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H. pylori (H. pylori) infection is considered the leading cause of gastric cancer. Gastric cancer is currently a common cancer with high incidence and mortality rates, but it is expected that the incidence rate will gradually decrease as the H. pylori infection prevalence decreases in the future. When evaluating the effectiveness of gastric cancer prevention strategies, it is essential to note the differences in long-term cumulative risks between H. pylori-infected and uninfected populations, but this has not yet been precisely evaluated. In this study, we aimed to estimate the cumulative incidence risks of developing gastric cancer from birth to 85 years among H. pylori-infected and uninfected populations by using population-based cancer registry data and birth year-specific H. pylori infection prevalence rates. Death from gastric cancer and other causes of death were considered in the estimations of the adjusted cumulative incidence risks stratified by sex and H. pylori infection status. After performing 5000 Monte Carlo simulations with repeated random sampling using observed cancer incidence in selected three prefectures (Fukui, Nagasaki, Yamagata) of prefectural population-based cancer registry in Japan, the mean adjusted cumulative incidence risk for gastric cancer in the H. pylori-infected population was 17.0% for males and 7.7% for females and 1.0% for males and 0.5% for females in the uninfected population. These results calculated with Japanese cancer registry data may be useful in considering and evaluating future prevention strategies for gastric cancer in Japan. This article is protected by copyright. All rights reserved.

BackgroundIn Japan, there are ongoing efforts to shift the gastric cancer prevention and control policy priorities from barium-based screening to Helicobacter pylori (H. pylori)-oriented primary prevention. A comprehensive summary of the evidence regarding the effects of H. pylori eradication on the risk of gastric cancer could inform policy decisions.MethodsWe conducted a systematic review and meta-analysis of published studies evaluating the effectiveness of H. pylori eradication for the prevention of gastric cancer in otherwise healthy individuals (primary prevention) and early gastric cancer patients (tertiary prevention).ResultsIn total, 19 studies were included. Three moderate-quality observational cohort studies showed that H. pylori eradication may be associated with a decreased risk of gastric cancer in healthy asymptomatic Japanese people. There is moderate certainty regarding the effectiveness of H. pylori eradication in patients with gastrointestinal diseases, such as peptic ulcers. A meta-analysis of 10 observational studies with otherwise healthy individuals (mainly peptic ulcer patients) yielded an overall risk ratio of 0.34 (95% CI: 0.25–0.46). Regarding tertiary prevention, the overall risk ratio for developing metachronous gastric cancer was 0.50 (95% CI: 0.39–0.66) in the eradication group in a meta-analysis of nine studies involving early gastric cancer patients who underwent endoscopic resection.ConclusionH. pylori eradication is effective in preventing gastric cancer in the Japanese population, regardless of symptoms. Well-designed, large cohort studies are warranted to determine the long-term efficacy and safety of H. pylori eradication in the context of reducing the gastric cancer burden through population-based screening and treatment.

Evidence on the efficacy of glycemic control for diabetic peripheral neuropathy (DPN) is limited in patients with type 2 diabetes mellitus. Despite the known relationship between hemoglobin A1c (HbA1c) and DPN, the parameters (e.g., mean values or variability) that play an important role have not been elucidated.The objective of this study was to explore factors associated with DPN, including long-term HbA1c parameters, among patients with type 2 diabetes, in a large-scale longitudinal study.We conducted a case-control study using a medical claims database. We extracted data of patients with type 2 diabetes and disease records of DPN (indicating that they received treatment for DPN) and those without DPN records (controls), and matched for age, sex, index year, and duration since the first type 2 diabetes record. A logistic regression analysis was performed to explore factors associated with DPN, and a receiver-operating characteristic analysis to estimate the optimal mean HbA1c target.Of 1,792,037 patients with type 2 diabetes, data from 1632 patients (816 per group) were analyzed. The mean HbA1c levels in the 3-year observation period were 7.2 ± 1.0% in the DPN group and 6.9 ± 1.1% in the control group. Elevated 3-year mean HbA1c levels were significantly associated with DPN records (adjusted odds ratio: 1.23, 95% confidence interval 1.06-1.42), while HbA1c variability was not significantly associated. The mean HbA1c levels that discriminated between patients with and without DPN records were 6.5% (unadjusted) and 7.1% (adjusted).The development or progression of DPN in patients with type 2 diabetes was associated with the 3-year mean HbA1c level in real-world data.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have long-term benefits but are limited by side effects. We assessed the health and economic burden of renal events associated with NSAID use in patients with osteoarthritis (OA) and/or chronic low back pain (CLBP). This retrospective, large-scale, medical claims database study of Japanese patients receiving NSAIDs for OA and/or CLBP between 2009 and 2018 assessed the incidence of renal events and effect of treatment duration, mode of administration, and usage consistency of NSAIDs. Of 180,371 patients, NSAIDs were prescribed as first-line analgesics in 89.3%. Incidence per 10,000 person-years (95% confidence interval [CI]) for renal events was 23.46 (21.84–25.08) and for progression of chronic kidney disease (CKD) was 267.12 (189.93–344.32). Longer treatment duration (> 1 to ≤ 3 years, risk ratio [RR] 1.32, 95% CI 1.12–1.54; P = 0.0007; > 3 to ≤ 5 years, RR: 1.38, 95% CI 1.04–1.84; P = 0.0254 vs.

