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Background: There has been an exponential growth in the availability of apps, resulting in increased use of pregnancy apps. However, information on resources and use of apps among pregnant women is relatively limited., Objective: The aim of this study is to map the current information resources and the use of pregnancy apps among pregnant women in Flanders., Methods: A cross-sectional study was conducted, using a semistructured survey (April-June 2019) consisting of four different domains: (1) demographics; (2) use of devices; (3) sources of information; and (4) use of pregnancy apps. Women were recruited by social media, flyers, and paper questionnaires at prenatal consultations. Statistical analysis was mainly focused on descriptive statistics. Differences in continuous and categorical variables were tested using independent Student t tests and chi-square tests. Correlations were investigated between maternal characteristics and the women's responses., Results: In total, 311 women completed the entire questionnaire. Obstetricians were the primary source of information (268/311, 86.2%) for pregnant women, followed by websites/internet (267/311, 85.9%) and apps (233/311, 74.9%). The information that was most searched for was information about the development of the baby (275/311, 88.5%), discomfort/complaints (251/311, 80.7%) and health during pregnancy (248/311, 79.7%), administrative/practical issues (233/311, 74.9%), and breastfeeding (176/311, 56.6%). About half of the women (172/311, 55.3%) downloaded a pregnancy app, and primarily searched app stores (133/311, 43.0%). Pregnant women who are single asked their mothers (22/30, 73.3%) or other family members (13/30, 43.3%) for significantly more information than did married women (mother [in law]: 82/160, 51.3%, P=.02; family members: 35/160, 21.9%, P=.01). Pregnant women with lower education were significantly more likely to have a PC or laptop than those with higher education (72/73, 98.6% vs 203/237, 85.5%; P=.008), and to consult other family members for pregnancy information (30/73, 41.1% vs 55/237, 23.1%; P<.001), but were less likely to consult a gynecologist (70/73, 95.9% vs 198/237, 83.5%; P=.001). They also followed more prenatal sessions (59/73, 80.8% vs 77/237, 32.5%; P=.04) and were more likely to search for information regarding discomfort/complaints during pregnancy (65/73, 89% vs 188/237, 79.5%; P=.02). Compared to multigravida, primigravida were more likely to solicit advice about their pregnancy from other women in their social networks (family members: primigravida 44/109, 40.4% vs multigravida 40/199, 20.1%; P<.001; other pregnant women: primigravida 58/109, 53.2% vs multigravida 80/199, 40.2%; P<.03)., Conclusions: Health care professionals need to be aware that apps are important and are a growing source of information for pregnant women. Concerns rise about the quality and safety of those apps, as only a limited number of apps are subjected to an external quality check. Therefore, it is important that health care providers refer to high-quality digital resources and take the opportunity to discuss digital information with pregnant women., (©Dorien Lanssens, Inge M Thijs, Pauline Dreesen, Ann Van Hecke, Pascal Coorevits, Gitte Gaethofs, Joyce Derycke, Inge Tency. Originally published in JMIR Formative Research (https://formative.jmir.org), 11.10.2022.)

Background: Observational data from the retrospective, non-randomized Pregnancy REmote MOnitoring I (PREMOM I) study showed that remote monitoring (RM) may be beneficial for prenatal observation of women at risk for gestational hypertensive disorders (GHD) in terms of clinical outcomes, health economics, and stakeholder perceptions. PREMOM II is a prospective, randomized, multicenter follow-up study that was performed to explore these promising results., Methods: After providing written consent, 3922 pregnant women aged ≥18 years who are at increased risk of developing GHD will be randomized (1:1:1 ratio) to (a) conventional care (control group), (b) a patient self-monitoring group, and (c) a midwife-assisted RM group. The women in each group will be further divided (1:1 ratio) to evaluate the outcomes of targeted or non-targeted (conventional) antihypertensive medication. Women will be recruited in five hospitals in Flanders, Belgium: Ziekenhuis Oost-Limburg, Universitaire Ziekenhuis Antwerpen, Universitaire Ziekenhuis Leuven, AZ Sint Jan Brugge-Oostende, and AZ Sint Lucas Brugge. The primary outcomes are: (1) numbers and types of prenatal visits; (2) maternal outcomes; (3) neonatal outcomes; (4) the applicability and performance of RM; and (5) compliance with RM and self-monitoring. The secondary outcomes are: (1) cost-effectiveness and willingness to pay; (2) patient-reported outcome measures (PROMS) questionnaires on the experiences of the participants; and (3) the maternal and perinatal outcomes according to the type of antihypertensive medication. Demographic, and maternal and neonatal outcomes are collected from the patients' electronic records. Blood pressure and compliance rate will be obtained from an online digital coordination platform for remote data handling. Information about the healthcare-related costs will be obtained from the National Coordination Committee of Belgian Health Insurance Companies (Intermutualistisch Agentschap). PROMS will be assessed using validated questionnaires., Discussion: To our knowledge, this is the first randomized trial comparing midwife-assisted RM and self-monitoring of prenatal blood pressure versus conventional management among women at increased risk of GHD. Positive results of this study may lead to a practical framework for caregivers, hospital management, and payers to introduce RM into the prenatal care programs of high-risk pregnancies., Trial Registration: This study was registered on clinicaltrials.gov , identification number NCT04031430. Registered 24 July 2019, https://clinicaltrials.gov/ct2/show/NCT04031430?cond=premom+ii&draw=2&rank=1 .

