Home blood pressure-lowering effect of digital therapeutics in hypertension: impact of body weight and salt intake.

Lifestyle modifications, including body weight reduction and salt restriction, help reduce blood pressure (BP). This study investigated the effects of body mass index (BMI) and salt intake on home BP reductions in unmedicated patients with hypertension receiving guideline-based lifestyle modification from doctors (control group) or with the addition of a digital therapeutics intervention. Data from the HERB Digital Hypertension 1 (HERB-DH1) pivotal trial were analyzed. Home BP was measured for 7 days before each study visit (baseline, and 4/8/12 weeks). Body weight was measured at each visit and salt intake questionnaire was answered at baseline and 12 weeks. This analysis included 302 patients with sufficient home BP monitoring data (digital therapeutics: 156; control group: 146). The reduction in morning home SBP from baseline to 12 weeks was significantly greater in the digital therapeutics vs. control group for patients with baseline BMI ≥ 25 kg/m2 and higher salt intake group (self-reported salt intake score ≥ 14) (-5.1 mmHg, p < 0.01). Patients in the digital therapeutics group who experienced a reduction in BMI and an improvement in salt intake score during the 12-week study also had a significantly greater reduction in morning home SBP compared with patients in the control group (-7.2 mmHg, p < 0.01). The digital therapeutic intervention reduced home BP the most in unmedicated patients with hypertension with high baseline BMI and salt intake score. Those with improvements in both BMI and salt intake during the digital therapeutics intervention achieved the greatest reduction in home BP vs. control.Clinical trial registration: Japan Registry of Clinical Trials (jRCT2032190148).

Cost-effectiveness of digital therapeutics for essential hypertension.

Hypertension increases the risk of cardiovascular and other diseases. Lifestyle modification is a significant component of nonpharmacological treatments for hypertension. We previously reported the clinical efficacy of digital therapeutics (DTx) in the HERB-DH1 trial. However, there is still a lack of cost-effectiveness assessments evaluating the impact of prescription DTx. This study aimed to analyze the cost-effectiveness of using prescription DTx in treating hypertension. We developed a monthly cycle Markov model and conducted Monte Carlo simulations using the HERB-DH1 trial data to investigate quality-adjusted life-years (QALYs) and the cost of DTx for hypertension plus guideline-based lifestyle modification consultation treatment as usual (TAU), comparing DTx + TAU and TAU-only groups with a lifetime horizon. The model inputs were obtained from the HERB-DH1 trial, published or publicly available data, and expert assumptions. The incremental cost-effectiveness ratio (ICER) per QALY was used as the benchmark for cost-effectiveness. We performed probabilistic sensitivity analyses (PSAs) using the Monte Carlo simulation with two million sets. The DTx + TAU strategy produced 18.778 QALYs and was associated with ¥3,924,075 ($34,122) expected costs, compared with 18.686 QALYs and ¥3,813,358 ($33,160) generated by the TAU-only strategy over a lifetime horizon, resulting in an ICER of ¥1,199,880 ($10,434)/QALY gained for DTx + TAU. The monthly cost and attrition rate of DTx for hypertension have a significant impact on ICERs. In the PSA, the probability of the DTx arm being a cost-effective option was 87.8% at a threshold value of ¥5 million ($43,478)/QALY gained. In conclusion, the DTx + TAU strategy was more cost-effective than the TAU-only strategy.

Efficacy of a digital therapeutics system in the management of essential hypertension: the HERB-DH1 pivotal trial.

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.

Digital therapeutics for essential hypertension using a smartphone application: A randomized, open-label, multicenter pilot study.

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.

A multicenter clinical trial to assess the efficacy of the digital therapeutics for essential hypertension: Rationale and design of the HERB-DH1 trial.

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.

Efficacy of the Ascure Smoking Cessation Program: Retrospective Study.

