Background About 14.9% of people (9.9 million) registered with primary care practices in England and Wales are prescribed medication for hypertension. However, many do not take their medication as prescribed. To address this problem, we need scalable interventions. Objective To develop a scalable low-cost intervention to support medication adherence in people prescribed medication for hypertension in primary care, and to obtain precise and robust estimates of the effectiveness and cost-effectiveness of the intervention compared with usual care. Design Systematic reviews and meta-analyses; qualitative meta-synthesis; interviews and focus groups; expert consultations; pre-testing study; randomised feasibility trial; randomised controlled trial of effectiveness and cost-effectiveness; economic modelling. Setting and participants Primary care practices in England and Wales. Patients prescribed medication for hypertension with poorly controlled blood pressure. Interventions Very brief intervention delivered by a practice nurse or healthcare assistant followed by a digital intervention (text messaging programme or smartphone app). Main outcome measures Acceptability, feasibility, fidelity and cost of the interventions. Systolic blood pressure. Biochemical and self-reported measures of medication adherence. Results Our systematic reviews showed that both app-based and face-to-face interventions in patients with long-term conditions have a positive effect on medication adherence. The meta-synthesis of published qualitative studies showed that: digital interventions to support medication use were perceived as acceptable and useful; a digital intervention would be more effective if it was personalised and tailored; barriers to using digital interventions included lack of interest, lack of confidence and lack of proficiency and experience in using the technology; digital interventions should be simple, easy to navigate and age-appropriate; patients wanted accurate information on their health condition, potential side effects of medication and health consequences of non-adherence; reminder notifications and a self-monitoring feature were perceived as helpful by some patients; some patients suggested that a digital intervention should enable them to communicate with pharmacies, but practitioners were concerned that this would increase their workload. The interview and focus group study identified several barriers to adherence, including forgetting, unpleasant side effects and reluctance to medicate. A digital intervention to support medication adherence was acceptable to patients if it was user-friendly, the content was tailored to the user, and the privacy of user data was protected. Simple reminder messages for taking medication and reordering prescriptions were considered more useful by patients than those providing information on the benefits of medication or the consequences of non-adherence. Patients preferred to receive feedback on their adherence levels in the form of a simple graph, percentage score or statistic. Practitioners thought that it would be feasible to introduce a digital intervention to patients in a very brief face-to-face consultation. In the pre-testing study, participants reported that the interventions we developed were easy to use and that they would recommend them to others. The feasibility trial showed that the combined intervention was acceptable and that a large cost-effectiveness trial was feasible. The main trial showed no difference between arms in systolic blood pressure or medication adherence at 12-month follow-up. The estimate (95% confidence interval) for the difference in means between arms in self-measured systolic blood pressure at 12 months was −0.61 mmHg (−3.05 to 1.82), p = 0.62 [for intervention vs. control (reference group)]. In the base case analysis, the intervention had a mean incremental cost-effectiveness ratio below the usual willingness-to-pay thresholds in the National Health Service in the United Kingdom. The probability of cost-effectiveness was between 77% and 80% at willingness-to-pay thresholds of £15,000, £20,000 and £30,000 per quality-adjusted life-year, but the confidence intervals are wide and cross zero, indicating some chance that the intervention could be less effective and more costly. Limitations The effectiveness trial was conducted during the COVID-19 pandemic. To reduce the risk of infection, the very brief intervention was delivered by telephone instead of face-to-face, and all study measurements were conducted remotely. This may have led to lower response rates and data quality and lower effectiveness of the intervention. A significant proportion (24%) of participants did not have raised blood pressure at baseline, and self-reported medication adherence was high at baseline, which reduced the possible scope for an intervention effect. Conclusions The findings on effectiveness do not support the commissioning of the intervention in United Kingdom primary care. The cost-effectiveness findings are more equivocal, showing a high probability of being cost-effective at standard United Kingdom willingness-to-pay thresholds, but with some uncertainty. Future work Future research should address the challenge of identifying and recruiting people who are poorly adherent and have raised blood pressure and test the intervention in this group. Variants such as face-to-face delivery, adding a follow-up consultation or a purely digital version could also be investigated. Study registration This study is registered as CRD42017080150; CRD42020164049; ISRCTN12805654; ISRCTN74504989; ISRCTN82013652. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0615-20013) and is published in full in Programme Grants for Applied Research; Vol. 14, No. 18. See the NIHR Funding and Awards website for further award information. Plain language summary About 15% of people (10 million) registered with primary care practices in England and Wales are prescribed medication for hypertension (high blood pressure). However, many do not take their medication as prescribed, which may harm their health and increases health service costs. To address this problem, we need low-cost interventions that can reach all the people who need them. This research programme aimed to develop a new intervention to support people with poorly controlled blood pressure to take their hypertension medication as prescribed and to assess how well it worked and how much it cost compared with usual care only. The findings would inform a decision on whether to introduce the intervention in primary care practices in the United Kingdom. We used a range of different research methods, including literature reviews, interviews and focus groups, and randomised controlled trials. The intervention we developed has two parts: a very brief intervention delivered by a practice nurse or healthcare assistant by telephone, followed by a digital intervention (individually tailored text messages for up to 420 days or a smartphone app). In the main trial, 537 participants received either the intervention or just usual care and were followed up 12 months later. The intervention was low cost, but it was not effective: the results showed no difference in blood pressure or medication adherence between the two groups at 12 months. Not all participants had raised blood pressure at the start of the study, and many were already taking their medication as prescribed; this may explain why the intervention did not work. The findings suggest that the intervention should not be introduced in United Kingdom primary care practices before showing that it works in patients who do not take their medication as prescribed and have raised blood pressure. Scientific summary Background Hypertension is a global health challenge accounting for 8.5 million deaths worldwide despite the availability of low-cost pharmaceutical treatment. About 14.9% of people (9.9 million) registered with primary care practices in England and Wales are prescribed medication for hypertension. However, many patients with hypertension do not take their medications as prescribed – 42% in the UK according to one study. Non-adherence to antihypertensive medication is associated with increased risk of suboptimal blood pressure (BP) control, complications and all-cause mortality, and increased healthcare costs. Primary care practitioners have an important role in supporting patients to adhere to their prescribed medication. However, they lack time to provide ongoing support for adherence, and their time is expensive. A potential solution is for a practitioner such as a practice nurse to deliver a very brief intervention (VBI) during a consultation and to use a digital intervention such as text messaging or a smartphone app to support subsequent adherence. About 96% of UK adults use a mobile phone, and in 93% of cases, this is a smartphone; the corresponding figures for those aged 65 and above are 88% and 77%. This suggests that digital interventions have the potential to reach the majority of this population. Digital interventions have several other advantages over traditional interventions: they can be fully automated; provide information that is highly tailored to the individual; be interactive; be available at any time; deliver support in real time; deliver support with high fidelity; and be easily updated. Recent meta-analyses have reported promising findings for the effectiveness of nurse-led and digital interventions to improve medication adherence and reduce BP in people with hypertension. The interventions examined in these reviews varied widely in content and delivery, and the digital interventions that have been evaluated to date have not made full use of individual tailoring, interactivity and other features that may increase user engagement and potential effectiveness. Objectives The PAM programme (Programme on Adherence to Medication) aimed to develop and evaluate an intervention to support medication adherence that combines a VBI from a practice nurse or healthcare assistant with a digital intervention (text messaging programme or smartphone app). Such an intervention would be inexpensive to deliver, scalable and potentially cost-effective. The objectives were: To develop a scalable low-cost intervention to support medication adherence in people prescribed treatment for hypertension in primary care. To evaluate the acceptability and feasibility of the intervention and the feasibility of conducting a (cost-)effectiveness trial. To provide precise and robust estimates of the effectiveness and cost-effectiveness of the intervention compared with usual care (UC). To develop an economic model of the cost-effectiveness of medication adherence interventions. To inform a decision on whether to implement the intervention in primary care. Methods The target group is patients in primary care practices in England and Wales who do not take their antihypertensive medication as prescribed and have raised BP. Methods used were: Systematic reviews of randomised controlled trials of app-based (9 trials) and face-to-face interventions (20 trials) to support medication adherence, with random-effects meta-analyses. A meta-synthesis of 30 published qualitative studies of adults taking medication for cardiovascular-related long-term health conditions (e.g. type 2 diabetes, hypertension) and/or healthcare practitioners who treat patients with cardiovascular conditions who were asked about their views and experiences of digital interventions to support medication adherence. Interviews with 11 healthcare practitioners [6 practice nurses, 2 healthcare assistants, 2 practice pharmacists, 1 general practitioner (GP)] and 6 patients, and 4 focus groups, with a total of 14 patients, to gather views on the acceptability and content of digital interventions for medication adherence. Expert consultations with 2 commissioners, 2 academics, 2 nurses, 2 patients and 10 GPs. Participants were e-mailed a description of the proposed intervention, a description of the proposed design of the randomised feasibility study and a link to an online questionnaire that asked their views on the delivery mode and content of the intervention and on the proposed feasibility study. Commissioners were asked about the evidence needed to inform a decision whether to commission the intervention. Pre-testing study of early versions of the digital interventions to assess acceptability. The text messaging intervention was used by 22 patients with hypertension for 28 days, and four of them also used the smartphone app for an additional 28 days. Data were collected by weekly telephone interviews, questionnaires and log files showing how they had used the interventions. Randomised feasibility trial to assess the feasibility and acceptability of the PAM intervention and the feasibility of conducting a large cost-effectiveness trial. Patients with hypertension who had raised BP and were non-adherent to their prescribed medication as indicated by their practice records and practice GP assessment were eligible for the study. One hundred and one eligible patients from nine general practices in the East of England and London were randomised to receiving the PAM intervention (N = 61) or UC only (N = 40). Randomised controlled trial to estimate the effectiveness and cost-effectiveness of the PAM intervention to improve medication adherence and reduce BP compared with UC only, to inform a decision on whether to implement the intervention in primary care (‘main trial’). A total of 573 eligible patients from 57 practices in England and Wales were individually randomised, stratified by practitioner, to the PAM intervention or control (UC only) and followed up at 12 months. The primary outcome was systolic blood pressure (SBP). The analysis was based on 537 participants. Within-trial economic analysis of the cost-effectiveness of the PAM intervention compared with UC alone. The main cost-effectiveness measure was the incremental cost per quality-adjusted life-year (QALY) gained, and the analysis included extensive deterministic and probabilistic sensitivity analyses. Results Systematic reviews The findings from the meta-analysis of app-based interventions showed that, at follow-up, patients in the intervention groups were more likely to self-report adherence to medication than those in the comparator groups [odds ratio 2.12, 95% confidence interval (CI) 1.64 to 2.75, n = 988, p < 0.0005]. None of the behaviour change techniques (BCTs) used in the interventions was significantly associated with intervention effect size. In the meta-analysis of face-to-face interventions, statistically significant pooled effects were found favouring the intervention arm over the control arm for several Medication Event Monitoring System measures of adherence, for example, percentage of prescribed doses taken on time over a period of 3 weeks to 2 months [mean difference (MD) 9.34, 95% CI 4.36 to 14.33, n = 3,667, p = 0.0002]. We also found significant between-arm effects for a self-report measure of adherence (Morisky scale). The impact of BCTs on intervention effectiveness could not be estimated as the analyses were underpowered. Taken together, these reviews supported our proposal to use face-to-face and digital components in the PAM intervention. However, we were unable to identify promising BCTs for potential inclusion in the proposed intervention. Meta-synthesis of previous qualitative studies The main findings from the meta-synthesis of published qualitative studies were: digital interventions to support medication use were perceived as acceptable and useful; a digital intervention would be more effective if it was personalised and tailored; barriers to using digital interventions included lack of interest, lack of confidence and lack of proficiency and experience in using the technology; digital interventions should be simple, easy to navigate and age-appropriate; patients wanted accurate information on their health condition, potential side effects of medication and health consequences of non-adherence; reminder notifications and a self-monitoring feature were perceived as helpful by some patients but unnecessary by others; some patients suggested that a digital intervention should enable them to communicate with pharmacies, but practitioners were concerned that this would increase their workload. Interviews and focus groups with practitioners and patients This study identified several barriers to adherence, including forgetting, unpleasant side effects and reluctance to medicate. A digital intervention to support medication adherence, either via text messages or smartphone app, was acceptable to patients, provided that it was user-friendly, the content was tailored to the user and the privacy of user data was protected. Simple reminder messages for taking medication and reordering prescriptions were considered more useful by patients than those providing information on the benefits of medication or the consequences of non-adherence, which were favoured by practitioners. Rather than messages of encouragement, patients preferred to receive feedback on their adherence levels in the form of a simple graph, percentage score or statistic. All the practitioners thought that it would be feasible to introduce a digital intervention to patients in a very brief face-to-face discussion during a primary care consultation. Expert consultations There was substantial similarity of views between the different stakeholders. They found the concept of a VBI delivered face-to-face by a healthcare practitioner acceptable. However, they felt that it was not feasible to address possible reasons for medication non-adherence in a VBI, and that the intervention should be limited to emphasising the importance of taking medication as prescribed and signposting the patient to a digital intervention. Pre-testing study Participants reported that the interventions were easy to use and that they would recommend them to other people. They were satisfied with the frequency of the messages and the content of the daily reminder and weekly query messages, but they were somewhat less satisfied with the content of the daily non-reminder (advice) messages. The response rate to the query messages was 100%, indicating a high degree of engagement. Randomised feasibility trial All 101 participants had their BP measured at baseline, and the vast majority provided a urine sample for chemical adherence testing. Participants were on average 65.8 years of age, 54% male, with a substantial minority (35%) from the most deprived areas, based on practice postcode. Baseline characteristics were similar in the two arms. At 3-month follow-up, 83% of participants had their BP measured and provided a urine sample, and the percentage was similar in the two arms. Ninety-two per cent of participants randomised to the intervention arm opted to receive text messages, and 8% opted to use the app. Ninety per cent responded to the tailoring questions which were administered digitally. Four intervention participants actively disengaged from the digital intervention by sending a STOP message. Seventy-two per cent continued to use the digital intervention for at least 1 month. The post-trial interviews showed that intervention participants found the intervention to be acceptable. Participants were satisfied with the baseline and follow-up consultations and the study procedures, and there were no concerns among control participants about being randomised to this arm. Practitioners also confirmed that the study procedures and intervention were acceptable. From baseline to follow-up, mean SBP reduced from 146.9 mmHg to 136.9 mmHg in the intervention arm compared with no change in the control arm (adjusted MD 9.2 mmHg, 95% CI 5.7 to 12.6), and biochemically measured adherence increased to a greater extent in the intervention arm than in the control arm, suggesting that the intervention was potentially effective. The findings from this trial showed that the intervention was acceptable to participants and that most offered the digital intervention used it, at least in the short term. The trial procedures were demonstrated to be practicable. Together with the findings on trial uptake and retention rates, this suggested that a large cost-effectiveness trial was feasible. Main trial Baseline characteristics were similar in the two arms. The majority of participants were recruited from practices in the East of England. Similar to the feasibility trial, 56% were male and mean age was 66.5 years. The vast majority categorised themselves as being of White ethnicity, but there was a range of deprivation levels, based on participant home postcode. Mean BP, obtained from practice records before randomisation, was 145/82 mmHg, again similar to the sample in the feasibility trial. Of participants, 75.8% had a BP reading above the accepted cut-off of 140/90 mmHg and 71.7% had a SBP reading above 140. We were, therefore, partially successful in recruiting a sample of participants who had a raised BP even though they were prescribed antihypertensive medication. The estimate (95% CI) for the difference in means between arms in the primary outcome of self-measured SBP at 12 months was −0.61 mmHg (−3.05 to 1.82), p = 0.62 [for intervention vs. control (reference group)]. Thus, the estimated effect was very small, and the detectable effect size of 5 mmHg did not fall within the CI. The estimate for the difference in means between arms for SBP obtained from practice records was 1.04 mmHg (−1.56 to 3.65), p = 0.43. Thus, the intervention appeared to have no effect on SBP. There was also no effect of the intervention on biochemically measured adherence. Of the 392 participants who provided a urine sample at follow-up, 388 (99.0%) were found to have at least one antihypertensive medication (or metabolite) in their urine. Based on the urinalysis, 94.3% of participants were categorised as ‘fully adherent’, 4.8% as ‘partially adherent’ and only 0.9% as ‘non-adherent’. There was no difference in these percentages between trial arms. Self-reported adherence at 12 months was also high, with no difference between trial arms. The mean score on the five-item Medication Adherence Report Scale questionnaire was 23.8 [standard deviation 1.7] out of a maximum score of 25 (based on 387 participants who provided 12-month data on this scale). Of the intervention participants, 212 (77.9%) opted to receive text messages; 60 (22.1%) opted to use the app, and 39 of these became active users. On average, participants were satisfied with the combined intervention (VBI plus digital intervention) and thought that it was acceptable and effective. However, 61.0% used the digital intervention for less than 3 months, with the main reasons being not needing any further support and finding the messages annoying. Economic analysis The total mean intervention cost per patient was £30. In the base case analysis, the intervention was found to be cost-effective compared with UC, with a mean estimated incremental cost-effectiveness ratio (ICER) of £1231 per QALY gained (95% CI −£13,156 to £19,535) and mean incremental net monetary benefit (INMB) of £289 (95% CI −£498 to £1026) at a willingness-to-pay (WTP) threshold of £15,000/QALY. The INMB rose to £400 (95% CI −£643 to £1383) and £621 (95% CI −£933 to £2104) for £20,000/QALY and £30,000/QALY, respectively. The probability that the intervention is cost-effective was between 77% and 80% for these WTP thresholds. Limitations The effectiveness trial was conducted during the COVID-19 pandemic. To reduce the risk of infection, the VBI was delivered by telephone instead of face-to-face, and all study measurements were conducted remotely. This may have led to lower response rates and data quality and lower effectiveness of the intervention. A significant proportion (24%) of participants did not have raised BP at baseline, and self-reported medication adherence was high at baseline, which reduced the possible scope for an intervention effect. Conclusions The combination of a VBI delivered by a practice nurse or healthcare assistant and a digital intervention was acceptable to both patients and practitioners. However, although the feasibility trial showed promising results, the main trial showed no effect of the intervention on medication adherence or SBP at 12 months. The cost-effectiveness findings showed a mean ICER below the usual WTP thresholds, but the CIs are wide and cross zero, indicating some chance that the intervention could be less effective and more costly compared with UC only. The effectiveness findings do not support the commissioning of the intervention in UK primary care. Future research should address the challenge of identifying and recruiting people who are poorly adherent. If it is feasible to recruit patients who are non-adherent to their prescribed antihypertensive medication and have raised BP, the intervention could be tested with the VBI delivered remotely or face-to-face. Variants such as adding a follow-up consultation or testing a purely digital version could also be investigated. The economic model developed for this programme can provide the basis for future economic evaluations of similar interventions across a range of different conditions. Study registration This study is registered as CRD42017080150; CRD42020164049; ISRCTN12805654; ISRCTN74504989; ISRCTN82013652. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0615-20013) and is published in full in Programme Grants for Applied Research; Vol. 14, No. 18. See the NIHR Funding and Awards website for further award information.

