Improving treatment adherence for blood pressure lowering via mobile phone SMS-messages in South Africa: a qualitative evaluation of the SMS-text Adherence SuppoRt (StAR) trial

BACKGROUND:Effective use of proven treatments for high blood pressure, a preventable health risk, is challenging for many patients. Prompts via mobile phone SMS-text messaging may improve adherence to clinic visits and treatment, though more research is needed on impact and patient perceptions of such support interventions, especially in low-resource settings.METHOD:An individually-randomised controlled trial in a primary care clinic in Cape Town (2012-14), tested the effect of an adherence support intervention delivered via SMS-texts, on blood pressure control and adherence to medication, for hypertensive patients. (Trial registration: ClinicalTrials.gov NCT02019823). We report on a qualitative evaluation that explored the trial participants' experiences and responses to the SMS-text messages, and identified barriers and facilitators to delivering adherence support via patients' own mobile phones. Two focus groups and fifteen individual interviews were conducted. We used comparative and thematic analysis approaches to identify themes and triangulated our analysis amongst three researchers. RESULTS: Most participants were comfortable with the technology of using SMS-text messages. Messages were experienced as acceptable, relevant and useful to a broad range of participants. The SMS-content, the respectful tone and the delivery (timing of reminders and frequency) and the relational aspect of trial participation (feeling cared for) were all highly valued. A subgroup who benefitted the most, were those who had been struggling with adherence due to high levels of personal stress. The intervention appeared to coincide with their readiness for change, and provided practical and emotional support for improving adherence behaviour. Change may have been facilitated through increased acknowledgement of their health status and attitudinal change towards greater self-responsibility. Complex interaction of psycho-social stressors and health service problems were reported as broader challenges to adherence behaviours. CONCLUSION: Adherence support for treatment of raised blood pressure, delivered via SMS-text message on the patient's own phone, was found to be acceptable, relevant and helpful, even for those who already had their own reminder systems in place. Our findings begin to identify for whom and what core elements of the SMS-text message intervention appear to work best in a low-resource operational setting, issues that future research should explore in greater depth

Intervention development of a brief messaging intervention for a randomised controlled trial to improve diabetes treatment adherence in sub-Saharan Africa

Background Brief messaging interventions, including Short Message Service (SMS) text-messages, delivered via mobile device platforms, show promise to support and improve treatment adherence. To understand how these interventions work, and to facilitate transparency, we need clear descriptions of the intervention development process. Method We describe and reflect on the process of designing and pretesting an evidence- and theory-informed brief messaging intervention, to improve diabetes treatment adherence in sub-Saharan Africa. We followed the stepwise approach recommended by the Medical Research Council, United Kingdom (MRC UK) Framework for Development and Evaluation of Complex Health Interventions and guidance for mobile health intervention development. Results We used a four-phase, iterative approach that first generated primary and secondary evidence on the lived experience of diabetes, diabetes treatment services and mobile-phone use. Second, we designed a type 2 diabetes-specific, brief text-message library, building on our previous hypertension text-message library, as well as drawing on the primary and secondary data from phase one, and on expert opinion. We then mapped the brief text-messages onto behaviour change (COM-B) theoretical constructs. Third, we refined and finalised the newly developed brief text-message library through stakeholder consultation and translated it into three local languages. Finally, we piloted the intervention by pre-testing the automated delivery of the brief text-messages in the trial sites in Malawi and South Africa. The final SMS text Adherence suppoRt for people with type 2 diabetes (StAR2D) intervention was tested in a randomised controlled trial in Malawi and South Africa (trial registration: ISRCTN70768808 ). Conclusion The complexity of public health interventions requires that we give more attention to intervention development work. Our documentation and reflection on the StAR2D intervention development process promotes transparency, replicability, assessment of intervention quality, and comparison with other studies

Efficacy of a text messaging (SMS) based intervention for adults with hypertension: protocol for the StAR (SMS Text-message Adherence suppoRt trial) randomised controlled trial

Abstract Background Interventions to support people with hypertension in attending clinics and taking their medication have potential to improve outcomes, but delivery on a wide scale and at low cost is challenging. Some trials evaluating clinical interventions using short message service (SMS) text-messaging systems have shown important outcomes, although evidence is limited. We have developed a novel SMS system integrated with clinical care for use by people with hypertension in a low-resource setting. We aim to test the efficacy of the system in improving blood pressure control and treatment adherence compared to usual care. Methods/design The SMS Text-message Adherence suppoRt trial (StAR) is a pragmatic individually randomised three-arm parallel group trial in adults treated for hypertension at a single primary care centre in Cape Town, South Africa. The intervention is a structured programme of clinic appointment, medication pick-up reminders, medication adherence support and hypertension-related education delivered remotely using an automated system with either informational or interactive SMS text-messages. Usual care is supplemented by infrequent non-hypertension related SMS text-messages. Participants are 1:1:1 individually randomised, to usual care or to one of the two active interventions using minimisation to dynamically adjust for gender, age, baseline systolic blood pressure, years with hypertension, and previous clinic attendance. The primary outcome is the change in mean systolic blood pressure at 12-month follow-up from baseline measured with research staff blinded to trial allocation. Secondary outcomes include the proportion of patients with 80% or more of days medication available, proportion of participants achieving a systolic blood pressure less than 140 mmHg and a diastolic blood pressure less than 90 mmHg, hospital admissions, health status, retention in clinical care, satisfaction with treatment and care, and patient related quality of life. Anonymised demographic data are collected on non-participants. Discussion The StAR trial uses a novel, low cost system based on widely available mobile phone technology to deliver the SMS-based intervention, manage communication with patients, and measure clinically relevant outcomes. The results will inform implementation and wider use of mobile phone based interventions for health care delivery in a low-resource setting. Trial registration NCT0201982

