in BRIEF®2 T-scores for ERI (p = 0.008), but not for BRI, CRI, or GEC (p > 0.05). At OLE Year 1, 78% (n = 45) of total children/young adults had ≥50% MCSF reduction (50% [n = 29] achieved ≥75% MCSF reduction) and 22% (n = 13) of total children/young adults had <50% MCSF reduction (12% [n = 7] showed <25% MCSF reduction). The ≥50% MCSF reduction group was significantly more likely to achieve clinically meaningful improvement (RCI ≥ 95% certainty) in ERI (p = 0.002) and in CRI (p = 0.001) than the <50% MCSF reduction group. There were no significant differences in the proportions of children and young adults in the 2 MCSF reduction groups showing clinically meaningful worsening (RCI ≥ 80% certainty) on the BRIEF®2 indexes/composite. SignificanceIn children and young adults with DS, the magnitude of reduction in MCSF after long-term treatment with adjunctive fenfluramine was associated with clinically meaningful levels of improvement in everyday EF. Seventy-eight percent (78%) of children and young adults treated with adjunctive fenfluramine for 1 year in the OLE study achieved ≥50% reduction in MCSF, for a magnitude of efficacy associated with a significantly greater likelihood of experiencing clinically meaningful improvement in emotion regulation and cognitive regulation.

A textual-based featuring approach for depression detection using machine learning classifiers and social media texts

Depression is one of the leading causes of suicide worldwide. However, a large percentage of cases of depression go undiagnosed and, thus, untreated. Previous studies have found that messages posted by individuals with major depressive disorder on social media platforms can be analysed to predict if they are suffering, or likely to suffer, from depression. This study aims to determine whether machine learning could be effectively used to detect signs of depression in social media users by analysing their social media posts—especially when those messages do not explicitly contain specific keywords such as ‘depression’ or ‘diagnosis’. To this end, we investigate several text preprocessing and textual-based featuring methods along with machine learning classifiers, including single and ensemble models, to propose a generalised approach for depression detection using social media texts. We first use two public, labelled Twitter datasets to train and test the machine learning models, and then another three non-Twitter depression-class-only datasets (sourced from Facebook, Reddit, and an electronic diary) to test the performance of our trained models against other social media sources. Experimental results indicate that the proposed approach is able to effectively detect depression via social media texts even when the training datasets do not contain specific keywords (such as ‘depression’ and ‘diagnose’), as well as when unrelated datasets are used for testing.

Design of a Randomized Controlled Trial of Percutaneous Posterior Tibial Nerve Stimulation for the Treatment of Refractory Fecal Incontinence in Women: The NeurOmodulaTion for Accidental Bowel Leakage Study.

High-level evidence for second-line noninvasive treatments for fecal incontinence in women is limited. We present the rationale for and design of the NeuromOdulaTion for Accidental Bowel Leakage trial, a randomized controlled trial of percutaneous tibial nerve stimulation (PTNS) and validated sham stimulation in women with refractory accidental bowel leakage. The rationale and goals for a 2-part study with a run-in phase, use of a generic pulse generator for PTNS and sham stimulation, masking, participant inclusion, primary and secondary outcome measures, and adverse event collection are described. A superiority design will be used to compare change from baseline in St. Mark's score after 12 weekly stimulation sessions between PTNS and sham. Responders to initial treatment (PTNS or sham) will be assigned to scheduled or "as needed" intervention for up to 1 year. Secondary outcome measures include incontinence episodes and other bowel events recorded in a 14-day electronic bowel diary, general and condition-specific quality of life instruments, adaptive behavior, global impression of improvement, symptom control, and sexual function. Sample size calculations determined that 165 participants (110 PTNS and 55 sham) would provide 90% power to detect greater than or equal to 4-point difference between PTNS and sham in change from baseline in St. Mark's score at 12 weeks. The methods for the NeuromOdulaTion for Accidental Bowel Leakage trial will provide high-level evidence of the effectiveness and optimal maintenance therapy schedule of a low-cost PTNS protocol in community-dwelling women seeking second-line intervention for refractory accidental bowel leakage.