The condensation heat transfer and frictional pressure drop characteristics of the zeotropic binary mixture R32/R1123 inside two horizontal multiport extruded tubes with different channel shapes were experimentally investigated. The experiments were conducted at a mass flux of 50–400 kgm-2s-1 and an average saturation temperature of 40 ℃. The effects of mass flux, quality, heat flux, and channel shape on the condensation heat transfer were quantified. The heat transfer coefficient and the frictional pressure drop of R32/R1123 were compared with those of pure R32 obtained using the same test multiport extruded tubes. The heat transfer coefficient of R32/R1123 was lower than that of R32 across all mass flux and quality conditions. The frictional pressure drop of R32/R1123 was 20–30% lower than that of R32 at the same mass flux and quality conditions. The correlations of previous studies agreed well with the obtained frictional pressure drop of R32/R1123, with a mean deviation of 17%. The obtained heat transfer coefficient of R32/R1123 was predictable with a mean deviation of -5.2% using the previous correlations proposed for multiport extruded tubes considering the heat transfer reduction due to the thermal resistance caused by temperature glide.

Background Pancreatic cancer treatment is evolving, but few studies have examined a nationwide trend in the treatment patterns. The purpose of this study was to clarify real-world treatment patterns for pancreatic cancer in Japan. Methods This retrospective study examined the treatment patterns among 68 479 patients, who had pancreatic cancer diagnosis in Medical Data Vision claims database from 2010 to 2018. We extracted relevant data on treatment options, including chemotherapy, surgery and their combination. For patients who had undergone chemotherapy, we sought to analyse the use of different chemotherapy regimens. In addition, we examined the trend in treatment patterns by age group ( Results The trend in treatment options of pancreatic cancer remained stable from 2010 to 2018, with chemotherapy being the most common therapeutic option and surgery performed in approximately half that of chemotherapy. On the other hand, the use of chemotherapy regimen had changed during the same period. Although gemcitabine was the most commonly administrated single-agent regimen in 2010, gemcitabine + nab-paclitaxel was the most frequently used therapeutic agent in 2018. In the older age groups (age ≥80), the majority of patients was untreated (supposedly received supportive care), and the use of conventional regimens such as gemcitabine or S-1 was common among those undergoing chemotherapy. Conclusions Although chemotherapy has been the main treatment option for pancreatic cancer, the regimens of choice have increased significantly during the last decade. With accumulating evidence on combination chemotherapy, treatment options may further evolve in the future.

The flow boiling heat transfer and pressure drop of zeotropic binary mixture R1234yf/R32 were experimentally investigated inside a horizontal multiport tube with rectangular minichannels. Local heat transfer coefficients were quantified under mass fluxes in the range 50–400 kgm−2s−1, heat fluxes in the range 5–20 kWm−2, and circulation compositions of 80/20 and 50/50mass%. The obtained heat transfer coefficient of the mixtures were compared with those of pure components under the same experimental conditions. The heat transfer of the mixtures was strongly influenced by mass flux, vapor quality, and mass fraction, whereas the influence of heat flux on heat transfer was small. The heat transfer coefficients of the mixtures were lower than those of the pure components under most conditions owing to mass diffusion resistance and temperature glide; however, the heat transfer coefficients of the mixtures were same or higher than those of R1234yf at high mass flux and high vapor quality regions. The frictional pressure drops of the mixtures increased with increasing mass flux, vapor quality, and mass fraction of R1234yf. The database encompassing more than 900 and 190 for boiling heat transfer coefficient and frictional pressure drop were compared with available previous correlations. Previous correlations underestimated the heat transfer coefficients of the mixtures, especially for data with higher temperature glide and dominant forced convective heat transfer. The proposed correlation shows good agreement with the heat transfer coefficients of the R1234yf/R32 mixtures with mean and mean absolute deviations of −5.0% and 10.3%, respectively.

Biliary tract cancer (BTC) has not been considered a tobacco-related cancer, largely because of inconclusive results from epidemiological studies. We herein evaluate the association between cigarette smoking and risk of death from BTC by anatomic subsite and sex using data from a large, prospective cohort study in Japan.The present study included 97,030 Japanese individuals who were enrolled in 1988-1990 and followed until 31 December 2009. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the association of BTC with cigarette smoking, including smoking status, number of cigarettes smoked per day, and pack-years of smoking.During a mean follow-up of 16.2 years, we documented 484 deaths (187 from gallbladder cancers and 297 from cancers of other and unspecified biliary tract parts). After adjustment for sex, age, body mass index, alcohol consumption, and history of gallstones, current smokers had a higher risk of death due to BTC (RR = 1.35, 95% CI = 1.01-1.79) than never smokers. In the analyses by anatomic subsite, current smoking was associated with an increased risk of death from gallbladder cancer (RR = 1.89 95% CI = 1.19-3.02), whereas no evidence of an association was noted for cancers of other and unspecified biliary tract parts (RR = 1.10, 95% CI = 0.77-1.58). Moreover, mortality risk increased with an increasing number of cigarettes smoked per day and pack-years of smoking, particularly for gallbladder cancer in men.Cigarette smoking is associated with an increased risk of death from BTC, particularly gallbladder cancer, in Japanese men.

