INTRODUCTION:Migraine-related stigma (MiRS) and social burden is increasingly recognized. We assessed perspectives and attitudes toward migraine in people with and without migraine in Japan. METHODS:OVERCOME (Japan) was a cross-sectional, population-based web survey of people with and without migraine (July-September 2020). People with migraine were individuals who met the modified International Classification of Headache Disorders criteria or had self-reported physician-diagnosed migraine. People without migraine were selected per quota sampling to represent the Japanese adult population. People with migraine reported their experiences on stigma and social burden and answered how frequently they experienced stigma using the MiRS questionnaire. Associations between MiRS and disability and MiRS and interictal burden were examined using the migraine disability assessment and Migraine Interictal Burden Scale-4. People without migraine reported their experiences and attitudes toward people with migraine by answering an 11-item attitudinal migraine questionnaire. RESULTS:A total of 17,071 and 2008 people with and without migraine, respectively, completed the survey. Overall, 11,228 (65.8%) respondents with migraine reported that they have never experienced stigma or burden; however, of the 12,383 employed respondents, 5841 (47.2%) reported that their current employers are not "extremely" or "very" understanding about their conditions. Moreover, ∼30%-40% of respondents "sometimes," "often," or "very often" hid their migraine from others. The proportion of respondents who experienced stigma often or very often, as assessed by MiRS, was 16.5%; this increased with the increasing number of monthly migraine headache days. The proportion of respondents with moderate-to-severe disability and interictal burden increased with increasing stigma. Among respondents without migraine, the proportion holding a stigmatizing attitude toward those with migraine was low (<15%); ∼80% had never experienced work- or family-related stigma or burden. CONCLUSION:MiRS and burden exist but may be hidden and underrecognized in Japan. Disease awareness and education may be important to prevent and reduce stigma and burden.

454 Background: Patient preference is an important factor in selecting appropriate treatment choices. Although underutilized, the standard of care for MIUC is with NAC, whereas evidence for adjuvant therapy is less clear. With the introduction of novel adjuvant treatments such as immune checkpoint inhibitors, treatment options are expected to expand. This study examines whether preferences for adjuvant therapy is impacted in MIUC patients receiving NAC. Methods: A cross-sectional, web-based survey included patients ≥ 18 years old who self-reported being diagnosed with MIUC and underwent radical cystectomy or nephroureterectomy without recurrence. Patients were recruited from the US, UK, Canada, France, and Germany (May–Sep 2021). A DCE using 2 adjuvant treatment profiles included 8 attributes: cancer-free survival, overall survival (OS), hypothyroidism requiring life-long hormone therapy, risk of a serious adverse event (requiring medical intervention/possible hospitalization), nausea, fatigue, diarrhea, and a dosing regimen (frequency of treatment and monitoring); an opt-out option of no treatment was also shown. Patients were grouped according to self-reported receipt of NAC. Descriptive statistics and hierarchical Bayesian logistic model with estimated preference weights were used. Relative importance estimates (mean ± standard error), or how much the attribute ranges accounted for the variation in preferences, were computed for each attribute. Bivariate comparisons used t-tests. Results: This interim analysis identified 205 patients (70.7% of target sample; US, n = 99; Germany, n = 60; UK, n = 31; Canada, n = 14; France, n = 1). Of 82 patients (40.0%) receiving NAC, 32.7% were patients > 65 years and 55.1% were male; receipt of NAC did not differ by age ( P = 0.248) or sex ( P = 0.731). Patients were willing to accept increased risk in toxicities for increased treatment efficacy. Specifically, mean relative importance of treatment attributes showed that difference in median OS (25 months compared to 78 months) was most important (34.6% ± 1.6), although less so for those who did not receive NAC (30.2% ± 2.4 vs 37.5% ± 2.0; P = 0.022). Patients chose an adjuvant treatment option over ‘no treatment’ 91% of the time, with similar findings by NAC status. Conclusions: Preliminary data indicates that receipt of NAC impacts preferences for adjuvant treatment attributes. However, regardless of these attributes, patients still preferred adjuvant treatment over none. These results suggest that providing standard of care NAC does not reduce patient preference for adjuvant therapy; rather, patient preferences for adjuvant treatment attributes vary by treatment history, with implications for improving quality of care and outcomes.

