Choosing blood pressure thresholds to inform pregnancy care in the community: An analysis of cluster trials.

OBJECTIVE: To inform digital health design by evaluating diagnostic test properties of antenatal blood pressure (BP) outputs and levels to identify women at risk of adverse outcomes. DESIGN: Planned secondary analysis of cluster randomised trials. SETTING: India, Pakistan, Mozambique. POPULATION: Women with in-community BP measurements and known pregnancy outcomes. METHODS: Blood pressure was defined by its outputs (systolic and/or diastolic, systolic only, diastolic only or mean arterial pressure [calculated]) and level: normotension-1 (<135/85 mmHg), normotension-2 (135-139/85-89 mmHg), non-severe hypertension (140-149/90-99 mmHg; 150-154/100-104 mmHg; 155-159/105-109 mmHg) and severe hypertension (≥160/110 mmHg). Dose-response (adjusted risk ratio [aRR]) and diagnostic test properties (negative [-LR] and positive [+LR] likelihood ratios) were estimated. MAIN OUTCOME MEASURES: Maternal/perinatal composites of mortality/morbidity. RESULTS: Among 21 069 pregnancies, different BP outputs had similar aRR, -LR, and +LR for adverse outcomes. No BP level (even normotension-1) was associated with low risk (all -LR ≥0.20). Across outcomes, risks rose progressively with higher BP levels above normotension-1. For each of maternal central nervous system events and stillbirth, BP ≥155/105 mmHg showed at least good diagnostic test performance (+LR ≥5.0) and BP ≥135/85 mmHg at least fair performance, similar to BP ≥140/90 mmHg (+LR 2.0-4.99). CONCLUSIONS: In the community, normal BP values do not provide reassurance about subsequent adverse outcomes. Given the similar performance of BP cut-offs of 135/85 and 140/90 mmHg for hypertension, and 155/105 and 160/110 mmHg for severe hypertension, digital decision support for women in the community should consider using these lower thresholds.

Variability of respiratory rate measurements in neonates- every minute counts.

BACKGROUND: Respiratory rate is difficult to measure, especially in neonates who have an irregular breathing pattern. The World Health Organisation recommends a one-minute count, but there is limited data to support this length of observation. We sought to evaluate agreement between the respiratory rate (RR) derived from capnography in neonates, over 15 s, 30 s, 120 s and 300 s, against the recommended 60 s. METHODS: Neonates at two hospitals in Nairobi were recruited and had capnograph waveforms recorded using the Masimo Rad 97. A single high quality 5 min epoch was randomly chosen from each subject. For each selected epoch, the mean RR was calculated using a breath-detection algorithm applied to the waveform. The RR in the first 60 s was compared to the mean RR measured over the first 15 s, 30 s, 120 s, full 300 s, and last 60 s. We calculated bias and limits of agreement for each comparison and used Bland-Altman plots for visual comparisons. RESULTS: A total of 306 capnographs were analysed from individual subjects. The subjects had a median gestation age of 39 weeks with slightly more females (52.3%) than males (47.7%). The majority of the population were term neonates (70.1%) with 39 (12.8%) having a primary respiratory pathology. There was poor agreement between all the comparisons based on the limits of agreement [confidence interval], ranging between 11.9 [- 6.79 to 6.23] breaths per minute in the one versus 2 min comparison, and 34.7 [- 17.59 to 20.53] breaths per minute in the first versus last minute comparison. Worsening agreement was observed in plots with higher RRs. CONCLUSIONS: Neonates have high variability of RR, even over a short period of time. A slight degradation in the agreement is noted over periods shorter than 1 min. However, this is smaller than observations done 3 min apart in the same subject. Longer periods of observation also reduce agreement. For device developers, precise synchronization is needed when comparing devices to reduce the impact of RR variation. For clinicians, where possible, continuous or repeated monitoring of neonates would be preferable to one time RR measurements.

Community-level interventions for pre-eclampsia (CLIP) in Pakistan: A cluster randomised controlled trial.