Antihypertensive treatment is effective at reducing the risk of cardiovascular disease, but is associated with adverse events, particularly in older patients with frailty. As a result, deprescribing antihypertensive medications is recommended in some clinical guidelines despite limited evidence from a few small randomised controlled trials. The aim of the OPTIMISE2 trial is to examine the safety, efficacy and cost-effectiveness of deprescribing antihypertensive treatment in older adults with controlled systolic blood pressure, who are at higher risk of adverse events. The OPTIMISE2 trial aims to enrol 3014 participants into the trial and actively follow them up for 1 year. Participants are aged 75 years and above and taking two or more blood pressure lowering drugs, with controlled blood pressure readings (systolic blood pressure < 140 mmHg if aged 75–79 years or < 150 mmHg if aged 80+ years), frail and/or at a higher risk of serious drug-related side effects of hypotension, syncope and falls. The trial randomises (1:1) participants to either step-down medication reduction (withdrawal of one antihypertensive medication at a time, at 4-week intervals with regular monitoring of blood pressure) or usual care (no medication reduction mandated). The choice of medications to withdraw is at the discretion of participating general practitioners or prescribers. The primary outcome is emergency hospitalisation or death within 1 year of randomisation. The primary objective is to determine whether antihypertensive deprescribing is non-inferior to usual care, with up to a 5

