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1.
Evol Dev ; 26(2): e12474, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38425004

ABSTRACT

The telencephalon of ray-finned fishes undergoes eversion, which is very different to the evagination that occurs in most other vertebrates. Ventricle morphogenesis is key to build an everted telencephalon. Thus, here we use the apical marker zona occludens 1 to understand ventricle morphology, extension of the tela choroidea and the eversion process during early telencephalon development of four teleost species: giant danio (Devario aequipinnatus), blind cavefish (Astyanax mexicanus), medaka (Oryzias latipes), and paradise fish (Macroposus opercularis). In addition, by using immunohistochemistry against tubulin and calcium-binding proteins, we analyze the general morphology of the telencephalon, showing changes in the location and extension of the olfactory bulb and other telencephalic regions from 2 to 5 days of development. We also analyze the impact of abnormal eye and telencephalon morphogenesis on eversion, showing that cyclops mutants do undergo eversion despite very dramatic abnormal eye morphology. We discuss how the formation of the telencephalic ventricle in teleost fish, with its characteristic shape, is a crucial event during eversion.


Subject(s)
Fishes , Telencephalon , Animals , Larva , Telencephalon/anatomy & histology , Vertebrates , Morphogenesis
2.
Acta Neuropathol ; 147(1): 7, 2024 01 04.
Article in English | MEDLINE | ID: mdl-38175261

ABSTRACT

Tau hyperphosphorylation and aggregation is a common feature of many dementia-causing neurodegenerative diseases. Tau can be phosphorylated at up to 85 different sites, and there is increasing interest in whether tau phosphorylation at specific epitopes, by specific kinases, plays an important role in disease progression. The AMP-activated protein kinase (AMPK)-related enzyme NUAK1 has been identified as a potential mediator of tau pathology, whereby NUAK1-mediated phosphorylation of tau at Ser356 prevents the degradation of tau by the proteasome, further exacerbating tau hyperphosphorylation and accumulation. This study provides a detailed characterisation of the association of p-tau Ser356 with progression of Alzheimer's disease pathology, identifying a Braak stage-dependent increase in p-tau Ser356 protein levels and an almost ubiquitous presence in neurofibrillary tangles. We also demonstrate, using sub-diffraction-limit resolution array tomography imaging, that p-tau Ser356 co-localises with synapses in AD postmortem brain tissue, increasing evidence that this form of tau may play important roles in AD progression. To assess the potential impacts of pharmacological NUAK inhibition in an ex vivo system that retains multiple cell types and brain-relevant neuronal architecture, we treated postnatal mouse organotypic brain slice cultures from wildtype or APP/PS1 littermates with the commercially available NUAK1/2 inhibitor WZ4003. Whilst there were no genotype-specific effects, we found that WZ4003 results in a culture-phase-dependent loss of total tau and p-tau Ser356, which corresponds with a reduction in neuronal and synaptic proteins. By contrast, application of WZ4003 to live human brain slice cultures results in a specific lowering of p-tau Ser356, alongside increased neuronal tubulin protein. This work identifies differential responses of postnatal mouse organotypic brain slice cultures and adult human brain slice cultures to NUAK1 inhibition that will be important to consider in future work developing tau-targeting therapeutics for human disease.


Subject(s)
Alzheimer Disease , Adult , Humans , Animals , Mice , Brain , Anilides , Neurofibrillary Tangles , Protein Kinases , Repressor Proteins
3.
EMBO Rep ; 23(11): e52493, 2022 11 07.
Article in English | MEDLINE | ID: mdl-36194673

ABSTRACT

Our understanding of the cell behaviours and cytoskeletal requirements of axon formation is largely derived from in vitro models but how these relate to axon formation in vivo is not clear. In vitro, neurons progress through a well-defined multineurite stage to form an axon and both actin and microtubules cooperate to drive the first steps in neurite and axon morphogenesis. However, these steps are not recapitulated in vivo, and it is not clear whether the underlying cell biological mechanisms may differ also. Here, we investigate the mechanisms that regulate axon formation in embryonic zebrafish spinal neurons in vivo. We find microtubule organising centres are located distant from the site of axon initiation, and microtubule plus-ends are not enriched in the axon during axon initiation. Focal F-actin accumulation precedes axon formation, and we find that nocodazole-treated neurons with no detectable microtubules are still able to form nascent axonal protrusions that are approximately 10-µm long, dilated and relatively long-lived. We suggest spinal axon formation in vivo is fundamentally different from axon formation in in vitro models.


