BACKGROUND: Our previous observational cohort study, the Kashima Scan Study (KSS), identified associations between lifestyle, cerebral small vessel disease (SVD) as detected by magnetic resonance imaging of the brain, and disease outcomes including cognitive impairment and vascular diseases. However, established modifiers of the outcomes such as genetic background, drinking and exercise habits, and socioeconomic status were not considered. Regarding genetic factors in particular, the ALDH2 rs671 variant, East Asian-specific diversity, and APOE status are expected to have strong effects. The aim of KSS-2 is to examine the interactions of genetic background, lifestyle factors including drinking habit, socioeconomic status, and/or SVD markers for cognitive impairment, vascular disease, and death. METHOD: The KSS-2 is a prospective regional observational study of a healthy Japanese cohort that will clarify lifestyle habits to better maintain brain health from midlife by genotype. Japanese adults who underwent brain health checkups at their own expense are enrolled and will be followed-up for 10 years. We will extend the protocol of the KSS to include genetic background and potential confounding factors, including lifestyle (including drinking and exercise habit) and socioeconomic status, and perform survival analyses. The study outcomes are cognitive impairment, vascular events, and death. RESULTS: We enrolled 908 healthy adults (mean age 64.2 years; range 35 to 84 years; 41% male) from September 1, 2018 until December 31, 2024. CONCLUSION This study will provide important insights into the development of individualized health intervention strategies.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Cerebral Small Vessel Diseases/diagnostic imaging* ; Japan/epidemiology* ; Life Style ; Magnetic Resonance Imaging ; Prospective Studies ; Observational Studies as Topic

Background/Aims: The precise incidence of symptomatic uncomplicated diverticular disease (SUDD) and its effects on the quality of life (QOL) remain unclear, particularly in Asian patients with right-sided SUDD. We assess the prevalence of SUDD and its impact on QOL in a real-world population. Methods: Five institutional cohorts of patients who received outpatient treatment for unexplained abdominal symptoms from January 15, 2020 to March 31, 2022, were included. All patients underwent colonoscopy. SUDD was defined as the presence of recurrent abdominal symptoms, particularly pain in the lower right or left quadrant lasting > 24 hours in patients with diverticulosis at the site of pain. The 36-item short-form health survey was used to assess QOL. Results: Diverticula were identified in 108 of 361 patients. Among these 108 patients, 31% had SUDD, which was right-sided in 39% of cases.Of the 50 patients with right-sided diverticula, 36% had SUDD, as did 15 of 35 patients with left-sided diverticula (43%). Among the 33 patients with SUDD, diverticula were right-sided, left-sided, and bilateral in 39%, 45%, and 15% of patients, respectively. Diarrhea was more frequent in the SUDD group than in the non-SUDD group. Patients with SUDD had significantly lower physical, mental, and role/social component scores than those without SUDD. Conclusions It is important to recognize that patients with SUDD account for as high as 31% of outpatients with unexplained abdominal symptoms; these patients have diarrhea and a low QOL. The presence of right-sided SUDD was characteristic of Asian patients.

BACKGROUND/AIMS: This study compared the efficacy of multimatrix mesalazine 2.4 g/day and 4.8 g/day with controlled-release mesalazine 2.25 g/day. METHODS: In this multicenter, randomized, double-blind study, 251 patients with mildly to moderately active ulcerative colitis received multimatrix mesalazine 2.4 g/day once daily (Multimatrix-2.4), 4.8 g/day once daily (Multimatrix-4.8), or controlled-release (time-dependent) mesalazine 2.25 g/day 3 times daily (Time-2.25) for 8 weeks. The primary efficacy endpoint was the change in the ulcerative colitis-disease activity index (UC-DAI) score. RESULTS: The mean change in the UC-DAI score and standard deviation in the per protocol set was −1.9±2.5 for Multimatrix-2.4 and −2.4±2.8 for Time-2.25. The difference between Multimatrix-2.4 and Time-2.25 was 0.3 (two-sided 95% confidence interval [CI], −0.5 to 1.1), thus non-inferiority was not demonstrated based on the pre-defined non-inferiority margin (1.0). In the full analysis set, the difference between Multimatrix-4.8 and Time-2.25 was −1.2 (two-sided 95% CI, −2.0 to −0.5), and the mean change in UC-DAI score in the FAS was −3.3 (two-sided 95% CI, −3.9 to −2.8) for Multimatrix-4.8 and −1.9 (two-sided 95% CI, −2.5 to −1.3) for Multimatrix-2.4, indicating that Multimatrix-4.8 was more effective than Time-2.25 and Multimatrix-2.4. There was no difference among the treatment groups in terms of safety. CONCLUSIONS: This study showed that the efficacy of multimatrix mesalazine 2.4 g/day was comparable to controlled release mesalazine 2.25 g/day, although non-inferiority was not demonstrated. Importantly, this was the first study to indicate that multimatrix mesalazine 4.8 g/day was more effective than 2.4g/day with no associated safety concerns.
Colitis, Ulcerative* ; Double-Blind Method* ; Humans ; Mesalamine* ; Ulcer*