BACKGROUND:For many women who experience hypertension in pregnancy, raised blood pressure continues into the postpartum period, usually settling over the first 6-12 weeks. Blood pressure control during this time appears to be important for long-term cardiovascular health but care appears to be haphazard. This study aimed to understand UK National Health Service usual postpartum care for such women. METHODS:A cross-sectional online survey was designed and piloted by a multidisciplinary team of midwives, obstetricians, primary care researchers, patient representatives, and a general practitioner, to capture current practice including blood pressure monitoring, antihypertensive prescribing, and use of self-monitoring; there were 38 questions. The survey was delivered via the Doctors.net (for obstetricians and general practitioners) and Joint Information Systems Committee (JISC) online platforms (for Midwives) from May to November 2023. RESULTS:A total of 253 clinicians responded to the survey, including 101 General Practitioners, 100 doctors working in maternity care, trained in obstetrics (obstetricians) or with specialist expertise in medical disorders in pregnancy (obstetric physicians), 50 midwives, and 2 maternity support workers. Women's care generally transferred from secondary to primary care at around two weeks postpartum, although this was not consistent, and there were differences in practice, awareness, and expectations between professions around the management of hypertension and responsibility. Communication barriers between professional groups and a need for better guidance and co-ordination were highlighted, and most professionals agreed that self-measured blood pressure readings could support postpartum care for those with hypertension. CONCLUSIONS:The survey highlighted variations in the practice and expectations of different healthcare professionals involved in postpartum care. The time when care was transferred from hospital to primary care was not consistent, with potential for women's care to fall through gaps. The transfer of information and women's ability to access care at this time were highlighted as problematic.

OBJECTIVES:Hypertensive disorders of pregnancy (HDP), including preeclampsia, pose lifelong health risks for women and infants. Although HDP interventions are increasingly evaluated for cost-effectiveness, methodological challenges and heterogeneity between studies exist. This systematic review examines how economic evaluations have been conducted, focusing on methodology, outcome measurement, perspectives, time horizons, and cost-effectiveness conclusions. METHODS:Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, we searched MEDLINE, Embase, EconLit, and Web of Science from inception to December 31, 2024 for cost-effectiveness, cost-utility, cost-benefit, cost-consequence, and cost-minimization analyses of HDP interventions. Searching was updated on November 4, 2025. Data on costs, outcomes, and methodology were extracted. Reporting quality was evaluated using Consolidated Health Economic Evaluation Reporting Standards 2022. RESULTS:Thirty-five included studies covered interventions from prevention to management. One-third of cost-effectiveness and cost-utility studies reported only women's outcomes. Among those capturing maternal and infant outcomes, more than half estimated cost-effectiveness using outcomes for only 1 party. The remainder generated results for mothers and infants but using different approaches. Long-term maternal cardiovascular risks and infant outcomes were rarely extrapolated. Most studies adopted healthcare perspectives. Screening, prevention, and diagnostic interventions were frequently cost-effective, whereas evidence for treatment and management strategies was mixed. Most studies reported cost per preeclampsia case averted; fewer applied generic measures, limiting comparability. CONCLUSIONS:Economic evaluations of HDP interventions face methodological challenges, particularly in capturing joint maternal and infant impacts. Furthermore, future studies should use adequate time horizons, wider perspectives, and generic health outcomes to ensure that cost-effectiveness evidence captures the full value of HDP interventions and informs policies optimizing maternal and neonatal health.

Background Structured medication reviews (SMRs) were introduced in 2020 to address polypharmacy in patients most at risk of medicines-related harm. Aim To evaluate the impact of SMRs on prescribing in primary care. Design and setting Retrospective observational cohort study of electronic health records from patients aged ≥65 years, prescribed ≥1 medications, and fulfilling the specific eligibility criteria for an SMR, registered at practices contributing data to the Oxford Clinical Informatics Digital Hub, between 1 April 2020 and 30 September 2022. Method The association between SMRs and prescription changes was examined by matching individuals who received an SMR to individuals who did not receive an SMR, according to age, sex, and primary care practice, using cumulative density sampling. Analyses were undertaken using adjusted logistic regression. Results Of 635 698 eligible patients, 82 285 (12.9%, 95% confidence interval [CI] = 12.9 to 13.0) received ≥1 SMR during the study observation period. In those prescribed potentially inappropriate drug combinations prior to an SMR, between 12.5% and 40.0% were corrected up to 3 months later. In matched analyses, SMRs were most strongly associated with an increase in new prescriptions of angiotensin-converting enzyme inhibitors (adjusted odds ratio [aOR] 1.56, 95% CI = 1.35 to 1.81), statins (aOR 1.78, 95% CI = 1.57 to 2.02), and antidepressants (aOR 1.45, 95% CI = 1.28 to 1.63). SMRs were also most strongly associated with stopping these drug classes in those previously prescribed treatment. Conclusion SMRs were associated with starting new medications and stopping existing prescriptions compared with usual care. Further work is needed to understand if these changes improved patient outcomes.

Hypertensive disorders of pregnancy, experienced by around 10% of women, are among the most severe health problems affecting people during and following pregnancy. Symptoms can persist in the weeks and months following birth, with potential to impact longer-term health. Postnatal care has long been recognised as a critical period for mother and baby, and emerging evidence suggests it is a window of opportunity for cardiac remodelling after a hypertensive pregnancy. But provision is often not fit for purpose and haphazard. To understand what care women receive, how it gets done, and additional barriers for minority or socially deprived groups, we undertook interviews and focus groups with 44 women with a recent hypertensive pregnancy and interviews with 36 health professionals providing postnatal care in National Health Service (NHS) maternity care, primary care and community services in England. Analysis revealed that, despite the first six weeks being an important period for managing blood pressure, women often fall through the cracks between secondary and primary care. Invisible to these siloed clinical specialities, women are faced with new self-management and surveillance responsibilities alongside the work of new motherhood. Analysis, informed by Meleis’s transitions theory and Gidden’s concept of ‘distanciation’, develops Scott’s ‘sociology of nothing’ to explore responsibilities and consequences of being ‘unseen’ between services.

