Oral administration of the amino acids cystine and theanine attenuates the adverse events of S-1 adjuvant chemotherapy in gastrointestinal cancer patients.

BACKGROUND: Nutritional therapy is used to reduce the adverse events (AEs) of anticancer drugs. Here, we determined whether the amino acids cystine and theanine, which provide substrates for glutathione, attenuated the AEs of S-1 adjuvant chemotherapy. METHODS: Patients scheduled to receive S-1 adjuvant chemotherapy were randomized to the C/T or the control groups. The C/T group received 700 mg cystine and 280 mg theanine orally 1 week before the administration of S-1, which then continued for 5 weeks. Each group received S-1 for 4 weeks. Blood sampling was performed and AEs were evaluated (CTCAE ver. 4.0) before and after the administration of S-1. S-1 was discontinued when AEs ≥ grade 2 occurred. RESULTS: The incidences of AEs of any grade and those over grade 2 were lower in the C/T group than in the controls. The incidence of diarrhea (G ≥ 2) was significantly less (p < 0.05) in the C/T group (3.1 %) than in the controls (25.8 %). The duration and completion rate of the S-1 adjuvant chemotherapy were significantly longer (p < 0.01) and higher (p < 0.01), respectively, in the C/T group (complete ratio: 75.0 %, duration: 24.8 ± 5.8 days) than in the controls (complete ratio: 35.5 %, duration: 20.0 ± 7.7 days). CONCLUSIONS: The oral administration of cystine and theanine attenuated the AEs of S-1 adjuvant chemotherapy and increased the S-1 completion rate, suggesting that cystine and theanine is a useful supportive care for chemotherapy.

[BASELINE SCREENING USING INTERFERON-GAMMA RELEASE ASSAY SUGGESTS AN INCREASED RISK OF MYCOBACTERIUM TUBERCULOSIS INFECTION AMONG EMPLOYEES IN A JAPANESE GENERAL HOSPITAL].

OBJECTIVES: This retrospective study aimed to assess the risk of tuberculosis infection for the employees of a Japanese hospital using baseline interferon-gamma release assay (IGRA). The risk was defined as exposure to the hospital environment. METHODS: In total, 870 hospital employees including 161 new employees, 582 for baseline assay, and 127 for contact examination (709 subjects in the post-employment group) were examined from December 2010 to April 2012. The new employees were considered as the "non-exposure" group, whereas the post-employment group was considered as the "exposure" group. Multiple logistic regression analyses were used to calculate the odds ratio (OR) for IGRA positivity, adjusted for gender, smoking history, and alcohol intake (model 1), and for years of employment (model 2). RESULTS: The exposure group was significantly associated with an increased risk of positive IGRA results, even when adjusted for years of employment (OR: 4.1; 95% confidence interval: 1.4-17.6; P = 0.007). Subgroup analyses stratified by profession indicated a significantly increased OR for laboratory technicians, doctors, and nurses in both models. No correlation was observed between the length of employment and IGRA positivity. CONCLUSION: Exposure to the hospital environment increased the risk of tuberculosis infection for employees irrespective of the length of employment. Laboratory technicians, doctors, and nurses were at the highest risk of infection.

Characteristics of Top-Searched Individuals in Japan's Yen for Docs Conflicts of Interest Database During the COVID-19 Pandemic.

Purpose Transparency in healthcare has led to increased public disclosure of doctors' conflicts of interest, with the "Yen for Docs Database" in Japan emerging as a pivotal source. Nevertheless, there remains ambiguity regarding the backgrounds and influence of highly-searched persons, especially during the COVID-19 pandemic. The primary objective of this study was to examine if the database was utilized for its intended purpose in 2021, a year marked by the introduction of vaccines and treatments, the addition of new COVID-19-related data, and the frequent appearances of expert statements in various media outlets. Methods We conducted a descriptive analysis on the 10 most frequently searched individuals in the "Yen for Docs Database" between August 27 and September 23, 2021, and determined the amount of money they received from pharmaceutical companies and other organizations over the four-year period between 2016 and 2019. To characterize frequently searched individuals' academic profiles and appearances in the mass media, we identified their h-index and affiliation, their activity on Twitter, and the number of TV appearances. Results There were 72,904 searches during the study period, with the top person accounting for 4,905 of those searches. All top 10 were male, mostly affiliated with universities and specialists in infectious diseases or related fields. Their median number of COVID-19 articles was five, and the median h-index was 34. Four of these top 10 had Twitter accounts, with followers ranging from 12,000 to 195,000. The median amount received from pharmaceutical entities over four years was $154,930, ranging from $809 to $705,502. Conclusions In the Yen for Docs Database, a significant portion of searches during the COVID-19 pandemic was concentrated on a selected group of healthcare professionals with considerable payments over the years, and they exhibited prominent academic and media profiles. These observations highlight the need for more transparent conflicts of interest disclosure among physicians with public visibility.

