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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.Vonoprazan is dominant or cost-effective compared with esomeprazole and lansoprazole in patients taking LDA for secondary prevention of CV events.

Tomiki Sumiyoshi,1 Hiroyuki Uchida,2 Koichiro Watanabe,3 Masato Oosawa,4 Hongye Ren,5 Yoshiya Moriguchi,6 Keita Fujikawa,4 Jovelle Fernandez4 1Department of Preventive Intervention for Psychiatric Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan; 2Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; 3Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan; 4Japan Medical Office, Takeda Pharmaceutical Company Limited, Osaka, Japan; 5Medical Affairs, H. Lundbeck A/S, Copenhagen, Denmark; 6Medical Affairs, Lundbeck Japan KK, Tokyo, JapanCorrespondence: Tomiki Sumiyoshi, Department of Preventive Intervention for Psychiatric Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan, Tel +81-42-341-2711 ext. 6234, Fax +81-42-346-1979, Email sumiyot@ncnp.go.jpPurpose: 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.Keywords: PDQ-D-20, PDQ-D-5, cognition, functional impairment, major depressive disorder

Studies on the efficacy of prescription omega-3 polyunsaturated fatty acids to reduce cardiovascular events have produced conflicting results. 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. 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). 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. ClinicalTrials.gov, NCT02285166.

Nobutaka Hattori,1 Yoshiko Okada,2 Yayoi Kawata,3 Yoshihiko Furusawa,3 Takumi Imai,4 Hisako Yoshida,4 Mihoko Ota,3 Masaki Arai,3 Ayumi Shintani,4 Jovelle Fernandez3 1Department of Neurology, Juntendo University, Tokyo, Japan; 2Japan Parkinson Congress, Tokyo, Japan; 3Japan Medical Office, Takeda Pharmaceutical Company Limited, Tokyo, Japan; 4Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, JapanCorrespondence: Yoshihiko Furusawa, Japan Medical Office, Takeda Pharmaceutical Company Limited, 2 Chome-1-1 Nihonbashihoncho, Chuo City, Tokyo, 103-0023, Japan, Tel +81-3-3278-2111, Fax +81-3-3278-2000, Email yoshihiko.furusawa@takeda.comObjective: 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.Keywords: Parkinson’s disease, COVID-19, questionnaire design, caregiver burden

Purpose Short bowel syndrome (SBS) with intestinal failure (SBS-IF) requires long-term parenteral nutrition (PN). This study investigated the real-world etiologies of SBS, treatment patterns, and PN-related outcomes among adult patients with SBS-IF in Japan. Methods This retrospective, observational cohort study was based on data from April, 2008 to January, 2020 from one of the largest hospital-based claim databases in Japan. Analyzed patients were aged ≥ 16 years, had received continuous PN for ≥ 6 months, and had SBS or undergone SBS-related surgery with a diagnosis of a causative disease. The primary endpoint was PN weaning. Results We analyzed data for 393 patients. The most frequent causes of SBS-IF were ileus (31.8%), Crohn’s disease (20.1%), and mesenteric ischemia (16.0%). Of 144/393 (36.6%) patients who were weaned off their PN, 48 (33.3%) were subsequently restarted on PN. Of 276/393 (70.2%) patients whose PN was initiated in hospital, 156 (56.5%) transitioned to home management. The mean duration of initial PN was 450.4 and 675.5 days for patients who were able or unable to be weaned off PN, respectively. Sepsis (67.4%), catheter-related bloodstream infections (49.1%), and liver disorders (45.0%) were the most reported PN-related complications. Conclusions Most patients with SBS-IF in Japan could not be weaned off PN and suffered life-threatening complications.