Introduction Hypertension is a global health challenge accounting for 8.5 million deaths worldwide despite the availability of low-cost pharmaceutical treatment. About 14.9% of people (9.9 million) registered with primary care practices in England and Wales are prescribed medication for hypertension. However, many patients with hypertension and associated conditions do not take their medications as prescribed. Non-adherence to antihypertensive medication is associated with increased risk of suboptimal blood pressure (BP) control, complications and all-cause mortality, and increased healthcare costs. The Programme on Adherence to Medication (PAM) trial will estimate the effectiveness and cost-effectiveness of a medication adherence intervention in patients prescribed medication for hypertension with poorly controlled blood pressure in primary care. Methods A two-arm multicentre individually randomised controlled parallel group superiority trial recruiting patients prescribed medication for hypertension with poorly controlled BP in primary care practices in England and Wales. The target sample size is 542. Participants in the Intervention group will receive a very brief intervention delivered remotely (by telephone or video call) by a practice nurse or healthcare assistant followed by a digital intervention (text messaging or smartphone app) in addition to usual care; control group participants will receive usual care alone. The primary outcome is systolic BP measured at 12 months. Medication adherence will be measured by chemical adherence testing of urine samples and self-report. An economic evaluation and a process evaluation will be undertaken. Ethics and dissemination The Cambridge East Independent Research Ethics Committee (REC reference 19/EE/0354), the Health Research Authority (HRA) and Health and Care Research Wales (HCRW) approved the trial. The findings will be disseminated to the scientific community, participating practitioners and patients, relevant patient groups and the public using a range of methods, including journal articles, conference presentations, newsletters and the Programme website. Trial registration number The UK’s Clinical Trial Registry ISRCTN82013652

Background Postural hypotension is associated with excess mortality, falls, and cognitive decline. Postural hypotension is poorly recorded in routine general practice records. Few studies have explored measurement and diagnosis of postural hypotension in general practice. Aim To understand how postural hypotension is measured, diagnosed, and managed in general practice. Design and setting This was an online survey of general practice staff in England. Method Clinical research networks distributed the survey to practices, seeking individual responses from any clinical staff involved in routine blood pressure (BP) measurement.Responses were analysed according to role and demographic data using descriptive statistics. Multivariable modelling of checking for postural BP measurements was performed. Results There were 703 responses from 243 general practices (mean practice-level response rate 17%). Half (362; 51%) of responders were doctors, 196 (28%) nurses, and 77 (11%) healthcare assistants (HCAs). In total, 8% (58/703) did not routinely check for postural hypotension, usually citing time constraints. For the remaining 92%, postural symptoms were the predominant reason for checking (97% responders, 627/645); only 24% cited any other guideline indication for postural hypotension testing. The study found that 77% used sit-to-stand BP measurements; approximately one-quarter measured standing BP for >1 min. On regression modelling, other professionals tested less for postural hypotension than doctors (odds ratios: nurses 0.323, 95% confidence interval [CI] = 0.117 to 0.894, HCAs 0.102, 95% CI = 0.032 to 0.325, and pharmacists 0.099, 95% CI = 0.023 to 0.411). Conclusion Awareness of reasons, besides symptoms, and adherence to guidelines for postural hypotension testing, are low. Time is the key barrier to improved testing for postural hypotension. Clarity on pragmatic methods of measuring postural hypotension in general practice would also facilitate measurement uptake.

Introduction: Stroke is often followed by vascular cognitive impairment and vascular dementia, the most feared complications of stroke. However, understanding of post-stroke cognitive impairment remains limited. Methods: Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD) is an observational cohort study of post-stroke cognition. Patients with haemorrhagic or ischaemic stroke, or transient ischaemic attack, were recruited within six weeks of stroke from hospitals across the UK. Consent was obtained from patients with capacity or from relatives/friends in those without capacity. The primary outcome is dementia rate and its severity at two years assessed using a 7-level ordinal cognition outcome. Final dementia rate will be compared in those with mild stroke/TIA (worst NIHSS <=7) versus severe stroke (NIHSS >7). Secondary outcomes will include cognitive impairment, function, mood and quality of life, and predictors of cognitive impairment at one and two years. Data are shown as number (%), median [interquartile range, IQR] or mean (standard deviation, SD). Results: We recruited 2441 patients from 50 hospitals. Of these, 2432 (99.6%) had a qualifying event of stroke or TIA. The mean age was 68.2 years (SD 13.5), females 979 (40.3%), ethnic minority 170 (7.0%), NIHSS <=7 1962 (80.7%), onset to recruitment 5 days [IQR 3-13] and diagnosis ICH 192 (7.9%), ischaemic stroke 2097 (86.2%), TIA 143 (5.9%). The distribution of cognition at baseline (within 6 weeks of onset) was: normal 1300 (53.5%), minor neurocognitive disorder-single domain 351 (14.4%), minor neurocognitive disorder-multi domain 263 (10.8%), major neurocognitive disorder-mild 387 (15.9%), major neurocognitive disorder-moderate 108 (4.4%) and major neurocognitive disorder-severe 23 (0.1%). Participants with more severe stroke were recruited later (8 [IQR 3-17] vs 5 [2-11] days, p<0.001), less likely to have capacity (86.3% vs 96.8%, p<0.001) and more likely to have had an intracerebral haemorrhage (12.0% vs 6.8%, p<0.001). Conclusion: We provide baseline data with the statistical analysis plan in the appendix. The data highlight the substantial under-appreciated cognitive burden of stroke, even in the first few days and weeks after onset.

BACKGROUND:Good hypertension care requires accurate blood pressure (BP) measurement with BP monitors validated as accurate. The British and Irish Hypertension Society maintains a peer-reviewed list of validated monitors, independent of commercial interests. The list informs National Institute for Health and Care Excellence hypertension guidance and NHS monitor procurement. An updated universal standard protocol for BP device validation was introduced in 2018. AIM:Review the literature to establish which validation protocols are now being used; has this changed since publication of the universal protocol, and what proportion of recently published BP monitor validations fully meet protocol validation criteria? METHOD:Systematic review searches of Medline and Embase from 2018 to September 2025 identified BP monitor validation studies. Citations and full texts were screened independently by two authors. Included studies were reviewed independently by two authors against checklists of protocol criteria. Disagreements were resolved through discussion and/or arbitration by lead authors. RESULTS:Seven reviewers screened 1780 unique citations, reviewing 216 full texts to date. Nine reviewers have double-extracted data from 157 publications reporting 197 device validation studies. Overall, 104 (63%) used universal protocols. While 184 (93%) validations were reported as successful by authors, only 146 (74%) fulfilled all protocol criteria on review. Thus, we considered 51 (26%) published successful validations inadequate, due to non-fulfilment of key validation criteria and/or violations of BP measurement protocols such as incomplete BP range coverage. CONCLUSION:This review highlights inadequacies in current journal peer-review processes, justifying our approach to provide impartial guidance for health professionals, purchasers, and the public.

BACKGROUND:Structured medication reviews (SMRs) were introduced into primary care in England in 2020 for patients living with multiple long-term conditions (MLTC), polypharmacy, increased frailty, in care homes, or at risk of medicines-related harm. SMRs aim to optimise the therapeutic potential of medication and reduce medicine-related harms through holistic reviews. AIM:To explore the day-to-day work being undertaken with, and by, clinical pharmacists to implement, embed, and integrate SMRs into practice, and consider how to optimise SMRs. DESIGN AND SETTING:Qualitative one-to-one interviews with clinical pharmacists undertaking SMRs and SMR service leaders/managers (SMR leads) in England between February 2023 and November 2024. METHOD:Participants were recruited as part of a wider evaluation of the roll-out of SMRs in England. Interview topic guides and qualitative data analysis were informed by normalisation process theory. RESULTS:Eighteen clinical pharmacists and five SMR leads participated. Participants reported often having to explain the purpose of SMRs and clinical pharmacists' roles to patients, partly owing to patients not being informed about SMRs. Participants valued SMRs and expressed that trust-building and tailored consultations were important for optimising medications. Integration of SMRs into routine practice varied because of high workload, inconsistent leadership support, inadequate administrative/pharmacist technician resource, and lack of training. However, participants described SMRs as valuable for identifying and addressing unmet needs and supporting holistic, person-centred care across MLTC pathways. CONCLUSION:The findings demonstrate the need for improved information on SMRs for patients and primary care teams, adequate and appropriate resource allocation, and enhanced support for consultation skills training to optimise medicines use.

BACKGROUND:While antihypertensive treatment prevents cardiovascular events, it may also increase risks such as falls in patients with frailty. The Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTiMISE) trial found that deprescribing one antihypertensive drug did not result in worse short-term blood pressure control and long-term follow-up showed no observed harm, but its generalisability to routine clinical practice remains uncertain. OBJECTIVE:This study aimed to calibrate the OPTiMISE effect to a representative primary care population in England. METHODS:We calibrated the OPTiMISE treatment effect using inverse probability weighting (IPW) based on trial inclusion likelihood. The trial enrolled 569 adults aged ≥80 years with controlled blood pressure on ≥2 antihypertensive drugs. A target population was reconstructed from electronic health records of 24 participating practices and extrapolated to all English adults aged ≥80 years, prescribed ≥2 antihypertensive drugs, using NHS Digital data. The primary outcome was all-cause hospitalisation or death. Weighted Cox models estimated calibrated hazard ratios (HRs). RESULTS:The target population included 798 179 individuals (median age 84 years [81-87], 48% female). Compared with OPTiMISE participants, a higher proportion of individuals in target population were overtly frail (25% vs. 11%). After calibration using IPW, deprescribing was not associated with higher risk of hospitalisation or death [calibrated HR 0.94 (95% CI: 0.73-1.22)], similar to the long-term follow-up of OPTiMISE [HR 0.93 (95% CI: 0.76-1.12)], although with a slightly wider confidence interval. CONCLUSIONS:Calibrating OPTiMISE findings to a representative primary care population frailer than the original participants suggests that the original trial findings could be translated into a real-world population.