Subject(s)
Microtubules , Zebrafish , Animals , Axons/physiology , Neurons , Neurites , Actins
4.
Development ; 147(24)2020 12 23.
Article in English | MEDLINE | ID: mdl-33361092

ABSTRACT

Using the zebrafish neural tube as a model, we uncover the in vivo mechanisms allowing the generation of two opposing apical epithelial surfaces within the centre of an initially unpolarised, solid organ. We show that Mpp5a and Rab11a play a dual role in coordinating the generation of ipsilateral junctional belts whilst simultaneously releasing contralateral adhesions across the centre of the tissue. We show that Mpp5a- and Rab11a-mediated resolution of cell-cell adhesions are both necessary for midline lumen opening and contribute to later maintenance of epithelial organisation. We propose that these roles for both Mpp5a and Rab11a operate through the transmembrane protein Crumbs. In light of a recent conflicting publication, we also clarify that the junction-remodelling role of Mpp5a is not specific to dividing cells.


Subject(s)
Guanylate Cyclase/genetics , Morphogenesis/genetics , Zebrafish Proteins/genetics , Zebrafish/growth & development , rab GTP-Binding Proteins/genetics , Animals , Cell Polarity/genetics , Epithelial Cells/metabolism , Gene Expression Regulation, Developmental/genetics , Intercellular Junctions/genetics , Membrane Proteins , Neural Tube/growth & development , Zebrafish/genetics
5.
Curr Opin Crit Care ; 29(1): 34-39, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36539965

ABSTRACT

PURPOSE OF REVIEW: Home oxygen monitoring and therapy have been increasingly used in the management of patients with chronic diseases. The COVID-19 pandemic has prompted the rapid uptake of remote monitoring programmes to support people with COVID-19 at home. This review discusses the recent evidence and learning in home oxygen monitoring and therapy from the pandemic. RECENT FINDINGS: Many home oxygen monitoring programmes were established around the world during the pandemic, mostly in high-income countries to support early detection of hypoxaemia and/or early hospital discharge. The characteristics of these programmes vary widely in the type of monitoring (self-monitoring or clinician-monitoring) and the patient risk groups targeted. There is a lack of evidence for benefits on clinical outcomes, including mortality, and on reductions in healthcare utilisation or cost-effectiveness, but programmes are viewed positively by patients. Recent studies have highlighted the potential bias in pulse oximetry in people with darker skin. SUMMARY: Recent evidence indicates that home oxygen monitoring therapy programmes are feasible in acute disease, but further research is needed to establish whether they improve patient outcomes, are cost-effective and to understand their equity impact.


Subject(s)
COVID-19 , Pandemics , Humans , COVID-19/epidemiology , COVID-19/therapy , Patient Discharge , Oxygen
6.
Health Econ ; 32(9): 2080-2097, 2023 09.
Article in English | MEDLINE | ID: mdl-37232044

ABSTRACT

Health systems around the world are aiming to improve the integration of health and social care services to deliver better care for patients. Existing evaluations have focused exclusively on the impact of care integration on health outcomes and found little effect. That suggests the need to take a step back and ask whether integrated care programmes actually lead to greater clinical integration of care and indeed whether greater integration is associated with improved health outcomes. We propose a mediation analysis approach to address these two fundamental questions when evaluating integrated care programmes. We illustrate our approach by re-examining the impact of an English integrated care program on clinical integration and assessing whether greater integration is causally associated with fewer admissions for ambulatory care sensitive conditions. We measure clinical integration using a concentration index of outpatient referrals at the general practice level. While we find that the scheme increased integration of primary and secondary care, clinical integration did not mediate a decrease in unplanned hospital admissions. Our analysis emphasizes the need to better understand the hypothesized causal impact of integration on health outcomes and demonstrates how mediation analysis can inform future evaluations and program design.