BACKGROUND: Smoking cessation helps extend a healthy life span and reduces medical expenses. However, the standard 12-week smoking cessation program in Japan has several notable problems. First, only 30% of participants complete this program. Second, participants may choose not to participate unless they have a strong motivation to quit smoking, such as health problems. Third, the program does not provide enough support during the period between clinical visits and after 12 weeks. OBJECTIVE: This study examined the efficacy of the 24-week ascure program to address the problems of accessibility and continuous support. The program combines online mentoring, over-the-counter pharmacotherapy, and a smartphone app. METHODS: Using a retrospective study design, we investigated data for 177 adult smokers who were enrolled in the ascure smoking cessation program between August 2017 and August 2018. The primary outcomes were continuous abstinence rates (CARs) during weeks 9-12 and weeks 21-24. To confirm smoking status, we performed salivary cotinine testing at weeks 12 and 24. We also evaluated the program adherence rate. Finally, we performed exploratory analysis to determine the factors associated with continuous abstinence at weeks 21-24 to provide insights for assisting with long-term continuous abstinence. RESULTS: The CARs of all participants for weeks 9-12 and weeks 21-24 were 48.6% (95% CI 41.2-56.0) and 47.5% (95% CI 40.0-54.8), respectively. Program adherence rates were relatively high throughout (72% at week 12 and 60% at week 24). In the analysis of the factors related to the CAR at weeks 21-24, the number of entries in the app's digital diary and number of educational videos watched during the first 12 weeks were significant factors. CONCLUSIONS: The ascure program achieved favorable CARs, and participants showed high adherence. Proactive usage of the smartphone app may help contribute to smoking cessation success in the long-term.

Clinical Outcomes of Second-Line Chemotherapy in Patients with Previously Treated Advanced Thymic Carcinoma: A Retrospective Analysis of 191 Patients from the NEJ023 Study.

BACKGROUND: Owing to the rarity of this tumor, there is limited information about second-line chemotherapy for patients with previously treated advanced thymic carcinoma. MATERIAL AND METHODS: We performed a multi-institutional, retrospective study named NEJ023 for patients with advanced thymic carcinoma. Patients without indications for curative treatment were treated with chemotherapy from 1995 to 2014 at 40 institutions in the North East Japan Study Group. Demographic and clinicopathologic characteristics, data on treatment methods, and outcomes of second-line chemotherapy were obtained from medical records. RESULTS: In total, 191 patients were enrolled in this study. Second-line chemotherapy included platinum-based doublets in 57.6% of patients, other multidrug chemotherapy (e.g., cisplatin, doxorubicin, vincristine, and cyclophosphamide) in 13.6%, and monotherapy in 28.8%. The median follow-up time was 50.5 months, and the median overall survival (OS) from the start of second-line chemotherapy was 22.4 (95% confidence interval, 17.5-26.7) months. The average response rate (RR) was 20.0% overall; it was 21.6% for patients treated with platinum-based doublet chemotherapy, 13.6% for those treated with other multidrug chemotherapy, and 19.6% for those treated with single agent chemotherapy. There was no significant difference in OS between platinum-based doublet chemotherapy, other multidrug chemotherapy, and monotherapy (the median OS was 22.4, 25.7, and 21.4 months, respectively). CONCLUSION: The median OS was 22.4 months in patients with advanced thymic carcinoma treated with second-line chemotherapy. There were no significant differences in RR and OS between monotherapy and multidrug chemotherapy in this study. IMPLICATIONS FOR PRACTICE: Owing to the rarity of this tumor, there is limited information about second-line chemotherapy for patients with previously treated advanced thymic carcinoma. This is the largest data for those patients treated with second-line chemotherapy. This study suggests there is no significant difference in efficacy between monotherapy and multidrug chemotherapy for previously treated advanced thymic carcinoma. This result can support the adequacy to select monotherapy as treatment of those patients.

Comparing Telemedicine and Face-to-Face Consultation Based on the Standard Smoking Cessation Program for Nicotine Dependence: Protocol for a Randomized Controlled Trial.