Background: Medical smartphone apps and mobile health devices are rapidly entering mainstream use because of the rising number of smartphone users. Consequently, a large amount of consumer-generated data is being collected. Technological advances in innovative sensory systems have enabled data connectivity and aggregation to become cornerstones in developing workable solutions for remote monitoring systems in clinical practice. However, few systems are currently available to handle such data, especially for clinical use., Objective: The aim of this study was to develop and implement the digital health research platform for mobile health (DHARMA) that combines data saved in different formats from a variety of sources into a single integrated digital platform suitable for mobile remote monitoring studies., Methods: DHARMA comprises a smartphone app, a Web-based platform, and custom middleware and has been developed to collect, store, process, and visualize data from different vendor-specific sensors. The middleware is a component-based system with independent building blocks for user authentication, study and patient administration, data handling, questionnaire management, patient files, and reporting., Results: A prototype version of the research platform has been tested and deployed in multiple clinical studies. In this study, we used the platform for the follow-up of pregnant women at risk of developing pre-eclampsia. The patients' blood pressure, weight, and activity were semi-automatically captured at home using different devices. DHARMA automatically collected and stored data from each source and enabled data processing for the end users in terms of study-specific parameters, thresholds, and visualization., Conclusions: The increasing use of mobile health apps and connected medical devices is leading to a large amount of data for collection. There has been limited investment in handling and aggregating data from different sources for use in academic and clinical research focusing on remote monitoring studies. In this study, we created a modular mobile health research platform to collect and integrate data from a variety of third-party devices in several patient populations. The functionality of the platform was demonstrated in a real-life setting among women with high-risk pregnancies., (©Thijs Vandenberk, Valerie Storms, Dorien Lanssens, Hélène De Cannière, Christophe JP Smeets, Inge M Thijs, Tooba Batool, Yves Vanrompay, Pieter M Vandervoort, Lars Grieten. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 29.10.2019.)

Background: Pregnancy-induced hypertension (PIH) is associated with high levels of morbidity and mortality in mothers, fetuses, and newborns. New technologies, such as remote monitoring (RM), were introduced in 2015 into the care of patients at risk of PIH in Ziekenhuis Oost-Limburg (Genk, Belgium) to improve both maternal and neonatal outcomes. In developing new strategies for obstetric care in pregnant women, including RM, it is important to understand the psychosocial characteristics associated with adherence to RM to optimize care., Objective: The aim of this study was to explore the role of patients' psychosocial characteristics (severity of depression or anxiety, cognitive factors, attachment styles, and personality traits) in their adherence to RM., Methods: Questionnaires were sent by email to 108 mothers the day after they entered an RM program for pregnant women at risk of PIH. The Generalized Anxiety Disorder Assessment-7 and Patient Health Questionnaire-9 (PHQ-9) were used to assess anxiety and the severity of depression, respectively; an adaptation of the Pain Catastrophizing Scale was used to assess cognitive factors; and attachment and personality were measured with the Experiences in Close Relationships-Revised Scale (ECR-R), the Depressive Experiences Questionnaire, and the Multidimensional Perfectionism Scale, respectively., Results: The moderate adherence group showed significantly higher levels of anxiety and depression, negative cognitions, and insecure attachment styles, especially compared with the over adherence group. The low adherence group scored significantly higher than the other groups on other-oriented perfectionism. There were no significant differences between the good and over adherence groups. Single linear regression showed that the answers on the PHQ-9 and ECR-R questionnaires were significantly related to the adherence rate., Conclusions: This study demonstrates the relationships between adherence to RM and patient characteristics in women at risk of PIH. Alertness toward the group of women who show less than optimal adherence is essential. These findings call for further research on the management of PIH and the importance of individual tailoring of RM in this patient group., Trial Registration: ClinicalTrials.gov NCT03509272; https://clinicaltrials.gov/ct2/show/NCT03509272., (©Thijs Vandenberk, Dorien Lanssens, Valerie Storms, Inge M Thijs, Lotte Bamelis, Lars Grieten, Wilfried Gyselaers, Eileen Tang, Patrick Luyten. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 28.08.2019.)

