Objective: The package inserts are official clinical decision-making documents that provide pharmacological treatment information. However, it has been noted that package inserts on perinatal drug usage differ greatly from expert opinions. This study identified Japanese package insert drugs that are contraindicated for pregnant women and compared them to foreign risk categories.Methods: The survey included 19,022 drugs on the drug pricing list as of April 2022, with package inserts available on the Pharmaceuticals and Medical Devices Agency website. We retrieved the package inserts with the word “pregnant” in the “Contraindications” section and reviewed the descriptions to exclude those that satisfied the exclusion criteria. We also checked the foreign risk categories of contraindicated ingredients for pregnant women. This study used the Australian Therapeutic Goods Administration’s categorization for prescribing medicines in pregnancy (the TGA classification).Results: Of the 19,022 medicines studied, 4,111 (21.6%) were contraindicated for pregnant women. Conversely, 19 (5.1%) ingredients categorized under the relatively safe TGA classifications A, B1, and B2 were also contraindicated for pregnant Japanese women.Conclusion: This study revealed that Japanese package inserts contraindicate over 20% of drugs for pregnant women. On the other hand, some forbidden ingredients did not match the foreign risk categories. Therefore, healthcare professionals should be aware of the limitations of Japanese package inserts concerning pregnant women and make careful decisions based on both package inserts and additional drug information.

Background/Aims: Intestinal Behçet disease is typically associated with ileocecal punched-out ulcers and significant morbidity and mortality. Intestinal ultrasound is a noninvasive imaging technique for disease monitoring. However, no previous reports have compared intestinal ultrasound with endoscopic ulcer activity or histopathological findings for intestinal Behçet disease. We evaluated the usefulness of intestinal ultrasound for assessing the activity of ileocecal ulcers in intestinal Behçet disease. Methods: We retrospectively compared intestinal ultrasound findings with 73 corresponding endoscopic images and 6 resected specimens. The intestinal ultrasound findings were assessed for 7 parameters (bowel wall thickness, vascularity [evaluated using the modified Limberg score with color Doppler], bowel wall stratification, white-plaque sign [strong hyperechogenic lines or spots], mesenteric lymphadenopathy, extramural phlegmons, and fistulas), and endoscopic ulcer activity was classified into active, healing, and scar stages. Histopathological findings were evaluated by consensus among experienced pathologists. Results: Bowel wall thickness (P< 0.001), vascularity (P< 0.001), loss of bowel wall stratification (P= 0.015), and white-plague sign (P= 0.013) were significantly exacerbated in the endoscopic active ulcer stage. Receiver operating characteristic curve analysis revealed that a bowel wall thickness of > 5.5 mm (sensitivity 89.7%, specificity 85.3%) was potentially useful for detecting active lesions. When compared with histopathological findings, an increase in bowel wall thickness reflected the ulcer marginal ridge, and the white-plaque sign reflected the ulcer bottom. Conclusions Intestinal ultrasound is useful for monitoring intestinal ulcer activity in intestinal Behçet disease.

Background: No consensus exists regarding which anthropometric measurements are related to bone mineral density (BMD), and this relationship may vary according to sex and age. A large Japanese cohort was analyzed to provide an understanding of the relationship between BMD and anthropometry while adjusting for known confounding factors. Methods: Our cohort included 10,827 participants who underwent multiple medical checkups including distal forearm BMD scans. Participants were stratified into four groups according to age (≥50 years or <50 years) and sex. The BMD values were adjusted for confounding factors, after which single and partial correlation analyses were performed. The prevalence of osteopenia was plotted for each weight index (weight or body mass index [BMI]) class. Results: Cross-sectional studies revealed that weight was more favorably correlated than BMI in the older group (R=0.278 and 0.212 in men and R=0.304 and 0.220 in women, respectively), whereas weight and BMI were weakly correlated in the younger age groups. The prevalence of osteopenia exhibited a negative linear relationship with weight among older women ≥50 years of age, and an accelerated increase was observed with decreasing weight in older men weighing <50 kg and younger women weighing <60 kg. When weight was replaced with BMI, the prevalence was low in most subgroups classified by weight. Conclusions Weight, rather than BMI, was the most important indicator of osteopenia but it might not be predictive of future bone loss.

