Development and validation of a 13-item short version of the inflammatory bowel disease self-efficacy scale.

BACKGROUND: The inflammatory bowel disease self-efficacy scale (IBD-SES) is an instrument used across many countries to measure important health outcomes of patients with inflammatory bowel disease (IBD). We aimed to develop and validate a substantially shorter version of this scale to reduce patients' response burden. METHODS: A total of 919 patients with IBD, 482 recruited from an IBD clinic and 437 recruited online, completed the Japanese version of the original, 29-item IBD-SES. These data were then used to develop a shorter version of the scale. The original 29 items of the IBD-SES were reduced with three analytic steps: assessing ceiling and floor effect, testing correlation between items, and assessing test-retest reliability. The resulting 13-item IBD-SES was evaluated for construct validity by confirmatory factor analysis, criterion validity by Pearson correlation coefficients with original version, and internal consistency by item-total correlations and the Cronbach's α coefficient. RESULTS: The short version consisted of the same four subscales "managing stress and emotions," "managing medical care," "managing symptoms and disease," and "maintaining remission" as the original scale. The fit indices of the final model were as follows: normed chi-square, 7.18 (p < 0.001); comparative fit index, 0.94; goodness-of-fit index, 0.93; adjusted goodness-of-fit index, 0.89; parsimony goodness-of-fit index, 0.60; and root mean square error of approximation, 0.084. Correlation of each subscale with the original scale was high (0.97-0.98). Cronbach's α for each subscale ranged from 0.68 to 0.86. CONCLUSIONS: A short version of the IBD-SES was developed. The results confirmed the improved validity, reliability, and psychometric properties of the IBD-SES. TRIAL REGISTRATION: Not applicable.

Safety and effectiveness of rasagiline in patients with Parkinson's disease in Japan: a post-marketing surveillance study.

BACKGROUND: Rasagiline is a monoamine oxidase B inhibitor for the treatment of Parkinson's disease (PD). This study assessed the safety and effectiveness of rasagiline in patients with PD in routine clinical practice in Japan. RESEARCH DESIGN AND METHODS: This multicenter, prospective, observational study (148 sites) enrolled patients (1 November 2018-31 October 2020) with PD. Patients received rasagiline orally 1 mg once daily; maximum observation period was 24 months. The incidence of adverse drug reactions (ADRs) was evaluated; effectiveness was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III total score. RESULTS: The safety analysis set comprised 961 patients (mean age, 72.50 years; 53.80% female; mean duration of PD, 6.82 years). Mean treatment duration was 14.74 months, with 42.25% receiving rasagiline for ≥ 19 months; 189 (19.67%) had ≥ 1 ADR. Common ADRs were dyskinesia (4.06%), orthostatic hypotension (2.29%), hallucination (1.87%), visual hallucination, nausea, fall (1.56% each), dizziness (1.35%), and somnolence (1.25%). Mean (standard deviation) UPDRS Part III total score was 28.5 (14.35) at baseline and 25.5 (14.98) at the final assessment. CONCLUSIONS: No new concerns in safety and effectiveness regarding rasagiline in Japanese patients with PD were raised. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03727139; Japan Pharmaceutical Information Center Clinical Trials Information: JapicCTI-184181.

A web-based survey on self-management for patients with inflammatory bowel disease in Japan.

BACKGROUND/AIMS: Self-management (SMN) is a recognized component of care for chronic conditions, yet its importance in the context of inflammatory bowel disease (IBD) is unclear. This study evaluates the status of SMN and its relationship with quality of life (QOL) in Japanese patients with IBD. METHODS: A web-based survey was conducted among adult (≥20 years old) Japanese patients with ulcerative colitis (UC) or Crohn's disease (CD). Registered members of an online IBD information platform completed a 45-item survey covering demographics, diet, treatment, physical condition, stress management, financial concerns, support services, and QOL. SMN was operationally defined by dietary and lifestyle behaviours, and contingency analysis was used to test for associated factors. Individual-level contributions to SMN were identified with logistic regression. RESULTS: There were 372 responses to the survey (211 with UC, 161 with CD). Approximately 60% of participants practiced SMN and these patients were 4-24% more likely to report positive QOL than those who did not. SMN was more common in patients with CD than those with UC. SMN practice was also associated with IBD-related hospitalisation/surgery and consultation with others about IBD (e.g. physicians, nurses, patients). CONCLUSIONS: The results of this study suggest an association between the practice of SMN and positive QOL in patients with IBD in Japan.