Background: In 2015, we performed a cost analysis of a prenatal remote monitoring (RM) program compared with conventional care (CC) for women diagnosed with gestational hypertensive disorders (GHD). Introduction: We investigated where the cost savings were distributed by dividing our patient population into three subgroups, according to the gestational age (GA) at the time of delivery: (1) <34 weeks; (2) 34-37 weeks; and (3) >37 weeks of GA. Materials and Methods: Health care costs were calculated from patient-specific hospital bills at Ziekenhuis Oost Limburg (Genk, Belgium) in 2015-2016. Cost comparisons were made from the perspectives of the Belgium national health care system (HCS), the National Institution for Insurance of Disease and Disability (RIZIV), and the costs to individual patients. Results: A total of 256 pregnant women were included, 80 (31.25%) of whom received RM and 176 (68.75%) of whom received CC. The greatest difference in costs between RM and CC was in the group that delivered before 34 weeks of GA, followed by the group who delivered after 37 weeks of GA, and then the group of women who delivered at 34-37 weeks of GA. Most of the cost savings were in neonatal care, for both the three separate study subgroups and the total study group. Discussion and Conclusion: Our data showed that RM is more cost-effective than CC for pregnant women with GHD. Further investigation of the effects of RM on the long-term economic and social costs is recommended, together with an analysis of the price that should be asked for RM services.

Background: The Pregnancy Remote Monitoring (PREMOM) study enrolled pregnant women at increased risk of developing hypertensive disorders of pregnancy and investigated the effect of remote monitoring in addition to their prenatal follow-up., Objective: The objective of this study was to investigate the perceptions and experiences of remote monitoring among mothers, midwives, and obstetricians who participated in the PREMOM study., Methods: We developed specific questionnaires for the mothers, midwives, and obstetricians addressing 5 domains: (1) prior knowledge and experience of remote monitoring, (2) reactions to abnormal values, (3) privacy, (4) quality and patient safety, and (5) financial aspects. We also questioned the health care providers about which issues they considered important when implementing remote monitoring. We used a 5-point Likert scale to provide objective scores. It was possible to add free-text feedback at every question., Results: A total of 91 participants completed the questionnaires. The mothers, midwives, and obstetricians reported positive experiences and perceptions of remote monitoring, although most of them had no or little prior experience with this technology. They supported a further rollout of remote monitoring in Belgium. Nearly three-quarters of the mothers (34/47, 72%) did not report any problems with taking the measurements at the required times. Almost half of the mothers (19/47, 40%) wanted to be contacted within 3 to 12 hours after abnormal measurement values, preferably by telephone., Conclusions: Although most of midwives and obstetricians had no or very little experience with remote monitoring before enrolling in the PREMOM study, they reported, based on their one-year experience, that remote monitoring was an important component in the follow-up of high-risk pregnancies and would recommend it to their colleagues and pregnant patients., Trial Registration: ClinicalTrials.gov NCT03246737; https://clinicaltrials.gov/ct2/show/NCT03246737 (Archived by WebCite at http://www.webcitation.org/76KVnHSYY)., (©Dorien Lanssens, Thijs Vandenberk, Joy Lodewijckx, Tessa Peeters, Valerie Storms, Inge M Thijs, Lars Grieten, Wilfried Gyselaers. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 15.04.2019.)

Background: Cardiac resynchronisation therapy (CRT) is an established treatment for heart failure (HF) with reduced ejection fraction. CRT devices are equipped with remote monitoring functions, which are pivotal in the detection of device problems, but may also facilitate disease management. The aim of this study was to provide a comprehensive overview of the clinical interventions taken based on remote monitoring., Methods: This is a single centre observational study of consecutive CRT patients (n = 192) participating in protocol-driven remote follow-up. Incoming technical- and disease-related alerts were analysed together with subsequently triggered interventions., Results: During 34 ± 13 months of follow-up, 1372 alert-containing notifications were received (2.53 per patient-year of follow-up), comprising 1696 unique alerts (3.12 per patient-year of follow-up). In 60%, notifications resulted in a phone contact. Technical alerts constituted 8% of incoming alerts (0.23 per patient-year of follow-up). Rhythm (1.43 per patient-year of follow-up) and bioimpedance alerts (0.98 per patient-year of follow-up) were the most frequent disease-related alerts. Notifications included a rhythm alert in 39%, which triggered referral to the emergency room (4%), outpatient cardiology clinic (36%) or general practitioner (7%), or resulted in medication changes (13%). Sole bioimpedance notifications resulted in a telephone contact in 91%, which triggered outpatient evaluation in 8% versus medication changes in 10%. Clinical outcome was excellent with 97% 1-year survival., Conclusions: Remote CRT follow-up resulted in 0.23 technical- versus 2.64 disease-related alerts annually. Rhythm and bioimpedance notifications constituted the majority of incoming notifications which triggered an actual intervention in 22% and 15% of cases, respectively.