The synthesis of three fluorogenic chitobiosyl derivatives, modified at the non-reducing 4′-OH with, either a methyl, an isopropyl or a cyclohexylmethyl substituent, is described. The 4′-capped 4-methylumbelliferyl chitobiosides are hydrolysed by the human chitinase CHIT1 following Michaelis–Menten kinetics and in contrast to unmodified chitobiosyl-4-methylumbelliferone do not undergo transglycosylation. The compounds are also relatively poor hexosaminidase substrates and thus provide useful alternatives to 4′-deoxychitobiosyl-4-methylumbelliferone, previously reported by us as fluorogenic substrate to monitor CHIT1 activity as a marker for Gaucher disease state.

Electronic health records (EHRs) are a real-time aggregate of patient health and related data for improved care and outcomes. Inconsistencies in patient data within and between healthcare systems may result from variability in collection methods, documentation, and coding practices, in addition to longitudinal changes in a patient's profile. This study examines the impact of multiple entries for patient demographic information on data quality in the US Cerner Real-World Data (CRWD).

Data on the prevalence of alopecia areata (AA) in Japan is limited and the epidemiology of the disease there is not well understood; therefore, it is critical to examine the prevalence and severity of AA in Japan to inform the need for future treatments and research. A cross-sectional, web-based survey was conducted in Japan from January through March 2021. A total of 45006 participants were identified through general population survey panels and asked about their experience with AA and hair loss. The Alopecia Assessment Tool and the Scalp Hair Assessment PRO (TM) were adopted to screen for history of AA and assess disease severity, respectively. Eligible participants submitted photos of their scalp, which were reviewed by three board-certified dermatologists to evaluate the presence and severity of AA. Prevalence and severity estimates were calculated using participants' self-reported data and verified through the dermatologists' assessments. The participant-reported point prevalence of AA was 2.18%. The adjusted point prevalence following physician adjudication using participant-submitted photos was 1.45%. Topical corticosteroids were the most commonly used treatments, with 34.6% of participants diagnosed with AA reported having ever used them. Participants also reported negative impacts on their mood (70.2%), self-esteem (55.8%), and social interactions (48.9%). Despite the social and emotional impact of hair loss, more than one third of those reporting a physician diagnosis of AA were not currently seeking treatment. The current study identified an estimated prevalence of AA in Japan between 1.45% and 2.18% based on the survey results and physician-adjudication of those findings. Considering the impactful psychological burden of AA, the survey results showing that 38.90% of surveyed patients do not currently seek treatment may indicate an unmet need for remedies.

Background Gaucher disease (GD) is a rare autosomal recessive lysosomal storage disorder. GD types 2 and 3 are known as neuronopathic Gaucher disease (nGD) because they have brain involvement that progresses over time. Implementing a systematic approach to the collection of real-world clinical and patient-relevant outcomes data in nGD presents an opportunity to fill critical knowledge gaps and ultimately help healthcare providers in the management of this patient population. This paper summarizes the development of a patient-initiated Gaucher Registry for Development Innovation and Analysis of Neuronopathic Disease (GARDIAN). Methods The International Gaucher Alliance led the GARDIAN planning, including governance, scope, stakeholder involvement, platform, and reporting. Registry element input was determined in a series of meetings with clinical experts, patients, and caregivers, who identified key clinical variables and the draft content of nGD patient-reported outcomes (PRO) and observer-reported outcomes (ObsRO) focusing on symptoms, patient physical and emotional functioning. These were then tested in cognitive interviews with patients with nGD (> 12 years of age) and caregivers. Results Core registry data elements (n = 138) were identified by seven global clinical experts from Egypt, Germany, Israel, Japan, United Kingdom (UK), and United State (US) and reviewed via online Delphi method by 14 additional clinicians with experience of nGD from six countries and three pharmaceutical representatives. The elements were consistent with those identified via interviews with 10 patients/caregivers with nGD from Japan, Sweden, UK, and US. Key domains identified were demographics, diagnostic information, health status, clinical symptomatology, laboratory testing, treatment, healthcare resource utilization, aids/home improvements, and patient/caregiver burden and quality of life, specifically physical functioning, self-care, daily and social activities, emotional impacts, support services, and caregiver-specific impacts. Nine caregivers and six patients from the US, UK, China, Mexico, Egypt, and Japan participated in the cognitive interviews that informed revisions to ensure that all items are understandable and interpreted as intended. Conclusions The comprehensive set of clinical and patient relevant outcomes data, developed collaboratively among all stakeholders, to be reported using GARDIAN will bridge the many gaps in the understanding of nGD and align with regulatory frameworks on real-world data needs.

