Current experience and future potential of facilitating access to digital NHS primary care services in England: the Di-Facto mixed-methods study.

Background: Current National Health Service policy in England encourages enhanced digital access in primary care service provision. In this study, we investigate 'digital facilitation' - that range of processes, procedures and personnel which seeks to support National Health Service primary care patients in their uptake and use of online services. Objectives: Identify, characterise and explore the potential benefits and challenges associated with different models of digital facilitation currently in use in general practice which are aimed at improving patient access to online services in general practice in England. Use the resulting intelligence to design a framework for future evaluations of the effectiveness and cost effectiveness of such interventions. Explore how patients with mental health conditions experience digital facilitation and gauge their need for this support. Design: Observational mixed-methods study (literature review, surveys, ethnographic observation and interviews); formal synthesis of findings. Setting: General practice in four regions of England. Participants: Practice survey: 156 staff. Patient survey: 3051 patients. Mental health survey: 756 patients. General practitioner patient survey: 3 million responders. Ethnographic case-studies: 8 practices; interviews with 36 staff, 33 patients and 10 patients with a mental health condition. Stakeholder interviews: 19 participants. Intervention: Digital facilitation as undertaken in general practice. Main outcome measures: Patient and practice staff reported use of, and views of, digital facilitation. Data sources: Surveys, qualitative research; national General Practitioner Patient Survey (2019-22). Review methods: Scoping-review methodology applied to academic and grey literature published 2015-20. Results: While we did find examples of digital facilitation in routine practice, these often involved using passive or reactive modes of support. The context of COVID, and the necessary acceleration (at that time) of the move to a digital-first model of primary care, shaped the way digital facilitation was delivered. There was lack of clarity over where the responsibility for facilitation efforts lay; it was viewed as the responsibility of 'others'. Patients living with mental health conditions had similar needs and experiences regarding digital facilitation to other patients. Limitations: The context of the COVID pandemic placed limitations on the project. Fewer practices responded to the practice survey than anticipated; reconfiguration of general practices to support COVID measures was a key consideration during non-participant observation with social distancing and other measures still in place during fieldwork. Conclusions: Digital facilitation, while not a widely recognised concept, is important in supporting the move to a National Health Service with enhanced digital opportunities and enhanced digital access. General practice staff are allocating resources to provide such efforts in general practices in England. The establishment of clear lines of responsibility, the development of digital tools and platforms that work for patients and practice staff, and investment in staff time and training are needed if digital facilitation is to support the intended digital revolution. Future work: We did not find one single dominant or preferred model of digital facilitation which might reasonably be considered to form the basis of an intervention to be tested. Rather, there is a need to co-develop such an intervention with patients, general practice staff and relevant policy experts. We outline a framework for a future evaluation of such an intervention. Study registration: This study is registered as ResearchRegistry6523 (www.researchregistry.com/browse-the-registry#home/?view_2_search=Di-Facto&view_2_page=1) and PROSPERO CRD42020189019 (www.crd.york.ac.uk/prospero/display_record.php?RecordID=189019). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR128268) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 32. See the NIHR Funding and Awards website for further award information.

Online services are common in the National Health Service. This research looked at 'digital facilitation' in general practices. Digital facilitation is about supporting National Health Service patients in their use of online services. We aimed to understand how much digital facilitation is being used by general practices. We also looked at how digital facilitation happens and if it affects the number of people using online services. We looked at previous research to help us understand what approaches have been used to support patients to use online services. We used surveys to ask staff at general practices what they were already doing, and to ask patients about their experiences. We observed digital facilitation in general practices and spoke to patients and staff to help us understand the benefits and challenges of different approaches. We combined findings from the three stages outlined above to identify key aspects of digital facilitation. All stages of our research included discussions with the project's patient advisory group. We found that digital facilitation is seen as important and has many forms. Most general practices are using passive and reactive types of facilitation. An example of passive facilitation, initiated by the service but not involving direct inter-personal interaction, is the use of text messaging relating to ordering of repeat prescriptions online. An example of reactive facilitation is providing a response to a patient-initiated query regarding online access. There is clear scope to develop a more proactive approach to facilitation that actively engages patients. Our research highlights a lack of clarity over who is responsible for digital facilitation. Different people (patients, staff, policy-makers) often think that the responsibility lies with others. Investment in digital facilitation is needed. Tools and platforms for digital facilitation that meet patients' and general practices' needs should be developed.

Neuropsychiatric symptoms in cognitive decline and Alzheimer's disease: biomarker discovery using plasma proteomics.