Text2PreventCVD: protocol for a systematic review and individual participant data meta-analysis of text message-based interventions for the prevention of cardiovascular diseases

Introduction: Text message interventions have been shown to be effective in prevention and management of several non-communicable disease risk factors. However, the extent to which their effects might vary in different participants and settings is uncertain. We aim to conduct a systematic review and individual participant data (IPD) meta-analysis of randomised clinical trials examining text message interventions aimed to prevent cardiovascular diseases (CVD) through modification of cardiovascular risk factors (CVRFs). Methods and analysis: Systematic review and IPD meta-analysis will be conducted according to Preferred Reporting Items for Systematic review and Meta-Analysis of IPD (PRISMA-IPD) guidelines. Electronic database of published studies (MEDLINE, EMBASE, PsycINFO and Cochrane Library) and international trial registries will be searched to identify relevant randomised clinical trials. Authors of studies meeting the inclusion criteria will be invited to join the IPD meta-analysis group and contribute study data to the common database. The primary outcome will be the difference between intervention and control groups in blood pressure at 6-month follow-up. Key secondary outcomes include effects on lipid parameters, body mass index, smoking levels and self-reported quality of life. If sufficient data is available, we will also analyse blood pressure and other secondary outcomes at 12 months. IPD meta-analysis will be performed using a one-step approach and modelling data simultaneously while accounting for the clustering of the participants within studies. This study will use the existing data to assess the effectiveness of text message-based interventions on CVRFs, the consistency of any effects by participant subgroups and across different healthcare settings. Ethics and dissemination: Ethical approval was obtained for the individual studies by the trial investigators from relevant local ethics committees. This study will include anonymised data for secondary analysis and investigators will be asked to check that this is consistent with their existing approvals. Results will be disseminated via scientific forums including peer-reviewed publications and presentations at international conferences

Implementation barriers for mHealth for non-communicable diseases management in low and middle income countries: a scoping review and field-based views from implementers.

Background: Mobile health (mHealth) has been hailed as a potential gamechanger for non-communicable disease (NCD) management, especially in low- and middle-income countries (LMIC). Individual studies illustrate barriers to implementation and scale-up, but an overview of implementation issues for NCD mHealth interventions in LMIC is lacking. This paper explores implementation issues from two perspectives: information in published papers and field-based knowledge by people working in this field. Methods: Through a scoping review publications on mHealth interventions for NCDs in LMIC were identified and assessed with the WHO mHealth Evidence Reporting and Assessment (mERA) tool. A two-stage web-based survey on implementation barriers was performed within a NCD research network and through two online platforms on mHealth targeting researchers and implementors. Results: 16 studies were included in the scoping review. Short Message Service (SMS) messaging was the main implementation tool. Most studies focused on patient-centered outcomes. Most studies did not report on process measures and on contextual conditions influencing implementation decisions. Few publications reported on implementation barriers. The websurvey included twelve projects and the responses revealed additional information, especially on practical barriers related to the patients' characteristics, low demand, technical requirements, integration with health services and with the wider context. Many interventions used low-cost software and devices with limited capacity that not allowed linkage with routine data or patient records, which incurred fragmented delivery and increased workload. Conclusion: Text messaging is a dominant mHealth tool for patient-directed of quality improvement interventions in LMIC. Publications report little on implementation barriers, while a questionnaire among implementors reveals significant barriers and strategies to address them. This information is relevant for decisions on scale-up of mHealth in the domain of NCD. Further knowledge should be gathered on implementation issues, and the conditions that allow universal coverage

Mobile phone text-messaging interventions aimed to prevent cardiovascular diseases (Text2PreventCVD): systematic review and individual patient data meta-analysis