BACKGROUND AND AIM This study aimed to determine the efficacy and safety of vedolizumab treatment with or without concomitant immunomodulator use in Japanese patients with moderate-to-severe ulcerative colitis. METHODS Among enrolled patients in a phase 3 study conducted in Japan (clinicaltrials.gov, NCT02039505), data from patients allocated to 300-mg intravenous vedolizumab for induction and maintenance phases were used for this exploratory analysis. Efficacy endpoints were clinical response, clinical remission, and mucosal healing at week 10 and clinical remission and mucosal healing at week 60, and disease worsening and treatment failure during the maintenance phase. RESULTS At week 10, the differences in clinical response, clinical remission, and mucosal healing rates between the subgroups (those with concomitant immunomodulator use minus those without) were 0.7 (95% confidence interval: -14.3, 15.7), 3.3 (95% confidence interval: -8.5, 15.2), and 1.8 (95% confidence interval: -13.0, 16.5), respectively. At week 60, the differences in clinical remission and mucosal healing between the subgroups with and without concomitant immunomodulator use were 26.1 (95% confidence interval: -3.5, 55.6) and 29.9 (95% confidence interval: 1.4, 58.4), respectively. The proportions of patients without treatment failure at day 330 of the maintenance phase were 90.7% with concomitant immunomodulator use and 73.7% without. No marked differences in incidence of infections were observed between subgroups. CONCLUSIONS This study suggested the possibility that concomitant immunomodulator use may be beneficial to maintain the clinical efficacy of vedolizumab.

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.

Tomiki Sumiyoshi,1 Koichiro Watanabe,2 Shinichi Noto,3 Shigeru Sakamoto,4 Yoshiya Moriguchi,5 Lene Hammer-Helmich,6 Jovelle Fernandez4 1Department of Preventive Intervention for Psychiatric Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan; 2Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan; 3Faculty of Rehabilitation, Niigata University of Health and Welfare, Niigata, Japan; 4Japan Medical Office, Takeda Pharmaceutical Company Limited, Tokyo, Japan; 5Medical Affairs, Lundbeck Japan KK, Tokyo, Japan; 6Medical Affairs Value Evidence, H. Lundbeck A/S, Valby, DenmarkCorrespondence: Tomiki SumiyoshiDepartment of Preventive Intervention for Psychiatric Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8551, JapanTel +81 42 341 2711Fax +81 42 346 3569Email sumiyot@ncnp.go.jpBackground: Accumulating evidence suggests the presence of cognitive impairment in patients with major depressive disorder (MDD), which affects their psychosocial function and quality of life (QoL). PERFORM-J (Prospective Epidemiological Research on Functioning Outcomes Related to MDD in Japan) is an observational, multicenter study to assess longitudinal changes in depressive symptoms, psychomotor speed, subjective cognitive function, and psychosocial function.Methods: Five hundred and eighteen Japanese outpatients with MDD initiating new antidepressant monotherapy (first-line or switch from previous drug) as part of their routine medical care participated in this study. Assessments at baseline and over the 6-month observation period included physician-rated depression severity (Montgomery–Åsberg Depression Rating Scale), psychomotor speed (Digit Symbol Substitution Test; DSST), subjective cognition (Perceived Deficits Questionnaire–Depression), psychosocial function (Sheehan Disability Scale), and QoL (EuroQol-5 Dimension-5 Level).Results: Antidepressant treatment for 6 months improved depressive symptoms and subjective cognitive impairment (cognitive complaints), whereas psychomotor speed remained impaired (ie, DSST total score was > 1 standard deviation below the norm) in 35.6% of patients at 6 months. Impairment of subjective cognition, but not psychomotor speed at month 2 was associated with poor psychosocial function and QoL at 6 months. There was a trend for higher relapse rates at 6 months in patients with greater subjective cognitive impairment at 2 months.Conclusion: These findings highlight the importance of evaluating cognitive difficulties to predict long-term outcomes in patients with MDD. Early intervention for cognitive complaints may decrease the relapse rate, which warrants further study.Keywords: cognition, depression, functional outcome, quality of life, Japan

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.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.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.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.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.