A Systematic Review of Self-Management Interventions for Patients with Inflammatory Bowel Disease.

Introduction: Previous studies have reported the effectiveness of inflammatory bowel disease (IBD) self-management. However, it is unclear which types of self-management interventions are effective. We conducted a systematic literature review to clarify the status and efficacy of self-management interventions for IBD. Methods: Searches were performed in databases including Embase, Medline, and Cochrane Library. Randomized, controlled studies of interventions in adult human participants with IBD involving a self-management component published in English from 2000 to 2020 were included. Studies were stratified based on study design, baseline demographic characteristics, methodological quality, and how outcomes were measured and analyzed for statistically significant improvements in outcomes, such as psychological health, quality of life, and healthcare resource usage. Results: Among 50 studies included, 31 considered patients with IBD and 14 and 5 focused on patients with ulcerative colitis and Crohn's disease, respectively. Improvements in an outcome were reported in 33 (66%) studies. Most of the interventions that significantly improved an outcome index were based on symptom management and many of these were also delivered in combination with provision of information. We also note that among effective interventions, many were conducted with individualized and patient-participatory activities, and multidisciplinary healthcare practitioners were responsible for delivery of the interventions. Conclusion: Ongoing interventions that focus on symptom management with provision of information may support self-management behavior in patients with IBD. A participatory intervention targeting individuals was suggested to be an effective intervention method.

Association of ulcerative colitis symptom severity and proctocolectomy with multidimensional patient-reported outcomes: a cross-sectional study.

BACKGROUND: The YOu and Ulcerative colitis: Registry and Social network (YOURS) is a large-scale, multicenter, patient-focused registry investigating the effects of lifestyle, psychological factors, and clinical practice patterns on patient-reported outcomes in patients with ulcerative colitis in Japan. In this initial cross-sectional baseline analysis, we comprehensively explored impacts of symptom severity or proctocolectomy on nine patient-reported outcomes. METHODS: Patients receiving tertiary care at medical institutions were consecutively enrolled in the YOURS registry. The patients completed validated questionnaires on lifestyle, psychosocial factors, and disease-related symptoms. Severity of symptoms was classified with self-graded stool frequency and rectal bleeding scores (categories: remission, active disease [mild, moderate, severe]). The effects of symptom severity or proctocolectomy on nine scales for quality of life, fatigue, anxiety/depression, work productivity, and sleep were assessed by comparing standardized mean differences of the patient-reported outcome scores. RESULTS: Of the 1971 survey responses analyzed, 1346 (68.3%) patients were in remission, 583 (29.6%) had active disease, and 42 (2.1%) had undergone proctocolectomy. A linear relationship between increasing symptom severity and worsening quality of life, fatigue, anxiety, depression, and work productivity was observed. Patients with even mild symptoms had worse scores than patients in remission. Patients who had undergone proctocolectomy also had worse scores than patients in remission. CONCLUSIONS: Ulcerative colitis was associated with reduced mood, quality of life, fatigue, and work productivity even in patients with mild symptoms, suggesting that management of active ulcerative colitis may improve patient-reported outcomes irrespective of disease severity. (UMIN Clinical Trials Registry: UMIN000031995, https://www.umin.ac.jp/ctr/index-j.htm ).

Survey on the Impact of the COVID-19 Pandemic on Patients with Parkinson's Disease and Their Caregivers in Japan.

Objective: The coronavirus disease 2019 (COVID-19) pandemic changed the lives of patients with Parkinson's disease (PD) and their caregivers. This study aimed to investigate changes in patient behavior and PD symptoms and their effect on caregiver burden resulting from the COVID-19 pandemic in Japan. Methods: This nationwide, observational, cross-sectional survey included patients with self-reported PD and caregivers (members of the Japan Parkinson's Disease Association). The primary objective was to evaluate changes in behaviors, self-assessed PD symptoms, and caregiver burden from pre-COVID-19 (February 2020) to post-national state of emergency (August 2020 and February 2021). Results: Responses from 1883 patients and 1382 caregivers from 7610 distributed surveys were analyzed. Mean (standard deviation) age of patients and caregivers was 71.6 (8.2) and 68.5 (11.4) years, respectively; 41.6% of patients had a Hoehn and Yahr (HY) scale of 3. Patients (>40.0%) reported decreased frequency of going out. Most patients (>70.0%) reported no change in treatment visit frequency, voluntary training, or rehabilitation and nursing care insurance services. Symptoms worsened for approximately 7-30% of patients; the proportion with HY scale 4-5 increased from pre-COVID-19 (25.2%) to February 2021 (40.1%). Aggravated symptoms included bradykinesia, walking, gait speed, depressed mood, fatigue, and apathy. Caregivers' burden increased because of patients' worsened symptoms and reduced time going out. Conclusion: Control measures during infectious disease epidemics should consider that patients' symptoms may worsen; therefore, patient and caregiver support is needed to reduce burden of care.

