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      Achieving Rapid Blood Pressure Control With Digital Therapeutics: Retrospective Cohort and Machine Learning Study

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          Abstract

          Background

          Behavioral therapies, such as electronic counseling and self-monitoring dispensed through mobile apps, have been shown to improve blood pressure, but the results vary and long-term engagement is a challenge. Machine learning is a rapidly advancing discipline that can be used to generate predictive and responsive models for the management and treatment of chronic conditions and shows potential for meaningfully improving outcomes.

          Objective

          The objectives of this retrospective analysis were to examine the effect of a novel digital therapeutic on blood pressure in adults with hypertension and to explore the ability of machine learning to predict participant completion of the intervention.

          Methods

          Participants with hypertension, who engaged with the digital intervention for at least 2 weeks and had paired blood pressure values, were identified from the intervention database. Participants were required to be ≥18 years old, reside in the United States, and own a smartphone. The digital intervention offers personalized behavior therapy, including goal setting, skill building, and self-monitoring. Participants reported blood pressure values at will, and changes were calculated using averages of baseline and final values for each participant. Machine learning was used to generate a model of participants who would complete the intervention. Random forest models were trained at days 1, 3, and 7 of the intervention, and the generalizability of the models was assessed using leave-one-out cross-validation.

          Results

          The primary cohort comprised 172 participants with hypertension, having paired blood pressure values, who were engaged with the intervention. Of the total, 86.1% participants were women, the mean age was 55.0 years (95% CI 53.7-56.2), baseline systolic blood pressure was 138.9 mmHg (95% CI 136.6-141.3), and diastolic was 86.2 mmHg (95% CI 84.8-87.7). Mean change was –11.5 mmHg for systolic blood pressure and –5.9 mmHg for diastolic blood pressure over a mean of 62.6 days ( P<.001). Among participants with stage 2 hypertension, mean change was –17.6 mmHg for systolic blood pressure and –8.8 mmHg for diastolic blood pressure. Changes in blood pressure remained significant in a mixed-effects model accounting for the baseline systolic blood pressure, age, gender, and body mass index ( P<.001). A total of 43% of the participants tracking their blood pressure at 12 weeks achieved the 2017 American College of Cardiology/American Heart Association definition of blood pressure control. The 7-day predictive model for intervention completion was trained on 427 participants, and the area under the receiver operating characteristic curve was .78.

          Conclusions

          Reductions in blood pressure were observed in adults with hypertension who used the digital therapeutic. The degree of blood pressure reduction was clinically meaningful and achieved rapidly by a majority of the studied participants. Greater improvement was observed in participants with more severe hypertension at baseline. A successful proof of concept for using machine learning to predict intervention completion was presented.

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          Most cited references16

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          VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines

          Background Vaccine development in the post-genomic era often begins with the in silico screening of genome information, with the most probable protective antigens being predicted rather than requiring causative microorganisms to be grown. Despite the obvious advantages of this approach – such as speed and cost efficiency – its success remains dependent on the accuracy of antigen prediction. Most approaches use sequence alignment to identify antigens. This is problematic for several reasons. Some proteins lack obvious sequence similarity, although they may share similar structures and biological properties. The antigenicity of a sequence may be encoded in a subtle and recondite manner not amendable to direct identification by sequence alignment. The discovery of truly novel antigens will be frustrated by their lack of similarity to antigens of known provenance. To overcome the limitations of alignment-dependent methods, we propose a new alignment-free approach for antigen prediction, which is based on auto cross covariance (ACC) transformation of protein sequences into uniform vectors of principal amino acid properties. Results Bacterial, viral and tumour protein datasets were used to derive models for prediction of whole protein antigenicity. Every set consisted of 100 known antigens and 100 non-antigens. The derived models were tested by internal leave-one-out cross-validation and external validation using test sets. An additional five training sets for each class of antigens were used to test the stability of the discrimination between antigens and non-antigens. The models performed well in both validations showing prediction accuracy of 70% to 89%. The models were implemented in a server, which we call VaxiJen. Conclusion VaxiJen is the first server for alignment-independent prediction of protective antigens. It was developed to allow antigen classification solely based on the physicochemical properties of proteins without recourse to sequence alignment. The server can be used on its own or in combination with alignment-based prediction methods. It is freely-available online at the URL: .
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            Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial.