Observational study of financial and non-financial conflicts of interest among the Japanese government advisory board members concerning coronavirus disease 2019.

This cross-sectional analysis aimed to assess the extent of conflicts of interest among the Japanese government coronavirus disease 2019 (COVID-19) advisory board members and elucidate the accuracy of conflicts of interest (COI) disclosure and management strategies. Using the payment data from all 79 pharmaceutical companies in Japan between 2017 and 2019 and direct research grants from the Japanese government between 2019 and 2020, we evaluated the extent of financial and non-financial COI among all 20 Japanese government COVID-19 advisory board members. The Ethic Committee of the Medical Governance Research Institute approved this study. Japanese government COVID-19 advisory board members were predominantly male (75.0%) and physicians (50.0%). Between 2019 and 2020, 2 members (10.0%) received a total of $819,244 in government research funding. Another 5 members (25.0%) received $532,127 in payments, including $276,722 in personal fees, from 31 pharmaceutical companies between 2017 and 2019. The average value of the pharmaceutical payments was $9155 (standard deviation: $12,975). Furthermore, neither the Ministry of Health, Labor, and Welfare nor the Japanese Cabinet Secretariat disclosed financial or non-financial COI with industry. Additionally, the government had no policies for managing COI among advisory board members. This study found that the Japanese government COVID-19 advisory board had financial and non-financial COI with pharmaceutical companies and the government. Furthermore, personal communication received as part of this research indicated that there were no rigorous COI management strategies for the COVID-19 advisory board members. Any government must ensure the independence of scientific advisory boards by implementing more rigorous and transparent management strategies that require the declaration and public disclosure of all COI.

Pre-hypertension as a significant predictor of chronic kidney disease in a general population: the Ohasama Study.

BACKGROUND: Hypertension is associated with an increased risk of development of chronic kidney disease (CKD). However, it is unclear whether pre-hypertension is related to the incidence of CKD. METHODS: The incidence of CKD defined as positive proteinuria or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2) was examined in 2150 inhabitants without pre-existing CKD from the general Japanese population. The association of blood pressure and CKD incidence was examined using a Cox regression model adjusted for age, sex, habitual smoking and drinking, obesity, history of cardiovascular disease, diabetes mellitus or hypercholesterolemia, eGFR at baseline, number of follow-up examinations and year of baseline examination. Participants were categorized according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. RESULTS: Participants were categorized into normotension (n = 586, 27.3 % ), pre-hypertension (n = 815, 37.9 % ), Stage 1 hypertension (n = 386, 18.0 % ) and Stage 2 hypertension (n = 363, 16.9 % ). During a mean follow-up of 6.5 years (14 023 person-years), 461 incidences of CKD were recorded. Compared to normotension, adjusted hazard ratios of CKD were significantly higher for pre-hypertension (1.49, P < 0.003), Stage 1 (1.83, P < 0.001) and Stage 2 (2.55, P < 0.001) hypertension. The population-attributable fraction of pre-hypertension (12.1 % ) was considered to be compatible to that of Stage 1 (8.6 % ) and Stage 2 (14.9 % ) hypertension. CONCLUSION: This was the first study to demonstrate that pre-hypertension was significantly associated with an increased risk of CKD and was one of the considerable causes of CKD in the general population.

Validation of the Parama-Tech PS-501 device for office blood pressure measurement according to the international protocol.

The PS-501 device (Parama-Tech, Fukuoka, Japan), an automated device for office blood pressure measurement based on the Korotkoff method and designed for professional use in clinical settings, was validated. Consecutive outpatients with hypertension and ≥30 years old at an outpatient hypertension clinic were recruited. According to the European Society of Hypertension protocol, 33 participants were included in the validation study (phase 1, n = 15; phase 2, n = 18). The cuff deflation rate can be selected manually from 2, 3, and 4 mm Hg/beat. The validation was performed with the device deflating at a rate of 2 mm Hg/beat. All blood pressure readings were measured on the left arm. The tested device passed all criteria for both systolic and diastolic blood pressure measurements. The mean (± standard deviation) differences in systolic and diastolic blood pressure between the tested device and the mean of observer readings were -1.9 ± 4.6 and -2.5 ± 2.9 mm Hg, respectively. The PS-501 device for office blood pressure measurement passed all the validation criteria of the European Society of Hypertension and can therefore be recommended for clinical use in an adult population.

Mother-offspring aggregation in home versus conventional blood pressure in the Tohoku Study of Child Development (TSCD).