Background A variety of small mobile phone text messaging interventions have indicated improvement in risk factors for cardiovascular disease (CVD). Yet the extent of this improvement and whether it impacts multiple risk factors together is uncertain. We aimed to conduct a systematic review and individual patient data (IPD) meta-analysis to investigate the effects of text-messaging interventions for CVD prevention. Methods Electronic databases were searched to identify trials investigating a text-messaging intervention focusing on CVD prevention with the potential to modify at least two CVD risk factors in adults. The main outcome was blood pressure (BP). We conducted standard and IPD meta-analysis on pooled data. We accounted for clustering of patients within studies and the primary analysis used random-effects models. Sensitivity and subgroup analyses were performed. Results Nine trials were included in the systematic review involving 3779 participants and 5 (n=2612) contributed data to the IPD meta-analysis. Standard metaanalysis showed that the weighted mean differences are as follows: systolic blood pressure (SBP), −4.13 mm Hg (95% CI −11.07 to 2.81, p<0.0001); diastolic blood pressure (DBP), −1.11 mm Hg (−1.91 to −0.31, p=0.002); and body mass index (BMI), −0.32 (−0.49 to −0.16, p=0.000). In the IPD meta-analysis, the mean difference are as follows: SBP, −1.3 mm Hg (−5.4 to 2.7, p=0.5236); DBP, −0.8 mm Hg (−2.5 to 1.0, p=0.3912); and BMI, −0.2 (−0.8 to 0.4, p=0.5200) in the random-effects model. The impact on other risk factors is described, but there were insufficient data to conduct meta-analyses. Conclusion Mobile phone text-messaging interventions have modest impacts on BP and BMI. Simultaneous but small impacts on multiple risk factors are likely to be clinically relevant and improve outcome, but there are currently insufficient data in pooled analyses to examine the extent to which simultaneous reduction in multiple risk factors occurs

Mobile Messaging Support Versus Usual Care for People With Type 2 Diabetes on Glycemic Control: Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Health outcomes for people treated for type 2 diabetes could be substantially improved in sub-Saharan Africa. Failure to take medicine regularly to treat diabetes has been identified as a major problem. Resources to identify and support patients who are not making the best use of medicine in low- and middle-income settings are scarce. Mobile phones are widely available in these settings, including among people with diabetes; linked technologies, such as short message service (SMS) text messaging, have shown promise in delivering low-cost interventions efficiently. However, evidence showing that these interventions will work when carried out at a larger scale and measuring the extent to which they will improve health outcomes when added to usual care is limited. OBJECTIVE: The objective of this trial is to test the effectiveness of sending brief, automated SMS text messages for improving health outcomes and medication adherence in patients with type 2 diabetes compared to an active control. METHODS: We will carry out a randomized trial recruiting from clinics in two contrasting settings in sub-Saharan Africa: Cape Town, South Africa, and Lilongwe, Malawi. Intervention messages will advise people about the benefits of their diabetes treatment and offer motivation and encouragement around lifestyle and use of medication. We allocated patients, using randomization with a minimization algorithm, to receive either three to four intervention messages per week or non-health-related messages every 6 weeks. We will follow up with participants for 12 months, measuring important risk factors for poor health outcomes and complications in diabetes. This will enable us to estimate potential health benefits, including the primary outcome of hemoglobin A1c (HbA1c) levels as a marker for long-term blood glucose control and a secondary outcome of blood pressure control. We will record the costs of performing these activities and estimate cost-effectiveness. We will also use process evaluation to capture the collection of medication and assess the reception of the intervention by participants and health care workers. RESULTS: Recruitment to the trial began in September 2016 and follow-up of participants was completed in October 2018. Data collection from electronic health records and other routinely collected sources is continuing. The database lock is anticipated in June 2019, followed by analysis and disclosing of group allocation. CONCLUSIONS: The knowledge gained from this study will have wide applications and advance the evidence base for effectiveness of mobile phone-based, brief text messaging on clinical outcomes and in large-scale, operational settings. It will provide evidence for cost-effectiveness and acceptability that will further inform policy development and decision making. We will work with a wide network that includes patients, clinicians, academics, industry, and policy makers to help us identify opportunities for informing people about the work and raise awareness of what is being developed and studied. TRIAL REGISTRATION: ISRCTN Registry ISRCTN70768808; http://www.isrctn.com/ISRCTN70768808 (Archived by WebCite at http://www.webcitation.org/786316Zqk). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12377

Home and Online Management and Evaluation of Blood Pressure (HOME BP) using a digital intervention in poorly controlled hypertension: randomised controlled trial

Objective: The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. Design: Unmasked randomised controlled trial with automated ascertainment of primary endpoint. Setting: 76 general practices in the United Kingdom. Participants: 622 people with treated but poorly controlled hypertension (&gt;140/90 mm Hg) and access to the internet. Interventions: Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. Main outcome measures: The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. Results: After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of −3.4 mm Hg (95% confidence interval −6.1 to −0.8 mm Hg) and a mean difference in diastolic blood pressure of −0.5 mm Hg (−1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. Conclusions: The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. Trial registration: ISRCTN13790648

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

StAR2D Patient Interview and Focus Group Guide: Formative Intervention development study

Interview guide used for the in-depth individual interviews and focus groups with patient participants in Phase 1 of the StAR2D study