Safety and Effectiveness of Vedolizumab in Patients with Moderate-to-Severe Ulcerative Colitis: An Interim Analysis of a Japanese Post-Marketing Surveillance Study.

INTRODUCTION: This ongoing post-marketing surveillance monitors the long-term safety and effectiveness of vedolizumab in routine clinical practice in patients with moderate-to-severe ulcerative colitis (UC) in Japan. This interim analysis assessed induction-phase data, covering the initial three doses of vedolizumab. METHODS: Patients were enrolled via a web-based electronic data capture system from approximately 250 institutions. Incidence of adverse events and treatment responses were assessed by the physicians after the patient had received three doses of vedolizumab or when the drug was discontinued, whichever occurred first. Therapeutic response was defined as any treatment response, including remission or improvement of complete or partial Mayo score, and was assessed in the total and stratified patient populations according to prior tumor necrosis factor alpha (TNFα) inhibitor treatments and/or baseline partial Mayo score. RESULTS: The total incidence of adverse drug reactions (ADRs) was 4.10% (11/268). Common ADRs were dizziness, nausea, and arthralgia, each reported in 0.75% of patients (2/268). Serious ADRs were herpes zoster oticus and UC, each reported in 0.37% of patients (1/268). Therapeutic response was reported in 84.5% (218/258) of all patients, 85.8% (127/148) of TNFα inhibitor-naïve patients, and 82.7% (91/110) of TNFα inhibitor-experienced patients. Among patients with partial Mayo score of ≥ 4 at baseline, partial Mayo score remission in patients without or with prior TNFα inhibitor treatment was 62.5% (60/96) and 45.6% (36/79), respectively. CONCLUSION: The results confirm a safety and effectiveness profile of vedolizumab consistent with that observed in previous trials. CLINICAL TRIAL REGISTRATION: JapicCTI-194603, NCT03824561.

Analytical and clinical validity of wearable, multi-sensor technology for assessment of motor function in patients with Parkinson's disease in Japan.

Continuous, objective monitoring of motor signs and symptoms may help improve tracking of disease progression and treatment response in Parkinson's disease (PD). This study assessed the analytical and clinical validity of multi-sensor smartwatch measurements in hospitalized and home-based settings (96 patients with PD; mean wear time 19 h/day) using a twice-daily virtual motor examination (VME) at times representing medication OFF/ON states. Digital measurement performance was better during inpatient clinical assessments for composite V-scores than single-sensor-derived features for bradykinesia (Spearman |r|= 0.63, reliability = 0.72), tremor (|r|= 0.41, reliability = 0.65), and overall motor features (|r|= 0.70, reliability = 0.67). Composite levodopa effect sizes during hospitalization were 0.51-1.44 for clinical assessments and 0.56-1.37 for VMEs. Reliability of digital measurements during home-based VMEs was 0.62-0.80 for scores derived from weekly averages and 0.24-0.66 for daily measurements. These results show that unsupervised digital measurements of motor features with wrist-worn sensors are sensitive to medication state and are reliable in naturalistic settings.Trial Registration: Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC-CTI): JapicCTI-194825; Registered June 25, 2019.

Computational Simulation Model to Predict Behavior Changes in Inflammatory Bowel Disease Patients during the COVID-19 Pandemic: Analysis of Two Regional Japanese Populations.