This systematic review and network meta-analysis aimed to assess the relative efficacy of vonoprazan and proton pump inhibitors (PPIs) on early heartburn symptom resolution in patients with erosive esophagitis.Limited available data directly compare the efficacy of vonoprazan, a first-in-class potassium-competitive acid blocker, with PPIs in erosive esophagitis.We conducted a systematic literature review (in MEDLINE and CENTRAL) and subsequent network meta-analysis according to Cochrane and PRISMA guidelines. Double-blind, randomized controlled trials in adults with erosive esophagitis treated with vonoprazan or a PPI were included in the analysis. Primary outcomes were heartburn symptom resolution rate on Day 1 and Day 7. The study was performed with all available data, using a random effects model within a Bayesian framework.Overall, 10 randomized controlled trials were included in the network meta-analysis. For heartburn resolution rate on Day 1 (9 of 10 trials), vonoprazan 20 mg once daily (QD) was superior to placebo (median odds ratio=16.75, 95% credible interval: 2.16-207.80). Point estimates numerically favored vonoprazan 20 mg QD over other comparators. For heartburn resolution rate on Day 7 (10 of 10 trials), vonoprazan 20 mg QD was superior to placebo and other comparators except rabeprazole 20 mg QD. Point estimates numerically favored vonoprazan 20 mg QD over rabeprazole 20 mg QD.In this study, vonoprazan 20 mg QD was equally effective in heartburn resolution on Day 1, and equally or more effective on Day 7 versus PPIs in adults with erosive esophagitis.

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.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.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%).Pediatric patients with SBS-IF faced difficulties when weaning off PN and rates of life-threatening complications were high.

Background In Japan, anagrelide has been approved for use in patients with essential thrombocythemia. Here, the safety and efficacy of anagrelide was assessed in clinical practice as post-marketing surveillance. Subgroup analyses were conducted to compare patients (1) with or without a history of cytoreductive therapy (CRT), (2) Methods Data were collected for all patients who received anagrelide, with an observation period of 12 months after treatment initiation. Results Of the 648 patients, 54.3% experienced adverse drug reactions (ADRs). The most commonly reported ADRs were headaches, palpitations, and anemia. No significant difference was observed in overall ADRs across patient subgroups. A significantly higher incidence of headaches was observed in patients P P P Conclusions This surveillance showed that anagrelide has a tolerable safety and efficacy profile.

Physicians are often required to make treatment decisions for patients with Crohn's disease on the basis of limited objective information about the state of the patient's gastrointestinal tissue while aiming to achieve mucosal healing. Tools to predict changes in mucosal health with treatment are needed. We evaluated a computational approach integrating a mechanistic model of Crohn's disease with a responder classifier to predict temporal changes in mucosal health.A hybrid mechanistic-statistical platform was developed to predict biomarker and tissue health time courses in patients with Crohn's disease. Eligible patients from the VERSIFY study (n = 69) were classified into archetypical response cohorts using a decision tree based on early treatment data and baseline characteristics. A virtual patient matching algorithm assigned a digital twin to each patient from their corresponding response cohort. The digital twin was used to forecast response to treatment using the mechanistic model.The responder classifier predicted endoscopic remission and mucosal healing for treatment with vedolizumab over 26 weeks, with overall sensitivities of 80% and 75% and overall specificities of 69% and 70%, respectively. Predictions for changes in tissue damage over time in the validation set (n = 31), a measure of the overall performance of the platform, were considered good (at least 70% of data points matched), fair (at least 50%), and poor (less than 50%) for 71%, 23%, and 6% of patients, respectively.Hybrid computational tools including mechanistic components represent a promising form of decision support that can predict outcomes and patient progress in Crohn's disease.

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.

Background Evidence is accumulating for the presence of cognitive impairment in patients with major depressive disorder (MDD). The Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder in Japan (PERFORM-J) study is a 6-month, non-interventional, prospective, multicenter, epidemiological study. Using baseline data, the relationship between cognitive symptoms and psychosocial function was analyzed in Japanese patients with MDD. Methods A total of 518 Japanese outpatients (aged 18–65 years) with MDD initiating new antidepressant monotherapy (first-line or switch from a previous drug) participated. Assessment measures were: physician-rated Montgomery-Asberg Depression Rating Scale (MADRS) (depression severity); Digit Symbol Substitution Test (DSST) (objective cognition); and patient-rated Perceived Deficits Questionnaire – Depression (PDQ-D) (subjective cognition); Sheehan Disability Scale (SDS); Work Productivity and Activity Impairment questionnaire (WPAI) (psychosocial function); and EuroQol-5 Dimension-5 Level (quality of life). Results Over half of patients exhibited a greater than 1 standard deviation decline below norm in objective cognition, as measured by the DSST. Severity of depressive symptoms correlated positively with subjective (PDQ-D), but not objective (DSST) cognition. Depression severity and subjective cognition were significantly associated with psychosocial function, as measured by the SDS and WPAI (except the absenteeism items). Conversely, the association between objective cognition and psychosocial function was not significant. Limitations Only outpatients were recruited. Occupations and job-related stress levels were not taken into account. Conclusions Japanese patients with MDD presented a high incidence of cognitive impairment. The relationships between cognitive and psychosocial function in these patients suggest a need for therapeutics targeting cognitive impairment of MDD.