Background In Japan, most gastric cancers are associated with gastric mucosal atrophy caused by chronic infection with Helicobacter pylori (H. pylori). Recognizing the condition of the gastric mucosa and determining the infection status of H. pylori are important for predicting the individual risk of gastric cancer. This study aimed to determine the proportion of Japanese adults with a healthy gastric mucosa (without H. pylori infection) among 12 birth-year groups encompassing 1935–1990 by morphological images. Methods The gastric mucosa was classified as healthy or having gastritis based on routine double-contrast upper gastrointestinal barium X-ray radiography. The participants included 41 957 healthy Japanese adults. Serum or urine H. pylori antibody levels were also assessed. Results In total, 25 424 participants had healthy mucosa without a history of H. pylori eradication. The proportions of participants with a healthy mucosa by birth year were 19.8% (57/288), 27.1% (306/1128), 32.4% (569/1756), 37.6% (1808/4811), 49.2% (3207/6522), 60.1% (3966/6550), 71.2% (5224/7342), 77.2% (5114/6624), 80.6% (3342/4149), 85.0% (1404/1652), 85.3% (302/354) and 94.7% (125/132) in 1935, 1940, 1945, 1950, 1955, 1960, 1965, 1970, 1975, 1980, 1985 and after 1990, respectively (P for trend Conclusions The proportion of participants with normal gastric mucosa linearly increased with the birth years. The prevalence of morphologically healthy gastric mucosa could have consistently increased with decreasing prevalence of H. pylori infection.

Helicobacter pylori infection is a well-established risk factor for gastric cancer and has been linked to other gastrointestinal diseases, including pancreatic and biliary tract cancers; however, the relevance of enterohepatic non-H. pylori helicobacters to the pathophysiology of these diseases remains unclear.We estimated the prevalence of two enterohepatic non-H. pylori helicobacters (Helicobacter hepaticus and Helicobacter bilis) in the framework of a hospital-based case-control study involving 121 patients with biliary tract cancer, pancreatic cancer, or other gastrointestinal diseases. Bile and blood samples were collected from the patients undergoing endoscopic retrograde cholangiopancreatography. The presence of H. bilis, H. hepaticus, and other Helicobacter spp. was examined using bacterial culture, PCR-based detection, and serological tests.Culture of Helicobacter spp. from biliary brush samples was unsuccessful. Approximately 13.0% (15/115) of the bile samples collected from patients with a variety of gastrointestinal cancers, including pancreatic and biliary tract cancers, tested positive for one of the enterohepatic non-H. pylori helicobacter species as determined by PCR. Specifically, H. bilis and H. hepaticus DNA were detected in 11 and 4 bile samples, respectively. Approximately 20%-40% of the patients tested positive for serum non-H. pylori helicobacter IgG antibodies. The seroprevalence of H. bilis and H. hepaticus in the patients without evidence of H. pylori infection appeared to be higher in the pancreatic cancer group than in the control group.Our findings suggest a role for Helicobacter spp., especially H. bilis and H. hepaticus, in the etiology of pancreatic and biliary tract cancers.

The guidelines for osteoarthritis (OA) treatment recommend different therapies including pharmacotherapy, and several analgesic options are available for pain management. In Japan, research on hip and knee OA treatment trends is scarce and OA-related healthcare costs are unknown. Therefore, this study aimed to examine the treatment and healthcare cost trends among Japanese patients with hip or knee OA. This was a cross-sectional study held between 2013 and 2019, using a medical claims database. The demographic and treatment characteristics of hip or knee OA patients for each year were descriptively analyzed and the medians for healthcare utilization and all-cause healthcare costs were calculated. The yearly mean age of 59,218 hip OA and 270,722 knee OA patients ranged from 66.3 to 68.6 years and 71.1 to 73.1 years, respectively. The prevalence of comorbidities was higher in knee OA than hip OA. In both groups, > 70% of patients were female, and the most common treatment was pain-related medication. In hip OA, topical and systemic nonsteroidal anti-inflammatory drugs (NSAIDs) were mostly used throughout the study period (34.1–41.4% and 32.0–40.3%, respectively). Similarly, in knee OA, topical and systemic NSAIDs were used in 58.3–63.3% and 36.5–46.0% patients, respectively. Increase in the use of acetaminophens (10.9% in hip OA and 10.2% in the knee OA) and weak opioids (3.7%, and 3.4%, respectively) from 2013 to 2019 were observed. Most patients were treated as outpatients in both groups. The median all-cause healthcare costs were approximately 35,000 JPY for hip OA and 74,000 JPY for knee OA. Although a considerable change in total healthcare cost was not observed in our study, the contents of medical treatment and cost breakdown were greatly altered due to the treatment and cost for OA itself, and the treatment and cost for comorbidities. Similar studies to investigate such a trend may help predict necessary resources and social needs. Thus, further investigation utilizing other databases is needed.

Aim The aim is to investigate the actual situation of accidental ingestion of magnets in children in Japan and the clinical features of the resulting gastrointestinal damage. Methods We developed a questionnaire and sent it to 496 board-certified training hospitals nationwide. Information was collected on the number of children with accidental magnet intake from 2015 to 2017, witnesses of magnet intake, number and type of magnets, presence or absence of gastrointestinal injury, treatment, etc RESULTS: The number of cases of accidental ingestion of magnets within the study period was 104, with a median age of 2 years. About half of the incidents were unwitnessed. There were 33 cases of accidental ingestion of multiple magnets. Among them, oesophagogastroduodenoscopy was performed in 4 children and surgery in 10, and significantly invasive treatment was required in comparison with single-magnet ingestion. Gastrointestinal injury was observed in 11 cases, 10 of which were caused by multiple-magnet ingestion. All 10 of these patients underwent surgical treatment. There was no mortality. Conclusion The incidence of accidental magnet ingestion in Japan is estimated to be 50-70 per year. Unwitnessed cases are not uncommon. Multiple magnet ingestion often causes gastrointestinal injury. Many cases of gastrointestinal injury are caused by ingestion of magnetic toys.

Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P, Previous genome-wide association studies have identified risk loci for pancreatic cancer but were centered on individuals of European ancestry. Here the authors identify GP2 gene variants associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

BACKGROUND Distributions of serum pepsinogen (PG) values were assessed in Helicobacter pylori-infected and non-infected junior high school students (aged 12-15 years) in Japan. METHODS All junior high school students (1,225 in total) in Sasayama city, who were basically healthy, were asked to provide urine and serum samples, which were used to measure urine and serum H. pylori antibodies using ELISA kits and PG values. The subjects, whose urine and serum antibodies were both positive, were considered H. pylori infected. RESULTS Of the 187 subjects who provided urine and blood samples, 8 were infected, 4 had discrepant results, 4 had negative serum antibody titers no less than 3.0 U/ml, and 171 were non-infected. In the H. pylori non-infected subjects, the median PG I and PG II values and PG I to PG II ratio (PG I/II) were 40.8 ng/mL, 9.5 ng/mL, and 4.4, respectively, whereas in the infected subjects, these values were 55.4 ng/mL, 17.0 ng/mL, and 3.3, respectively (each P < 0.01). In the non-infected subjects, PG I and PG II were significantly higher in males than in females (P < 0.01). CONCLUSIONS The PG I and PG II values were higher, and the PG I/II was lower in H. pylori infected students than in non-infected students. In H. pylori non-infected students, males showed higher PG I and PG II values than females. The distributions of PG values in junior high school students differed from those in adults.

Background Serum Helicobacter pylori (H. pylori) antibody kits (LZ and LIA) using the latex agglutination immunoassay method are commercially available, but few studies have been performed to determine their diagnostic accuracy or to compare their results with those of enzyme-linked immunosorbent assay (ELISA) kits (EP and EIA). Methods Sera were obtained from 213 hospital outpatients with dyspeptic symptoms. The serological results were compared with the result of the 13C-urea breath test (UBT) which seems to be reliable. Results Of the 213 subjects, 154 were diagnosed as positive for H. pylori infection according to the UBT. The sensitivities and specificities of these tests were 97.4% and 76.3%, 98.1% and 78.0%, 99.4% and 74.6%, and 98.1% and 71.2% for the EP, LZ, EIA and LIA tests, respectively. When the 13 subjects whose seropositive results of the four kits were completely opposite to the negative results of the UBT were excluded, the specificities of evaluated kits were all higher than 90%. The concordance rate between the EP and EIA tests was 98.1% (Spearman's rank correlation coefficient = 0.83) and that between the LZ and LIA tests was 97.1% (correlation coefficient = 0.91). The LZ gave higher antibody titer value than EP (p Conclusions The latex immunoassay method provided the same reliability to ELISA in terms of the diagnostic accuracy for current H. pylori infection, although we should take into account the titer value differences by each test method in practical use.

The causal relationship betweenA case-control study consisting of 275 gastric cancer patients and 275 age- and sex-matched controls was performed. SerumFor cutoff values of 1.25, 1.5, 1.75, 2.0, and 2.3 EV, the ORs (95% confidence intervals) were 67.7 (9.1, 502), 37.2 (8.8, 157), 21.3 (9.0, 60.2), 25.5 (9.0, 72.7), and 25.9 (9.2, 73.2), respectively.These results suggest that the risk ratio of gastric cancer between subjects with and without history of

Background The secular trend in the prevalence of Helicobacter pylori (H. pylori) infection among children and adolescents in Japan has not been well documented. Materials and Methods We reviewed all relevant literature published between 1991 and 2017, focusing on the relationship between the prevalence of H. pylori infection and birth year. Our literature search covered all journal articles, conference proceedings and meeting abstracts that reported the prevalence of H. pylori infection in Japanese subjects under 20 years of age. Results We examined the prevalence of H. pylori infection according to birth year on the basis of data points, which comprised 20,269 subjects of 81 groups. Three-coefficient logistic regression analysis was performed to examine the trend in H. pylori prevalence. The prevalence was approximately 10% in the individuals born in 1985, but it decreased to 3% in the individuals born in 2011. The plot of H. pylori prevalence against birth year clearly indicated a birth-cohort effect: the earlier the birth year, the higher the prevalence. Conclusions Our analysis revealed a rapidly decreasing prevalence of H. pylori infection among Japanese children and adolescents over the past three decades.

Esophageal cancer is prevalent in Cixian, China, but the etiology of this disease remains largely unknown. Therefore, we explored this by conducting a DNA adductome analysis. Both tumorous and nontumorous tissues were collected from patients who underwent surgical procedures at Cixian Cancer Hospital and the Fourth Hospital of Hebei Medical University, which is in a low-incidence area. N2-(3,4,5,6-Tetrahydro-2H-pyran-2-yl)deoxyguanosine (THP-dG) was the major adduct detected in samples from esophageal cancer patients in Cixian. The precursor of THP-dG, N-nitrosopiperidine (NPIP), exhibited a strong mutagenic activity under metabolic activation in the Ames test and a significant dose-dependent increase in mutation frequency during an in vivo mutagenicity test with guanine phosphoribosyltransferase (gpt) delta rats. The NPIP-induced mutation was dominated by A:T to C:G transversions, followed by G:C to A:T and A:T to G:C transitions, in the liver and esophagus of animal samples. A similar mutational pattern...

