Comparison of the incidence of bleeding between baloxavir marboxil and other anti-influenza drugs among outpatients with influenza virus infection: A retrospective cohort study using an employment-based health insurance claims database in Japan.

PURPOSE: Alerts for bleeding events are included in the Japanese package inserts of some anti-influenza drugs, including baloxavir marboxil and oseltamivir. However, there are few reports on the incidence of bleeding events during treatment with anti-influenza drugs. This large-scale quantitative assessment compared the incidence of bleeding events in influenza patients treated with baloxavir and other anti-influenza drugs and in untreated patients. METHODS: This retrospective cohort study used a large-scale Japanese employment-based health insurance claims database provided by JMDC Inc. and included outpatients diagnosed with influenza between October 1, 2018 and April 11, 2019. Bleeding events were identified by International Classification of Diseases 10th revision codes. Incidences were compared between patients treated with baloxavir or neuraminidase inhibitors and untreated patients. Odds ratios were calculated after exact matching to adjust for potential confounders. RESULTS: Among 529 201 influenza episodes, 30 964 were untreated and 498 237 were treated with anti-influenza drugs: baloxavir, 207 630; oseltamivir, 143 722; zanamivir, 28 208; peramivir, 5304; laninamivir, 113 373. Crude incidence proportions for total bleeding up to 20 days after influenza diagnosis were similar among treated groups, with a slightly higher value for peramivir (0.21% vs. 0.19% for baloxavir, oseltamivir, zanamivir, and laninamivir), and 0.30% in untreated patients. After exact matching, the incidence of bleeding for baloxavir was similar to that for other anti-influenza treatments (odds ratios for baloxavir were 0.90-0.99 compared to other therapies). CONCLUSIONS: Based on real-world observation using a large-scale claims database, a similar incidence of bleeding events was observed in recipients of the different anti-influenza drugs.

Lifestyle behaviors associated with the initiation of renal replacement therapy in Japanese patients with chronic kidney disease: a retrospective cohort study using a claims database linked with specific health checkup results.

BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for progression to an end-stage renal disease requiring dialysis or kidney transplantation. We investigated the association of lifestyle behaviors with the initiation of renal replacement therapy (RRT) among CKD patients using an employment-based health insurance claims database linked with specific health checkup (SHC) data. METHODS: This retrospective cohort study included 149,620 CKD patients aged 40-74 years who underwent a SHC between April 2008 and March 2016. CKD patients were identified using ICD-10 diagnostic codes and SHC results. We investigated lifestyle behaviors recorded at SHC. Initiation of RRT was defined by medical procedure claims. Lifestyle behaviors related to the initiation of RRT were identified using a Cox proportional hazards regression model with recency-weighted cumulative exposure as a time-dependent covariate. RESULTS: During 384,042 patient-years of follow-up by the end of March 2016, 295 dialysis and no kidney transplantation cases were identified. Current smoking (hazard ratio: 1.87, 95% confidence interval, 1.04─3.36), skipping breakfast (4.80, 1.98─11.62), and taking sufficient rest along with sleep (2.09, 1.14─3.85) were associated with the initiation of RRT. CONCLUSIONS: Among CKD patients, the lifestyle behaviors of smoking, skipping breakfast, and sufficient rest along with sleep were independently associated with the initiation of RRT. Our study strengthens the importance of monitoring lifestyle behaviors to delay the progression of mild CKD to RRT in the Japanese working generation. A substantial portion of subjects had missing data for eGFR and drinking frequency, warranting verification of these results in prospective studies.

Blood Pressure Phenotypes Defined by Ambulatory Blood Pressure Monitoring and Carotid Artery Changes in Community-Dwelling Older Japanese Adults: The Ohasama Study.

White coat hypertension is defined as elevated blood pressure in the office, but a normal blood pressure out-of-office, whereas masked hypertension is defined as elevated blood pressure in the office, but normal out-of-office blood pressure. The objective was to investigate the associations between these blood pressure phenotypes and carotid artery changes. Conventional blood pressure, ambulatory blood pressure, and carotid ultrasonography were evaluated in 851 Ohasama residents (31.8% men; mean age 66.3 years). The blood pressure phenotypes were defined by the ordinary thresholds (140/90 mmHg for conventional blood pressure, 135/85 mmHg for daytime blood pressure) and then by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) thresholds for hypertension (130/80 mmHg for both conventional and daytime blood pressure), irrespective of antihypertensive medication treatment status. Blood pressure phenotypes were linearly associated with the mean intima-media thickness of the carotid artery in ascending order for sustained normal blood pressure, white coat hypertension, masked hypertension, and sustained hypertension according to the ordinary thresholds and the 2017 ACC/AHA thresholds (both linear trends P < 0.0001) after adjustments for possible confounding factors. The odds ratios for the presence of carotid plaques showed similar linear trends with the blood pressure phenotypes according to the 2017 ACC/AHA thresholds (linear trend P < 0.0191). In conclusion, there was a close relationship between blood pressure phenotypes and carotid artery changes, suggesting that blood pressure phenotypes as defined by ambulatory blood pressure are potentially useful for risk stratification of carotid artery changes in the Japanese general population.