Real‐world outcomes with recombinant factor IX Fc fusion protein (rFIXFc) prophylaxis: Longitudinal follow‐up in a national adult cohort

In 2017, all people with severe haemophilia B (PWSHB) in Ireland switched from standard half-life (SHL) recombinant FIX (rFIX) to rFIX Fc fusion protein (rFIXFc) prophylaxis. To evaluate prophylaxis regimens, bleeding rates and factor usage for two years of rFIXFc prophylaxis in a real-world setting. Data collected retrospectively from electronic diaries and medical records of PWSHB for a two-year period on rFIXFc prophylaxis were compared with paired baseline data on SHL rFIX treatment. 28 PWSHB (≥18years) were enrolled, and at switchover 79% were receiving prophylaxis and 21% episodic treatment with SHL rFIX. At 24months following switchover, all remained on rFIXFc prophylaxis with reduced infusion frequency; median dose per infusion once weekly (55IU/kg, 20/28), every 10days (63IU/kg, 2/28) or every 14days (98IU/kg, 6/28). Median annualised bleed rate improved significantly on rFIXFc prophylaxis (2.0 versus 3.3 on SHL FIX) (p=0.01). Median FIX trough level with once-weekly infusions was 0.09IU/ml (0.06-0.14IU/ml). Management of bleeding episodes was similar with rFIXFc and SHL rFIX; one infusion was sufficient to treat 74% and 77% of bleeds, respectively, with similar total median treatment per bleeding episode. Factor consumption reduced by 28% with rFIXFc prophylaxis (57IU/kg/week, range 40-86IU/kg/week) compared with SHL rFIX (79IU/kg/week, range 44-210IU/kg/week) (p=0.002). This study provides important insights into real-world experience of switching to rFIXFc prophylaxis in an adult population, demonstrating high rates of prophylaxis, with reduced infusion frequency, bleeding and FIX consumption.

587 Temporal Daily Relationships Between Sleep Deficiency and Pain in Youth with Systemic Lupus Erythematosus

Abstract Introduction Systemic Lupus Erythematosus (SLE) is a chronic, inflammatory autoimmune disorder characterized by recurrent episodes of pain and is more prevalent in youth of color. Although sleep deficiency (poor quality and an inadequate amount of sleep) and pain are interrelated, most of what is known about SLE pain and sleep rely on reports from adults. Less is known about these associations in youth with SLE, leaving a critical gap in care for this population. This study aims to describe the temporal daily relationships between sleep deficiency and pain in 11-to 18-year-old youth with SLE. Methods Twenty-three youth (n=21 girls, n=9 Hispanic) with SLE (mean age=14.7 □ 2.2) participated in the study. Youth wore actigraphy and completed electronic sleep diaries for consecutive 10 days. Actigraphic sleep variables (Total Sleep Time [TST], Sleep Efficiency [SE]) and self-reported Sleep Quality (diary SQ) were examined as predictors of next-day pain in the morning. Average daytime pain was examined as a predictor of nighttime sleep (both actigraphic and self-reported sleep variables). Pubertal stage and ethnicity (Hispanic vs. Non-Hispanic) were entered as covariates in all models. Results Of the sample, the mean TST was 7 □ 1.2 hours and the mean SE was 73.5 □ 9.2% as measured by actigraphy. On average, diary SQ negatively predicted next-day pain in the morning (p &amp;lt;.001). On average, pain negatively predicted TST (p &amp;lt;.05) and diary SQ (p &amp;lt;.001). The within-subject relationships between sleep and next-day pain were not significant. Daytime pain predicted neither actigraphic nor self-reported sleep quality. Conclusion Poor sleep is a modifiable behavior, and improving sleep quality may reduce pain intensity in youth with SLE. Although further study is needed, the findings suggest that sleep is a potential target for interventions to alleviate symptoms of pain in this population. Support (if any) This work was funded by NIH/NINR P30NR016585 (MPI: MMH, TMW), R21NR017471 (TMW); University of Washington, School of Nursing, Research and Intramural Funding (RIFP); Hester McLaws Nursing Scholarship.