Background Practical criteria for the use of serum pepsinogen (PG) values in diagnosing Helicobacter pylori infection have not yet been determined. Methods The results of gastric endoscopies, H. pylori infection tests, and PG values were retrospectively reviewed. Subjects were assigned to groups, including never-infected (with neither infection nor gastric mucosal atrophy), infected (with atrophy or findings indicating infection in endoscopy and positive infection tests except for antibody tests), and ex-infected (with gastric mucosal atrophy and negative infection tests, except for antibody tests). The optimal criteria with combined use of the PG II concentrations and the PG I/PG II ratio were investigated separately for PG measurements obtained with the chemiluminescent magnetic particle immunoassay (CLIA) and latex agglutination (LA) methods, such that the specificity was greater than 70% and the sensitivity was no less than 95% among the never-infected and infected subjects. Similar analyses were performed by combining the data from ex-infected and infected subjects. Results For the CLIA (LA) method, the optimal criterion among 349 (397) never-infected and 748 (863) infected subjects was a PG II value of at least 10 (12) ng/mL or a PG I/PG II ratio no more than 5.0 (4.0), which produced 96.3% (95.1%) sensitivity and 82.8% (72.8%) specificity. When 172 (236) ex-infected subjects were included, the optimal criterion was the same, and the sensitivity was 89.1% (86.9%). Conclusions The above criteria may be practical for clinical use, and PG tests using these criteria might prevent unnecessary endoscopic examinations for never-infected subjects.

BACKGROUND Very limited data are available on childhood gastric cancer. Using a retrospective survey and literature review, we assessed the clinical features of gastric cancer in children and adolescents. METHODS We collected information on childhood gastric cancer from pediatricians of 518 hospitals that issue the title of "certified board pediatrician" approved by Japan Pediatric Society, using a questionnaire on background, diagnosis year, onset symptoms, tumor location, histology, nodular gastritis, Helicobacter pylori testing, treatment, and prognosis. Studies were collected using PubMed and the NPO Japan Medical Abstracts Society database. Data for childhood gastric cancer were abstracted from the Japanese Vital Statistics database. RESULTS Of the 518 hospitals, 349 returned the questionnaire, which identified four patients. Literature review identified 77 cases of gastric cancer, and we analyzed data for 80 children 10 years old, and there were no sex differences. Onset symptoms ranged from abdominal pain to non-localized. Sixteen of 44 children had a family history of cancer; 10 had a family history of gastric cancer. Histologically, approximately 80% had undifferentiated-type carcinoma. Prognosis was extremely poor, and two of three tested children were positive for H. pylori infection. Childhood gastric cancer death has been declining. CONCLUSIONS Childhood gastric cancer is rare in Japan, and information on H. pylori in childhood gastric cancer patients is limited. Declining childhood gastric cancer rates may reflect the decreasing prevalence of infection but further study is necessary to clarify the relationship between H. pylori and gastric cancer.

The two-phase flow characteristics of R32 were experimentally investigated for horizontal multiport rectangular minichannels with hydraulic diameters of 0.5 and 1.0 mm. The two-phase flow was observed using a high-speed camera, with a mass velocity range of 30–400 kgm−2s−1 at a saturation temperature of 15 °C. The effects of mass velocity, quality, and channel size on the two-phase flow were clarified. The observed two-phase flow was classified into intermittent, transition, and annular flow regimes. The intermittent flow regime was observed at a lower quality region. The quality of transition from intermittent to transition flow regimes decreased with increasing mass velocity and channel size. Previously proposed flow regime maps could not predict the two-phase flow regime in multiport rectangular minichannels with sufficient accuracy. Thus, a new prediction method of flow regimes for multiport minichannels, considering channel size, was developed.

Context The real-world burden of gastrointestinal (GI) events associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in Japanese patients with osteoarthritis (OA) and/or chronic low back pain (CLBP) remains unreported. Objective To assess the incidence and economic burden of NSAID-induced GI events by using data from large-scale real-world databases. Methods We used the Japanese Medical Data Center database to retrospectively evaluate anonymized claims data of medical insurance beneficiaries employed by middle- to large-size Japanese companies who were prescribed NSAIDs for OA and/or CLBP between 2009 and 2018. Results Overall, 180,371 patients were included in the analysis, of whom 32.9% had OA, 53.8% had CLBP, and 13.4% had both OA and CLBP. NSAIDs were administered as first-line analgesics to 161,152 (89.3%) of the patients in the sample, in oral form to 90.3% and as topical patches to 80.4%. A total of 65.1% used combined oral/topical patches. Of the 21.0% of patients consistently using NSAIDs (percentage of days supplied ≥70%), 54.5% received patches. A total of 51.5% patients used NSAIDs for >1 to ≤6 months. The incidence of GI events was 9.97 per 10,000 person-years (95% confidence interval: 8.92–11.03). The risk of developing GI events was high in elderly patients and patients with comorbidities and remained similar for patients receiving oral vs. topical NSAIDs. Longer treatment duration and consistent NSAID use increased the risk of GI events. The cost (median [interquartile range]) of medications (n = 327) was US$ 80.70 ($14.10, $201.40), that of hospitalization (n = 33) was US$ 2,035.50 ($1,517.80, $2,431.90), and that of endoscopic surgery (n = 52) was US$ 418.20 ($418.20, $418.20). Conclusion NSAID-associated GI toxicity imposes a significant health and economic burden on patients with OA and/or CLBP, irrespective of whether oral or topical NSAIDs are used.