BACKGROUND AND OBJECTIVES: Neuropsychiatric symptoms (NPS) are common in older people with cognitive impairment and Alzheimer's disease (AD). No biomarkers to detect the related pathology or predict the clinical evolution of NPS are available yet. This study aimed to identify plasma proteins that may serve as biomarkers for NPS and NPS-related clinical disease progression. METHODS: A panel of 190 plasma proteins was quantified using Luminex xMAP in the Alzheimer's Disease Neuroimaging Initiative cohort. NPS and cognitive performance were assessed at baseline and after 1 and 2 years. Logistic regression, receiver operating characteristic analysis and cross-validation were used to address the relations of interest. RESULTS: A total of 507 participants with mild cognitive impairment (n=396) or mild AD dementia (n=111) were considered. Selected plasma proteins improved the prediction of NPS (area under the curve (AUC) from 0.61 to 0.76, p<0.001) and future NPS (AUC from 0.63 to 0.80, p<0.001) when added to a reference model. Distinct protein panels were identified for single symptoms. Among the selected proteins, ANGT, CCL1 and IL3 were associated with NPS at all three time points while CCL1, serum glutamic oxaloacetic transaminase and complement factor H were also associated with cognitive decline. The associations were independent of the presence of cerebral AD pathology as assessed using cerebrospinal fluid biomarkers. CONCLUSIONS: Plasma proteins are associated with NPS and improve prediction of future NPS.

Aortic reservoir-excess pressure parameters are associated with worse cognitive function in people with untreated stage II/III hypertension.

OBJECTIVE: Hypertension is a recognized risk factor for the development of cognitive impairment and dementia in older adults. Aortic stiffness and altered haemodynamics could promote the transmission of detrimental high pressure pulsatility into the cerebral circulation, potentially damaging brain microvasculature and leading to cognitive impairment. We determined whether reservoir-excess pressure parameters were associated with cognitive function in people with hypertension (HT) and normotension (NT). METHODS: We studied 35 middle-aged and older treatment-naïve stage II/III HT (office systolic BP 176 ±â€Š17 mmHg) and 35 age-, sex- and body mass index-matched NT (office systolic BP 127 ±â€Š8 mmHg). Parameters derived from reservoir-excess pressure analysis including reservoir pressure integral (INTPR), excess pressure integral (INTXSP), systolic rate constant (SRC), diastolic rate constant (DRC) and pulse wave velocity (PWV) were calculated from an ensemble-averaged aortic pressure waveform derived from radial artery tonometry. Cognitive function was assessed using the Addenbrooke's Cognitive Examination Revised (ACE-R), Trail Making Test Part A (TMT-A) and Part B (TMT-B). RESULTS: All reservoir-excess pressure parameters were greater in HT than NT (all P < 0.05). Greater INTXSP was associated with lower ACE-R score (rs = -0.31), longer TMT-A (r = 0.31) and TMT-B (r = 0.38). Likewise, greater DRC and PWV were also associated with lower ACE-R score (rs = -0.27 and rs = -0.33), longer TMT-A (r = 0.51 and r = 0.40) and TMT-B (r = 0.38 and r = 0.32). Greater INTXSP, DRC and PWV are consistently associated with worse cognitive function in this study. CONCLUSIONS: These observations support a potential mechanistic link between adverse haemodynamics and a heightened risk of cognitive impairment in older adults with hypertension.

Exploring How Patients Are Supported to Use Online Services in Primary Care in England Through "Digital Facilitation": Survey Study.