OBJECTIVES: To reduce all-cause maternal and perinatal mortality and major morbidity through Lady Health Worker (LHW)-facilitated community engagement and early diagnosis, stabilization and referral of women with preeclampsia, an important contributor to adverse maternal and perinatal outcomes given delays in early detection and initial management. STUDY DESIGN: In the Pakistan Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomized controlled trial (NCT01911494), LHWs engaged the community, recruited pregnant women from 20 union councils (clusters), undertook mobile health-guided clinical assessment for preeclampsia, and referral to facilities after stabilization. MAIN OUTCOME MEASURES: The primary outcome was a composite of maternal, fetal and newborn mortality and major morbidity. FINDINGS: We recruited 39,446 women in intervention (N = 20,264) and control clusters (N = 19,182) with minimal loss to follow-up (3∙7% vs. 4∙5%, respectively). The primary outcome did not differ between intervention (26·6%) and control (21·9%) clusters (adjusted odds ratio, aOR, 1∙20 [95% confidence interval 0∙84-1∙72]; p = 0∙31). There was reduction in stillbirths (0·89 [0·81-0·99]; p = 0·03), but no impact on maternal death (1·08 [0·69, 1·71]; p = 0·74) or morbidity (1·12 [0·57, 2·16]; p = 0·77); early (0·95 [0·82-1·09]; p = 0·46) or late neonatal deaths (1·23 [0·97-1·55]; p = 0·09); or neonatal morbidity (1·22 [0·77, 1·96]; p = 0·40). Improvements in outcome rates were observed with 4-7 (p = 0·015) and ≥8 (p < 0·001) (vs. 0) CLIP contacts. INTERPRETATION: The CLIP intervention was well accepted by the community and implemented by LHWs. Lack of effects on adverse outcomes could relate to quality care for mothers with pre-eclampsia in health facilities. Future strategies for community outreach must also be accompanied by health facility strengthening. FUNDING: The University of British Columbia (PRE-EMPT), a grantee of the Bill & Melinda Gates Foundation (OPP1017337).

Community level interventions for pre-eclampsia (CLIP) in India: A cluster randomised controlled trial.

OBJECTIVES: Pregnancy hypertension is associated with 7.1% of maternal deaths in India. The objective of this trial was to assess whether task-sharing care might reduce adverse pregnancy outcomes related to delays in triage, transport, and treatment. STUDY DESIGN: The Indian Community-Level Interventions for Pre-eclampsia (CLIP) open-label cluster randomised controlled trial (NCT01911494) recruited pregnant women in 12 clusters (initial four-cluster internal pilot) in Belagavi and Bagalkote, Karnataka. The CLIP intervention (6 clusters) consisted of community engagement, community health workers (CHW) provided mobile health (mHeath)-guided clinical assessment, initial treatment, and referral to facility either urgently (<4 h) or non-urgently (<24 h), dependent on algorithm-defined risk. Treatment effect was estimated by multi-level logistic regression modelling, adjusted for prognostically-significant baseline variables. Predefined secondary analyses included safety and evaluation of the intensity of mHealth-guided CHW-provided contacts. MAIN OUTCOME MEASURES: 20% reduction in composite of maternal, fetal, and newborn mortality and major morbidity. RESULTS: All 14,783 recruited pregnancies (7839 intervention, 6944 control) were followed-up. The primary outcome did not differ between intervention and control arms (adjusted odds ratio (aOR) 0.92 [95% confidence interval 0.74, 1.15]; p = 0.47; intraclass correlation coefficient 0.013). There were no intervention-related safety concerns following administration of either methyldopa or MgSO4, and 401 facility referrals. Compared with intervention arm women without CLIP contacts, those with ≥8 contacts suffered fewer stillbirths (aOR 0.19 [0.10, 0.35]; p < 0.001), at the probable expense of survivable neonatal morbidity (aOR 1.39 [0.97, 1.99]; p = 0.072). CONCLUSIONS: As implemented, solely community-level interventions focussed on pre-eclampsia did not improve outcomes in northwest Karnataka.

Community-level interventions for pre-eclampsia (CLIP) in Mozambique: A cluster randomised controlled trial.

OBJECTIVES: Pregnancy hypertension is the third leading cause of maternal mortality in Mozambique and contributes significantly to fetal and neonatal mortality. The objective of this trial was to assess whether task-sharing care might reduce adverse pregnancy outcomes related to delays in triage, transport, and treatment. STUDY DESIGN: The Mozambique Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trial (NCT01911494) recruited pregnant women in 12 administrative posts (clusters) in Maputo and Gaza Provinces. The CLIP intervention (6 clusters) consisted of community engagement, community health worker-provided mobile health-guided clinical assessment, initial treatment, and referral to facility either urgently (<4hrs) or non-urgently (<24hrs), dependent on algorithm-defined risk. Treatment effect was estimated by multi-level logistic regression modelling, adjusted for prognostically-significant baseline variables. Predefined secondary analyses included safety and evaluation of the intensity of CLIP contacts. MAIN OUTCOME MEASURES: 20% reduction in composite of maternal, fetal, and newborn mortality and major morbidity. RESULTS: 15,013 women (15,123 pregnancies) were recruited in intervention (N = 7930; 2·0% loss to follow-up (LTFU)) and control (N = 7190; 2·8% LTFU) clusters. The primary outcome did not differ between intervention and control clusters (adjusted odds ratio (aOR) 1·31, 95% confidence interval (CI) [0·70, 2·48]; p = 0·40). Compared with intervention arm women without CLIP contacts, those with ≥8 contacts experienced fewer primary outcomes (aOR 0·79 (95% CI 0·63, 0·99); p = 0·041), primarily due to improved maternal outcomes (aOR 0·72 (95% CI 0·53, 0·97); p = 0·033). INTERPRETATION: As generally implemented, the CLIP intervention did not improve pregnancy outcomes; community implementation of the WHO eight contact model may be beneficial. FUNDING: The University of British Columbia (PRE-EMPT), a grantee of the Bill & Melinda Gates Foundation (OPP1017337).