Subject(s)
Delivery of Health Care, Integrated , Mediation Analysis , Referral and Consultation , Outpatients , Hospitalization , Humans
7.
Mol Cell ; 57(2): 219-34, 2015 Jan 22.
Article in English | MEDLINE | ID: mdl-25578879

ABSTRACT

Phosphatidylinositol 3-phosphate (PI(3)P), the product of class III PI3K VPS34, recruits specific autophagic effectors, like WIPI2, during the initial steps of autophagosome biogenesis and thereby regulates canonical autophagy. However, mammalian cells can produce autophagosomes through enigmatic noncanonical VPS34-independent pathways. Here we show that PI(5)P can regulate autophagy via PI(3)P effectors and thereby identify a mechanistic explanation for forms of noncanonical autophagy. PI(5)P synthesis by the phosphatidylinositol 5-kinase PIKfyve was required for autophagosome biogenesis, and it increased levels of PI(5)P, stimulated autophagy, and reduced the levels of autophagic substrates. Inactivation of VPS34 impaired recruitment of WIPI2 and DFCP1 to autophagic precursors, reduced ATG5-ATG12 conjugation, and compromised autophagosome formation. However, these phenotypes were rescued by PI(5)P in VPS34-inactivated cells. These findings provide a mechanistic framework for alternative VPS34-independent autophagy-initiating pathways, like glucose starvation, and unravel a cytoplasmic function for PI(5)P, which previously has been linked predominantly to nuclear roles.


Subject(s)
Autophagy , Phagosomes/physiology , Phosphatidylinositol Phosphates/physiology , Animals , Autophagy-Related Proteins , Carrier Proteins/metabolism , HeLa Cells , Humans , Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism , Mice , Microtubule-Associated Proteins/metabolism , Phosphatidylinositol 3-Kinases/metabolism
8.
BMC Med Inform Decis Mak ; 23(1): 158, 2023 08 12.
Article in English | MEDLINE | ID: mdl-37573388

ABSTRACT

BACKGROUND: In the era of electronic health records (EHR), the ability to share clinical data is a key facilitator of healthcare delivery. Since the introduction of EHRs, this aspect has been extensively studied from the perspective of healthcare providers. Less often explored are the day-to-day challenges surrounding the procurement, deployment, maintenance, and use of interoperable EHR systems, from the perspective of healthcare administrators, such as chief clinical information officers (CCIOs). OBJECTIVE: Our study aims to capture the perceptions of CCIOs on the current state of EHR interoperability in the NHS, its impact on patient safety, the perceived facilitators and barriers to improving EHR interoperability, and what the future of EHR development in the NHS may entail. METHODS: Semi-structured interviews were conducted between November 2020 - October 2021. Convenience sampling was employed to recruit NHS England CCIOs. Interviews were digitally recorded and transcribed verbatim. A thematic analysis was performed by two independent researchers to identify emerging themes. RESULTS: Fifteen CCIOs participated in the study. Participants reported that limited EHR interoperability contributed to the inability to easily access and transfer data into a unified source, thus resulting in data fragmentation. The resulting lack of clarity on patients' health status negatively impacts patient safety through suboptimal care coordination, duplication of efforts, and more defensive practice. Facilitators to improving interoperability included the recognition of the need by clinicians, patient expectations, and the inherent centralised nature of the NHS. Barriers included systems usability difficulties, and institutional, data management, and financial-related challenges. Looking ahead, participants acknowledged that realising that vision across the NHS would require a renewed focus on mandating data standards, user-centred design, greater patient involvement, and encouraging inter-organisational collaboration. CONCLUSION: Tackling poor interoperability will require solutions both at the technical level and in the wider policy context. This will involve demanding interoperability functionalities from the outset in procurement contracts, fostering greater inter-organisation cooperation on implementation strategies, and encouraging systems vendors to prioritise interoperability in their products. Only by comprehensively addressing these challenges would the full potential promised by the use of fully interoperable EHRs be realised.