Managing inflammatory bowel disease (IBD) is a major challenge for physicians and patients during the COVID-19 pandemic. To understand the impact of the pandemic on patient behaviors and disruptions in medical care, we used a combination of population-based modeling, system dynamics simulation, and linear optimization. Synthetic IBD populations in Tokyo and Hokkaido were created by localizing an existing US-based synthetic IBD population using data from the Ministry of Health, Labor, and Welfare in Japan. A clinical pathway of IBD-specific disease progression was constructed and calibrated using longitudinal claims data from JMDC Inc for patients with IBD before and during the COVID-19 pandemic. Key points considered for disruptions in patient behavior (demand) and medical care (supply) were diagnosis of new patients, clinic visits for new patients seeking care and diagnosed patients receiving continuous care, number of procedures, and the interval between procedures or biologic prescriptions. COVID-19 had a large initial impact and subsequent smaller impacts on demand and supply despite higher infection rates. Our population model (Behavior Predictor) and patient treatment simulation model (Demand Simulator) represent the dynamics of clinical care demand among patients with IBD in Japan, both in recapitulating historical demand curves and simulating future demand during disruption scenarios, such as pandemic, earthquake, and economic crisis.

Cross-sectional web-based survey among haematologists and gastroenterologists in Japan to identify the key factors for early diagnosis of Gaucher disease.

BACKGROUND: Gaucher disease (GD) is a rare, inherited metabolic disorder resulting from glucocerebrosidase deficiency. Patients benefit from early treatment as complications can arise from delayed diagnosis. AIMS: To measure GD awareness among Japanese haematologists and gastroenterologists, who are the specialists most likely to encounter patients with symptoms recognised in the Gaucher Earlier Diagnosis Consensus (GED-C), such as hepatosplenomegaly and thrombocytopenia. Additionally, we aimed to determine key signs from the GED-C associated with early diagnosis. METHODS: A quantitative web survey assessed Japanese haematologists and gastroenterologists for their (i) basic awareness of GD, (ii) explicit awareness of GD signs, (iii) explicit awareness of GD treatments and (iv) accuracy in suspecting GD in model patients. RESULTS: Survey results from 160 haematologists and 166 gastroenterologists indicated that more than 50% of haematologists were aware of GD symptoms, diagnostic criteria and/or treatments, and 38% of them had experienced or suspected GD. The majority of gastroenterologists were unaware of GD or knew the disease only by name, with 20% experiencing or suspecting GD in practice. Almost 70% of haematologists knew of enzyme replacement therapy, while 47% of gastroenterologists were not aware of any treatments for GD. Of the GED-C items, an awareness of bone-associated signs was correlated with accurate GD diagnosis in model patients and this awareness was greater among haematologists than gastroenterologists. CONCLUSIONS: The present study showed that haematologists had greater awareness of GD than gastroenterologists, and that bone pain may be a key sign of GD to enhance early diagnosis.

Effect of omega-3 fatty acids on cardiovascular events in high-risk patients with hypertriglyceridemia in Japan: a 3-year post-marketing surveillance study (OCEAN3 survey).

BACKGROUND: Studies on the efficacy of prescription omega-3 polyunsaturated fatty acids to reduce cardiovascular events have produced conflicting results. RESEARCH DESIGN AND METHODS: This 3-year prospective post-marketing surveillance study evaluated the effect of omega-3-acid ethyl esters (O3AEE; usual dosage 2 g/day) on cardiovascular events in high-risk statin-treated Japanese patients with hypertriglyceridemia. Statin-treated patients not receiving O3AEE were included as a reference cohort. The composite primary endpoint was cardiovascular death, myocardial infarction, stroke, angina requiring coronary revascularization, or peripheral arterial disease requiring surgery or peripheral arterial intervention. RESULTS: At 3 years, Kaplan-Meier estimated cumulative incidence of the primary endpoint was 2.5% (95% confidence interval, 2.1%-2.9%) in O3AEE-treated patients (N = 6,580) and 2.7% (2.4%-3.1%) in non-O3AEE-treated patients (N = 7,784; hazard ratio, 0.99; 95% confidence interval, 0.79-1.23). Incidence of heart failure requiring hospitalization was 0.4% with O3AEE versus 0.8% in non-O3AEE-treated patients (hazard ratio, 0.47; 95% confidence interval, 0.28-0.78; P < 0.05). CONCLUSIONS: Among patients receiving statins, cardiovascular event incidence did not differ significantly between O3AEE-treated patients and non-O3AEE-treated patients. Further studies are required before definitive conclusions can be drawn on the effect of O3AEE on cardiovascular event incidence in high-risk patients with hypertriglyceridemia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02285166.

Long-term safety and effectiveness of vonoprazan for prevention of gastric and duodenal ulcer recurrence in patients on nonsteroidal anti-inflammatory drugs in Japan: a 12-month post-marketing surveillance study.

