Prevalence of treatment-resistant hypertension after considering pseudo-resistance and morbidity: a cross-sectional study in Irish primary care

peer-reviewedBackground To confirm treatment-resistant hypertension (TRH), ambulatory blood pressure measurement (ABPM) must exclude white-coat hypertension (WCH), three or more medications should be prescribed at the optimal doses tolerated, and non-adherence and lifestyle should be examined. Most previous studies have not adequately considered pseudo-resistance and merely provide an apparent TRH (aTRH) prevalence figure. Aim To conduct a cross-sectional study of the prevalence of aTRH in general practice, and then consider pseudo-resistance and morbidity. Design and setting With support, 16 practices ran an anatomical therapeutic chemical (ATC) drug search, identifying patients on any possible hypertensive medications, and then a search of individual patients' electronic records took place. Method ABPM was used to rule out WCH. The World Health Organization-defined daily dosing guidelines determined adequate dosing. Adherence was defined as whether patients requested nine or more repeat monthly prescriptions within the past year. Results Sixteen practices participated (n = 50 172), and 646 patients had aTRH. Dosing was adequate in 19% of patients, 84% were adherent to medications, as defined by prescription refill, and 43% had ever had an ABPM. Using a BP cut-off of 140/90 mmHg, the prevalence of aTRH was 9% (95% confidence interval [CI] = 9.0 to 10.0). Consideration of pseudo-resistance further reduced prevalence rates to 3% (95% CI = 3.0 to 4.0). Conclusion Reviewing individual patient records results in a lower estimate of prevalence of TRH than has been previously reported. Further consideration for individual patients of pseudo-resistance additionally lowers these estimates, and may be all that is required for management in the vast majority of cases.PUBLISHEDpeer-reviewe

The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research:Antibody testing results, April – June 2021

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort which recruited pregnant women in 1990-1992 and has followed these women, their partners (Generation 0; G0) and their offspring (Generation 1; G1) ever since. The study reacted rapidly and repeatedly to the coronavirus disease 2019 (COVID-19) pandemic, deploying multiple online questionnaires and a previous home-based antibody test in October 2020. A second antibody test, in collaboration with ten other longitudinal population studies, was completed by 4,622 ALSPAC participants between April and June 2021. Of 4,241 participants with a valid spike protein antibody test result (8.2% were void), indicating antibody response to either COVID-19 vaccination or natural infection, 3,172 were positive (74.8%). Generational differences were substantial, with 2,463/2,555 G0 participants classified positive (96.4%) compared to 709/1,686 G1 participants (42.1%). Of 4,199 participants with a valid nucleocapsid antibody test result (9.2% were void), suggesting potential and recent natural infection, 493 were positive (11.7%); 248/2,526 G0 participants (9.8%) and 245/1,673 G1 participants (14.6%) tested positive, respectively. We also compare results for this round of testing to that undertaken in October 2020. Future work will combine these test results with additional sources of data to identify participants’ COVID-19 infection and vaccination status. These ALSPAC COVID-19 serology data are being complemented with linkage to health records and Public Health England pillar testing results as they become available, in addition to four previous questionnaire waves and a prior antibody test. Data have been released as an update to the previous COVID-19 datasets. These comprise: 1) a standard dataset containing all participant responses to all four previous questionnaires with key sociodemographic factors; and 2) individual participant-specific release files enabling bespoke research across all areas supported by the study. This data note describes the second ALSPAC antibody test and the data obtained from it

Stress monitoring using wearable sensors:a pilot study and stress-predict dataset