Subject(s)
Electronic Health Records , State Medicine , Humans , Delivery of Health Care , Qualitative Research , England
9.
Emerg Med J ; 40(6): 460-465, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36854617

ABSTRACT

BACKGROUND: To identify the impact of enrolment onto a national pulse oximetry remote monitoring programme for COVID-19 (COVID-19 Oximetry @home; CO@h) on health service use and mortality in patients attending Emergency Departments (EDs). METHODS: We conducted a retrospective matched cohort study of patients enrolled onto the CO@h pathway from EDs in England. We included all patients with a positive COVID-19 test from 1 October 2020 to 3 May 2021 who attended ED from 3 days before to 10 days after the date of the test. All patients who were admitted or died on the same or following day to the first ED attendance within the time window were excluded. In the primary analysis, participants enrolled onto CO@h were matched using demographic and clinical criteria to participants who were not enrolled. Five outcome measures were examined within 28 days of first ED attendance: (1) Death from any cause; (2) Any subsequent ED attendance; (3) Any emergency hospital admission; (4) Critical care admission; and (5) Length of stay. RESULTS: 15 621 participants were included in the primary analysis, of whom 639 were enrolled onto CO@h and 14 982 were controls. Odds of death were 52% lower in those enrolled (95% CI 7% to 75%) compared with those not enrolled onto CO@h. Odds of any ED attendance or admission were 37% (95% CI 16% to 63%) and 59% (95% CI 32% to 91%) higher, respectively, in those enrolled. Of those admitted, those enrolled had 53% (95% CI 7% to 76%) lower odds of critical care admission. There was no significant impact on length of stay. CONCLUSIONS: These findings indicate that for patients assessed in ED, pulse oximetry remote monitoring may be a clinically effective and safe model for early detection of hypoxia and escalation. However, possible selection biases might limit the generalisability to other populations.


Subject(s)
COVID-19 , Humans , Cohort Studies , Retrospective Studies , Patient Acceptance of Health Care , Oximetry , Emergency Service, Hospital
10.
J Vis Commun Med ; 46(3): 143-146, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37791405

ABSTRACT

Waiting lists for Ear, Nose and Throat (ENT) outpatient appointments are currently the longest that they have ever been. The Aneurin Bevan University Health Board has adopted a unique Clinical Photography ENT triage service to tackle this. General Practitioner referrals are triaged by ENT consultants, to identify those patients in whom otoscopic imaging could be used to detect a serious otological condition or to enable virtual management. They are triaged to Clinical Photography, to undergo digital imaging which is reviewed in a virtual clinic alongside the initial referral. 72 patients have completed the pathway, with 51.3% discharged without requirement for face-to-face consultant appointment. 9.7% were upgraded to urgent or 2 week waits. This intervention is predicted to help identify patients on the waiting list with potentially serious disease so that they do not wait excessively, and to reduce waiting times for outpatient appointments in ENT.


Subject(s)
General Practitioners , Triage , Humans , Referral and Consultation , Waiting Lists , Photography
11.
BMC Public Health ; 22(1): 75, 2022 01 12.
Article in English | MEDLINE | ID: mdl-35022003

ABSTRACT

BACKGROUND: NHS hospitals do not have clearly defined geographic populations to whom they provide care, with patients able to attend any hospital. Identifying a core population for a hospital trust, particularly those in urban areas where there are multiple providers and high population churn, is essential to understanding local key health needs especially given the move to integrated care systems. This can enable effective planning and delivery of preventive interventions and community engagement, rather than simply treating those presenting to services. In this article we describe a practical method for identifying a hospital's catchment population based on where potential patients are most likely to reside, and describe that population's size, demographic and social profile, and the key health needs. METHODS: A 30% proportional flow method was used to identify a catchment population using an acute hospital trust in West London as an example. Records of all hospital attendances between 1st April 2017 and 31st March 2018 were analysed using Hospital Episode Statistics. Any Lower Layer Super Output Areas where 30% or more of residents who attended any hospital for care did so at the example trust were assigned to the catchment area. Publicly available local and national datasets were then applied to identify and describe the population's key health needs. RESULTS: A catchment comprising 617,709 people, of an equal gender-split (50.4% male) and predominantly working age (15 to 64 years) population was identified. Thirty nine point six percent of residents identified as being from Black and Minority Ethnic (BAME) groups, a similar proportion that reported being born abroad, with over 85 languages spoken. Health indicators were estimated, including: a healthy life expectancy difference of over twenty years; bowel cancer screening coverage of 48.8%; chlamydia diagnosis rates of 2,136 per 100,000; prevalence of visible dental decay among five-year-olds of 27.9%. CONCLUSIONS: We define a blueprint by which a catchment can be defined for a hospital trust and demonstrate the value a hospital-view of the local population could provide in understanding local health needs and enabling population-level health improvement interventions. While an individual approach allows tailoring to local context and need, there could be an efficiency saving were such public health information made routinely and regularly available for every NHS hospital.