Knowledge of patient outcomes and treatment effectiveness associated with acute migraine treatments in Japan is lacking. To describe patient-reported outcomes (PROs) and treatment effectiveness in three acute treatment groups from OVERCOME (Japan): over-the-counter (OTC) only, prescription nonsteroidal anti-inflammatory drugs/acetaminophen (Rx-NSAIDs/ACE) only, and triptans. OVERCOME (Japan) was an observational, cross-sectional, population-based web survey of people with migraine (July–September 2020). PROs, including the Migraine-Specific Quality of Life Questionnaire (MSQ), Migraine Interictal Burden Scale (MIBS-4), Migraine Disability Assessment (MIDAS), and Work Productivity and Activity Impairment Questionnaire: Migraine (WPAI-M), were compared pairwise between treatment groups. Logistic regression was used to examine treatment effectiveness. The analysis included 9075 survey respondents (OTC only: n = 5791; Rx-NSAIDs/ACE only: n = 751; triptans: n = 2533). Triptan users reported the lowest MSQ scores, most severe disability (MIDAS: 20.7

Objective This study assessed associations between severity of, and prescription medication use for, chronic low back pain (CLBP) and health-related quality of life, health status, work productivity, and healthcare resource utilization. Methods This cross-sectional study utilized SF-12, EQ-5D-5L, and work productivity and activity impairment (WPAI) questionnaires, and visits to healthcare providers among adults with self-reported CLBP participating in the National Health and Wellness Survey in Germany, France, UK, Italy, and Spain. Respondents were stratified into four groups according to pain severity (mild or moderate/severe) and prescription medication use (Rx-treated or Rx-untreated). Differences between groups were estimated using generalized linear models controlling for sociodemographics and health characteristics. Results Of 2086 respondents with CLBP, 683 had mild pain (276 Rx-untreated, 407 Rx-treated) and 1403 had moderate/severe pain (781 Rx-untreated, 622 Rx-treated). Respondents with moderate/severe pain had significantly worse health-related quality of life (SF-12v2 physical component summary), health status (EQ-5D-5L), and both absenteeism and presenteeism compared with those with mild pain, including Rx-untreated (moderate/severe pain Rx-untreated vs. mild pain Rx-untreated, p <= 0.05) and Rx-treated (moderate/severe pain Rx-treated vs. mild pain Rx-treated, p <= 0.05) groups. Significantly more visits to healthcare providers in the last 6 months were reported for moderate/severe pain compared with mild pain for Rx-treated (least squares mean 13.01 vs. 10.93, p = 0.012) but not Rx-untreated (8.72 vs. 7.61, p = 0.072) groups. Health-related quality of life (SF-12v2 physical component summary) and health status (EQ-5D-5L), as well as absenteeism and presenteeism, were significantly worse, and healthcare utilization was significantly higher, in the moderate/severe pain Rx-treated group compared with all other groups (all p <= 0.05). Conclusion Greater severity of CLBP was associated with worse health-related quality of life, health status, and absenteeism and presenteeism, irrespective of prescription medication use. Greater severity of CLBP was associated with increased healthcare utilization in prescription medication users.