With the recent advancements in the field of wearable technologies, the opportunity to monitor stress continuously using different physiological variables has gained significant interest. The early detection of stress can help improve healthcare and minimizes the negative impact of long-term stress. This paper reports outcomes of a pilot study and associated stress-monitoring dataset, named the “Stress-Predict Dataset”, created by collecting physiological signals from healthy subjects using wrist-worn watches with a photoplethysmogram (PPG) sensor. While wearing these watches, 35 healthy volunteers underwent a series of tasks (i.e., Stroop color test, Trier Social Stress Test and Hyperventilation Provocation Test), along with a rest period in-between each task. They also answered questionnaires designed to induce stress levels compatible with daily life. The changes in the blood volume pulse (BVP) and heart rate were recorded by the watch and were labelled as occurring during stress-inducing tasks or a rest period (no stress). Additionally, respiratory rate was estimated using the BVP signal. Statistical models and personalised adaptive reference ranges were used to determine the utility of the proposed stressors and the extracted variables (heart rate and respiratory rate). The analysis showed that the interview session was the most significant stress stimulus, causing a significant variation in heart rate of 27 (77%) participants and respiratory rate of 28 (80%) participants out of 35. The outcomes of this study contribute to the understanding the role of stressors and their association with physiological response and provide a dataset to help develop new wearable solutions for more reliable, valid, and sensitive physio-logical stress monitoring

Designing an e-learning tool to support health practitioners caring for patients taking multiple medications

Background: Population ageing and improvements in healthcare mean the number of people living with two or more chronic conditions, or ‘multimorbidity’, is rapidly increasing. This presents a challenge to current disease-specific care delivery models. Adherence to prescribed medications appears particularly challenging for individuals living with multimorbidity, given the often-complex drug regimens required to treat multiple conditions. Poor adherence is associated with increased mortality, as well as wasted healthcare resources. Supporting medication adherence is a key priority for general practitioners (GPs) and practice nurses as they are responsible for much of the disease counselling and medication prescribing associated with chronic illnesses. Despite this, practical resources and training for health practitioners on how to promote adherence in practice is currently lacking. Informed by the principles of patient and public involvement (PPI), the aim of this research was to develop a patient informed e-learning resource to help GPs and nurses support medication adherence. Method: Utilising collective intelligence (CI) and scenario-based design (SBD) methodology, input was gathered from key stakeholders in medication adherence to gain insights into barriers to supporting people with multimorbidity who are receiving polypharmacy, strategies for overcoming these barriers, and user needs and requirements to inform the design of the e-learning tool. Results: In total, 67 barriers to supporting people who are taking multiple medications were identified across 8 barrier categories. 162 options for overcoming the identified barriers were then generated. This data was used in the design of a flexible e-learning tool for continuous professional development, that has been integrated into general practice and clinical education programmes as a supportive tool. Conclusions: Using CI and SBD methodology was an effective way of facilitating collaboration, idea-generation, and the co-creation of design solutions amongst a diverse group of stakeholders. This approach could be usefully applied to address other complex healthcare-related challenges

Multi-ancestry Mendelian randomization of omics traits revealing drug targets of COVID-19 severity

BACKGROUND: Recent omic studies prioritised several drug targets associated with coronavirus disease 2019 (COVID-19) severity. However, little evidence was provided to systematically estimate the effect of drug targets on COVID-19 severity in multiple ancestries. METHODS: In this study, we applied Mendelian randomization (MR) and colocalization approaches to understand the putative causal effects of 16,059 transcripts and 1608 proteins on COVID-19 severity in European and effects of 610 proteins on COVID-19 severity in African ancestry. We further integrated genetics, clinical and literature evidence to prioritise drug targets. Additional sensitivity analyses including multi-trait colocalization and phenome-wide MR were conducted to test for MR assumptions. FINDINGS: MR and colocalization prioritized four protein targets, FCRL3, ICAM5, ENTPD5 and OAS1 that showed effect on COVID-19 severity in European ancestry. One protein target, SERPINA1 showed a stronger effect in African ancestry but much weaker effect in European ancestry (odds ratio [OR] in Africans=0.369, 95%CI=0.203 to 0.668, P = 9.96 × 10(−4); OR in Europeans=1.021, 95%CI=0.901 to 1.157, P = 0.745), which suggested that increased level of SERPINA1 will reduce COVID-19 risk in African ancestry. One protein, ICAM1 showed suggestive effect on COVID-19 severity in both ancestries (OR in Europeans=1.152, 95%CI=1.063 to 1.249, P = 5.94 × 10(−4); OR in Africans=1.481, 95%CI=1.008 to 2.176; P = 0.045). The OAS1, SERPINA1 and ICAM1 effects were replicated using updated COVID-19 severity data in the two ancestries respectively, where alternative splicing events in OAS1 and ICAM1 also showed marginal effects on COVID-19 severity in Europeans. The phenome-wide MR of the prioritised targets on 622 complex traits provided information on potential beneficial effects on other diseases and suggested little evidence of adverse effects on major complications. INTERPRETATION: Our study identified six proteins as showing putative causal effects on COVID-19 severity. OAS1 and SERPINA1 were targets of existing drugs in trials as potential COVID-19 treatments. ICAM1, ICAM5 and FCRL3 are related to the immune system. Across the six targets, OAS1 has no reliable instrument in African ancestry; SERPINA1, FCRL3, ICAM5 and ENTPD5 showed a different level of putative causal evidence in European and African ancestries, which highlights the importance of more powerful ancestry-specific GWAS and value of multi-ancestry MR in informing the effects of drug targets on COVID-19 across different populations. This study provides a first step towards clinical investigation of beneficial and adverse effects of COVID-19 drug targets. FUNDING: No