Subject(s)
State Medicine , Trust , Adolescent , Adult , Catchment Area, Health , Female , Hospitals, Urban , Humans , London/epidemiology , Male , Middle Aged , Young Adult
12.
J Med Internet Res ; 24(9): e38144, 2022 09 15.
Article in English | MEDLINE | ID: mdl-36107486

ABSTRACT

BACKGROUND: Electronic health records (EHRs) and poor system interoperability are well-known issues in the use of health information technologies in most high-income countries worldwide. Despite the abundance of literature exploring their relationship, their practical implications on patient safety and quality of care remain unclear. OBJECTIVE: This study aimed to examine how EHR interoperability affects patient safety, or other dimensions of care quality, in high-income health care settings. METHODS: A systematic search was conducted using 4 web-based medical journal repositories and grey literature sources. The publications included were published in English between 2010 and 2022, pertaining to EHR use, interoperability, and patient safety or care quality in high-income settings. Screening was completed by 3 researchers in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Risk of bias assessments were performed using the Risk of Bias in Non-randomized Studies of Interventions and the Cochrane Risk of Bias 2 tools. The findings were presented as a narrative synthesis and mapped based on the Institute of Medicine's framework for health care quality. RESULTS: A total of 12 studies met the inclusion criteria to be included in our review. The findings were categorized into 6 common outcome measure categories: patient safety events, medication safety, data accuracy and errors, care effectiveness, productivity, and cost savings. EHR interoperability positively influenced medication safety, reduced patient safety events, and reduced costs. Improvements in time saving and clinical workflow are mixed. However, true measures of effect are difficult to determine with certainty because of the heterogeneity in the outcome measures used and notable variation in study quality. CONCLUSIONS: The benefits of EHR interoperability on the quality and safety of care remain unclear and reflect extensive heterogeneity in the interventions, designs, and outcome measures used. The establishment of common health information technology research outcome measures would support higher-quality research on the topic. Future research efforts should focus on both the positive and negative impacts of interoperable EHR interventions and explore patient perspectives, given the growing trend for patient involvement and stewardship over their own electronic clinical data. TRIAL REGISTRATION: PROSPERO CRD42020209285; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=209285. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2020-044941.


Subject(s)
Electronic Health Records , Patient Safety , Developed Countries , Humans , Income , Quality of Health Care , United States
13.
Emerg Med J ; 39(8): 575-582, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35418406

ABSTRACT

BACKGROUND: To identify the population-level impact of a national pulse oximetry remote monitoring programme for COVID-19 (COVID Oximetry @home (CO@h)) in England on mortality and health service use. METHODS: We conducted a retrospective cohort study using a stepped wedge pre-implementation and post-implementation design, including all 106 Clinical Commissioning Groups (CCGs) in England implementing a local CO@h programme. All symptomatic people with a positive COVID-19 PCR test result from 1 October 2020 to 3 May 2021, and who were aged ≥65 years or identified as clinically extremely vulnerable were included. Care home residents were excluded. A pre-intervention period before implementation of the CO@h programme in each CCG was compared with a post-intervention period after implementation. Five outcome measures within 28 days of a positive COVID-19 test: (i) death from any cause; (ii) any ED attendance; (iii) any emergency hospital admission; (iv) critical care admission and (v) total length of hospital stay. RESULTS: 217 650 people were eligible and included in the analysis. Total enrolment onto the programme was low, with enrolment data received for only 5527 (2.5%) of the eligible population. The period of implementation of the programme was not associated with mortality or length of hospital stay. The period of implementation was associated with increased health service utilisation with a 12% increase in the odds of ED attendance (95% CI: 6% to 18%) and emergency hospital admission (95% CI: 5% to 20%) and a 24% increase in the odds of critical care admission in those admitted (95% CI: 5% to 47%). In a secondary analysis of CO@h sites with at least 10% or 20% of eligible people enrolled, there was no significant association with any outcome measure. CONCLUSION: At a population level, there was no association with mortality before and after the implementation period of the CO@h programme, and small increases in health service utilisation were observed. However, lower than expected enrolment is likely to have diluted the effects of the programme at a population level.