Objectives: In 2015, we showed the value of a remote monitoring (RM) follow-up program for women diagnosed with gestational hypertensive disorders (GHDs) compared with women who received conventional care (CC). We want to confirm or refute the conclusions drawn in 2015, by including data from 2016., Study Design: A two year retrospective study in which all women diagnosed with GHD, who underwent prenatal follow-up at the outpatients prenatal clinic of Ziekenhuis Oost-Limburg (Genk, Belgium) during 2015 and 2016, were included. Of the 320 women diagnosed with GHD, ninety (28.13%) were monitored with RM. The other 230 (71.88%) GHD pregnancies were monitored with CC. Differences in continuous and categorical variables in maternal demographics and characteristics were tested using Unpaired Student's two sampled t-test or Mann Whitney U test and the c 2 test. Both a univariate and multivariate analysis were performed for analyzing prenatal follow up and gestational outcomes. All statistical analyses are done at nominal level a = 0.05., Results: The RM group had more women diagnosed with gestational hypertension but less with pre-eclampsia when compared to the CC group (69.77% versus 42.79% and 19.77% versus 44.19% respectively). In both uni- and multivariate analyses, the RM group had, when compared to the CC group, less prenatal admission (51.62% versus 71.63%), less prenatal admissions until the moment of the delivery (31.40% versus 57.67%), less induced starts of the birth process (43.00% versus 32.09%), more spontaneous starts of the birth process (32.86% versus 46.51%), more births after 37 weeks of gestational age in pregnancies complicated with gestational hypertension (91.67% versus 53.33%) and pregnancies complicated with pre-eclampsia (58.82% versus 53.33%). In multivariate analysis, a reduction in total number of prenatal visits was visible in the RM group when compared to the CC group (b = -1.76; CI = -2.74-0.77). Only in the univariate analysis was the mean gestational age at delivery between 34 and 37 weeks of gestation in pregnancies complicated with gestational hypertension higher in the CC group versus the RM group (35 w 4/7 (±0.49) versus 34 w 6/7 (±0.00).These conclusions were almost the same as in the analyses of 2015, except (1) there wasn't a difference anymore in NICU admissions between the RM and CC group in the analyses of 2015-2016 and (2) a significant decrease in total number of visits is reported in the RM group in the dataset of 2015-2016, which wasn't visible in the dataset of 2015., Conclusions: This study demonstrates that RM provides opportunities to offer timely interventions to pregnant women who require them., (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Remote monitoring in obstetrics is relatively new; some studies have shown its effectiveness for both mother and child. However, few studies have evaluated the economic impact compared to conventional care, and no cost analysis of a remote monitoring prenatal follow-up program for women diagnosed with gestational hypertensive diseases (GHD) has been published., Objective: The aim of this study was to assess the costs of remote monitoring versus conventional care relative to reported benefits., Methods: Patient data from the Pregnancy Remote Monitoring (PREMOM) study were used. Health care costs were calculated from patient-specific hospital bills of Ziekenhuis Oost-Limburg (Genk, Belgium) in 2015. Cost comparison was made from three perspectives: the Belgian national health care system (HCS), the National Institution for Insurance of Disease and Disability (RIZIV), and costs for individual patients. The calculations were made for four major domains: prenatal follow-up, prenatal admission to the hospital, maternal and neonatal care at and after delivery, and total amount of costs. A simulation exercise was made in which it was calculated how much could be demanded of RIZIV for funding the remote monitoring service., Results: A total of 140 pregnancies were included, of which 43 received remote monitoring (30.7%) and 97 received conventional care (69.2%). From the three perspectives, there were no differences in costs for prenatal follow-up. Compared to conventional care, remote monitoring patients had 34.51% less HCS and 41.72% less RIZIV costs for laboratory test results (HCS: mean €0.00 [SD €55.34] vs mean €38.28 [SD € 44.08], P<.001; RIZIV: mean €21.09 [SD €27.94] vs mean €36.19 [SD €41.36], P<.001) and a reduction of 47.16% in HCS and 48.19% in RIZIV costs for neonatal care (HCS: mean €989.66 [SD €3020.22] vs mean €1872.92 [SD €5058.31], P<.001; RIZIV: mean €872.97 [SD €2761.64] vs mean €1684.86 [SD €4702.20], P<.001). HCS costs for medication were 1.92% lower in remote monitoring than conventional care (mean €209.22 [SD €213.32] vs mean €231.32 [SD 67.09], P=.02), but were 0.69% higher for RIZIV (mean €122.60 [SD €92.02] vs mean €121.78 [SD €20.77], P<.001). Overall HCS costs for remote monitoring were mean €4233.31 (SD €3463.31) per person and mean €4973.69 (SD €5219.00) per person for conventional care (P=.82), a reduction of €740.38 (14.89%) per person, with savings mainly for RIZIV of €848.97 per person (23.18%; mean €2797.42 [SD €2905.18] vs mean €3646.39 [SD €4878.47], P=.19). When an additional fee of €525.07 per month per pregnant woman for funding remote monitoring costs is demanded, remote monitoring is acceptable in their costs for HCS, RIZIV, and individual patients., Conclusions: In the current organization of Belgian health care, a remote monitoring prenatal follow-up of women with GHD is cost saving for the global health care system, mainly via savings for the insurance institution RIZIV., (©Dorien Lanssens, Thijs Vandenberk, Christophe JP Smeets, Hélène De Cannière, Sharona Vonck, Jade Claessens, Yenthel Heyrman, Dominique Vandijck, Valerie Storms, Inge M Thijs, Lars Grieten, Wilfried Gyselaers. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 26.03.2018.)