BACKGROUND: Smoking is a major public health concern. In Japan, a 12-week standard smoking cessation support program is available, however, its required face-to-face visits are a key obstacle in completing the program. Telemedicine is a useful way to provide medical treatment at a distance. Although telemedicine for smoking cessation using an internet-based video system has the potential for ensuring better clinical outcomes for patients with nicotine dependence, its efficacy is unclear. OBJECTIVE: The aim of this study is to determine the efficacy and feasibility of a smoking cessation support program using an internet-based video system compared with a face-to-face program among patients with nicotine dependence. METHODS: This study will be a randomized, controlled, open-label, multicenter trial. Participants randomized to the intervention arm will undergo an internet-based smoking cessation program, whereas control participants will undergo a standard face-to-face program. We will use the CureApp Smoking Cessation (CASC) for both arms, which consists of the CASC smartphone app for patients and a Web-based patient information management system for clinicians with a mobile carbon monoxide checking device. The primary endpoint will be the continuous abstinence rate (CAR) from weeks 9 to 12. Secondary endpoints will be: (1) the smoking cessation success rate at 4, 8, 12, and 24 weeks; (2) CAR from weeks 9 to 24; (3) changes in scores on the mood and physical symptoms scale and 12-Item French Version Of The Tobacco Craving Questionnaire; (4) Kano Test for Social Nicotine Dependence scores at 8, 12, and 24 weeks; (5) time to first lapse after the first visit; (6) nicotine dependence and cognition scale scores at 12 and 24 weeks; (7) usage rate of the CASC; (8) qualitative questionnaire about the usability and acceptability of telemedicine; and (9) presence of product problems or adverse events. RESULTS: We will recruit 114 participants who are nicotine-dependent but otherwise healthy adults from March to July 2018 and follow up with them until January 2019 (24 weeks). We expect all study results to be available by the end of March 2019. CONCLUSIONS: This will be the first randomized controlled trial to evaluate the efficacy and feasibility of an internet-based (telemedicine) smoking cessation support program relative to a face-to-face program among patients with nicotine dependence. We expect that the efficacy of the telemedicine smoking cessation support program will not be clinically worse than the face-to-face program. If this trial demonstrates that telemedicine does not have clinically worse efficacy and feasibility than a conventional face-to-face program, physicians can begin to offer a more flexible smoking cessation program to patients who may otherwise give up on trying such programs. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry: UMIN000031620; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035975. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12701.

Clinical Efficacy of Telemedicine Compared to Face-to-Face Clinic Visits for Smoking Cessation: Multicenter Open-Label Randomized Controlled Noninferiority Trial.

BACKGROUND: Tobacco is a major public health concern. A 12-week standard smoking cessation program is available in Japan; however, it requires face-to-face clinic visits, which has been one of the key obstacles to completing the program, leading to a low smoking cessation success rate. Telemedicine using internet-based video counseling instead of regular clinic visits could address this obstacle. OBJECTIVE: This study aimed to evaluate the efficacy and feasibility of an internet-based remote smoking cessation support program compared with the standard face-to-face clinical visit program among patients with nicotine dependence. METHODS: This study was a randomized, controlled, open-label, multicenter, noninferiority trial. We recruited nicotine-dependent adults from March to June 2018. Participants randomized to the telemedicine arm received internet-based video counseling, whereas control participants received standard face-to-face clinic visits at each time point in the smoking cessation program. Both arms received a CureApp Smoking Cessation smartphone app with a mobile exhaled carbon monoxide checker. The primary outcome was a continuous abstinence rate (CAR) from weeks 9 to 12. Full analysis set was used for data analysis. RESULTS: We randomized 115 participants with nicotine dependence: 58 were allocated to the telemedicine (internet-based video counseling) arm and 57, to the control (standard face-to-face clinical visit) arm. We analyzed all 115 participants for the primary outcome. Both telemedicine and control groups had similar CARs from weeks 9 to 12 (81.0% vs 78.9%; absolute difference, 2.1%; 95% CI -12.8 to 17.0), and the lower limit of the difference between groups (-12.8%) was greater than the prespecified limit (-15%). CONCLUSIONS: The application of telemedicine using internet-based video counseling as a smoking cessation program had a similar CAR from weeks 9 to 12 as that of the standard face-to-face clinical visit program. The efficacy of the telemedicine-based smoking cessation program was not inferior to that of the standard visit-based smoking cessation program. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry: UMIN000031620; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035975.