Subject(s)
COVID-19 , COVID-19/epidemiology , Hospitalization , Humans , Oximetry , Patient Acceptance of Health Care , Retrospective Studies
14.
Ann Surg ; 274(6): 904-912, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34402804

ABSTRACT

OBJECTIVES: The PREDICT study aimed to determine how the COVID-19 pandemic affected surgical services and surgical patients and to identify predictors of outcomes in this cohort. BACKGROUND: High mortality rates were reported for surgical patients with COVID-19 in the early stages of the pandemic. However, the indirect impact of the pandemic on this cohort is not understood, and risk predictors are yet to be identified. METHODS: PREDICT is an international longitudinal cohort study comprising surgical patients presenting to hospital between March and August 2020, conducted alongside a survey of staff redeployment and departmental restructuring. A subgroup analysis of 3176 adult emergency patients, recruited by 55 teams across 18 countries is presented. RESULTS: Among adult emergency surgical patients, all-cause in-hospital mortality (IHM) was 3.6%, compared to 15.5% for those with COVID-19. However, only 14.1% received a COVID-19 test on admission in March, increasing to 76.5% by July.Higher Clinical Frailty Scale scores (CFS >7 aOR 18.87), ASA grade above 2 (aOR 4.29), and COVID-19 infection (aOR 5.12) were independently associated with significantly increased IHM.The peak months of the first wave were independently associated with significantly higher IHM (March aOR 4.34; April aOR 4.25; May aOR 3.97), compared to non-peak months.During the study, UK operating theatre capacity decreased by a mean of 63.6% with a concomitant 27.3% reduction in surgical staffing. CONCLUSION: The first wave of the COVID-19 pandemic significantly impacted surgical patients, both directly through co-morbid infection and indirectly as shown by increasing mortality in peak months, irrespective of COVID-19 status.Higher CFS scores and ASA grades strongly predict outcomes in surgical patients and are an important risk assessment tool during the pandemic.


Subject(s)
COVID-19/epidemiology , Emergencies/epidemiology , Emergency Service, Hospital/statistics & numerical data , General Surgery/statistics & numerical data , SARS-CoV-2 , Surveys and Questionnaires , Adult , Aged , Comorbidity , Female , Follow-Up Studies , Global Health , Hospital Mortality/trends , Humans , Male , Middle Aged , Pandemics
15.
BMC Med ; 19(1): 117, 2021 05 12.
Article in English | MEDLINE | ID: mdl-33975593

ABSTRACT

BACKGROUND: Hypertension is the largest single contributor to the global burden of disease, affecting an estimated 1.39 billion people worldwide. Clinical practice guidelines (CPGs) can aid in the effective management of this common condition, however, inconsistencies exist between CPGs, and the extent of this is unknown. Understanding the differences in CPG recommendations across income settings may provide an important means of understanding some of the global variations in clinical outcomes related to hypertension. AIMS: This study aims to analyse the variation between hypertension CPGs globally. It aims to assess the variation in three areas: diagnostic threshold and staging, treatment and target blood pressure (BP) recommendations in hypertension. METHODS: A search was conducted on the MEDLINE repository to identify national and international hypertension CPGs from 2010 to May 2020. An additional country-specific grey-literature search was conducted for all countries and territories of the world as identified by the World Bank. Data describing the diagnosis, staging, treatment and target blood pressure were extracted from CPGs, and variations between CPGs for these domains were analysed. RESULTS: Forty-eight CPGs from across all World Bank income settings were selected for analysis. Ninety-six per cent of guidelines defined hypertension as a clinic-based BP of ≥140/90 mmHg, and 87% of guidelines recommended a target BP of < 140/90 mmHg. In the pharmacological treatment of hypertension, eight different first-step, 17 different second-step and six different third-step drug recommendations were observed. Low-income countries preferentially recommended diuretics (63%) in the first-step treatment, whilst high-income countries offered more choice between antihypertensive classes. Forty-four per cent of guidelines, of which 71% were from higher-income contexts recommended initiating treatment with dual-drug therapy at BP 160/100 mmHg or higher. CONCLUSION: This study found that CPGs remained largely consistent in the definition, staging and target BP recommendations for hypertension. Extensive variation was observed in treatment recommendations, particularly for second-line therapy. Variation existed between income settings; low-income countries prescribed cheaper drugs, offered less clinician choice in medications and initiated dual therapy at later stages than higher-income countries. Future research exploring the underlying drivers of this variation may improve outcomes for hypertensive patients across clinical contexts.