Background: The use of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) devices is expanding in the treatment of heart failure. Most of the current devices are equipped with remote monitoring functions, including bioimpedance for fluid status monitoring. The question remains whether bioimpedance measurements positively impact clinical outcome., Objective: The aim of this study was to provide a comprehensive overview of the clinical interventions taken based on remote bioimpedance monitoring alerts and their impact on clinical outcome., Methods: This is a single-center observational study of consecutive ICD and CRT patients (n=282) participating in protocol-driven remote follow-up. Bioimpedance alerts were analyzed with subsequently triggered interventions., Results: A total of 55.0% (155/282) of patients had an ICD or CRT device equipped with a remote bioimpedance algorithm. During 34 (SD 12) months of follow-up, 1751 remote monitoring alarm notifications were received (2.2 per patient-year of follow-up), comprising 2096 unique alerts (2.6 per patient-year of follow-up). Since 591 (28.2%) of all incoming alerts were bioimpedance-related, patients with an ICD or CRT including a bioimpedance algorithm had significantly more alerts (3.4 versus 1.8 alerts per patient-year of follow-up, P<.001). Bioimpedance-only alerts resulted in a phone contact in 91.0% (498/547) of cases, which triggered an actual intervention in 15.9% (87/547) of cases, since in 75.1% (411/547) of cases reenforcing heart failure education sufficed. Overall survival was lower in patients with a cardiovascular implantable electronic device with a bioimpedance algorithm; however, this difference was driven by differences in baseline characteristics (adjusted hazard ratio of 2.118, 95% CI 0.845-5.791). No significant differences between both groups were observed in terms of the number of follow-up visits in the outpatient heart failure clinic, the number of hospital admissions with a primary diagnosis of heart failure, or mean length of hospital stay., Conclusions: Bioimpedance-only alerts constituted a substantial amount of incoming alerts when turned on during remote follow-up and triggered an additional intervention in only 16% of cases since in 75% of cases, providing general heart failure education sufficed. The high frequency of heart failure education that was provided could have contributed to fewer heart failure-related hospitalizations despite significant differences in baseline characteristics., (©Christophe JP Smeets, Julie Vranken, Jo Van der Auwera, Frederik H Verbrugge, Wilfried Mullens, Matthias Dupont, Lars Grieten, Hélène De Cannière, Dorien Lanssens, Thijs Vandenberk, Valerie Storms, Inge M Thijs, Pieter M Vandervoort. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 23.11.2017.)