BACKGROUND: This study assessed the safety and effectiveness of vonoprazan for prevention of duodenal and gastric ulcer recurrence in patients on long-term nonsteroidal anti-inflammatory drugs (NSAIDs) in routine clinical practice. RESEARCH DESIGN AND METHODS: This 12-month, prospective, observational study (145 sites, Japan, September 2016-April 2020) analyzed patients with a history of gastric or duodenal ulcer who started once-daily vonoprazan and were receiving NSAIDs for pain. The primary outcome was the incidence of adverse drug reactions (ADRs). RESULTS: Most patients (86.7% [1099/1268]) received vonoprazan for at least 6 months. Most patients (98.6% [1250/1268]) received the 10-mg dose of vonoprazan, 38.3% (486/1268) received cyclooxygenase-2 inhibitors, and 61.7% (782/1268) received other NSAIDs. The overall incidence of ADRs was 0.71% (9/1268). Most commonly reported ADRs were gastrointestinal (0.32%), nervous system (0.16%), and hepatobiliary system (0.16%) disorders. The overall incidence of gastric or duodenal ulcer recurrence was 1.04% (95% CI 0.56-1.78). CONCLUSIONS: No new safety concerns were reported for vonoprazan for prevention of secondary ulcer or bleeding in patients receiving long-term NSAIDs. Vonoprazan was effective for preventing NSAID-related peptic ulcer recurrence in this real-world study. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03214198; Japan Pharmaceutical Information Center Clinical Trials Information: JapicCTI-163436.

Cost-Effectiveness of Vonoprazan Compared With Proton Pump Inhibitors in Patients Taking Low-Dose Aspirin for Secondary Prevention of Cardiovascular Events in Japan.

BACKGROUND: Low-dose aspirin (LDA) is used to prevent recurrent cardiovascular (CV) events, but is associated with upper gastrointestinal (GI) bleeding; concomitant use of a proton pump inhibitor (PPI) reduces this risk. This study aimed to assess the cost-effectiveness of vonoprazan compared with PPIs (lansoprazole and esomeprazole) in patients taking LDA for secondary prevention of CV events.Methods and Results: A Markov simulation model was developed to predict the number of GI bleeding and acute CV events using 3 strategies (vonoprazan+LDA, esomeprazole+LDA, and lansoprazole+LDA), which were translated into quality-adjusted life-years (QALYs) and costs. Transition probabilities and utilities were derived from the results of published literature, and medical costs were based on the Japanese National Health Insurance fee table and claims databases in 2020. Outcomes were projected over 30 years starting at age 65 years and discounted at 2% annually. Expected costs with esomeprazole 20 mg, lansoprazole 15 mg and vonoprazan 10 mg were JPY 1,225,657, JPY 943,930, and JPY 1,059,510, respectively. The QALY gain for vonoprazan vs. esomeprazole was 0.35, thus vonoprazan was dominant against esomeprazole. The QALY gain for vonoprazan vs. lansoprazole was 0.29 and the incremental cost-effectiveness ratio (ICER) was JPY 398,551, thus, vonoprazan was more cost-effective than lansoprazole. CONCLUSIONS: Vonoprazan is dominant or cost-effective compared with esomeprazole and lansoprazole in patients taking LDA for secondary prevention of CV events.

Development and Validation of a Japanese Version of the Inflammatory Bowel Disease Self-efficacy Scale and Cross-culture Study in Japan and the United States.

BACKGROUND: Self-efficacy is an important health outcome for patients with inflammatory bowel disease (IBD). We aimed to develop a Japanese version of the IBD-Self-Efficacy Scale (IBD-SES.J) and compare characteristics of self-efficacy of IBD patients with previously reported results from patients in the United States. METHODS: We conducted a questionnaire survey of patients with IBD from a specialized IBD clinic and respondents recruited online. Self-efficacy of patients in Japan and the United States were compared by Student t test and Cohen d coefficient to gauge effect size. RESULTS: A total of 919 valid responses were obtained: 482 patients from the specialized IBD clinic and 437 patients from the online survey. Significant differences (P < .01) were observed in the following 3 subscales: "managing stress and emotions," "managing symptoms and disease," and "maintaining remission" when comparing remission and active periods; and known-group validity was mostly confirmed. Cronbach's alpha coefficients of each subscale ranged between 0.85 and 0.94. Intraclass correlation coefficients (95% confidence intervals [CIs]) to assess test-retest reliability of each item were between 0.56 (95% CI, 0.47-0.64) and 0.78 (95% CI, 0.73-0.82). Self-efficacy scores for most items in Japanese patients with IBD were lower compared with patients in the United States, with moderate effect size (Cohen d > 0.5), especially in the subscale "managing stress and emotions." CONCLUSIONS: The study demonstrates the reliability and validity of the IBD-SESJ. Self-efficacy scores for most items in Japanese patients were lower than those of patients in the United States. Further investigation is required to understand cross-cultural score differences.