Ulcerative colitis (UC) is one of the major clinical phenotypes of inflammatory bowel diseases. Although 5-aminosalicylic acid (5-ASA) is widely used for UC and its efficacy and safety have been demonstrated, a few patients paradoxically develop a severe exacerbation of colitis by 5-ASA administration. It is crucial to know clinical features including endoscopic findings in this condition for making a correct diagnosis and a prompt decision to withdraw the medication. Here, we report case series with UC exacerbated by 5-ASA. Medical records of 8 UC patients experiencing an exacerbation of colitis after induction of 5-ASA that was improved by the withdrawal of 5-ASA but also re-aggravated by dose increase or re-administration of 5-ASA were reviewed. The patients were newly diagnosed with UC, started 5-ASA and developed an exacerbation in approximately 2 to 3 weeks. They did not appear to have systemic allergic reactions. Seven of the 8 patients had a high fever. Three of 5 patients who undertook total colonoscopy showed right-side-dominant colitis. These findings suggest clinical characteristics in this condition. Further assessment of clinical and endoscopic features in more cases is necessary for establishing diagnostic criteria and understanding underlying mechanisms in those cases where 5-ASA aggravates the colitis.
Colitis* ; Colitis, Ulcerative* ; Colonoscopy ; Diagnosis ; Fever ; Humans ; Hypersensitivity ; Inflammatory Bowel Diseases ; Medical Records ; Mesalamine* ; Phenotype ; Ulcer*

BACKGROUND/AIMS: This study assessed the efficacy and safety of high-dose multimatrix mesalazine once-daily (QD) compared to another form of high-dose mesalazine. METHODS: In this multicenter, randomized, double-blind study, 280 patients with mildly to moderately active ulcerative colitis (UC) received multimatrix mesalazine 4.8 g/day QD or pH-dependent-release mesalazine 3.6 g/day three times daily for 8 weeks. The primary endpoint was the change in the UC-Disease Activity Index (UC-DAI) at the end of the treatment period. RESULTS: The change in the UC-DAI (mean±standard deviation) in the per-protocol set was −2.6±2.47 in the multimatrix mesalazine 4.8 g/day group (n=134) and −1.8±2.64 in the pH-dependent-release mesalazine 3.6 g/day group (n=129). The difference in the mean change between the 2 groups was −0.7 (two-sided 95% confidence interval, −1.3 to −0.1). The noninferiority of multimatrix mesalazine 4.8 g/day to pH-dependent-release mesalazine 3.6 g/day was verified within the noninferiority margin (1.1). The superiority of multimatrix mesalazine 4.8 g/day to pH-dependent-release mesalazine 3.6 g/day was also investigated and confirmed in the full analysis set, according to the study protocol. In subgroup analyses, the effectiveness of multimatrix mesalazine 4.8 g/day was consistent in all subgroups. There was no difference in safety between the 2 treatment groups. CONCLUSIONS: Multimatrix mesalazine 4.8 g/day has higher efficacy and shows no difference in safety in mildly to moderately active UC, in comparison with pH-dependent-release mesalazine 3.6 g/day.
Colitis, Ulcerative* ; Double-Blind Method* ; Humans ; Mesalamine* ; Ulcer*

BACKGROUND/AIMS: This study compared the efficacy of once-daily administration of multimatrix mesalazine 2.4 g/day with multiple-dose mesalazine for the maintenance of remission. METHODS: In this multicenter, randomized, double-blind study, 203 patients with ulcerative colitis in remission received multimatrix mesalazine 2.4 g/day once-daily or time-dependent (controlled-release) mesalazine 2.25 g/day 3 times-daily for 48 weeks. The primary efficacy endpoint was the proportion of patients without rectal bleeding. RESULTS: The proportion of patients without rectal bleeding during the 48-week treatment period in the per protocol set was 84.8% (84/99) in the multimatrix mesalazine 2.4 g/day group and 78.0% (78/100) in the controlled-release mesalazine 2.25 g/day group. The difference between the 2 treatment groups was 6.8% (two-sided 95% confidence interval, −3.9% to 17.6%). The noninferiority margin of −10% was met in the comparison of multimatrix mesalazine 2.4 g/day once-daily with controlled-release mesalazine 2.25 g/day. Multimatrix mesalazine 2.4 g/day once-daily demonstrated consistent efficacy in all subgroups. There was no difference between the 2 treatment groups with regard to safety. CONCLUSIONS: A once-daily dose of 2 multimatrix mesalazine tablets (2.4 g) was not inferior to controlled-release mesalazine 2.25 g/day 3 times-daily in maintaining absence of rectal bleeding in ulcerative colitis.
Colitis, Ulcerative* ; Double-Blind Method* ; Hemorrhage ; Humans ; Mesalamine* ; Tablets ; Ulcer*