Background: Despite reported positive results of telemonitoring effectiveness in various health care domains, this new technology is rarely used in prenatal care. A few isolated investigations were performed in the past years but with conflicting results., Objective: The aim of this review was to (1) assess whether telemonitoring adds any substantial benefit to this patient population and (2) identify research gaps in this area to suggest goals for future research., Methods: This review includes studies exploring the effectiveness of telemonitoring interventions for pregnant women reported in the English language. Due to the paucity of research in this area, all reports including uncontrolled nonrandomized and randomized controlled studies were selected., Results: Fourteen studies, which performed their data collection from 1988 to 2010, met the inclusion criteria and were published from 1995 to present; four of the 14 published papers were multicenter randomized controlled trials (RCTs), five papers were single-center RCTs, three papers were retrospective studies, one paper was an observational study, and one paper was a qualitative study. Of the 14 papers, nine were available for a risk of bias assessment: three papers were classified as low risk, one as medium risk, and five as high risk. Furthermore, of those 14 papers, 13 focused on telemonitoring for maternal outcomes, and nine of the 14 papers focused on telemonitoring for fetal or neonatal outcomes. The studies reviewed report that telemonitoring can contribute to significant reductions in health care costs, (unscheduled) face-to-face visits, low neonatal birth weight, and admissions to the neonatal intensive care unit (NICU), as well as prolonged gestational age and improved feelings of maternal satisfaction when compared with a control group. When only studies with low risk of bias were taken into account, the added value of telemonitoring became less pronounced: the only added value of telemonitoring is for pregnant women who transmitted their uterine activity by telecommunication. They had significant prolonged pregnancy survivals, and the newborns were less likely to be of low birth weight or to be admitted to the NICU. Following these results, telemonitoring can only be recommended by pregnant women at risk for preterm delivery. It is however important to consider that these studies were published in the mid-90s, which limits their direct applicability given the current technologies and practice., Conclusions: This review shows that telemonitoring can be tentatively recommended for pregnant women at risk for preterm delivery. More recent RCTs with a blinded protocol are needed to strengthen the level of evidence around this topic and to have an insight in the added value of the technologies that are available nowadays. In addition, studies investigating patient satisfaction and economic effects in relation to telemonitoring are suggested for future research., (©Dorien Lanssens, Thijs Vandenberk, Inge M Thijs, Lars Grieten, Wilfried Gyselaers. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 27.09.2017.)

Background: Photoplethysmography (PPG) is a proven way to measure heart rate (HR). This technology is already available in smartphones, which allows measuring HR only by using the smartphone. Given the widespread availability of smartphones, this creates a scalable way to enable mobile HR monitoring. An essential precondition is that these technologies are as reliable and accurate as the current clinical (gold) standards. At this moment, there is no consensus on a gold standard method for the validation of HR apps. This results in different validation processes that do not always reflect the veracious outcome of comparison., Objective: The aim of this paper was to investigate and describe the necessary elements in validating and comparing HR apps versus standard technology., Methods: The FibriCheck (Qompium) app was used in two separate prospective nonrandomized studies. In the first study, the HR of the FibriCheck app was consecutively compared with 2 different Food and Drug Administration (FDA)-cleared HR devices: the Nonin oximeter and the AliveCor Mobile ECG. In the second study, a next step in validation was performed by comparing the beat-to-beat intervals of the FibriCheck app to a synchronized ECG recording., Results: In the first study, the HR (BPM, beats per minute) of 88 random subjects consecutively measured with the 3 devices showed a correlation coefficient of .834 between FibriCheck and Nonin, .88 between FibriCheck and AliveCor, and .897 between Nonin and AliveCor. A single way analysis of variance (ANOVA; P=.61 was executed to test the hypothesis that there were no significant differences between the HRs as measured by the 3 devices. In the second study, 20,298 (ms) R-R intervals (RRI)-peak-to-peak intervals (PPI) from 229 subjects were analyzed. This resulted in a positive correlation (rs=.993, root mean square deviation [RMSE]=23.04 ms, and normalized root mean square error [NRMSE]=0.012) between the PPI from FibriCheck and the RRI from the wearable ECG. There was no significant difference (P=.92) between these intervals., Conclusions: Our findings suggest that the most suitable method for the validation of an HR app is a simultaneous measurement of the HR by the smartphone app and an ECG system, compared on the basis of beat-to-beat analysis. This approach could lead to more correct assessments of the accuracy of HR apps., (©Thijs Vandenberk, Jelle Stans, Gertjan Van Schelvergem, Caroline Pelckmans, Christophe JP Smeets, Dorien Lanssens, Hélène De Cannière, Valerie Storms, Inge M Thijs, Pieter M Vandervoort. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 25.08.2017.)