Subject(s)
Hypertension , Antihypertensive Agents/therapeutic use , Blood Pressure , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiology
16.
Ann Pharmacother ; 55(11): 1333-1340, 2021 11.
Article in English | MEDLINE | ID: mdl-33641479

ABSTRACT

BACKGROUND: In a recent human reliability analysis (HRA) of simulated pediatric resuscitations, ineffective retrieval of preparation and administration instructions from online injectable medicines guidelines was a key factor contributing to medication administration errors (MAEs). OBJECTIVE: The aim of the present study was to use a specific HRA to understand where intravenous medicines guidelines are vulnerable to misinterpretation, focusing on deviations from expected practice (discrepancies) that contributed to large-magnitude and/or clinically significant MAEs. METHODS: Video recordings from the original study were reanalyzed to identify discrepancies in the steps required to find and extract information from the NHS Injectable Medicines Guide (IMG) website. These data were combined with MAE data from the same original study. RESULTS: In total, 44 discrepancies during use of the IMG were observed across 180 medication administrations. Of these discrepancies, 21 (48%) were associated with an MAE, 16 of which (36% of 44 discrepancies) made a major contribution to that error. There were more discrepancies (31 in total, 70%) during the steps required to access the correct drug webpage than there were in the steps required to read this information (13 in total, 30%). Discrepancies when using injectable medicines guidelines made a major contribution to 6 (27%) of 22 clinically significant and 4 (15%) of 27 large-magnitude MAEs. CONCLUSION AND RELEVANCE: Discrepancies during the use of an online injectable medicines guideline were often associated with subsequent MAEs, including those with potentially significant consequences. This highlights the need to test the usability of guidelines before clinical use.


Subject(s)
Medication Errors , Pharmaceutical Preparations , Administration, Intravenous , Child , Humans , Medication Errors/prevention & control , Reproducibility of Results , Resuscitation
17.
Eur Heart J Suppl ; 23(Suppl B): B131-B133, 2021 May.
Article in English | MEDLINE | ID: mdl-34733127

ABSTRACT

Accounting for an estimated 10.4 million deaths each year, arterial hypertension is a worldwide epidemic. However, it is a treatable condition that can be readily recognized with cost-effective blood pressure (BP) measurements. Alongside continuous improvements in BP control and treatment, worldwide strategies aim to achieve a high level of hypertension awareness. May Measurement Month (MMM) is a global campaign initiated by the International Society of Hypertension to raise awareness of high BP. Slovenia began with yearly cost-free BP measurements and awareness campaigns in 2005 when World Hypertension Day was announced by the World Hypertension League and in 2017, we joined the MMM initiative. In May 2019, we performed a cross-sectional survey following the standardized MMM protocol. Healthcare personnel obtained BP measurements in a sample of adult subjects (≥18 years) across all regions of the country, mostly in healthcare facilities and pharmacies. In total, 4974 individuals (61.1% female), with a mean age of 59.6 years, were screened. After multiple imputation for missing data, 3037 (61.1%) participants had hypertension. Of individuals not receiving antihypertensive medication, 973 (33.4%) were hypertensive. Of those who reported receiving antihypertensives, 1110 (53.8%) had uncontrolled BP. MMM19 was the largest BP screening campaign undertaken in Slovenia so far. We again identified a substantial number of participants with possible hypertension and uncontrolled BP despite taking antihypertensive medication, which were then referred to their general practitioners or dedicated hypertension centres for further evaluation and management. Taken together, our findings underline the importance of opportunistic screening programmes.