N-Terminal Pro-B-Type Natriuretic Peptide Is Not a Significant Predictor of Stroke Incidence After 5 Years　- The Ohasama Study.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been used for risk stratification in heart failure or acute coronary syndrome, but the beyond 5-year predictive value of NT-proBNP for stroke remains an unsettled issue in Asian patients. The aim of the present study was to clarify this point.Methods and Results:We followed 1,198 participants (33.4% men; mean age, 60.5±11.1 years old) in the Japanese general population for a median of 13.0 years. A first stroke occurred in 93 participants. Referencing previous reports, we stratified participants according to NT-proBNP 30.0, 55.0, and 125.0 pg/mL. Using the NT-proBNP <30.0 pg/mL group as a reference, adjusted HR for stroke (95% CI) in the NT-proBNP 30.0-54.9-pg/mL, 55.0-124.9-pg/mL, and ≥125.0-pg/mL groups were 1.92 (0.94-3.94), 1.77 (0.85-3.66), and 1.99 (0.86-4.61), respectively. With the maximum follow-up period set at 5 years, the hazard ratio of the NT-proBNP≥125.0-pg/mL group compared with the <30.0-pg/mL group increased significantly (HR, 4.51; 95% CI: 1.03-19.85). On extension of the maximum follow-up period, however, the association between NT-proBNP and stroke risk weakened. CONCLUSIONS: NT-proBNP was significantly associated with an elevated stroke risk. Given, however, that the predictive power decreased with the number of years after NT-proBNP measurement, NT-proBNP should be re-evaluated periodically in Asian patients.

Prevalence and Determinants of Masked Hypertension Among Black Nigerians Compared With a Reference Population.

Hitherto, diagnosis of hypertension in sub-Saharan Africa was largely based on conventional office blood pressure (BP). Data on the prevalence of masked hypertension (MH) in this region is scarce. Among individuals with normal office BP (<140/90 mm Hg), we compared the prevalence and determinants of MH diagnosed with self-monitored home blood pressure (≥135/85 mm Hg) among 293 Nigerians with a reference population consisting of 3615 subjects enrolled in the International Database on Home Blood Pressure in Relation to Cardiovascular Outcomes. In the reference population, the prevalence of MH was 14.6% overall and 11.1% and 39.6% in untreated and treated participants, respectively. Among Nigerians, the prevalence standardized to the sex and age distribution of the reference population was similar with rates of 14.4%, 8.6%, and 34.6%, respectively. The mutually adjusted odds ratios of having MH in Nigerians were 2.34 (95% confidence interval, 1.39-3.94) for a 10-year higher age, 1.92 (1.11-3.31) and 1.70 (1.14-2.53) for 10- or 5-mm Hg increments in systolic or diastolic office BP, and 3.05 (1.08-8.55) for being on antihypertensive therapy. The corresponding estimates in the reference population were similar with odds ratios of 1.80 (1.62-2.01), 1.64 (1.45-1.87), 1.13 (1.05-1.22), and 2.84 (2.21-3.64), respectively. In conclusion, MH is as common in Nigerians as in other populations with older age and higher levels of office BP being major risk factors. A significant proportion of true hypertensive subjects therefore remains undetected based on office BP, which is particularly relevant in sub-Saharan Africa, where hypertension is now a major cause of death.

Individual assessment of inherent arterial stiffness using nomogram and pulse wave velocity index: the Ohasama study.

We measured the brachial-ankle pulse wave velocity (baPWV) in 491 normotensives and determined the "PWV index" (measured baPWV-theoretical baPWV) in 491 normotensives and 83 controlled hypertensives. Linear regression analysis revealed that the theoretical baPWV (cm/sec) was 0.21 × age(2) (years(2))-13.73 × age (years) + 0.05 × mean arterial pressure(2) (mmHg(2)) + 3.95 × heart rate (bpm) + 36.49 × gender (1 male; 0 female) + 733 (R(2) = 0.53). The calculated PWV index was significantly higher in 13 smokers than 70 nonsmokers among controlled hypertensives. The calculated PWV index might provide more precise information about inherent arterial stiffness.

Cost-effectiveness of the introduction of home blood pressure measurement in patients with office hypertension.

OBJECTIVE: Cost-effectiveness of hypertension treatment is an important social and medical issue in Western as well as in Eastern countries, including Japan. Home blood pressure (HBP) measurements have a stronger predictive power for cardiovascular events than casual clinic blood pressure (CBP) measurements. Therefore, the introduction of HBP measurement for the diagnosis and treatment of hypertension should lead to a decrease in medical expenditure. This study presents calculations of the cost savings likely to take place when HBP is implemented for newly detected hypertensive subjects in Japan. DESIGN AND METHODS: We estimate the cost savings from the perspective of a Japanese healthcare system. To estimate the costs associated with changing from CBP to HBP measurement as the diagnostic tool, we constructed a simulation model using data from the Ohasama study. These calculations are based on current estimates for cost of treatment, prevalence of white-coat hypertension at baseline, and varying the incidence of new hypertension after the initial screening. RESULTS: When HBP measurement is not incorporated into the diagnostic process, the medical cost is estimated at US$10.89 million per 1000 subjects per 5 years. When HBP measurement is incorporated, the medical cost is estimated at US$9.33 million per 1000 subjects per 5 years. The reductions in medical costs vary from US$674,000 to US$2.51 million per 1000 subjects per 5 years for treatment of hypertension, when sensitivity analysis is performed. CONCLUSIONS: The introduction of HBP measurement for the treatment of hypertension is very useful for reducing medical costs.