Moving beyond silos: How do we provide distributed personalized medicine to pregnant women everywhere at scale? Insights from PRE-EMPT.

While we believe that pre-eclampsia matters-because it remains a leading cause of maternal and perinatal morbidity and mortality worldwide-we are convinced that the time has come to look beyond single clinical entities (e.g. pre-eclampsia, postpartum hemorrhage, obstetric sepsis) and to look for an integrated approach that will provide evidence-based personalized care to women wherever they encounter the health system. Accurate outcome prediction models are a powerful way to identify individuals at incrementally increased (and decreased) risks associated with a given condition. Integrating models with decision algorithms into mobile health (mHealth) applications could support community and first level facility healthcare providers to identify those women, fetuses, and newborns most at need of facility-based care, and to initiate lifesaving interventions in their communities prior to transportation. In our opinion, this offers the greatest opportunity to provide distributed individualized care at scale, and soon.

Usability and Feasibility of PIERS on the Move: An mHealth App for Pre-Eclampsia Triage.

BACKGROUND: Pre-eclampsia is one of the leading causes of maternal death and morbidity in low-resource countries due to delays in case identification and a shortage of health workers trained to manage the disorder. Pre-eclampsia Integrated Estimate of RiSk (PIERS) on the Move (PotM) is a low cost, easy-to-use, mobile health (mHealth) platform that has been created to aid health workers in making decisions around the management of hypertensive pregnant women. PotM combines two previously successful innovations into a mHealth app: the miniPIERS risk assessment model and the Phone Oximeter. OBJECTIVE: The aim of this study was to assess the usability of PotM (with mid-level health workers) for iteratively refining the system. METHODS: Development of the PotM user interface involved usability testing with target end-users in South Africa. Users were asked to complete clinical scenario tasks, speaking aloud to give feedback on the interface and then complete a questionnaire. The tool was then evaluated in a pilot clinical evaluation in Tygerberg Hospital, Cape Town. RESULTS: After ethical approval and informed consent, 37 nurses and midwives evaluated the tool. During Study 1, major issues in the functionality of the touch-screen keyboard and date scroll wheels were identified (total errors n=212); during Study 2 major improvements in navigation of the app were suggested (total errors n=144). Overall, users felt the app was usable using the Computer Systems Usability Questionnaire; median (range) values for Study 1 = 2 (1-6) and Study 2 = 1 (1-7). To demonstrate feasibility, PotM was used by one research nurse for the pilot clinical study. In total, more than 500 evaluations were performed on more than 200 patients. The median (interquartile range) time to complete an evaluation was 4 min 55 sec (3 min 25 sec to 6 min 56 sec). CONCLUSIONS: By including target end-users in the design and evaluation of PotM, we have developed an app that can be easily integrated into health care settings in low- and middle-income countries. Usability problems were often related to mobile phone features (eg, scroll wheels, touch screen use). Larger scale evaluation of the clinical impact of this tool is underway.

Development of mHealth applications for pre-eclampsia triage.

The development of mobile applications for the diagnosis and management of pregnant women with pre-eclampsia is described. These applications are designed for use by community-based health care providers (c-HCPs) in health facilities and during home visits to collect symptoms and perform clinical measurements (including pulse oximeter readings). The clinical data collected in women with pre-eclampsia are used as the inputs to a predictive model providing a risk score for the development of adverse outcomes. Based on this risk, the applications provide recommendations on treatment, referral, and reassessment. c-HCPs can access patient records across multiple visits, using multiple devices that are synchronized using a secure Research Electronic Data Capture server. A unique feature of these applications is the ability to measure oxygen saturation with a pulse oximeter connected to a smartphone (Phone Oximeter). The mobile health application development process, including challenges encountered and solutions are described.