Pankaj Gupta

Background: Hypertensive disorders of pregnancy affect around 10% of pregnant women and can continue following childbirth. Such hypertension that persists postnatally can be unpredictable and may have long-term health consequences but care can be sub-optimal with poor support as women transition from maternity to community services. However, there is little evidence to guide best practice for managing postnatal hypertension, and these gaps in evidence and care disproportionately affect women from minoritised ethnic and socioeconomically disadvantaged backgrounds. Previous work suggests self-management where women self-monitor blood pressure (BP) and self-titrate medication, overseen by clinicians, could improve BP control in the short and long term but has been limited to single geographical areas. The aim of the SNAP2 trial is to evaluate the clinical and cost effectiveness of a self-management intervention at scale. Methods: SNAP2 is a multi-centre unblinded randomised controlled trial. A planned sample of at least 628 participants across England with any pregnancy hypertension will be randomised within 7 days post birth to a digitally-supported self-management intervention, including self-monitoring of BP and clinician-guided titration of anti-hypertensive medication, or usual care. A cross-cutting theme is evaluating how health equity can best be ensured in postnatal hypertension management. The primary outcome is the difference in mean daytime ambulatory diastolic BP between intervention and usual care, measured between 22 to 39 weeks postpartum. Secondary outcomes include other measures of BP, maternal quality-of-life, medication adherence, adverse outcomes and readmission to hospital up to one year after birth. A qualitative process evaluation will explore how the intervention is implemented and integrated into women’s lives and clinical pathways. An economic analysis will evaluate within-trial cost and outcomes and long-term economic modelling. Discussion: The SNAP2 trial will provide essential data on the clinical and cost-effectiveness of a self-management intervention that, if proven effective, could improve current sub-optimal postnatal care for BP management. In-depth qualitative and equity data will provide important insight to inform potential implementation. Throughout the manuscript, in our references to women, we encompass all birthing people. Clinical trail number: https://doi.org/10.1186/ISRCTN11042045 .

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.

Nonadherence to antihypertensive medications is a major concern, with significant implications for healthcare systems and patient outcomes. Chemical adherence testing (CAT) is a recommended method to assess nonadherence objectively by detecting drugs or their metabolites in blood or urine samples. Interpretation of CAT results require relevant pharmacokinetic parameters. However, pharmacokinetic data in established sources are not graded for quality and not compiled into a single resource. We systematically collated and graded the literature on pharmacokinetic parameters for 20 commonly prescribed antihypertensive agents. A total of 53 suitable manuscripts were included. Pharmacokinetic data, including half-life and maximum concentration, were collated. Also, minimum concentration at regular dosing intervals was calculated. This resource allows clinicians and researchers to interpret CAT results with more confidence and accuracy and will help facilitate the interpretation of CAT. It also shows that there are significant gaps in available literature, and further research is needed.

To assess perceptions, motivations and barriers to treatment adherence depending on emotional, lifestyle, medical and non-adherence risk profiles in hypertensive patients. Cross-sectional data were obtained using an online anonymous survey. Four distinct global risk scores (medical, lifestyle, emotional and quality of life and non-adherence risk scores) were calculated based on the responses to specific groups of questions. 2615 treated hypertensive patients (≥18 years of age) from 5 European countries completed the questionnaire. Mean (SD) age was 69.6 years (5.8); 54% males. Overall, antihypertensive therapy represented a low burden in patients' daily life (2.9/10 in the Likert scale). Perfect self-reported adherence was claimed by 59.8% of participants. Reporting of non-adherence episodes to physicians was low (13% always/often). Participants with a high non-adherence risk score had a greater number of associated diseases (obesity, sleep disturbances, depression, and cardiac complications), a higher treatment-associated burden on daily life, a greater stress level and more antihypertensive pills per day (p < 0.001 for all). No correlation was found between the clinical and lifestyle risk scores and the risk of non-adherence. The emotional score correlated significantly with the non-adherence risk score (p < 001). Comparing patients with a low/middle risk to those with a high risk of non-adherence, female gender and age >65 year were associated with a lower odd ratio of non-adherence whereas depression, stress, family hardships, negative information on drugs and poor information were associated with higher odds of non-adherence. This large survey reveals several underestimated issues regarding patients' perspective in hypertension. It highlights the impact of emotions, exposure to family hardships, and stress on the risk of non-adherence. Non-adherence is underreported by patients; hence it remains mostly unrecognized.

During the COVID-19 pandemic, development of diagnostic tests was vital to chart the course and to reduce the impact of the infection. Continued testing and surveillance of vaccine escape will continue for years to come which presents an opportunity to integrate such testing into clinical biochemistry laboratories that form part of integrated healthcare testing. Here we describe a protocol for a targeted mass spectrometry based proteomic assay (COVIDCAP) developed to detect SARS-CoV-2 peptides from oro-nasopharyngeal swabs (ONP) and saliva. This uses novel SISCAPA antibodies bound to magnetic beads and subsequent analysis of captured and purified SARS-CoV-2 nucleocapsid (NCAP) peptides. The method involves immediate deactivation of the sample using an ethanolic solution. This simultaneously inactivates the virus and denatures viral proteins at sampling in contrast to the approach for RT-PCR testing, with benefits for the assay as well as for downstream processing. A plate-based preparation of the samples involving acetone precipitation followed by a short tryptic digestion and subsequent immunocapture allows LC-MS detection and quantification of peptides from the NCAP protein, in a 3-minute inject-to-inject assay with an LOD of 20 attomoles from starting sample. For 576 ONP swab samples taken as exemplars here, the sensitivity and specificity of this analysis is shown to be 97.0% and 96.6% respectively.

Hypertension is the leading modifiable risk factor for cardiovascular disease, but less than 50% have their blood pressure controlled. A possible avenue to support hypertension management is a holistic approach, using non-pharmacological interventions. Since hypertension is mediated in part by dysregulation of the autonomic nervous system (ANS), biofeedback may help improve hypertension management by targeted self-regulation and self-awareness of parameters that regulate the ANS. This systematic review aimed to assess the effectiveness of biofeedback on blood pressure in hypertensive patients. The review was pre-registered on PROSPERO and followed the PICO strategy. A total of 1782 articles were retrieved, 20 met the inclusion criteria. Sample sizes ranged from 15 to 301 participants; with a median age of 49.3 (43.3–55.0) years and 45% were female. There was a significant effect of biofeedback on systolic (−4.52, Z = 2.31, P = 0.02, CI [−8.35, −0.69]) and diastolic blood pressure (−5.19, Z = 3.54, P = 0.0004, CI [−8.07, −2.32]). Six different biofeedback modalities were used, with biofeedback delivered by psychologists, trained therapists and research assistants. There was no publication bias, heterogeneity was rated as substantial and data quality was rated to be poor. This review demonstrated that biofeedback had a significant effect on blood pressure. However, this should be viewed in the context of included studies being limited by heterogeneity and dated literature, meaning the research does not reflect the current biofeedback technology such as wearable devices. Future research should incorporate these technologies with robust methodology to fully understand the effect of biofeedback on hypertension.