            Weight loss, sodium reduction, increased physical activity, and limited alcohol intake are established recommendations that reduce blood pressure (BP). The Dietary Approaches to Stop Hypertension (DASH) diet also lowers BP. To date, no trial has evaluated the effects of simultaneously implementing these lifestyle recommendations. To determine the effect on BP of 2 multicomponent, behavioral interventions. Randomized trial with enrollment at 4 clinical centers (January 2000-June 2001) among 810 adults (mean [SD] age, 50 [8.9] years; 62% women; 34% African American) with above-optimal BP, including stage 1 hypertension (120-159 mm Hg systolic and 80-95 mm Hg diastolic), and who were not taking antihypertensive medications. Participants were randomized to one of 3 intervention groups: (1) "established," a behavioral intervention that implemented established recommendations (n = 268); (2) "established plus DASH,"which also implemented the DASH diet (n = 269); and (3) an "advice only" comparison group (n = 273). Blood pressure measurement and hypertension status at 6 months. Both behavioral interventions significantly reduced weight, improved fitness, and lowered sodium intake. The established plus DASH intervention also increased fruit, vegetable, and dairy intake. Across the groups, gradients in BP and hypertensive status were evident. After subtracting change in advice only, the mean net reduction in systolic BP was 3.7 mm Hg (P<.001) in the established group and 4.3 mm Hg (P<.001) in the established plus DASH group; the systolic BP difference between the established and established plus DASH groups was 0.6 mm Hg (P =.43). Compared with the baseline hypertension prevalence of 38%, the prevalence at 6 months was 26% in the advice only group, 17% in the established group (P =.01 compared with the advice only group), and 12% in the established plus DASH group (P<.001 compared with the advice only group; P =.12 compared with the established group). The prevalence of optimal BP (<120 mm Hg systolic and <80 mm Hg diastolic) was 19% in the advice only group, 30% in the established group (P =.005 compared with the advice only group), and 35% in the established plus DASH group (P<.001 compared with the advice only group; P =.24 compared with the established group). Individuals with above-optimal BP, including stage 1 hypertension, can make multiple lifestyle changes that lower BP and reduce their cardiovascular disease risk.
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              Hypertension Prevalence and Control Among Adults: United States, 2011-2014.

              Hypertension is a public health challenge in the United States because it directly increases the risk for cardiovascular disease (1). National and regional health initiatives, including Healthy People 2020, the Million Hearts Initiative, and the Community Preventive Services Task Force, have sought to increase public awareness of the health benefits of improving blood pressure control (2-4). This report presents updated estimates for the prevalence and control of hypertension in the United States for 2011-2014.
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                Author and article information

                Contributors
                Journal
                JMIR Cardio
                JMIR Cardio
                JCARD
                JMIR Cardio
                JMIR Publications (Toronto, Canada )
                2561-1011
                Jan-Jun 2019
                12 March 2019
                : 3
                : 1
                : e13030
                Affiliations
                [1 ] Better Therapeutics San Francsico, CA United States
                [2 ] Manifold, Inc Oakland, CA United States
                [3 ] Department of Nutrition Harvard TH Chan School of Public Health Harvard University Boston, MA United States
                [4 ] Yale-Griffin Prevention Research Center Griffin Hospital Yale School of Public Health Derby, CT United States
                Author notes
                Corresponding Author: Mark A Berman mark@ 123456bettertherapeutics.io
                Author information
                http://orcid.org/0000-0002-1458-9798
                http://orcid.org/0000-0003-1869-6555
                http://orcid.org/0000-0002-0836-2036
                http://orcid.org/0000-0002-2687-9063
                http://orcid.org/0000-0002-5154-5460
                http://orcid.org/0000-0002-2896-9871
                http://orcid.org/0000-0002-6822-0857
                http://orcid.org/0000-0001-6845-6192
                Article
                v3i1e13030
                10.2196/13030
                6834235
                31758792
                543a258a-61c2-4936-a660-515a98d45acc
                ©Nicole L Guthrie, Mark A Berman, Katherine L Edwards, Kevin J Appelbaum, Sourav Dey, Jason Carpenter, David M Eisenberg, David L Katz. Originally published in JMIR Cardio (http://cardio.jmir.org), 12.03.2019.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Cardio, is properly cited. The complete bibliographic information, a link to the original publication on http://cardio.jmir.org, as well as this copyright and license information must be included.

                History
                : 6 December 2018
                : 5 January 2019
                : 17 January 2019
                : 17 February 2019
                Categories
                Original Paper
                Original Paper

                hypertension,mobile health,mhealth,lifestyle medicine,digital therapeutics,digital medicine,machine learning, behavioral therapy

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