BACKGROUND Patients with major depressive disorder (MDD) frequently retain cognitive disturbances after recovery from mood symptoms. We investigated the relationship between early response of mood symptoms and/or remission, and residual cognitive disturbances after 6 months of antidepressant treatment. METHODS 518 patients with MDD were followed up for 6 months after antidepressant treatment initiation (first-line or switch from a previous drug). Subjective and objective cognitive disturbances were assessed by the Perceived Deficits Questionnaire - Depression (PDQ-D) and digit symbol substitution test (DSST), respectively. Depressive symptoms, as well as remission and early response to treatment, were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS). Multivariable linear and logistic regression models were used to adjust for confounders. RESULTS Early response of depressive mood (≥50% reduction in MADRS score at month 1) was related with fewer residual subjective cognitive symptoms, as evaluated by the PDQ-D at month 6 (p

Background and Aim: To evaluate the onset of symptomatic response with vedolizumab in patients with moderate-to-severe ulcerative colitis in Japan. Methods: Patients were randomized to receive vedolizumab 300 mg or placebo at Weeks 0, 2, and 6. Mayo subscores were analyzed in patients with baseline stool frequency (SF) ≥1 and rectal bleeding (RB) ≥1. In patients with baseline SF ≥2 and RB ≥1, the proportion who achieved SF ≤1 and RB = 0 was determined. Results: Patients were randomized to vedolizumab (n = 164) or placebo (n = 82). Decrease from baseline in mean SF subscore was greater with vedolizumab versus placebo from Week 2 (−6.6%; 95% confidence interval [CI], −16.2, 3.0), with a greater difference in anti-tumor necrosis factor (TNF)α-naive patients (vedolizumab vs. placebo, −13.2%; 95% CI, −29.7, 3.3). Mean percentage decrease from baseline RB subscore was numerically greater with vedolizumab versus placebo from Week 6 in anti-TNFα-naive patients (−10.7%; 95% CI, −33.0, 11.5). More patients in the anti-TNFα-naive subgroup achieved SF ≤1 and RB = 0 with vedolizumab versus placebo at Week 2 (14.8%; 95% CI, 2.5, 27.0) and Week 6 (20.3%; 95% CI, 4.4, 36.2). Patients with SF ≤1 and RB = 0 at Week 2 had higher clinical response, clinical remission, and mucosal healing rates at Week 10 than those without. Conclusions: Our results indicate that vedolizumab induces a rapid symptomatic response, particularly in anti-TNFα-naive patients, and suggest that early symptomatic improvement predicts treatment response at Week 10 (NCT02039505).

Background: In Japan, pharmacoeconomic requirements for list-price adjustment were institutionalized in April 2019 following provisional implementation of a new Health Technology Assessment (HTA) program 2016-2019. Since April 2019, submission of cost-effectiveness evidence to the Central Social Insurance Medical Council (Chuikyo) as part of the Japanese Ministry of Health, Labour, and Welfare has been mandatory for selected pharmaceuticals and medical devices.Methods: Based on a review of publications and commentaries since April 2019, together with views from a group of experts on key issues to be addressed, this report provides an update on recent HTA developments and key challenges still to be addressed.Results and Discussion: Japan's new HTA program is a first step toward development of a universal healthcare system that can be sustainable for many years into the future. Currently, Japan's HTA program requires provision of incremental cost-effectiveness ratios (ICERs) as evidence, with quality-adjusted life years as the preferred outcome measure. Prices can be adjusted both upward and downward according to the degree of the ICER estimate. Japan is the first country to have adopted an algorithmic method for "ICER-based" pricing; however, HTA measures that extend beyond a single ICER estimate are needed to take full advantage of HTA in the future. In particular, generation of evidence of value should support changes to the healthcare system so that incentives for innovation are not diminished while industry and government are not overburdened by the generation or assessment of evidence. There is a need to ensure scientifically sound HTA expertise across all sectors in Japan, and therefore enhancement of HTA literacy and capability among healthcare professionals, academia, government, and industry should be a priority.