A self-efficacy scale adapted for Japanese patients with inflammatory bowel disease was found to be reliable and valid. Low self-efficacy, especially in "managing stress and emotion" domain, was observed more in Japanese patients than patients in the United States.

Validation and Functional Relevance of the Short Form of the Perceived Deficits Questionnaire for Depression for Japanese Patients with Major Depressive Disorder.

Purpose: To validate the five-item version of the Perceived Deficits Questionnaire for Depression (PDQ-D-5) for assessing subjective cognitive function in Japanese patients with major depressive disorder (MDD) using data from the PERFORM-J study. Patients and Methods: A total of 518 Japanese outpatients diagnosed with MDD were assessed on severity of depressive symptoms, cognitive function, social and work function, and quality of life (QoL) over 6 months following initiation of antidepressant therapy. This post hoc analysis evaluated the internal consistency and convergent validity of the PDQ-D-5 in relation to the original PDQ-D-20. Correlations of scores on these measures were examined at each time point and over time. The same set of analyses was explored between PDQ-D-5 and the Patient Health Questionnaire-nine-item (PHQ-9), Montgomery-Asberg Depression Rating Scale (MADRS), Digit Symbol Substitution Test (DSST), five-level version of EQ-5D (EQ-5D-5L), Sheehan Disability Scale (SDS), and Work Productivity and Activity Impairment (WPAI) questionnaire. Results: PDQ-D-5 scores showed good internal consistency. Strong positive correlations were observed between PDQ-D-5 and PDQ-D-20 at each time point (correlation coefficient: baseline, 0.94; month 1, 0.94; month 2, 0.96; month 6, 0.96) and over time (0.92) (all p < 0.0001). Longitudinally, there were positive correlations between PDQ-D-5 scores versus those on the PHQ-9, MADRS, and SDS. Similarly, negative correlations were noted between PDQ-D-5 scores and EQ-5D-5L and DSST scores to a variable degree. There were moderate positive correlations over time between PDQ-D-5 and all WPAI subscale scores except those on absenteeism. Conclusion: PDQ-D-5 scores rated in Japanese patients with MDD were found to adequately represent scores on the PDQ-D-20. The short version also showed associations with several measures of functional outcome, depression severity and QoL. This validates the PDQ-D-5 as a feasible and clinically reliable tool to assess subjective experience on cognition, which is applicable to time-limited consultations. UMIN Clinical Trials Registry for Primary Study: UMIN000024320.

An observational study to investigate the relationship between plasma glucosylsphingosine (lyso-Gb1) concentration and treatment outcomes of patients with Gaucher disease in Japan.

BACKGROUND: Gaucher disease (GD) is an autosomal recessive disease caused by GBA1 mutations resulting in glucosylceramide accumulation in macrophages. GD is characterized by hepatosplenomegaly, anemia, thrombocytopenia, bone complications, and neurological complications. Glucosylsphingosine (lyso-Gb1), a deacylated form of glucosylceramide, has been identified as a promising biomarker for the diagnosis and treatment response in GD. The aim of this study was to examine the relationship between plasma lyso-Gb1 and therapeutic goals for GD (improvements in hepatomegaly, splenomegaly, anemia, thrombocytopenia, bone pain, and bone crisis), as well as disease type and GBA1 mutation type, in Japanese patients with GD receiving velaglucerase alfa, an enzyme replacement therapy (ERT). Furthermore, this study compared the plasma lyso-Gb1 concentration observed in Japanese patients included in this study with that observed in a previous non-Japanese clinical study. RESULTS: This non-interventional, open-label, multicenter observational cohort study (October 2020 to March 2021) included a total of 20 patients (of any age) with GD (type 1: n = 8; type 2: n = 9; type 3: n = 3) treated with velaglucerase alfa for ≥ 3 months. Median (minimum-maximum) duration of velaglucerase alfa treatment was 49.5 (3-107) months. A total of 14 (70.0%) patients achieved all therapeutic goals (i.e., 100% achievement; improvements in hepatomegaly, splenomegaly, anemia, thrombocytopenia, bone pain, and bone crisis). Overall, median (minimum-maximum) lyso-Gb1 concentration was 24.3 (2.1-150) ng/mL. Although not statistically significant, numerically lower plasma lyso-Gb1 concentrations were observed in patients with 100% achievement compared with those without; no statistically significant difference in plasma lyso-Gb1 concentration was observed between patients with different disease type or mutation type. Furthermore, lyso-Gb1 concentrations observed in Japanese patients were numerically lower than that observed in a previous study of non-Japanese patients with GD receiving ERT. CONCLUSIONS: In this study, high achievement rates of therapeutic goals with low lyso-Gb1 concentration were observed, demonstrating a correlation between therapeutic goals and lower plasma lyso-Gb1 concentration in Japanese patients with GD treated with velaglucerase alfa. This study further suggests that plasma lyso-Gb1 concentration may be a useful biomarker for treatment response in patients with GD.

