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Aims Digital therapeutics is a new approach to facilitate the non-pharmacological treatment of hypertension using software programmes such as smartphone applications and/or device algorithms. Based on promising findings from a small pilot trial, the HERB Digital Hypertension 1 (HERB-DH1) pivotal trial investigated the efficacy of digital therapeutics in patients with hypertension not receiving antihypertensive medication. Methods and results This prospective, open-label, randomized controlled study was performed at 12 sites in Japan. Patients with hypertension [office systolic blood pressure (SBP) 140 to <180 mmHg and 24 h SBP ≥130 mmHg] were randomly assigned 1:1 to the digital therapeutics group (HERB system + standard lifestyle modification) or control group (standard lifestyle modification alone). The primary efficacy endpoint was the mean change in 24 h ambulatory SBP from baseline to 12 weeks; key secondary efficacy endpoints were mean changes in office and home blood pressure (BP) from baseline to 12 weeks. All analyses were conducted in the full analysis set population. Between December 2019 and June 2020, 390 patients were randomly assigned to the digital therapeutics group (n  = 199) or control (n  = 191) group. Between-group differences in 24-h ambulatory, home, and office SBPs at 12 weeks were −2.4 (95% confidence interval −4.5 to −0.3), −4.3 (−6.7 to −1.9), and −3.6 (−6.2 to −1.0) mmHg, respectively. No major programme-related safety events occurred up to 24 weeks. Conclusion The HERB-DH1 pivotal study showed the superiority of digital therapeutics compared with standard lifestyle modification alone to reduce 24-h ambulatory, home, and office BPs in the absence of antihypertensive medications. [ABSTRACT FROM AUTHOR]

Hypertension is the most considerable but treatable risk factor for cardiovascular disease. Although physicians prescribe multiple antihypertensive drugs and promote lifestyle modifications, the real‐world blood pressure (BP) control rate remains poor. To improve BP target achievement, we developed a novel digital therapeutic—the HERB software system —to manage hypertension. Here, we performed a randomized pilot study to assess the safety and efficacy of the HERB system for hypertension. We recruited 146 patients with essential hypertension from March 2018 to March 2019. We allocated eligible patients to the intervention group (HERB system + standard lifestyle modification) or control group (standard lifestyle modification alone). The primary outcome was the mean change from baseline to 24 weeks in 24‐hour systolic BP (SBP) measured by ambulatory blood pressure monitoring (ABPM). The baseline characteristics in each group were well balanced; the mean age was approx. 57 years, and 67% were male. In the primary end point at 24 weeks, HERB intervention did not lower the mean change of 24‐hour SBP by ABPM compared with the controls (adjusted difference: −0.66 mmHg; p =.78). In an exploratory analysis focusing on antihypertensive drug‐naïve patients aged <65, the effects of the HERB intervention were significantly greater than the control for reducing 24‐hour SBP by ABPM at 16 weeks (adjusted difference: −7.6 mmHg; p =.013; and morning home SBP at 24 weeks (adjusted difference − 6.0 mmHg; p =.012). Thus, the HERB intervention did not achieve a primary efficacy end point. However, we observed that antihypertensive drug‐naïve adult hypertensive patients aged <65 years could be a potential HERB system‐effective target for further investigations of the efficacy of the system. [ABSTRACT FROM AUTHOR]

Digital therapeutics is a new approach to treat hypertension via using software programs such as smartphone apps and/or device algorithms. We develop a HERB system—new interactive smartphone app (HERB Mobile) with web‐based patient management console (HERB Console)—to lower blood pressure (BP) based on an algorithm that helps users to promote lifestyle modifications in conjunction with medically validated non‐pharmacological interventions. The app can assess the personalities, behavior characteristics, and hypertension determinants of each patient with hypertension to provide adequate guidance. To demonstrate the efficacy of the system, we designed a randomized, controlled, multicenter, open‐label trial "HERB‐DH1 (HERB digital hypertension 1)" to assess the efficacy of HERB system in patients with essential hypertension. The authors allocate patients to the intervention group (HERB system + standard lifestyle modification) or to the control group (standard lifestyle modification alone). In the intervention group, we provide the HERB Mobile for patients and the HERB Console for their primary physicians for 24 weeks. Both groups are instructed for standard lifestyle modifications based on the current recommendations in the Japanese Society of Hypertension 2019 guideline. The primary outcome is the mean change from baseline to 12 weeks in 24‐hour systolic BP measured by ambulatory BP monitoring. We started this study in December of 2019, and the trial results will be expected in early 2021. We believe that this trial enables us to verify the efficacy of the HERB system in patients with essential hypertension. [ABSTRACT FROM AUTHOR]