IntroductionUlcerative colitis (UC) is a chronic inflammatory disease that mainly affects the colon in young patients. Typical symptoms of UC are bloody diarrhoea and faecal urgency, which disturb the quality of life (QOL) of patients, and intractable UC leads to hospitalisation and colectomy. To improve relevant outcomes such as symptoms, QOL and colectomy, many clinical questions need to be resolved regarding what the ideal lifestyle, psychosocial burden and optimal practice patterns are. In this YOu and Ulcerative colitis: Registry and Social network (YOURS) study, we will investigate the effect of lifestyle, psychosocial factors and practice patterns on patient-reported outcomes (PRO), hospitalisation rate and colectomy rate in Japanese patients with UC.Methods and analysisFor this prospective cohort study, we recruited 2006 patients from five hospitals (Tokyo and Chiba; May 2018–January 2019). Patients will be able to access their own data and compare them with summarised data from all patients on the website beyond the YOURS study. At baseline, patients will answer a questionnaire regarding lifestyle (diet, exercise, sleep and work), psychosocial factors (stress, depression and social support) and PRO (symptoms and QOL). Information on practice patterns (eg, medications, endoscopy frequency) will be collected from electronic medical records. Gaps between patients’ needs and healthcare professionals’ practice will be identified. Follow-up surveys will be conducted periodically for approximately 3 years. Research questions suggested by patients and healthcare professionals may be used in subsequent surveys. Results from the YOURS study will demonstrate optimal UC management strategies to improve relevant outcomes.The study was approved by the ethics committees of five investigational sites before starting the study. The results will be submitted to journals.UMIN000031995.

Objective To determine whether treatments for precancerous cervical lesions were associated with lower pregnancy rates compared to rates in unexposed women and women who had a diagnostic cervical biopsy or colposcopy. Design Matched, retrospective cohort study. Setting Kaiser Permanente Northwest (KPNW), an integrated healthcare delivery system in Oregon and Washington. Patients Women 14 to 53 years old with KPNW enrollment during the period 1998 through 2009. Main Outcome Measure Pregnancy after exposure or index date. Pregnancy was defined using a validated algorithm and electronic medical records data. Results We observed 570 pregnancies following cervical treatment in 4,137 women, 1,533 pregnancies following a diagnostic procedure in 13,767 women, and 7,436 pregnancies in a frequency-matched sample of 81,435 women unexposed to treatment or diagnostic procedures. After adjusting for age and contraceptive use, we observed a higher rate of pregnancies in the treatment group compared to unexposed women (hazard ratio (HR) = 1.42, 95% confidence interval (CI): 1.30–1.55), but no difference in pregnancy rates between the treatment and diagnostic procedure groups (HR = 1.03, 95% CI: 0.93–1.13). Conclusions No adverse effects of cervical procedures on subsequent rates of pregnancy were observed in this cohort with up to twelve years of follow-up time.

Background/Aims Propensity scores provide an alternative to traditional regression modeling for assessing the effect of exposure on an outcome in the presence of confounders. We describe methods to establish propensity scores for a cohort of Kaiser Permanente Northwest (KPNW) members receiving surgical procedures of the cervix.

Background/Aims Persistent oncogenic human papillomavirus (HPV) infection may lead to precancerous lesions, which health providers may remove using surgical procedures before the lesions progress to cervical cancer. This paper describes the methods used to establish a retrospective cohort of Kaiser Permanente Northwest (KPNW) members to test hypotheses that surgical procedures involving the cervix affect subsequent reproductive health and pregnancy outcomes.