Objective: To describe the treatment patterns and time to next treatment (TTNT) in newly diagnosed multiple myeloma patients (MM) using a large-scale claims database in Japan.Design: Cohort studyMethods: The patients with newly diagnosed MM from 2008 to 2015 were classified into two groups: age <65 years, and age ≥65 years. Specific regimens and general regimens were identified with a complex algorithm considering interval of no therapy, additional and discontinued agents. Correspondingly, TTNT between the first- and second-line were measured among non-transplant patients with Kaplan-Meier method.Results: A total of 425 patients were eligible to participate in the analysis. The most common regimen for the treatment of MM was bortezomib-based regimens (52.9％ in the first-line, 28.2％ in later lines), followed by melphalan-prednisolone (27.1％ in the first-line, 12.9％ in later lines) and lenalidomide-based regimens (4.7％ in the first-line, 26.1％ in later lines). TTNT between the first- and second-line was 11.4 months and was seen to vary greatly with each regimen. A statistically longer TTNT was observed in subgroups of patients aged 65 years or over compared with patients aged younger than 65 years, but no statistical difference was found between conventional therapy and novel therapy.Conclusion: Based on the data from the study, patients with MM were commonly treated with novel agent-based regimens, especially bortezomib-based regimens. Between the first- and second-line therapies a relatively short TTNT was observed, indicating that therapies in clinical practice poorly complied with treatment guidelines.

PURPOSE: Peripheral artery disease (PAD) is a form of arteriosclerosis that occurs in the extremities and involves ischemia. Previous studies have reported that patients with periodontitis are at high risk for PAD. However, the relationship between these 2 diseases has not yet been fully elucidated. In this cross-sectional study, we investigated this relationship by comparing patients with PAD to those with arrhythmia (ARR) as a control group. METHODS: A large-scale survey was conducted of patients with cardiovascular disease who visited Tokyo Medical and Dental University Hospital. We investigated their oral condition and dental clinical measurements, including probing pocket depth, bleeding on probing, clinical attachment level, and number of missing teeth; we also collected salivary and subgingival plaque samples and peripheral blood samples. All patients with PAD were extracted from the whole population (n = 25), and a matching number of patients with ARR were extracted (n = 25). Simultaneously, ARR patients were matched to PAD patients in terms of age, gender, prevalence of diabetes, hypertension, dyslipidemia, obesity, and the smoking rate (n = 25 in both groups). Real-time polymerase chain reaction was performed to measure the bacterial counts, while the enzyme-linked immunosorbent assay method was used to measure anti-bacterial antibody titers and proinflammatory cytokine levels in serum. RESULTS: PAD patients had more missing teeth (18.4±2.0) and higher serum levels of C-reactive protein (1.57±0.85 mg/dL) and tumor necrosis factor-alpha (70.3±5.7 pg/mL) than ARR patients (12.0±1.7, 0.38±0.21 mg/dL, and 39.3±4.5 pg/mL, respectively). Meanwhile, no statistically significant differences were found in other dental clinical measurements, bacterial antibody titers, or bacterial counts between the 2 groups. CONCLUSIONS: Our findings suggested that PAD patients had poorer oral and periodontal state with enhanced systemic inflammation.
Arrhythmias, Cardiac ; Arteriosclerosis ; Bacterial Load ; C-Reactive Protein ; Cardiovascular Diseases ; Cross-Sectional Studies ; Dyslipidemias ; Enzyme-Linked Immunosorbent Assay ; Extremities ; Hemorrhage ; Humans ; Hypertension ; Inflammation ; Ischemia ; Methods ; Obesity ; Periodontitis ; Peripheral Arterial Disease ; Prevalence ; Real-Time Polymerase Chain Reaction ; Smoke ; Smoking ; Tooth ; Tumor Necrosis Factor-alpha