Hypertensive pregnancy increases risk of cognitive decline, stroke, and dementia, especially after preeclampsia. Women with prior hypertensive pregnancy show lower brain volumes, but it was unknown whether early postpartum blood pressure optimization could alter these outcomes. To evaluate whether an intervention designed to achieve better postpartum blood pressure control after a hypertensive pregnancy is associated with differences in brain volumes around 9 months post partum compared with usual care. This randomized clinical trial, the Physician Optimized Postpartum blood pressure self-management trial (POP-HT), was a prospective, open-label, blinded end-point study conducted at a single tertiary center in the UK. Participants were older than 18 years and had preeclampsia or gestational hypertension requiring antihypertensive treatment at hospital discharge. Enrollment began February 21, 2020; the last follow-up was on November 2, 2021; and the mean follow-up time was approximately 9 months. Secondary outcome analyses (primary results published 2022) were conducted May 2025. Telemonitored self-management with research physician-guided titration or usual postnatal care. This substudy analyzed the secondary outcomes T1-weighted magnetic resonance imaging (MRI) brain volumes (gray matter, white matter, cerebrospinal fluid, subcortical structures) acquired approximately 9 months post partum. Analyses used linear regression models adjusted for total intracranial volume. Of 252 eligible participants, 32 declined, and 220 were randomized (mean [SD] age, 33.4 [5.1] years). The T1 brain MRI of 157 participants was available for analysis; 96 participants (63%) had preeclampsia, and 56 (37%) had gestational hypertension. The intervention group (n = 81) had larger total white matter volumes (adjusted mean difference, 11.50 cm 3 ; 95% CI, 2.04 to 20.96; P = .02) compared with the usual care group (n = 71). In usual care, participants with preeclampsia had smaller putamen (adjusted mean difference, −0.83 cm 3 ; 95% CI, −1.20 to −0.46; P < .001), accumbens (adjusted mean difference, −0.15 cm 3 ; 95% CI, −0.24 to −0.05; P = .003), and pallidum (adjusted mean difference, −0.13 cm 3 ; 95% CI, −0.26 to −0.01; P = .04) volumes compared with those with gestational hypertension. These differences were not observed in the intervention group. This study found that short-term postpartum optimization of blood pressure control after hypertensive pregnancy was associated with larger brain volumes during the first year post partum. Because brain volume is a surrogate of brain health linked to tissue preservation and cognitive outcomes, these findings suggest potential neurovascular benefits that were most pronounced among women with preeclampsia. ClinicalTrials.gov Identifier: NCT04273854