Using data from the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE study in Japan (OVERCOME [Japan]), we describe the current status of the acute treatment of migraine in Japan. OVERCOME (Japan) was a cross-sectional, observational, population-based web survey of people with migraine in Japan (met modified International Classification of Headache Disorders criteria or had a physician diagnosis of migraine) conducted between July and September 2020. Respondents reported current acute medication use and effectiveness (assessed using the Migraine Treatment Optimization Questionnaire [mTOQ-4]). Cardiovascular history and risk factors of the respondents were also recorded. Potential unmet acute treatment needs were defined as insufficient effect of current acute treatments (mTOQ-4 score ≤ 5), a history of oral triptan use (and not currently taking any triptan), potential contraindications to triptans due to cardiovascular comorbidities, and/or cardiovascular risk factors. In total, 17,071 people with migraine in Japan completed the survey; 14,869 (87.1%) of these were currently using acute treatments. Poor effectiveness of current acute treatment was reported by 7170 respondents (42.0%), 900 respondents (5.3%) were former triptan users, 1759 (10.3%) had contraindications to triptans, and 9026 (52.9%) reported at least one cardiovascular risk factor. Overall, 12,649 (74.1%) of OVERCOME (Japan) respondents were categorized into one or more of these groups and were considered to have potential unmet acute treatment needs. Almost three-quarters of people with migraine in Japan may have potential unmet needs for acute treatment of migraine. There are substantial opportunities for improving care for people with migraine in Japan, including prescription of novel acute medications.

Esophageal cancer is the 8th-most common cancer and the 6th-most common cause of cancer-related deaths worldwide; 5-year overall survival is 18%. Patients with advanced esophageal squamous cell carcinoma (advESCC) most commonly receive systemic therapy. Platinum (Pt) and fluoropyrimidine (FP) doublet is the most common standard first line (1L) regimen. This study describes global and regional treatment patterns and outcomes, including healthcare resource utilization (HCRU) of patients with advESCC. This retrospective, non-interventional, cross-sectional study collected demographic and clinical data, as well as 1L treatment characteristics from the most recent medical charts of patients with advESCC treated by 425 physicians from Asian (Japan, Korea, Taiwan, and China) and Western (US, Canada, France, Germany, Italy, Spain, and UK) countries, September-October 2018. Regional bivariate comparisons were conducted. Patients with advESCC (Asia n=169; West n=256) who received 1L Pt+FP therapy had a mean (SD) age 64.4 (8.4) years and were 85.2% male. At diagnosis, fewer Asian compared to Western patients were diagnosed with metastases (42.0% versus 67.2%, respectively; p<0.001). No differences were observed for performance status at diagnosis and 1L initiation. Both physician rationale for treatment and treatment discontinuation differed by region (p≤0.004). Asian patients (36.1%) completed fewer planned number of 1L cycles compared to Western patients (54.7%) and the all-cause discontinuation of treatment (disease progression, treatment resistance/toxicity, or death) was higher in Asia (54.4%) versus the West (40.6%). Asian patients experienced more adverse events (AEs) and had higher HCRU, including AE-related hospitalizations (Asia=11.8 versus West=7.3; p=0.045). The percentage of patients who progressed or died following 1L was similar across regions (Asia=48.5% versus West=55.9%; p=0.138). Regionally, AE prevalence and treatment-related HCRU differed. Despite higher rates of discontinuation, increased AEs, and increased HCRU in Asia versus the West, the outcomes of a 1L standard treatment with Pt+FP were comparable in both regions.