578 Sleep Attitudes and Beliefs in Children with Juvenile Idiopathic Arthritis and Their Caregivers

Abstract Introduction Sleep deficiency is highly comorbid in children with juvenile idiopathic arthritis (JIA), affecting approximately 40% of children. In this study, we examined children’s and parents’ beliefs and attitudes about sleep, their self-efficacy, and self-regulation in sleep-related behaviors and managing JIA, and if these factors were associated with their self-report and actigraphic sleep patterns. Methods The sample included 44 children with JIA (22 girls; mean age 10.5±1.8) and their parents. Dyads completed the Dysfunctional Beliefs and Attitudes about Sleep Scale and Self-Efficacy Scale. Children completed the Index of self-regulation. Parents completed the Pittsburgh Sleep Quality Index and PROMIS sleep-disturbance. Children wore an actiwatch and completed electronic sleep diaries for ten days. Scored actigraphy variables included children’s total sleep time (TST), wake time after sleep onset (WASO), sleep efficiency (SE, %); sleep diaries included the variables of children’s time in bed (TIB). Parents’ self-reported variables included sleep-disturbances and sleep quality (SQ). Results Children’s mean TST was 7.7 hours (±0.7), mean SE of 77%, and mean WASO of 1.1 hours (±0.4). After adjusting for child sex and age, children’s beliefs and attitudes towards sleep (BAS) were positively correlated with their self-efficacy in carrying out sleep-related behaviors (r=.6, p&amp;lt;.0001). Parents’ BAS were positively correlated with child self-efficacy in sleep (r=.4, p&amp;lt;.05) and TIB (r=.4, p&amp;lt;.001). Children’s self-regulation was positively correlated with parents’ SQ (r=.4, p&amp;lt;.05). In the first regression model, parents’ self-efficacy in managing their child’s JIA and parents’ sleep disturbances explained 25% of the variance of children’s TST, (F(4,35)=2.8, p=.039). Both parents’ self-efficacy and sleep disturbances were significant predictors of children’s TST. In the second regression model, children’s self-regulation, self-efficacy, and parents’ sleep disturbances explained 32% of the variance of parents’ self-reported SQ, (F (3,39)= 6.12, p=.002). Conclusion The findings suggest that self-efficacy, self-regulation, BAS in both children and parents were associated with better sleep health. Interventions that incorporate parent-child shared decision making about sleep-related knowledge, motivation, skills for setting/achieving goals, and problem-solving strategies are needed for families with children with JIA and sleep deficiency. Support (if any) This work was supported by the NIH/ /NINR (P30NR016585, R21NR01747).

Itch and Sleep Improvements with Baricitinib in Patients with Atopic Dermatitis: A Post Hoc Analysis of 3 Phase 3 Studies.

IntroductionBurdensome symptoms of atopic dermatitis include itch and sleep disturbance. This post hoc analysis reports the effect of baricitinib on itch and sleep disturbance during the first week of treatment in 3 phase 3 studies.MethodsPatients were randomized 2:1:1:1 to once-daily placebo or baricitinib 1 mg, 2 mg, or 4 mg in the BREEZE-AD1 and -AD2 studies and 1:1:1 to once-daily placebo or baricitinib 2 mg or 4 mg in the BREEZE-AD7 study. Topical corticosteroids were only allowed in BREEZE-AD7. Patients completed the itch numerical rating scale and atopic dermatitis sleep scale (ADSS) items 1–3 using an electronic daily diary. Data were analyzed by study as least squares mean percent change from baseline in daily scores for the randomized patients. Mixed model repeated measures analysis was used to analyze change from baseline values.ResultsA total of 624, 615, and 329 patients were randomized in BREEZE-AD1, -AD2, and -AD7, respectively. Itch severity significantly improved with baricitinib 2 mg and 4 mg versus placebo starting at day 2 (1 day after first dose) in BREEZE-AD1 and -AD7 and at day 1 in BREEZE-AD2. Patients’ ability to fall asleep (ADSS item 1) significantly improved with baricitinib 2 mg and 4 mg versus placebo starting at day 2 in all three studies. There were significant improvements in patients waking due to itch (ADSS item 2) with baricitinib 4 mg versus placebo starting at day 2 in all three studies. Patients’ ability to return to sleep after being woken by itch (ADSS item 3) was significantly improved with baricitinib 4 mg versus placebo starting at day 2 in BREEZE-AD1 and -AD2 and at day 4 in BREEZE-AD7.ConclusionRapid onset of action, typically 1 day after taking the first dose of baricitinib, was observed consistently for the burdensome symptoms of itch and sleep disturbance.ClinicalTrials.gov identifiersBREEZE-AD1, NCT03334396; BREEZE-AD2, NCT03334422; BREEZE-AD7, NCT03733301.