OBJECTIVE: Few studies described the home blood pressure (HBP) in young children. Using intrafamilial correlations of blood pressure as research focus, we assessed the feasibility of HBP monitoring in this age group. METHODS: We enrolled 382 mothers (mean age 38.8 years) and singletons (7.0 years) in theTohoku Study of Child Development.We measured their conventional blood pressure (CBP; single reading) at an examination centre. Participants monitored HBP in the morning. We used the OMRON HEM-70801C for CBP and HBP measurement. In a separate group of 84 children (mean age 7.7 years), we compared blood pressure readings obtained by the OMRON monitor and the Dinamap Pro 100, a device approved by FDA for use in children. We used correlation coefficients as measure of intrafamilial aggregation, while accounting for the mothers' age, body mass index, heart rate and smoking and drinking habits and the children's age, height, and heart rate. RESULTS: Mother-offspring correlations were closer (P < or = 0.003) for HBP than CBP for systolic pressure [0.28 (P < 0.0001) vs 0.06 (P = 0.26)] and diastolic pressure [0.28 (P < 0.0001) vs 0.02 (P = 0.65)].The between-device differences (OMRON minus Dinamap) averaged 7.8 +/- 6.0 mmHg systolic and 5.8 +/- 5.5 mmHg diastolic. CONCLUSIONS: HBP monitoring is an easily applicable method to assess intrafamilial blood pressure aggregation in young children and outperforms CBP. Validation protocols for HBP devices in young children need revision, because the Korotkoff method is not practicable at this age and there is no agreed alternative reference method.

Eleven-Year Trend of Drug and Chemical Substance Overdose at a Local Emergency Hospital in Japan.

PURPOSE: The purpose of this study was to investigate long-term trends of overdose in the emergency department of a regional core hospital in Sendai, Miyagi Prefecture, Japan, and to identify patient characteristics as well as drugs and chemicals associated with overdose. METHODS: Patients who visited the emergency department from January 1, 2010, to December 31, 2020, and were diagnosed with a drug or chemical overdose were included in the study. We conducted a descriptive analysis based on the data collected. RESULTS: In total, 577 patients (mean 38.4 years old, female 75.0%) were considered, and 16.8% had a history of repeated overdose. The number of patients during the study period showed a downward trend, with slight increases in 2012 and 2020. In addition, the top four drugs suspected of causing overdose were over the counter (OTC) antipyretic analgesics and cold medicines (N=97), followed by flunitrazepam (N=80), etizolam (N=72), and brotizolam (N=70). CONCLUSION: There was a decreasing trend in overdose, and OTC medicines, sedatives, and anxiolytics were the primary medications causing overdose. OTC antipyretic analgesics and cold medicines were the most common suspected overdose drugs, with an increasing trend in the later years.

Guillain-Barre Syndrome After COVID-19 Vaccination: A Secondary Analysis of Domestic Safety Data by the Japanese Government.

Purpose The purpose of this study was to figure out the risk of Guillain-Barre syndrome (GBS) after coronavirus disease 2019 (COVID-19) vaccination, which has been reported as a rare adverse reaction. Methods Elucidating the characteristics, we performed a secondary analysis of the cases from February 2020 through January 2022, based on the publicly available spontaneous adverse reaction reports in Japan. Results We identified 115 cases, and all were after messenger RNA (mRNA) vaccination. Of all the cases, 69 (60.0%) were female and 44 (38.2%) were older than 65 years old. Severe GBS was reported by 38 males (median age 61.5 years) and 51 females (median age 55 years). The median interval from vaccination to the onset of symptoms was eight days for males and four days for females. Sequelae were reported in 18 patients (7 males, median age 81 years; 11 females, median age 51 years), 11 of whom were older than 65 years old. The estimated incidence was about 0.0001% (0.000058% for the Pfizer vaccine and about 0.000046% for the Moderna vaccine, respectively). Conclusions Spontaneous reports would have various biases, the incidence of GBS after mRNA vaccination was as low as in other existing vaccination programs, and it is important not to interpret that risk expansively.

Associated factors of home versus ambulatory heart rate variability in the general population: the Ohasama study.

We previously demonstrated that heart rate (HR) variability obtained by daytime ambulatory monitoring and that of daily home measurement associated differently with cardiovascular mortality risk; cardiovascular mortality was linked with decreased daytime ambulatory HR variability and increased day-by-day home HR variability. The aim of this study was to identify factors contributing to each variability, clarifying possible reasons for their different predictive values. We obtained daytime ambulatory HR and home HR in 538 individuals of a general Japanese population aged ≥55 years. Daytime ambulatory HR variability and day-by-day home HR variability were estimated as a standard deviation measured every 30 min by daytime ambulatory monitoring and day-by-day home measurements once in the morning for 4 weeks, respectively. There was only weak correlation between daytime ambulatory HR variability and day-by-day home HR variability (r = 0.08∼0.14). In a multiple regression model, daytime ambulatory HR variability was associated with daytime ambulatory HR (P < 0.0001), daytime ambulatory blood pressure (BP) variability (P < 0.0001), and male sex (P = 0.003), while negatively associated with daytime ambulatory systolic blood pressure (SBP) (P < 0.0001) and smoking (P = 0.038). Meanwhile, day-by-day home HR variability was positively associated with home HR (P < 0.0001), day-by-day home BP variability (P < 0.0001), and male sex (P = 0.018). Associated factors of daytime ambulatory HR variability and day-by-day home HR variability were different. Our findings suggest that HR variabilities by different intervals of measurements might be mediated by different mechanisms.