Real-world etiologies and treatments of pediatric short bowel syndrome in Japan.

BACKGROUND: Short bowel syndrome (SBS) is a rare disease that can result in intestinal failure (IF). Short bowel syndrome intestinal failure leads to stunted growth and development and high mortality rates. The primary goal of treatment is to enhance intestinal adaptation and nutrient absorption. Parenteral nutrition (PN) is used to support this process until enteral autonomy can be restored. Some patients experience prolonged partial or complete dependency on PN and face an increased risk of life-threatening catheter-related bloodstream infections and intestinal failure-associated liver disease. This study aimed to provide real-world insights into the patient characteristics and treatment dynamics of PN-dependent children with SBS-IF in Japan. METHODS: This retrospective observational study used anonymized information from a large hospital-based medical insurance database to identify pediatric patients who received PN for ≥6 months between April 2008 and January 2020. The primary endpoint was weaning from PN. Secondary endpoints included duration and complications of PN. RESULTS: Forty-eight children (mean age, 2.9 years) were eligible for inclusion. The most common causes of SBS-IF were mechanical bowel obstruction, functional bowel disorders, and Hirschsprung's disease. Twenty-two patients (45.8%) were weaned from PN during the study. The mean time to first weaning was 464.2 days and five patients (22.7%) restarted PN. The mean total duration of PN was 692.6 days in weaned patients and 1,170.9 days in unweaned patients. The most frequent complications were sepsis, catheter infections (both 79.2%), and liver dysfunction (64.6%). CONCLUSIONS: Pediatric patients with SBS-IF faced difficulties when weaning off PN and rates of life-threatening complications were high.

Association between baseline cognitive symptoms and the subsequent presenteeism and global function in patients with major depressive disorder.

Cognitive symptoms in major depressive disorder (MDD) contribute to impaired functional abilities and work productivity, particularly presenteeism. We investigated the association between baseline cognitive symptoms and subsequent presenteeism, and global functional impairment in Japanese patients with MDD from PERFORM-J (Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder in Japan) - a 6-month, multicenter, epidemiological study data. A total of 518 patients initiating antidepressant monotherapy (first-line or switched from another drug) were enrolled. Assessments include Perceived Deficits Questionnaire - Depression (PDQ-D) for cognitive complaints, Sheehan Disability Scale (SDS) for global function (analysed n = 318), and Work Productivity and Activity Impairment Questionnaire for presenteeism (analysed n = 122). A strong association between changes in presenteeism and changes in SDS scores (r: total = 0.636; work/school = 0.686) was observed. After adjusting for sociodemographic and MDD-related factors, patients without cognitive complaints at baseline showed lower odds of impaired presenteeism at 6 months versus patients with cognitive complaints (0.243, 95% CI: 0.079 to 0.747, p = 0.014) and also in patients with first episode of MDD against with recurrent MDD (0.327 (95% CI: 0.136 to 0.787). Similarly, patients without cognitive complaints had healthier global functioning (lower mean SDS total score) than patients with cognitive complaints (8.3 vs 11.2; 95% CI, -5.189 to -0.578; p = 0.014). First depressive episode (lower risk of presenteeism), being male, and low baseline SDS total score (better global functioning) were also associated with improved outcomes. These results highlight the potential value of baseline PDQ-D scores in predicting subsequent workplace and global functioning in patients undergoing treatment for MDD.