Sodium‐glucose cotransporter 2 (SGLT2) inhibitors reduce the occurrence of cardiovascular and renal complications in patients with type 2 diabetes mellitus (T2DM) and represent guideline‐recommended therapy in this indication. However, precise mechanisms underlying the beneficial cardiovascular effects of SGLT2 inhibitors are not fully understood. This study investigated the effects of the SGLT2 inhibitor, luseogliflozin, on arterial properties and home blood pressure (BP) in patients with T2DM. This multicenter, single‐arm study enrolled adults with T2DM, glycosylated hemoglobin (HbA1c) 6.5%‐8.9% in the previous 4 weeks, and an indication for new/additional antidiabetic therapy. Luseogliflozin 2.5 mg/d was given for 12 weeks. Primary outcome was change in cardio‐ankle vascular index (CAVI) from baseline to Week 4 and Week 12. Home and office BP, BP variability, and metabolic parameters were secondary endpoints. Forty‐seven patients (mean age 63.5 ± 10.7 years) treated with luseogliflozin were included in the full analysis set. CAVI did not change significantly from baseline (mean [95% confidence interval] 8.67 [8.37‐8.97]) to Week 12 (8.64 [8.38‐8.91]; P =.750), but there were significant reductions from baseline in morning home BP, HbA1c, body weight, body mass index, and serum uric acid levels during luseogliflozin therapy. The reduction in morning home systolic BP was ≥ 5 mm Hg and was independent of baseline BP and BP control status. In conclusion, there was no change in arterial stiffness (based on CAVI) during treatment with luseogliflozin, but changes in BP and metabolic parameters were consistent with the known beneficial effects of SGLT2 inhibitors in T2DM. [ABSTRACT FROM AUTHOR]

Background: Inconsistencies between the office and out-of-office blood pressure (BP) values (described as white-coat hypertension or masked hypertension) may be attributable in part to differences in the BP monitoring devices used., Methods: We studied consistency in the classification of BP control (well-controlled BP vs. uncontrolled BP) among office, home, and ambulatory BPs by using a validated "all-in-one" BP monitoring device. In the nationwide, general practitioner-based multicenter HI-JAMP study, 2,322 hypertensive patients treated with antihypertensive drugs underwent office BP measurements and 24-hour ambulatory BP monitoring (ABPM), consecutively followed by 5-day home BP monitoring (HBPM), for a total of seven BP measurement days., Results: Using the thresholds of the JSH2019 and ESC2018 guidelines, the patients with consistent classification of well-controlled status in the office (<140 mmHg) and home systolic BP (SBP) (<135 mmHg) (n = 970) also tended to have well-controlled 24-hour SBP (<130 mmHg) (n = 808, 83.3%). The patients with the consistent classification of uncontrolled status in office and home SBP (n = 579) also tended to have uncontrolled 24-hour SBP (n = 444, 80.9%). Among the patients with inconsistent classifications of office and home BP control (n = 803), 46.1% had inconsistent ABPM-vs.-HBPM out-of-office BP control status. When the 2017 ACC/AHA thresholds were applied as an alternative, the results were essentially the same., Conclusions: The combined assessment of the office and home BP is useful in clinical practice. Especially for patients whose office BP classification and home BP classification conflict, the complementary clinical use of both HBPM and ABPM might be recommended., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Development of new treatment methodologies for bone nonunion requires validated experimental models for their application into tissue engineering approaches. Critical-sized bone defect (CSBD) models identify the smallest size at which tissue defects fail to completely heal during the experimental period. The purpose of this study was to systematically determine a CSBD in rat femurs using external fixation. Thirty Fischer 344 rats were equally divided into six groups. Bone defects of 1, 2, 3, 4, 5, and 6 mm were created in the diaphysis of the femur, before external fixation. Defects were evaluated radiographically at weekly intervals and histologically at the predefined healing period of 8 weeks. Defects of 4 mm or more failed to achieve union in our model. Nonunions were characterized by the absence of a bridging callus and filling of the defect with fibrous and muscle tissue. Radiographically, bone ends in nonunions were rounded up to 4 weeks postsurgery. Our systematic approach for identification of a CSBD in rat femurs, revealed that externally fixed defects of 4 mm and larger, failed to heal within the 8-week time frame.