Altered Storage and Function of von Willebrand Factor in Human Cardiac Microvascular Endothelial Cells Isolated from Recipient Transplant Hearts

The assembly of von Willebrand factor (VWF) into ordered helical tubules within endothelial Weibel–Palade bodies (WPBs) is required for the efficient deployment of the protein at sites of vascular injury. VWF trafficking and storage are sensitive to cellular and environmental stresses that are associated with heart disease and heart failure. Altered storage of VWF manifests as a change in WPB morphology from a rod shape to a rounded shape and is associated with impaired VWF deployment during secretion. In this study, we examined the morphology, ultrastructure, molecular composition and kinetics of exocytosis of WPBs in cardiac microvascular endothelial cells isolated from explanted hearts of patients with a common form of heart failure, dilated cardiomyopathy (DCM; HCMECD), or from nominally healthy donors (controls; HCMECC). Using fluorescence microscopy, WPBs in HCMECC (n = 3 donors) showed the typical rod-shaped morphology containing VWF, P-selectin and tPA. In contrast, WPBs in primary cultures of HCMECD (n = 6 donors) were predominantly rounded in shape and lacked tissue plasminogen activator (t-PA). Ultrastructural analysis of HCMECD revealed a disordered arrangement of VWF tubules in nascent WPBs emerging from the trans-Golgi network. HCMECD WPBs still recruited Rab27A, Rab3B, Myosin-Rab Interacting Protein (MyRIP) and Synaptotagmin-like protein 4a (Slp4-a) and underwent regulated exocytosis with kinetics similar to that seen in HCMECc. However, secreted extracellular VWF strings from HCMECD were significantly shorter than for endothelial cells with rod-shaped WPBs, although VWF platelet binding was similar. Our observations suggest that VWF trafficking, storage and haemostatic potential are perturbed in HCMEC from DCM hearts

Investigating and evaluating evidence of the behavioural determinants of adherence to social distancing measures – A protocol for a scoping review of COVID-19 research

Background: The WHO has declared the outbreak of coronavirus disease 2019 (COVID-19) as a pandemic. With no vaccine currently available, using behavioural measures to reduce the spread of the virus within the population is an important tool in mitigating the effects of this pandemic. As such, social distancing measures are being implemented globally and have proven an effective tool in slowing the large-scale spread of the virus. Aim: This scoping review will focus on answering key questions about the state of the evidence on the behavioural determinants of adherence to social distancing measures in research on COVID-19. Methods: A scoping review will be conducted in accordance with guidelines for best practice. Literature searches will be conducted using online databases and grey literature sources. Databases will include Medline, Web of Science, Embase and PsycInfo, alongside relevant pre-print servers. Grey literature will be searched on Google Scholar. Screening, data extraction and quality appraisal will be conducted by members of the research team, with any discrepancies resolved by consensus discussion. Quality appraisal will be conducted using the Cochrane’s ROBINS-I tool, the Cochrane Risk of Bias tool, and the JBI Critical Appraisal Checklist where appropriate. Results will be analysed by mapping findings onto the Theoretical Domains Framework and visualising characteristics of the included studies using EviAtlas. This scoping review is pre-registered with Open Science Framework. Conclusions: The results of this study may facilitate the systematic development of behavioural interventions to increase adherence to social distancing measures