Background: Although remote monitoring (RM) has proven its added value in various health care domains, little is known about the remote follow-up of pregnant women diagnosed with a gestational hypertensive disorders (GHD)., Objective: The aim of this study was to evaluate the added value of a remote follow-up program for pregnant women diagnosed with GHD., Methods: A 1-year retrospective study was performed in the outpatient clinic of a 2nd level prenatal center where pregnant women with GHD received RM or conventional care (CC). Primary study endpoints include number of prenatal visits and admissions to the prenatal observation ward. Secondary outcomes include gestational outcome, mode of delivery, neonatal outcome, and admission to neonatal intensive care (NIC). Differences in continuous and categorical variables in maternal demographics and characteristics were tested using Unpaired Student's two sampled t test or Mann-Whitney U test and the chi-square test. Both a univariate and multivariate analysis were performed for analyzing prenatal follow-up and gestational outcomes. All statistical analyses were done at nominal level, Cronbach alpha=.05., Results: Of the 166 patients diagnosed with GHD, 53 received RM and 113 CC. After excluding 5 patients in the RM group and 15 in the CC group because of the missing data, 48 patients in RM group and 98 in CC group were taken into final analysis. The RM group had more women diagnosed with gestational hypertension, but less with preeclampsia when compared with CC (81.25% vs 42.86% and 14.58% vs 43.87%). Compared with CC, univariate analysis in RM showed less induction, more spontaneous labors, and less maternal and neonatal hospitalizations (48.98% vs 25.00%; 31.63% vs 60.42%; 74.49% vs 56.25%; and 27.55% vs 10.42%). This was also true in multivariate analysis, except for hospitalizations., Conclusions: An RM follow-up of women with GHD is a promising tool in the prenatal care. It opens the perspectives to reverse the current evolution of antenatal interventions leading to more interventions and as such to ever increasing medicalized antenatal care., (©Dorien Lanssens, Thijs Vandenberk, Christophe JP Smeets, Hélène De Cannière, Geert Molenberghs, Anne Van Moerbeke, Anne van den Hoogen, Tiziana Robijns, Sharona Vonck, Anneleen Staelens, Valerie Storms, Inge M Thijs, Lars Grieten, Wilfried Gyselaers. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 09.03.2017.)

Background: Biofilm formation is an important survival strategy of Salmonella in all environments. By mutant screening, we showed a knock-out mutant of fabR, encoding a repressor of unsaturated fatty acid biosynthesis (UFA), to have impaired biofilm formation. In order to unravel how this regulator impinges on Salmonella biofilm formation, we aimed at elucidating the S. Typhimurium FabR regulon. Hereto, we applied a combinatorial high-throughput approach, combining ChIP-chip with transcriptomics., Results: All the previously identified E. coli FabR transcriptional target genes (fabA, fabB and yqfA) were shown to be direct S. Typhimurium FabR targets as well. As we found a fabB overexpressing strain to partly mimic the biofilm defect of the fabR mutant, the effect of FabR on biofilms can be attributed at least partly to FabB, which plays a key role in UFA biosynthesis. Additionally, ChIP-chip identified a number of novel direct FabR targets (the intergenic regions between hpaR/hpaG and ddg/ydfZ) and yet putative direct targets (i.a. genes involved in tRNA metabolism, ribosome synthesis and translation). Next to UFA biosynthesis, a number of these direct targets and other indirect targets identified by transcriptomics (e.g. ribosomal genes, ompA, ompC, ompX, osmB, osmC, sseI), could possibly contribute to the effect of FabR on biofilm formation., Conclusion: Overall, our results point at the importance of FabR and UFA biosynthesis in Salmonella biofilm formation and their role as potential targets for biofilm inhibitory strategies.

Public online microarray databases contain tremendous amounts of expression data. Mining these data sources can provide a wealth of information on the underlying transcriptional networks. In this chapter, we illustrate how the web services COLOMBOS and DISTILLER can be used to identify condition-dependent coexpression modules by exploring compendia of public expression data. COLOMBOS is designed for user-specified query-driven analysis, whereas DISTILLER generates a global regulatory network overview. The user is guided through both web services by means of a case study in which condition-dependent coexpression modules comprising a gene of interest (i.e., "directed") are identified.