Objectives This study was designed to examine the diagnostic performance of the social and communication disorders checklist (SCDC) and strength and difficulties questionnaire (SDQ) to detect autism spectrum conditions (ASC), along with the social responsiveness scale‐second edition (SRS‐2) as reference, in a psychiatry outpatient setting. Methods We translated the SCDC into Japanese since its Japanese version was unavailable. We examined its test‐retest reliability as well as the internal consistency reliability and diagnostic performance of the three questionnaires among 41 Japanese psychiatric outpatients, using the best‐estimate diagnosis of ASC based on the diagnostic interview for social and communication disorders, as a gold standard. Results The test‐retest reliability was high for the SCDC. Although the internal consistency reliability was high for the SCDC and SRS‐2, that was low for the prosocial and peer problem subscales of the SDQ. The performance of the SCDC, SDQ, and SRS‐2 to detect ASC was moderate: the area under the ROC curve of 0.78, 0.78, and 0.84, respectively. Conclusions Although questionnaires to detect ASC, including the three examined, generally have only moderate performance in this setting, these can be successfully applied to high‐risk populations such as psychiatry outpatients, when multi‐level rather than dichotomous likelihood ratios are used.

Introduction We aimed to analyze the relationships between nonsteroidal anti-inflammatory drug (NSAID) treatment variables and the incidence of acute myocardial infarction (AMI) in Japanese patients with osteoarthritis (OA) and chronic low back pain (CLBP) using the data from a large-scale, real-world database. Methods We retrospectively analyzed anonymized claims data from the Japanese Medical Data Center of medical insurance beneficiaries who were prescribed NSAIDs for OA and/or CLBP from 2009 to 2018. Results Of 180,371 patients, 89.3% received NSAIDs as first-line analgesics (oral, 90.3%; patch, 80.4%; other transdermal drugs, 24.0%). Incidence of AMI was 10.27 per 10,000 person-years (95% confidence interval 9.20–11.34) in the entire study population. There was a trend towards increased risk in patients using NSAIDs for more than 5 years (P = 0.0784) than in those using NSAIDs for less than 1 year. Risk of AMI significantly increased with age and comorbidities of diabetes and cardiovascular disease (CVD). The risk for AMI was similar for patients who consistently used NSAIDs compared to those using them intermittently and patients who used patch compared to oral NSAIDs. Elderly patients used NSAIDs more consistently and used NSAID patches more frequently. Conclusion In Japanese patients with OA and CLBP, we saw a trend of increased risk for AMI in patients using NSAIDs for more than 5 years. Elderly patients had a higher prevalence of diabetes, hypertension, and other CVD which increased the risk of AMI. Although NSAID patches were preferred to oral NSAIDs in elderly patients, risk for AMI was similar between the two modalities. Therefore, we suggest using NSAIDs carefully, especially in elderly patients and those at risk of developing CVD. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01629-6.

The aim of this study was to further examine the relationship between milk intake and stroke mortality among the Japanese population. We used data from the Japan Collaborative Cohort (JACC) Study (total number of participants = 110,585, age range: 40&ndash, 79) to estimate the posterior acceleration factors (AF) as well as the hazard ratios (HR) comparing individuals with different milk intake frequencies against those who never consumed milk at the study baseline. These estimations were computed through a series of Bayesian survival models that employed a Markov Chain Monte Carlo simulation process. In total, 100,000 posterior samples were generated separately through four independent chains after model convergency was confirmed. Posterior probabilites that daily milk consumers had lower hazard or delayed mortality from strokes compared to non-consumers was 99.0% and 78.0% for men and women, respectively. Accordingly, the estimated posterior means of AF and HR for daily milk consumers were 0.88 (95% Credible Interval, CrI: 0.81, 0.96) and 0.80 (95% CrI: 0.69, 0.93) for men and 0.97 (95% CrI: 0.88, 1.10) and 0.95 (95% CrI: 0.80, 1.17) for women. In conclusion, data from the JACC study provided strong evidence that daily milk intake among Japanese men was associated with delayed and lower risk of mortality from stroke especially cerebral infarction.