Hypertensive disorders of pregnancy affect around 10

Background Raised blood pressure affects 10% of pregnancies worldwide, of which around half develop pre-eclampsia including proteinuria, causing maternal and perinatal morbidity and mortality. Objectives To develop and test interventions for self-monitoring of blood pressure designed to improve the detection and management of hypertension in pregnancy. Additionally, to test the accuracy of self-testing of urine for protein, a key marker of pre-eclampsia. Design and methods Development phase, a pilot trial, two large randomised controlled trials of self-monitoring of blood pressure interventions with integrated economic evaluations, linked qualitative work, a large survey and a diagnostic accuracy study of self-testing for proteinuria, and finally economic modelling. Setting and participants Antenatal clinics in 16 English hospitals. Participants were pregnant women and antenatal healthcare professionals. Patient and public involvement Comprehensive involvement from initial development through to dissemination, with collaboration from both individuals and relevant charities and organisations. Interventions Self-monitoring of blood pressure supported by app to improve the detection (BUMP1) and management (BUMP2) of raised blood pressure in pregnancy (WS3.2.1 and 2). Proteinuria self-testing by pregnant hypertensive women (UDIP, WS4). Main outcome measures Qualitative data informed the development of the BUMP App and trial (WS1). Feasibility of self-monitoring of blood pressure in hypertensive pregnancy (recruitment, retention, adherence and intervention persistence) (WS2). Prevalence of self-monitoring of blood pressure during pregnancy (WS3.1). Time to diagnosis of hypertension defined in routinely recorded clinical data (BUMP1, WS3.2.1) and difference in mean systolic blood pressure recorded by healthcare professionals between randomisation and birth (BUMP2, WS3.2.2). WS3.3 and 4.2 evaluated experiences with the trial and UDIP respectively using inductive and deductive thematic analysis. Within-trial cost–consequence analysis and long-term cost-effectiveness modelling (WS3.4 and WS5). Proteinuria testing accuracy (WS4.1). Results WS1: Areas important to staff included providing clear patient information and supporting them in decision-making in the context of discrepant readings. The intervention was optimised iteratively with pregnant women. WS2: A feasibility trial showed that the self-monitoring of blood pressure intervention was feasible and acceptable. WS3.1: Data from a survey of 5181 women showed that 19% of pregnant women were currently self-monitoring blood pressure but only 482/983 (49%) shared this information with healthcare professionals. WS3.2.1: Self-monitoring of blood pressure in addition to usual care did not lead to an earlier diagnosis of clinic hypertension in routinely recorded clinical data with no evidence of differences in maternal or perinatal outcomes or serious adverse events (BUMP1). WS3.2.2: Self-monitoring of blood pressure in pregnancy hypertension did not improve clinic blood pressure control, with no difference in maternal or perinatal outcomes or serious adverse events (BUMP2). WS3.3: Self-monitoring was generally accepted by women and professionals with differences in views of which blood pressure data to give precedence. Women found self-monitoring empowering, provided health professionals considered home readings in their management. On occasion self-monitoring proved unsettling due to uncertainty. WS3.4: Within trial economic analyses revealed no significant difference in overall total costs between trial arms in either BUMP1 or BUMP2. Women’s health-related quality of life (EQ-5D-5L) was similar between groups in both trials. WS4: Self-testing for proteinuria had a sensitivity of 0.71 (95% confidence interval 0.62 to 0.79) and a specificity of 0.89 (95% confidence interval 0.84 to 0.92) compared to laboratory protein–creatinine ratio testing and this was not clinically or statistically different when compared to healthcare professionals or a colorimetric monitor (UDIP, WS4.1). Self-testing was generally acceptable (WS4.2). WS5: Model frameworks capable of facilitating exploration of the long-term cost-effectiveness of combining self-monitoring of blood pressure with blood pressure treatment and management policies were developed for use in future research projects in the area. Implementation: Self-monitoring was rapidly and widely implemented during the pandemic but has yet to become fully embedded in clinical pathways. Limitations Self-monitoring of blood pressure by women in the control groups; difficulties in testing self-monitoring of blood pressure in clinical pathways in the absence of evidence or accepted treatment thresholds; process evaluation suggested women and professionals privileged different information. Conclusions Self-monitoring of blood pressure during higher risk or hypertensive pregnancy was feasible, acceptable, safe, and no more expensive, but did not improve the detection of hypertension or blood pressure control in those with hypertension when used alongside usual care. During the programme, self-monitoring of blood pressure entered common practice in pregnancy, a process accelerated by the pandemic. Pregnant women can read a dipstick for urinary protein with similar accuracy to healthcare professionals or colorimetric testing, and find this acceptable, suggesting that self-testing could be included in clinical pathways. Future work Future trials of interventions including self-monitoring of blood pressure should test strategies in the context of novel clinical pathways. Study registration This study is registered as Current Controlled Trials ISRCTN16018898. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme (NIHR award ref.: RP-PG-0614-20005) and is published in full in Programme Grants for Applied Research; Vol. 14, No. 3. See the NIHR Funding and Awards website for further award information. Plain language summary Background and aims Home monitoring of blood pressure supports the management of raised blood pressure (hypertension) in the general population, but little was known about its use in pregnancy. Similarly, little was known regarding self-testing for protein in the urine, a marker of pre-eclampsia which is a serious condition linked to hypertension in pregnancy. The BUMP programme aimed to develop and test blood pressure home monitoring and protein self-testing to see if these could improve the detection of raised blood pressure and/or proteinuria and management of hypertension in pregnancy. Findings Focus groups and interviews with healthcare professionals and development work (designing the intervention) with pregnant women supported the development of a user-friendly app, trial design and materials. A survey identified that one in five of pregnant women currently home monitor blood pressure, increasing to half of those with hypertension, though did not share these readings with healthcare professionals. The BUMP trials recruited more than 3000 women at higher risk of pre-eclampsia, or those with raised blood pressure. Participating women were randomly allocated to either usual care or usual care plus self-monitoring of blood pressure. Home monitoring of blood pressure did not result in earlier recording of hypertension in clinic. Over half of the women diagnosed with hypertension had raised blood pressure at home. For women with high blood pressure, home monitoring did not improve blood pressure control. Home monitoring of blood pressure was safe and engagement was high, with the majority of women continuing home monitoring throughout pregnancy. No differences in costs or quality of life were found. Pregnant women self-tested for urinary protein with similar accuracy to healthcare professionals and were happy to test finding it, convenient and reassuring. Staff found home readings valuable, although some were less willing to incorporate them into antenatal care. Conclusions Home monitoring of blood pressure during higher risk or hypertensive pregnancy was acceptable, safe, and no more expensive than usual care alone but it did not improve the detection of hypertension or blood pressure control in those with hypertension when used alongside usual care. Self-testing of urine for protein could support remote care of hypertensive women. Scientific summary Background Raised blood pressure (BP) affects 10% of pregnancies worldwide, of which around half develop pre-eclampsia, a leading cause of maternal and perinatal morbidity and mortality. Early detection of raised BP and/or proteinuria and subsequent management of pregnancy hypertension is therefore important and could be improved through self-monitoring whilst empowering women and allowing reduced antenatal visits. However, little evidence was available to guide the utilisation of self-monitoring in pregnancy. Objectives The overall aim of this programme was to evaluate whether self-monitoring of BP (SMBP) could improve the detection of raised BP during pregnancy, whether it was feasible for use in the titration of antihypertensive medication in pregnancy hypertension and whether women with raised BP in pregnancy could accurately test their urine for proteinuria, a key marker for pre-eclampsia. Linked qualitative and economic components examined patient and professional experiences of self-monitoring and responses to it along with cost-effectiveness within the trial and in the longer term. Key research questions WS1: Development What are the best self-monitoring interventions to use? How can SMBP and urine best integrate into current antenatal care pathways? WS2: Blood pressure self-monitoring during pregnancy for anti-hypertensive titration Is titration of antihypertensive medication during and after pregnancy using self-monitoring feasible? What is the participant and professional experience of such monitoring and titration? WS3: Self-monitoring to improve the detection and management of raised blood pressure in pregnancy What is current practice in BP self-monitoring in pregnancy? Can BP self-monitoring improve the detection and management of hypertension during pregnancy? How is BP self-monitoring in pregnancy implemented in daily life and routine clinical practice? Is BP self-monitoring in pregnancy cost-effective? WS4: Self-monitoring of urinary protein in hypertensive pregnancy Can pregnant women with hypertension accurately self-monitor for proteinuria and could this detect pre-eclampsia earlier than usual care? Is self-monitoring of urine practical and acceptable to hypertensive pregnant women, their midwives and obstetricians? WS5: Modelling of the potential long-term costs and consequences Is SMBP and protein in hypertensive pregnancy potentially cost-effective and what are the key parameters affecting this? Methods WS1: Development Focus groups and interviews were undertaken with NHS staff (including obstetricians, community and hospital midwives). We worked iteratively with women talking through their experiences of prototypes of the self-monitoring app and trial materials (Band R, Hinton L, Tucker KL, Chappell LC, Crawford C, Franssen M, et al. Intervention planning and modification of the BUMP intervention: a digital intervention for the early detection of raised blood pressure in pregnancy. Pilot Feasibility Stud 2019;5:153. https://doi.org/10.1186/s40814-019-0537-z; Hinton L, Hodgkinson J, Tucker KL, Rozmovits L, Chappell L, Greenfield S, et al. Exploring the potential for introducing home monitoring of blood pressure during pregnancy into maternity care: current views and experiences of staff – a qualitative study. BMJ Open 2020;10:e037874. https://doi.org/10.1136/bmjopen-2020-037874). WS2: Blood pressure self-monitoring during pregnancy for antihypertensive titration The OPTIMUM feasibility trial It was an unmasked randomised controlled trial (RCT) comparing a SMBP versus usual care for the management of pregnancy hypertension. Women with chronic (CH) or gestational hypertension (GH) from four UK centres were randomised (2 : 1) intervention to control. Primary outcomes were recruitment, retention, adherence and persistence with the intervention (Pealing LM, Tucker KL, Mackillop LH, Crawford C, Wilson H, Nickless A, et al.; OPTIMUM-BP Investigators. A randomised controlled trial of blood pressure self-monitoring in the management of hypertensive pregnancy. OPTIMUM-BP: a feasibility trial. Pregnancy Hypertens 2019;18:141–9. https://doi.org/10.1016/j.preghy.2019.09.018). WS3: Self-monitoring to improve the detection and management of raised blood pressure in pregnancy 3.1 BUMP survey Pregnant women from antenatal clinics in 16 hospitals in England were invited to complete a survey about SMBP. 3.2.1 The BUMP1 trial (Dougall G, Franssen M, Tucker KL, Yu L-M, Hinton L, Rivero-Arias O, et al. Blood pressure monitoring in high-risk pregnancy to improve the detection and monitoring of hypertension (the BUMP 1 and 2 trials): protocol for two linked randomised controlled trials. BMJ Open 2020;10:e034593. https://doi.org/10.1136/bmjopen-2019-034593) It was a multicentre, RCT that recruited pregnant women at higher risk of pre-eclampsia at 20 weeks’ gestation. Women were randomised to BP self-monitoring with telemonitoring and usual care or to usual care alone. The primary outcome was time to the first recorded raised BP taken by a healthcare professional (HCP). Trial registration: NCT03334149. Recruitment 2018–9. Final follow-up April 2020. 3.2.2 The BUMP2 trial It was a multicentre, RCT that recruited women with CH and GH up to 37 weeks’ gestation. Women were randomised to BP self-monitoring with telemonitoring and usual care or to usual care alone. The primary maternal outcome was the difference in mean systolic BP recorded by HCPs between study entry and childbirth. Analyses were by intention to treat (ITT) and stratified by CH or GH. Trial registration: NCT03334149. Recruitment 2018–19. Final follow-up May 2020. 3.3 BUMP trials qualitative process evaluation In-depth interviews were carried out with 39 trial participants and 7 women who declined to take part in the trials to explore their experiences of self-monitoring BP or reasons for choosing not to. Twenty-one HCPs involved in women’s care or in the administration of the trial were interviewed. Interviews were purposively sampled from study sites. A planned ethnographic study was not feasible. Inductive and deductive thematic analysis was carried out on both qualitative data sets. Interviews were analysed using a coding frame that was developed from the research aims and incorporating additional themes that emerged from the data. 3.4 BUMP within-trial economic analyses National Health Service (NHS) perspectives were used for both within trial cost–consequences analyses. Patient-level resource use data were extracted from clinical notes and costed and women’s health-related quality of life was measured during the trials using the EuroQol EQ-5D-5L questionnaire, with responses converted to single index scores. Mean costs and EQ-5D-5L scores were computed and compared between trial arms. Within BUMP2, analyses were conducted separately for CH and GH cohorts. WS4: Self-monitoring of urinary protein in hypertensive pregnancy 4.1 The UDIP study It was a diagnostic accuracy study that recruited 345 pregnant women to self-test for urinary protein using visually read dipsticks. The primary reference test was protein–creatinine ratio (PCR) and secondary index tests included testing by antenatal HCPs and an automated colorimetric reader. Primary outcome measures were sensitivity and specificity. 4.2 UDIP qualitative study In-depth interviews were carried out with 21 pregnant hypertensive or pre-eclamptic women who took part in the UDIP study, and 18 HCPs who had experience working in antenatal care. Five focus group totalling 15 participants were conducted with HCPs. WS5: Modelling of the potential long-term costs and consequences With no cost or effect differences observed overall or across pre-specified subgroups in the BUMP1 and BUMP2 trials, the need for long-term cost-effectiveness modelling was negated. Instead, model frameworks to facilitate future exploration of the potential long-term costs and effects of combining SMBP with BP management policies for the prevention of hypertension-related complications, were developed. The models cover the pregnancy pathway and a subsequent ten-year period to capture the risks, costs, and consequences of women developing cardiovascular disease. Model parameters are entered as distributions to enable probabilistic sensitivity analysis, and the frameworks facilitate results being presented for women with differing characteristics and for different intervention effect sizes. Results WS1: Development (Band R, Hinton L, Tucker KL, Chappell LC, Crawford C, Franssen M, et al. Intervention planning and modification of the BUMP intervention: a digital intervention for the early detection of raised blood pressure in pregnancy. Pilot Feasibility Stud 2019;5:153. https://doi.org/10.1186/s40814-019-0537-z; Hinton L, Hodgkinson J, Tucker KL, Rozmovits L, Chappell L, Greenfield S, et al. Exploring the potential for introducing home monitoring of blood pressure during pregnancy into maternity care: current views and experiences of staff – a qualitative study. BMJ Open 2020;10:e037874. https://doi.org/10.1136/bmjopen-2020-037874) Focus groups and interviews were conducted with 147 NHS staff at seven different hospital sites. Areas identified as important included: providing clear patient information and supporting staff in decision-making in the context of discrepant readings. Analyses suggested that SMBP would be welcomed by HCPs, while also highlighting potential barriers. This work and iterative development with pregnant women supported the development of a pragmatic and workable trial with user-friendly materials and app. WS2: Blood pressure self-monitoring during pregnancy for antihypertensive titration (Pealing LM, Tucker KL, Mackillop LH, Crawford C, Wilson H, Nickless A, et al.; OPTIMUM-BP Investigators. A randomised controlled trial of blood pressure self-monitoring in the management of hypertensive pregnancy. OPTIMUM-BP: a feasibility trial. Pregnancy Hypertens 2019;18:141–9. https://doi.org/10.1016/j.preghy.2019.09.018; Pealing L, Tucker KL, Fletcher B, Lawley E, Chappell LC, McManus RJ, Ziebland S. Perceptions and experiences of blood pressure self-monitoring during hypertensive pregnancy: a qualitative analysis of women’s and clinicians’ experiences in the OPTIMUM-BP trial. Pregnancy Hypertens 2022;30:113–23. https://doi.org/10.1016/j.preghy.2022.09.006) Women from four UK centres were randomised: 158/222 (71%) of those approached agreed, comprising 86 women with CH (55 SMBP, 31 control) and 72 with GH (49 SMBP, 23 control). Outcome data were available from 154 (97%). The median number of days with home BP readings per week was 5.5 [interquartile range (IQR) 3.1–6.5] for those with CH and 6.1 (4.5–6.7) with GH. Participating women persisted with the intervention for 80% time from enrolment until delivery. Recorded clinic and study BPs were similar for both groups. Interviews showed that the women found SMBP feasible and acceptable and were highly motivated and proactive in their monitoring. They reported greater control and knowledge, which provided reassurance. Most women reported that they responded appropriately for out-of-range readings or symptoms. WS3: Self-monitoring to improve the detection and management of raised blood pressure in pregnancy 3.1 The BUMP survey (Tucker KL, Hodgkinson J, Wilson HM, Crawford C, Stevens R, Lay-Flurrie S, et al. Current prevalence of self-monitoring of blood pressure during pregnancy: the BUMP survey. J Hypertens 2021;39:994–1001. https://doi.org/10.1097/HJH.0000000000002734) Completed surveys were received from 5181/5555 pregnant women (93%). The analysis showed that 983/5181 (19%) were currently SMBP. Around half of those were hypertensive 189/389 (49%) and 794/4792 (17%) were normotensive. However, only 482/983 (49%) of those that monitored their BP reported sharing this information with their obstetric and midwifery team. Comparison to hospital demographic data suggested that respondents were broadly representative.1 3.2.1 The BUMP1 trial (Tucker KL, Mort S, Yu LM, Campbell H, Rivero-Arias O, Wilson HM, et al.; BUMP Investigators. Effect of self-monitoring of blood pressure on diagnosis of hypertension during higher-risk pregnancy: the BUMP 1 randomized clinical trial. JAMA 2022;327:1656–65. https://doi.org/10.1001/jama.2022.4712) A total of 2441 women were randomised to BP self-monitoring plus usual care or usual care alone (n = 1218). Primary outcome data were available from 2346 (96%) women. Baseline characteristics were similar and 15.5% developed hypertension. Time to detection of clinic hypertension was not significantly different between groups: –1.6 days [95% confidence interval (CI) –8.1 to 4.9, p = 0.6]. There was no significant difference in the incidence of severe clinic hypertension [adjusted relative risk 1.2 (0.9 to 1.7), p = 0.3], in maternal and fetal outcomes, or serious adverse events. Most women who developed high BP had self-monitored their BP within a week of diagnosis (73%), and half had raised home BP readings prior to a clinic diagnosis. 3.2.2 The BUMP2 trial (Chappell LC, Tucker KL, Galal U, Yu L-M, Campbell H, Rivero-Arias O, et al.; BUMP 2 investigators. Effect of self-monitoring of blood pressure on blood pressure control in pregnant individuals with chronic or gestational hypertension: the BUMP 2 randomized clinical trial. JAMA 2022;327:1666–78. https://doi.org/10.1001/jama.2022.4726) Eight hundred and fifty pregnant women (454 with CH, 396 with GH) were enrolled into the BUMP2 trial: 430 were randomly allocated to BP self-monitoring (primary outcome available on 416 (96.7%) women) and 420 women to usual care (primary outcome available on 405 (96.4%) women). There was no evidence of difference in the mean systolic BP in those allocated to BP self-monitoring, in either the CH cohort [mean standard deviation (SD) systolic BP: 133.8 (10.3) mmHg in the self-monitoring group compared to 133.6 (11.1) mmHg in those with usual care (adjusted mean difference 0.03; 95% CI –1.73 to 1.79)] or the GH cohort [mean (SD) systolic BP: 137.6 (12.1) mmHg compared to 137.2 (10.8) mmHg in those with usual care (adjusted mean difference –0.03; 95% CI –2.29 to 2.24)]. 3.3 Qualitative process evaluation (Chisholm A, Tucker KL, Crawford C, Green M, Greenfield S, Hodgkinson J, et al. Self-monitoring blood pressure in pregnancy: evaluation of health professional experiences of the BUMP trials. BMC Pregnancy Childbirth 2024;35:88–95.https://doi.org/10.1016/j.preghy.2024.01.134) The majority of trial participants interviewed had positive experiences of self-monitoring, reporting it was reassuring, acceptable, convenient and sometimes led to the earlier detection of hypertension. Having their own series of BP readings could feel empowering but also introduced some uncertainty and new responsibility. Some women described delayed or selective reporting of high BP readings. Some women preferred not to self-monitor due to concerns about anxiety, fears of preoccupation with monitoring, low perceived risk of hypertension, or choosing to have an HCP present for BP measurement. Women’s accounts demonstrated that HCP engagement with BP self-monitoring varied. Healthcare professionals largely trusted home readings from the validated monitors used. Most said such measurements positively affected their clinical encounters and professional roles, amplifying the information on which to base decisions and enriching their relationships with women. Some felt SMBP gave women new responsibilities that required additional support from HCPs. 3.4 BUMP within-trial economic analyses(Campbell HE, Chappell LC, McManus RJ, Tucker KL, Crawford C, Green M, Rivero-Arias O. Detection and control of pregnancy hypertension using self-monitoring of blood pressure with automated telemonitoring: cost analyses of the BUMP randomized trials. Hypertension 2024;81:887–96. https://doi.org/10.1161/HYPERTENSIONAHA.123.22059) In BUMP1 and BUMP2, there were no significant differences between trial arms in EuroQol EQ-5D-5L scores at any time points. In both analyses, healthcare contacts and costs were also similar across resource use categories in each trial arm. In BUMP1, mean (standard error) total healthcare costs with SMBP and with usual care were £7200 (£323) and £7063 (£245) respectively, mean difference (95% CI), £151 (–£633 to £936). For the BUMP 2 chronic hypertension cohort, corresponding figures were £13,384 (£1230), £12,614 (£1081), and £323 (–£2904 to £3549) and for the gestational hypertension cohort were £11,456 (£901), £11,145 (£959), and £41 (–£2486 to £2567). WS4: Self-monitoring of urinary protein in hypertensive pregnancy WS4.1 UDIP (Jakubowski BE, Stevens R, Wilson H, Lavallee L, Brittain L, Crawford C, et al. Cross-sectional diagnostic accuracy study of self-testing for proteinuria during hypertensive pregnancies: the UDIP study. BJOG 2022;129:2142–8. https://doi.org/10.1111/1471-0528.17180) Hypertensive pregnant women were recruited: 335/345 (97%) had sufficient data to be included in the analysis of whom 118 (35.2%) had a positive PCR. Self-testing had a sensitivity of 0.71 [95% CI 0.62 to 0.79] and a specificity of 0.89 [95% CI 0.84 to 0.92] compared to PCR. Sensitivity and specificity of testing by HCPs and the colorimetric reader were similar: sensitivity 0.73 (95% CI 0.64 to 0.80) and 0.78 (95% CI 0.69 to 0.85) respectively; specificity 0.88 (95% CI 0.82 to 0.92) and 0.83 (95% CI 0.78 to 0.88) respectively. WS4.2 UDIP qualitative Associated qualitative work found that self-testing was acceptable to pregnant women and HCPs, and could provide an opportunity for pregnant women to be more involved in their care. WS5: Modelling of the potential long-term costs and consequences The model frameworks developed provide a facility for exploration of the potential cost-effectiveness of future SMBP-guided interventions for different cohorts of women affected by pregnancy hypertension and for differing levels of intervention effectiveness. We present no definitive cost-effectiveness results, instead running a series of hypothetical scenarios to illustrate the capabilities of the models. For example, simulating a hypothetical scenario in which a new SMBP-guided intervention could reduce the risk of a pregnant women developing pre-eclampsia by 10%, the modelling suggested that long-term cost-effectiveness could potentially vary between hypertensive pregnant women and women at risk of pregnancy hypertension. This is because hypertensive women face a greater likelihood of developing associated complications both during and following pregnancy, in turn suggesting a greater absolute level of benefit from a 10% reduction in complications via the mechanism of better BP control. Such hypotheses would of course require empirical testing in practice. Conclusions WS1: Development The BUMP intervention was developed and user tested for implementation in higher risk and hypertensive pregnant women in the BUMP trials. WS2: Blood pressure self-monitoring during pregnancy for antihypertensives titration – pilot trial This randomised feasibility trial of BP self-monitoring during hypertensive pregnancy indicated that a large RCT would be acceptable and feasible. WS3: Self-monitoring to improve the detection and management of raised blood pressure in pregnancy WS3.1: BUMP survey Healthcare professionals should be aware that many women are choosing to self-monitor their BP. They are advised to enquire about this proactively and consider providing information on BP monitoring in pregnancy. WS3.2.1: BUMP1 trial Self-monitoring of BP during higher risk pregnancy appears to be safe. However, it did not improve the detection of hypertension when used alongside usual care. Self-monitoring did provide prior notice of hypertension in many women suggesting it could be useful. Not all women will want to self-monitor meaning that an individualised approach will be needed. Further work is needed to assess the place of SMBP, for example, in remote consultations or alongside self-management. WS3.2.2: BUMP2 trial Blood pressure self-monitoring in pregnancy hypertension was not associated with a change in BP control, as assessed by clinic systolic BP, but appears to be safe, without evidence of harm or unintended deleterious effects on pregnancy outcomes. Not all women will want to self-monitor meaning that an individualised approach will be needed. Furthermore, the addition of further components of self-management may be required in order to achieve improvements in BP control and other pregnancy outcomes. WS3.3: Process evaluation The majority of women and HCPs involved in the trial found SMBP enhanced their experiences of the clinical encounter and the HCP–woman relationship. However, not all women found self-care helpful. Furthermore, selective or delayed reporting of raised readings, along with the pursuit of normal readings, and HCPs’ variable engagement with home readings could have impacted the performance of the BUMP intervention. SMBP by women in the usual care arm may have affected evidence for the intervention’s effectiveness in identifying or managing hypertension. WS3.4: Economic analysis The SMBP intervention as evaluated in the BUMP trials was not associated with changes in health-related quality of life or healthcare resource use or with, pregnancy hypertension. When coupled with findings that SMBP is both safe and acceptable to individuals, this is reassuring for healthcare providers upon whom the recent coronavirus