Background: Metabolic reconstructions (MRs) are common denominators in systems biology and represent biochemical, genetic, and genomic (BiGG) knowledge-bases for target organisms by capturing currently available information in a consistent, structured manner. Salmonella enterica subspecies I serovar Typhimurium is a human pathogen, causes various diseases and its increasing antibiotic resistance poses a public health problem., Results: Here, we describe a community-driven effort, in which more than 20 experts in S. Typhimurium biology and systems biology collaborated to reconcile and expand the S. Typhimurium BiGG knowledge-base. The consensus MR was obtained starting from two independently developed MRs for S. Typhimurium. Key results of this reconstruction jamboree include i) development and implementation of a community-based workflow for MR annotation and reconciliation; ii) incorporation of thermodynamic information; and iii) use of the consensus MR to identify potential multi-target drug therapy approaches., Conclusion: Taken together, with the growing number of parallel MRs a structured, community-driven approach will be necessary to maximize quality while increasing adoption of MRs in experimental design and interpretation.

Background: Non-coding RNAs (ncRNAs) play a crucial role in the intricate regulation of bacterial gene expression, allowing bacteria to quickly adapt to changing environments. In the past few years, a growing number of regulatory RNA elements have been predicted by computational methods, mostly in well-studied gamma-proteobacteria but lately in several alpha-proteobacteria as well. Here, we have compared an extensive compilation of these non-coding RNA predictions to intergenic expression data of a whole-genome high-resolution tiling array in the soil-dwelling alpha-proteobacterium Rhizobium etli., Results: Expression of 89 candidate ncRNAs was detected, both on the chromosome and on the six megaplasmids encompassing the R. etli genome. Of these, 11 correspond to functionally well characterized ncRNAs, 12 were previously identified in other alpha-proteobacteria but are as yet uncharacterized and 66 were computationally predicted earlier but had not been experimentally identified and were therefore classified as novel ncRNAs. The latter comprise 17 putative sRNAs and 49 putative cis-regulatory ncRNAs. A selection of these candidate ncRNAs was validated by RT-qPCR, Northern blotting and 5' RACE, confirming the existence of 4 ncRNAs. Interestingly, individual transcript levels of numerous ncRNAs varied during free-living growth and during interaction with the eukaryotic host plant, pointing to possible ncRNA-dependent regulation of these specialized processes., Conclusions: Our data support the practical value of previous ncRNA prediction algorithms and significantly expand the list of candidate ncRNAs encoded in the intergenic regions of R. etli and, by extension, of alpha-proteobacteria. Moreover, we show high-resolution tiling arrays to be suitable tools for studying intergenic ncRNA transcription profiles across the genome. The differential expression levels of some of these ncRNAs may indicate a role in adaptation to changing environmental conditions.

We present DISTILLER, a data integration framework for the inference of transcriptional module networks. Experimental validation of predicted targets for the well-studied fumarate nitrate reductase regulator showed the effectiveness of our approach in Escherichia coli. In addition, the condition dependency and modularity of the inferred transcriptional network was studied. Surprisingly, the level of regulatory complexity seemed lower than that which would be expected from RegulonDB, indicating that complex regulatory programs tend to decrease the degree of modularity.

The Salmonella enterica serovar Typhimurium HilA protein is the key regulator for the invasion of epithelial cells. By a combination of genome-wide location and transcript analysis, the HilA-dependent regulon has been delineated. Under invasion-inducing conditions, HilA binds to most of the known target genes and a number of new target genes. The sopB, sopE, and sopA genes, encoding effector proteins secreted by the type III secretion system on Salmonella pathogenicity island 1 (SPI-1), were identified as being both bound by HilA and differentially regulated in an HilA mutant. This suggests a cooperative role for HilA and InvF in the regulation of SPI-1-secreted effectors. Also, siiA, the first gene of SPI-4, is both bound by HilA and differentially regulated in an HilA mutant, thus linking this pathogenicity island to the invasion key regulator. Finally, the interactions of HilA with the SPI-2 secretion system gene ssaH and the flagellar gene flhD imply a repressor function for HilA under invasion-inducing conditions.

In the current omics era, innovative high-throughput technologies allow measuring temporal and conditional changes at various cellular levels. Although individual analysis of each of these omics data undoubtedly results into interesting findings, it is only by integrating them that gaining a global insight into cellular behaviour can be aimed at. A systems approach thus is predicated on data integration. However, because of the complexity of biological systems and the specificities of the data-generating technologies (noisiness, heterogeneity, etc.), integrating omics data in an attempt to reconstruct signalling networks is not trivial. Developing its methodologies constitutes a major research challenge. Besides for their intrinsic value towards health care, environment and industry, prokaryotes are ideal model systems to further develop these methods because of their lower regulatory complexity compared with eukaryotes, and the ease with which they can be manipulated. Several successful examples outlined in this review already show the potential of the systems approach for both fundamental and industrial applications, which would be time-consuming or impossible to develop solely through traditional reductionist approaches.