Background The 25-question Geriatric Locomotive Function Scale (GLFS-25) is widely used in daily clinical practice in evaluating locomotive syndrome (LS). The questionnaire contains 25 questions aiming to describe 6 aspects, including body pain, movement-related difficulty, usual care, social activities, cognitive status, and daily activities. However, its potential underlying latent factor structure of the questionnaire has not been fully examined so far. Methods Five hundred participants who were 60 years or older and were able to walk independently with or without a cane but had complaints of musculoskeletal disorders were recruited face to face at the out-patient ward of Aichi Medical University Hospital between April 2018 and June 2019. All participants completed the GLFS-25. Confirmatory factor analysis (CFA) models (single-factor model, 6-factor model as designed by the developers of the GLFS-25) were fitted and compared using Mplus 8.3 with a maximum likelihood minimization function. Modification indices, standardized expected parameter change were used, a standard strategy for scale development was followed in the search for an alternative and simpler model that could well fit the collected data. Cronbach’s α and its 95% confidence interval (CI) were also calculated. Results Mean (standard deviation) participants age was 72.6 (7.4) years old; 63.6% of them were women. Under the current criteria, 132 (26.4%) and 262 (52.4%) of the study subjects would be classified as LS stage 1 and stage 2, respectively. Overall, the Cronbach’s α (95% CI) for GLFS-25 evaluated using these data was 0.959 (0.953, 0.964). The single- and 6-factor models were rejected due to poor fit. The alternative models with either full 25 questions or a shortened GLFS-16 were found to fit the data better. These alternative models included three latent factors (body pain, movement-related difficulty, and psycho-social complication) and allowed for cross-loading and residual correlations. Discussion The findings of the CFA models provided evidence that the factor structure of the GLFS-25 might be simpler than the 6-factor model as suggested by the designers. The complex relationships between the latent factors and the observed items may also indicate that individual sub-scale use or simply combining the raw scores for evaluation is likely to be inadequate or unsatisfactory. Thus, future revisions of the scoring algorithm or questions of the GLFS-25 may be required.

The initial stage of degradation process of yttria partially stabilized zirconia thermal barrier coatings during heating at 1000–1450 K were observed in situ by transmission electron microscopy. The observation directly demonstrated that the formation of several kinds of oxides and resulting void growth started above 1000 K in the bond-coat layer near the interface with the thermally grown oxide layer, leading to the development of voids over the entire interface due to void coalescence. Such development of voids corresponds to the generation and propagation of thermally grown cracks, i.e., to the initial spallation of the coating.

Zirconium dioxide (ZrO2) nanoparticles were heated at 1200 K in a transmission electron microscope, and their surfaces were observed in situ via lattice imaging. The nanoparticles exhibited well-defined crystal habits while fluctuating the surface terrace structures. The stable surfaces and ridges were inferred from the fluctuation of the terraces, leading to the construction of the three-dimensional surface structures at 1200 K. By contrast, after the specimen cooled to room temperature, the surface fluctuation of the nanoparticles stopped and the crystal habit disappeared, implying that the crystal habit was maintained because of atomic diffusion during the surface fluctuation.

Background Helicobacter pylori infection is associated with gastric cancer; thus, early diagnosis and treatment are crucial. Given that H. pylori infection in adolescents or young adults has few symptoms, screening tests are necessary for this population. In this study, the accuracy of the rapid urine H. pylori antibody (u-HpAb) test was evaluated and compared with that of urine and serum H. pylori enzyme-linked immunosorbent assay (u-HpELISA and s-HpELISA, respectively) in junior high school students. Methods All 1,225 students attending the junior high schools in Sasayama City were invited to participate in this study. Urine and blood samples were assayed for anti-H. pylori immunoglobulin G antibodies, and rapid u-HpAb was performed by three investigators independently. When all investigators were in agreement, the test was confirmed as positive or negative. Non-concordance was defined as undetermined. Results In total, 187 students participated in this study and provided both urine and blood samples. Three students had undetermined rapid u-HpAb. Excluding these results, the positivity rate of rapid u-HpAb was 3.3% (6/184), whereas that for u-HpELISA and s-HpELISA was 4.8% (10/187) and 5.9% (11/187), respectively. Using s-HpELISA and u-HpELISA as the standards, the sensitivity, specificity, positive predictive value, and negative predictive value of rapid u-HpAb were 85.7%, 100%, 100%, and 99.4%, respectively, excluding the undetermined rapid u-HpAb results. Conclusions Rapid urine-HpAb test had excellent specificity but relatively low sensitivity.

We report the development of a new type of a 2000 K class high temperature stage for transmission electron microscopy (TEM) of various shaped nanostructured materials, i.e., nanometer-sized isolated nanostructures, such as particles, fibers, and thin films, and nanocrystalline bulk materials. The maximum temperature of the heating stage was 300–700 K higher than that of prevailing heating stages. In addition, we found that since the structure of the developed heating stage is simple, the stage can be applied to most of transmission electron microscopes without any additional modification. The stability of the heating stage was confirmed by In Situ high-resolution observation of the lattice fringes of the zirconium dioxide nanoparticles heated at 1183 K. We observed In Situ the nanoscale structural variation of titanium plate surfaces around 900 K and the melting of nanocrystalline iron thin films around 1808 K by this method. It was demonstrated that the heating stage is useful for the analysis of high temperature structural dynamics of various shaped nanostructured materials.

Esophageal cancer is prevalent in Cixian, China, but the etiology of this disease remains largely unknown. Therefore, we explored this by conducting a DNA adductome analysis. Both tumorous and nontumorous tissues were collected from patients who underwent surgical procedures at Cixian Cancer Hospital and the Fourth Hospital of Hebei Medical University, which is in a low-incidence area.