BACKGROUND:Hypertension induces structural and functional damage in multiple organs. Evidence of subclinical damage increases risk of vascular events and death but can be difficult to identify in the clinic. We developed a novel machine learning approach that quantifies current hypertension-associated multiorgan damage, mapping progression from health to advanced disease, in a pseudotemporal manner and predicts organ-specific disease progression trajectories. METHODS:We analyzed 566 multimodal imaging and nonimaging variables from 27 099 participants in the UK Biobank imaging substudy to develop a semisupervised contrastive trajectory inference (cTI) framework that models multiorgan alterations associated with hypertension exposure, including heart, brain, kidneys, vasculature, lungs, liver, and metabolic information. Model stability was validated through multiple internal validation steps, and external validity was tested on 5507 participants from the Atherosclerosis Risk in Communities study (ARIC). Clinical relevance was evaluated against existing risk scores and through ability to predict survival and incident multiorgan disease for up to 7 years, across both UK Biobank and ARIC. RESULTS:In the UK Biobank (mean age 63.27±7.48 years; 53.4% women) our global organ damage score (HyperScore) achieved an area under the curve of 0.964 (0.941-0.987) for identification of individuals with severe end-organ disease and robust stability in cross-validation with a mean root mean square error of 0.104±0.084. Survival odds differed significantly across HyperScore stages (P<0.001), whereas stratification by blood pressure was nonsignificant. We further revealed 6 hypertensive disease phenotypes (HyperTrajectory), characterized by predominant cardiac, lipoprotein, atherothrombosis, brain, cardiorenal, and liver features, respectively. External testing in ARIC confirmed stability of the model, with Jensen-Shannon distances as low as 0.10 for HyperScore distributions, without significant deviation in organ damage progression patterns (P>0.05) and consistent end-organ and outcome characteristics between ARIC and UK Biobank across HyperTrajectories. CONCLUSIONS:Machine learning-derived global organ damage scores are feasible in hypertension and enable identification of distinct hypertension-associated organ-disease phenotypes. New frameworks for hypertension assessment and monitoring using imaging to derive personalized risk assessment and phenotype-specific intervention may be achievable.