18.
Eur Heart J Suppl ; 23(Suppl B): B128-B130, 2021 May.
Article in English | MEDLINE | ID: mdl-34248437

ABSTRACT

High blood pressure (BP) is a major risk factor for cardiovascular diseases and was identified as the most significant single preventable cause of mortality. The prevalence of hypertension in Saudi Arabia is high. To raise awareness and identify undiagnosed hypertension, the Saudi Ministry of Health participated in the May Measurement Month (MMM) 2019 global screening initiative of the International Society of Hypertension. Ninety-two primary care centres across the Kingdom recruited respondents aged ≥18 years through opportunistic sampling, from 1 May to 30 August of 2019. Data collection included sociodemographic, lifestyle habits, environmental, and anthropometric indicators. Blood pressure was measured twice using automated BP devices. A total of 25 023 adults were screened with a mean age of 42.4 (16.7) years and a mean body mass index of 27.5 (6.0) kg/m2. In total, 43.6% of participants were females and 56.4% were males. Of all the participants with hypertension, 60.8% were aware, 60.8% were on antihypertensive medication, and 39.3% had controlled BP (systolic BP <140 mmHg and diastolic BP <90 mmHg). Moreover, out of 4440 participants on antihypertensive medication, only 64.6% had controlled BP. The high numbers of individuals with hypertension and with undiagnosed hypertension highlight the importance of BP screening campaigns to increase awareness, detection, and target treatment on a national level. Findings from this study can form a baseline by which to measure progress in future iterations of MMM.

19.
Eur Heart J Suppl ; 23(Suppl B): B144-B146, 2021 May.
Article in English | MEDLINE | ID: mdl-34248439

ABSTRACT

We performed a May Measurement Month (MMM) screening campaign among adult volunteers aged 18 years old and over in Tunisia. The objective was to raise awareness, and to estimate the prevalence, awareness, treatment, and control of hypertension, one of the main cardiovascular risk factors. Following the MMM protocol, three blood pressure (BP) measurements were taken by physicians and standard interviewing procedures were used to record medical history, socio-demographic, and cardiovascular disease risk factors. Hypertension was defined as a systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg or treatment with antihypertensive medication. From 11 271 adults screened, the prevalence of hypertension was 38.1%. Among those with hypertension, 72.5% were aware of their diagnosis, and 67.5% were treated. BP control was achieved in only 38.2% of all those with hypertension. The study highlights the magnitude of hypertension in Tunisia. There is an urgent need for implementing a comprehensive integrated population-based intervention programme to ameliorate the growing problem of hypertension.

20.
Eur Heart J Suppl ; 23(Suppl B): B70-B72, 2021 May.
Article in English | MEDLINE | ID: mdl-34220376

ABSTRACT

Cardiovascular diseases are not only the leading causes of mortality in Hungary but also the mortality rate is twice as high as the European Union average, so screening programmes identifying subjects with elevated blood pressure (BP) are of utmost importance. May Measurement Month (MMM) is an annual global initiative that began in 2017 aimed at raising awareness of high BP. Hungary joined the 3rd campaign of MMM in 2019 and an overview of the results are presented in this paper. An opportunistic cross-sectional survey of participants aged ≥18 years was carried out in May 2019. Hypertension was defined as systolic BP ≥140 mmHg and diastolic BP ≥90 mmHg or treatment for hypertension, statistical analysis followed the standard MMM protocol. In Hungary, 55 sites were set up in primary and secondary care facilities, in pharmacies, and in malls across all regions, in both cities and villages. Out of 2766 individuals screened, 1286 participants (46.5%) had hypertension. Out of 1869 participants not on antihypertensive medication, 389 (20.8%) had elevated BP. In the case of treated individuals (n = 897), 420 (46.8%) had uncontrolled hypertension. Almost every 2nd subject of the screened cohort had hypertension (treated and controlled, treated and uncontrolled, or untreated). In the untreated cohort, every 5th subject had elevated BP, whilst among patients on antihypertensive medication, every second had uncontrolled BP. By identifying almost one-third of the whole screened cohort with the possibility of newly diagnosed or uncontrolled hypertension, our results confirm the importance of BP screening campaigns.

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