About one-third of all children worldwide is infected with H. pylori and its prevalence is low in developed and high in developing countries. H. pylori is mainly acquired during childhood and transmission of the bacterium commonly proceeds from person to person, especially among family members. The most frequent transmission route is from the mother to children. Various gastrointestinal and extra-gastrointestinal diseases are reported to be associated with H. pylori in children and adolescents, but the strongest recommendation for testing and treating is introduced only with children and adolescents having peptic ulcer disease. Iron deficiency anemia and chronic immune thrombocytopenic purpura are also considered for testing and treating, but the effectiveness is somewhat controversial. Invasive diagnosis is recommended, whereas none of the available diagnostic tests have 100% accuracy for reliable diagnosis, and therefore at least two or more tests should be performed. Urea breath test is the most reliable among the non-invasive tests. Because the number of antibiotics-resistant H. pylori strains is increasing, it is desirable to conduct a drug susceptibility test before treatment and to select the corresponding regime. H. pylori has been proven to be a major cause of gastric cancer and 'screen-and-treat' strategies are recommended in communities at high risk of gastric cancer. However, the application to children and adolescents is controversial. An effective vaccine is desirable, but not yet available. Screen-and-treat for adolescents has started in a few areas in Japan, where conditions are well established. New prevention strategies for gastric cancer are awaited worldwide.

Background Since "Helicobacter pylori (H. pylori) infection" was set as the indication in the Japanese Society for Helicobacter Research (JSHR) Guidelines 2009, eradication treatment for H. pylori gastritis is covered under insurance since 2013 in Japan, and the number of H. pylori eradication has rapidly increased. Under such circumstances, JSHR has made the third revision to the "Guidelines for diagnosis and treatment of H. pylori infection" for the first time in 7 years. Methods The Guideline Committee held 10 meetings. Articles published between the establishment of the 2009 Guidelines and March 2016 were reviewed and classified according to the evidence level; the statements were revised on the basis of this review. After inviting public comments, the revised statements were finalized using the Delphi method. Results There was no change in the basic policy that H. pylori infectious disease is an indication for eradication. Other diseases presumed to be associated with H. pylori infection were added as indications. Serum pepsinogen level, endoscopic examination, and X-ray examination were added to the diagnostic methods. The effects of 1-week triple therapy consisting of potassium-competitive acid blocker (P-CAB), amoxicillin, and clarithromycin have improved, and high eradication rates can also be expected with proton pump inhibitors (PPI) or P-CAB combined with amoxicillin and metronidazole. If the susceptibility test is not performed, the triple PPI or P-CAB/amoxicillin/metronidazole therapy should be chosen, because the PPI/amoxicillin/metronidazole combination demonstrated a significantly higher eradication rate than PPI/amoxicillin/clarithromycin. In the proposal for gastric cancer prevention, we divided gastric cancer prevention measures by age from adolescent to elderly, who are at an increased gastric cancer risk, and presented measures for gastric cancer prevention primarily based on H. pylori eradication. Conclusion We expect the revised guidelines to facilitate appropriate interventions for patients with H. pylori infection and accomplish its eradication and prevention of gastric cancer.

Background Metronidazole is an antiprotozoal drug used to treat a broad spectrum of infectious diseases, including Helicobacter pylori (H pylori) infections. In Japan, metronidazole is approved for the eradication therapy of H pylori as a second-line regimen among adults, but it has not yet been approved for use among children and adolescents. Materials and methods To perform this narrative review, we searched the relevant literature on important events in the history of the use of metronidazole, its mechanisms of action, its efficacy, and the adverse effects reported in clinical trials or cohort studies in Japan. Results At present, metronidazole resistance has not been a serious issue in Japan in large part due to its restricted use. Emerging evidence from randomized controlled trials demonstrates higher eradication rates for metronidazole than for clarithromycin, supporting its use in both first-line and second-line eradication therapies. Among the reported adverse effects, there has been lingering concern over the potential carcinogenicity of metronidazole in humans. However, the possibility of an increased cancer risk is not limited to metronidazole; the long-term use of antibiotics has been linked to increased risk for some site-specific cancers. However, recent prospective studies have suggested that short-term exposure to antibiotics is not associated with an increased cancer risk. Conclusion Sensible use of metronidazole backed by research evidence could maximize the benefits associated with H pylori eradication in Japan.

Serum Helicobacter pylori (H. pylori) antibody kits (LZ and LIA) using the latex agglutination immunoassay method are commercially available, but few studies have been performed to determine their diagnostic accuracy or to compare their results with those of enzyme-linked immunosorbent assay (ELISA) kits (EP and EIA).Sera were obtained from 213 hospital outpatients with dyspeptic symptoms. The serological results were compared with the result of theOf the 213 subjects, 154 were diagnosed as positive for H. pylori infection according to the UBT. The sensitivities and specificities of these tests were 97.4% and 76.3%, 98.1% and 78.0%, 99.4% and 74.6%, and 98.1% and 71.2% for the EP, LZ, EIA and LIA tests, respectively. When the 13 subjects whose seropositive results of the four kits were completely opposite to the negative results of the UBT were excluded, the specificities of evaluated kits were all higher than 90%. The concordance rate between the EP and EIA tests was 98.1% (Spearman's rank correlation coefficient = 0.83) and that between the LZ and LIA tests was 97.1% (correlation coefficient = 0.91). The LZ gave higher antibody titer value than EP (p 0.0001, Z = 9.82; Wilcoxon signed-rank test), and EIA gave higher value than LIA (p 0.0001, Z = 6.43; Wilcoxon signed-rank test).The latex immunoassay method provided the same reliability to ELISA in terms of the diagnostic accuracy for current H. pylori infection, although we should take into account the titer value differences by each test method in practical use.