Abstract Background Esophageal cancer is a highly prevalent cancer associated with low survival, especially among those with advanced disease. Second‐line (2L) treatment patterns and related clinical outcomes of patients with advanced esophageal squamous cell carcinoma (advESCC) treated in routine clinical care were examined globally and regionally. Methods A retrospective, noninterventional study collected physician‐provided chart data of patients aged ≥20 years receiving either 2L active systemic therapy or BSC following first‐line active therapy for advESCC from 11 countries in Asian and Western regions (September–October 2018). Bivariate analyses examined treatment and outcomes by region. Results AdvESCC patients (Asia = 192; West = 195) were examined, of which 58.1% (Asia n = 101; West n = 124) received active systemic therapy. While regional differences in tumor classification and staging at diagnosis were observed with less advanced tumors in Asia, no regional differences for these characteristics at 2L initiation were reported. Both taxane‐ and nontaxane‐based therapies were used as 2L therapy among Asian and Western patients, although more western than Asian patients received immuno‐ or targeted therapies (17.0% vs. 3.0%; p = 0.001). Alopecia (10.7%), neutropenia (9.3%), and fatigue (9.3%) were the most‐commonly reported adverse events (AEs) in both regions. Significantly higher 2L AE‐related emergency room visits (Asia = 22.5% vs. West = 8.0%; p < 0.001) and hospitalizations (Asia = 25.9 ± 31.2 vs. West = 4.7 ± 7.0, p < 0.001) were observed in Asian than in Western patients. No regional differences were reported for response to 2L treatment or the percent of patients who received third‐line treatment/died. Conclusions While regional variations were observed throughout the course of a patient's advESCC journey, disease response and treatment outcomes were similar.

Information on race is often missing or incorrect in Electronic Health Records (EHR) potentially rendering study findings uninterpretable. This following seeks to characterize patients with unknown race. The 2021 US Cerner Real-World Data (CRWD), a cloud-based, de-identified, and Health Insurance Portability and Accountability Act-compliant dataset was examined. In the CRWD, race is mapped to a standardized set using the input and codes particular to each health system. Included were patients with ≥1 encounter in 2021 classified only as 'unknown' race (11.1%). Excluded from this group were patients with an invalid age (1.3%). Patient, health system, and encounter characteristics were assessed. Unknown race was grouped as: not asked/unknown (NA/UNK), refused/declined to answer (REF/DEC), and ethnicity reported (ETH). Chi-square tests and pairwise comparisons tested group differences. In 2021, 2,636,457 patients were identified as 'unknown' race, with NA/UNK=79.0%, REF/DEC=11.8%, and ETH=9.2%. By age groups, children (<18 years) compared to adults (18-64 years) or older adults (≥65 years) were more likely to report REF/DEC (14.9% versus 10.5% versus 10.6%; p<0.001). Race as ETH differed by age group at a decreasing frequency (<18 years=12.7%, 18-64 years=8.6%, ≥65 years=4.5%; p<0.001). Minimal but statistically significant differences in unknown-type reporting were observed by gender (p<0.001), however, more substantial differences were noted for zip code zone and health system (p<0.001). For example, patients residing in zip code zone 4 were more likely than those in other zones to report REF/DEC (39.3% versus 12.8%; p<0.001). Notably, data were unknown for zip code (22.9%) and gender (1.4%). Median annual number of encounters were NA/UNK=3, REF/DEC=7, and ETH=9. Missing and uninterpretable data, often quantified using the unknown category, can inform on poor data quality and bias. This study distinguishes between subgroups of patients with unknown race offering future opportunities for improving data quality, identifying at-risk groups, and developing health equity-related policies.