[Usefulness of early-stage intervention in mild hypertension: evidence from large-scale clinical trials].

Mild hypertension(stage 1 hypertension at ESC-ESH guideline 2007) defined as systolic blood pressure 140-159 mmHg and/or diastolic blood pressure 90-99 mmHg has been described as an established risk factor for cardiovascular events in guidelines on hypertension. Many trials have established the usefulness of treatment to moderate and severe hypertension with blood pressure levels of 160/100 or more. Some recent trials including patients with mild hypertension have also shown that antihypertensive treatment significantly reduced the risk of cardiovascular events, especially in patients with history of cardiovascular disease or diabetes. However, more studies are required to clarify the most appropriate antihypertensive drugs for the treatment of mild hypertension.

Detection of carotid atherosclerosis in individuals with masked hypertension and white-coat hypertension by self-measured blood pressure at home: the Ohasama study.

OBJECTIVE: To investigate carotid atherosclerosis in individuals with masked hypertension (MHT) and white-coat hypertension (WCHT) in a general population. METHODS: Self-measurement of blood pressure at home (HBP) and casual blood pressure (CBP) measurements were recorded in 812 individuals aged at least 55 years (mean 66.4 years) from the general Japanese population. The intima-media thickness (IMT) of the near and far wall of both common carotid arteries was measured and averaged. The relationships between carotid atherosclerosis (IMT and plaque) and the four blood pressure groups (sustained normal blood pressure: HBP < 135/85 mmHg, CBP < 140/90 mmHg; WCHT: HBP < 135/85 mmHg, CBP >or= 140/90 mmHg; MHT: HBP >or= 135/85 mmHg, CBP < 140/90 mmHg; sustained hypertension: HBP >or= 135/85 mmHg, CBP >or= 140/90 mmHg) were examined using multivariate analysis adjusted for possible confounding factors. RESULTS: Adjusted IMT in individuals with sustained hypertension [0.77 mm; 95% confidence interval (CI) 0.75 to 0.79 mm] and MHT (0.77 mm; 95% CI 0.73 to 0.80 mm) was significantly greater than in those with sustained normal blood pressure (0.71 mm; 95% CI 0.69 to 0.72 mm) and WCHT (0.72 mm; 95% CI 0.71 to 0.74 mm) (P < 0.0001). The odds ratios for the presence of plaques in all four groups were similar to the trends in IMT. CONCLUSIONS: Our findings imply that CBP measurements alone are insufficient to distinguish individuals at high risk of carotid atherosclerosis from those at low risk. However, these individuals do have distinct HBP measurements, suggesting that HBP measurement could become a valuable tool for predicting carotid atherosclerosis.

Ambulatory blood pressure, blood pressure variability and the prevalence of carotid artery alteration: the Ohasama study.

OBJECTIVES: To investigate the association between ambulatory blood pressure (BP) variables (level, short-term variability, circadian variation and morning pressor surge) and carotid artery alteration in a general population. METHODS: We measured ambulatory BP every 30 min in 775 participants (mean age 66.2 +/- 6.2 years, 68.8% women) from the Japanese general population. Short-term BP variability during the daytime and night-time were estimated as within-subject standard deviation of daytime and night-time BP, respectively. Circadian BP variation was calculated as the percentage decline in nocturnal BP. Morning pressor surge was defined as morning BP minus pre-waking BP. The extent of carotid artery alteration was evaluated as the average of common carotid intima-media thickness (IMT) and the presence of focal carotid plaque. RESULTS: Daytime and night-time BP values were more closely associated with carotid artery alteration than casual BP. With mutual adjustment for daytime and night-time BP, the latter (P < 0.0001) was more closely associated with IMT, which represents diffuse arterial thickening and arteriosclerosis, than daytime BP (P = 0.2). Night-time systolic BP variability was positively associated with carotid plaque (focal atherosclerotic lesions) independently of possible confounding factors, including night-time systolic BP (P = 0.01). A diminished nocturnal decline in systolic BP was associated with a greater IMT after adjustment for confounding factors (P = 0.03). A morning pressor surge was not associated with carotid artery alteration. CONCLUSION: Ambulatory BP levels and BP variability were closely associated with carotid artery alteration, suggesting that these parameters are independent risk factors or predictors of carotid artery alteration.