BACKGROUND:Serious muscle disorders are a concerning adverse event of statins, contributing to low statin uptake and poor adherence in the prevention of cardiovascular disease (CVD). We aimed to derive and validate a model predicting the risk of serious muscle disorders in individuals eligible for statin treatment, to better inform appropriate treatment decision making. METHODS:This was a retrospective cohort study using electronic health record data from the Clinical Practice Research Datalink (CPRD), with its Gold database for model derivation and Aurum database for external validation. Men aged 50 years or older and women aged 60 years or older, who were registered with CPRD between Jan 1, 1998 and Dec 31, 2018 in England, were included. A Fine-Gray model was developed to predict the 1-year, 5-year, and 10-year risks of serious muscle disorders associated with hospitalisation or death, adjusting for competing mortality risk. Model discrimination was assessed using C-index and D-statistic, calibration using the expected to observed (E/O) ratio, calibration slope, and calibration plot, and clinical utility using decision curve analysis. FINDINGS:A total of 1 785 207 individuals were included in the model derivation cohort and 3 889 504 individuals in the external validation cohort. The model consisted of 22 predictors, including statin prescription. The predicted risk of serious muscle disorders in most individuals was low (99·6% of the validation cohort had a 10-year risk below 10%). The model showed overall good discrimination and calibration, with C-index 0·782 (IQR 0·782-0·782), D-statistic 2·176 (95% CI 2·139-2·212), E/O ratio 1·151 (IQR 1·131-1·171), and calibration slope 1·063 (95% CI 1·052-1·073) for the 10-year prediction in the external validation. Decision curve analysis suggested a favourable net benefit of the model-assisted clinical decision making. INTERPRETATION:This model provides reliable prediction of personalised risk of serious muscle adverse events of statins, which, together with existing prediction tools for personalised CVD risk, could help patients and physicians better understand the benefit-to-harm balance of statins for an individual and support well informed shared decision making on statin treatment. FUNDING:British Heart Foundation, Wellcome Trust, and Royal Society.

Background Antihypertensive therapy is associated with an increased risk of adverse events, such as falls, in older patients and those with increasing levels of frailty. This study aimed to explore the association between antihypertensive treatment and serious adverse events in other patient subgroups in primary care according to sex, ethnicity, and socioeconomic status. Methods This retrospective observational cohort study used routinely collected primary care data from England, UK, in the Clinical Practice Research Datalink Aurum database between Jan 1, 1998, and Dec 31, 2018. Patients aged 40 years or older, without previous antihypertensive prescriptions, and with a systolic blood pressure reading of 130–179 mm Hg were included. The main outcome was first hospitalisation or death from a fall within 10 years of follow-up. Exposure was defined as the first antihypertensive prescription within 12 months after inclusion. Cox regression models adjusted for propensity scores were developed in sex, ethnicity, and socioeconomic status subgroups, and absolute risk differences were calculated. Findings 2 614 330 patients were included in the analyses, of whom 337 742 (12·9%) were in the exposed group and 2 276 588 were in the non-exposed group. Median age in the non-exposed group was 53 years (IQR 46–63); 1 141 885 (50·2%) were female and 1 134 703 (49·8%) were male; 1 120 659 (49·2%) were White, 561 427 (24·7%) were of mixed or other ethnicity, 64 377 (2·8%) were Black, and 53 338 (2·3%) were south Asian. In the exposed group, median age was 61 years (51–71); 166 639 (49·3%) were female and 171 103 (50·7%) were male; 196 432 (58·2%) were White, 66 460 (19·7%) were of mixed or other ethnicity, 13 668 (4·0%) were Black, and 10 948 (3·2%) were south Asian. The median follow-up time was 7·0 years (IQR 2·9–10·0). The main outcome of falls was observed in 110 874 patients (4·2% of the total population; 23 925 [7·1%] in the exposed group and 86 949 [3·8%] in the non-exposed group). The association between antihypertensive medication and hospitalisation or death due to falls was similar for both sexes (adjusted hazard ratio [aHR] 1·09 [95% CI 1·06–1·12] for male patients and 1·10 [1·07–1·12] for female patients). The associations (aHRs) in the different ethnicity groups were 1·32 (95% CI 1·13–1·53) in Black patients, 1·22 (1·05–1·41) in south Asian patients, 1·47 (1·29–1·66) in patients of mixed or other ethnicity, and 1·05 (1·03–1·07) in White patients. The most deprived group had an aHR of 1·02 (95% CI 0·99–1·06) and the least deprived group had an aHR of 1·16 (1·12–1·21). The absolute risk difference was low for all subgroups (≤12 events per 10 000 patients per year). Interpretation All subgroups of patients with antihypertensive prescriptions had an increased risk of hospitalisation or death due to falls versus those who were unexposed. No significant difference in risk of falls was observed based on sex, ethnicity, or social deprivation; therefore, no distinction should be made among these groups when considering the harms of antihypertensives in individual treatment decisions in primary care. Funding Wellcome Trust, Royal Society, and National Institute for Health Research School for Primary Care Research.