Objective The ObserVational survey of the Epidemiology, tReatment and Care of MigrainE (OVERCOME; United States) study is a multicohort, longitudinal web survey that assesses symptomatology, consulting, diagnosis, treatment, and impact of migraine in the United States. Background Regularly updating population-based views of migraine in the United States provides a method for assessing the quality of ongoing migraine care and identifying unmet needs. Methods The OVERCOME (US) 2018 migraine cohort involved: (I) creating a demographically representative sample of US adults using quota sampling (n = 97,478), (II) identifying people with active migraine in the past year via a validated migraine diagnostic questionnaire and/or self-reported medical diagnosis of migraine (n = 24,272), and (III) assessing consultation, diagnosis, and treatment of migraine (n = 21,143). The current manuscript evaluated whether those with low frequency episodic migraine (LFEM; 0-3 monthly headache days) differed from other categories on outcomes of interest. Results Among the migraine cohort (n = 21,143), 19,888 (94.1%) met our International Classification of Headache Disorders, 3rd edition-based case definition of migraine and 12,905 (61.0%) self-reported a medical diagnosis of migraine. Respondents' mean (SD) age was 42.2 (15.0) years; 15,697 (74.2%) were women. Having at least moderate disability was common (n = 8965; 42.4%) and around half (n = 10,783; 51.0%) had consulted a medical professional for migraine care in the past year. Only 4792 (22.7%) of respondents were currently using a triptan. Overall, 8539 (40.4%) were eligible for migraine preventive medication and 3555 (16.8%) were currently using migraine preventive medication. Those with LFEM differed from moderate and high frequency episodic migraine and chronic migraine on nearly all measures of consulting, diagnosis, and treatment. Conclusion The OVERCOME (US) 2018 cohort revealed slow but steady progress in diagnosis and preventive treatment of migraine. However, despite significant impact among the population, many with migraine have unmet needs related to consulting for migraine, migraine diagnosis, and getting potentially beneficial migraine treatment. Moreover, it demonstrated the heterogeneity and varying unmet needs within episodic migraine.

Disease-specific outcomes measures are lacking for type 2 and 3 Gaucher Disease (GD), where neurological signs are present (nGD). GD is a rare genetic metabolic disorder; treatment aims to manage symptoms, prevent irreversible damage, and improve quality of life. To collaborate with patients and caregivers to develop nGD-specific patient- and observer-reported outcomes (PRO and ObsRO) measures focusing on symptoms and health-related quality of life.

Response styles, the tendency to systematically provide one type of answer over another, may impact the comparability of patient-reported outcomes (PROs) across countries. We examined the effect of country-level response styles on PROs of patients with migraine in nationally representative surveys. Respondents aged ≥18 years, with a self-reported medical diagnosis of migraine, and who reported current prescription migraine medication use were identified from the National Health and Wellness Survey: China (2020; n=790), France (2020; n=981), Germany (2020; n=639), Italy (2020; n=748), Japan (2019; n=651), South Korea (2020; n=1009), Spain (2020; n=603), Taiwan (2020; n=747); UK (2020; n=722); and US (2019; n=4118). PROs included migraine severity, treatment satisfaction (not available for South Korea or Taiwan), and Work Productivity and Activity Impairment (WPAI). After calculating and controlling for a general response style factor, descriptive statistics examining group differences were conducted. Preliminary results indicated the presence of country-level differences in response styles (reference points). Respondents (n=11,008) were on average 43.2 (SD=14.7) years old and 69.3% female, with an average of 4.2 (SD=6.0) migraine events (past 30 days). After accounting for response styles (group differences in reference points), average medication satisfaction across countries was similar (mean=5.0, SD=1.4), however higher top 2 box medication satisfaction ratings were shown in the US=42.1% relative to Germany=40.4%, UK=38.2%, France=36.8%, Spain=33.3%, China=28.4%, Japan=26.3%, and Italy=24.6%. Work impairment differed by country where the 90th percentile for absenteeism varied from 50% in the US, 33%-78% in Europe, and 18%-30% in Asian countries. However, the 90th percentile for presenteeism was similar across countries (70-80%). Results from these nationally representative surveys showed the presence of country-specific response styles to migraine-related items for subjective and validated PROs. Accounting for the influences of response styles, such as culture, should be considered when interpreting outcome measures among patients with migraine.

Gaucher Disease (GD) is a rare inherited metabolic disorder. Type 2 and Type 3 are neuronopathic and often result in infant death or progressive neurological deterioration. Current drug therapies do not cross the blood brain barrier and thus do not treat neuronopathic GD (nGD). GARDIAN data will generate real-world evidence on the natural history and impact of disease and will inform clinical trial design and healthcare decision making. The objective is to describe the development of a patient registry specific to nGD.