BACKGROUND: Health service policy in many jurisdictions is driving greater investment into digital primary care services. While some patients and practices may benefit, there are concerns that not all are able or wish to access primary care services online. "Digital facilitation" is the "range of processes, procedures, and personnel seeking to support patients in their uptake and use of online services" and may address such concerns. OBJECTIVE: As part of a multimethod research program, we undertook surveys of practice staff and patients to gain insight into the support being offered by practices and explore patients' experiences of this support. METHODS: General practices from 4 regions of England were sent a questionnaire exploring the modes of digital facilitation offered, the personnel involved in its delivery, and views on the motivations and drivers for providing support. Moreover, 12,822 patients registered with 62 general practices (predominantly those providing practice survey responses) were sent a questionnaire exploring their experiences of any support offered by their practice to use online services. RESULTS: Almost one-third of practices (156/500, 31.2%) responded to the practice survey, with most reporting using passive modes of digital facilitation (eg, display, leaflets, and SMS text messages) and few using active modes (eg, offering tablets or computers or using practice champions). However, 90.9% (130/143) reported providing ad hoc support. Practices agreed that it was the responsibility of both the practice (105/144, 72.9%) and the wider National Health Service (118/143, 82.5%) to support patients in using online services and that providing such support benefited the practice (126/144, 87.5%) and their patients (132/144, 91.7%). Nearly a quarter of the patients (3051/12,822, 23.8%) responded to the patient survey, with few (522/3051, 17.11% or less) reporting awareness of any modes of digital facilitation apart from text messages and emails (1205/3051, 39.5%) and only 13.36% (392/2935) reporting receiving support to use online services. Adjusted logistic regression analyses showed that older patients had a lower likelihood of 4 outcomes: being aware of, or of using, digital facilitation efforts, or being told about or being helped to use online services (all P<.05), particularly with regard to being helped to use online services (adjusted odds ratio for patients aged 85 years versus those aged 55-64 years: 0.08, 95% CI 0.02-0.36). However, ethnic minority participants or those for whom their first language was not English had positive associations with these outcomes. CONCLUSIONS: General practices recognize that patients would benefit from support to access online services. However, the support provided is often passive or ad hoc, and patients were seldom aware of digital facilitation efforts that their practice provided. There is potential to increase engagement with online primary care services by providing more support for all patients, particularly to provide targeted support for older patients.

Plasma neurofilament light, glial fibrillary acid protein, and phosphorylated tau 181 as biomarkers for neuropsychiatric symptoms and related clinical disease progression.

BACKGROUND: Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer's disease (AD) pathology and cognitive decline. METHODS: One hundred and fifty-one participants with normal cognition (n = 76) or mild cognitive impairment (n = 75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Different regression and ROC analyses were used to address the associations of interest. RESULTS: None of the three plasma biomarker was associated with NPS at baseline. Higher GFAP levels were associated with the presence of NPS at follow-up (OR = 2.8, p = .002) and both, higher NfL and higher GFAP with an increase in the NPI-Q severity score over time (ß = 0.25, p = .034 and ß = 0.30, p = .013, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.72 to 0.88, p = .002) and AD pathology (AUC 0.78 to 0.87, p = .010), but not of cognitive decline (AUC 0.79 to 0.85, p = .081). CONCLUSION: Plasma NfL and GFAP are both associated with future NPS and NPS severity change. Considering the presence of NPS along with blood-based AD-biomarkers may improve the prediction of clinical progression of NPS over time and inform clinical decision-making in non-demented older people.

Choice of antiretroviral therapy has low impact on weight gain.

OBJECTIVE: Antiretroviral therapy (ART) containing integrase inhibitors (INSTIs) and/or tenofovir alafenamide (TAF) has been associated with greater weight gain. Yet few studies have delineated between exposure to 'anchor' drugs [protease inhibitors (PI), nonnucleoside reverse transcriptase inhibitors (NNRTI) or INSTIs] and exposure to nucleoside reverse transcriptase inhibitors (NRTIs). DESIGN: In this cohort of antiretroviral drug-naive patients who initiated ART from 2008-2022, we analyzed BMI gain for eight contemporary 'anchor' drugs and three contemporary NRTIs during the first 3 years of ART. We censored patients if they stopped, switched, or added another antiretroviral drug to their regimen. METHODS: We used generalized estimating equations (GEE) to assess the association between BMI gain and choice of ART and a nonlinear mixed model for the marginal coefficients of determination. We adjusted for time, baseline demographic and HIV-characteristics, and time-updated HIV and substance use-related variables. RESULTS: The median BMI gain in 4 194 patients over 3 years was + 1.9 kg/m 2 [interquartile range (IQR) 0.1-4.1]. Most patients were black (55%) and men (77%). Multivariable modeling from 20 528 BMI measurements revealed that the type of ART accounted for just 9% of the predicted BMI change. Only efavirenz (EFV) and tenofovir disoproxil fumarate (TDF) were independently associated with (lower) weight gain but no differences were observed between INSTIs, PIs, and rilpivirine, or between TAF and abacavir. CONCLUSION: The choice of initial ART had little impact on weight gain. INSTIs or TAF were not independently associated with weight change after ART initiation, but EFV and TDF were.

Geographic variation in projected US forest aboveground carbon responses to climate change and atmospheric deposition.

Forest composition and ecosystem services are sensitive to anthropogenic pressures like climate change and atmospheric deposition of nitrogen (N) and sulfur (S). Here we extend recent forest projections for the current cohort of trees in the contiguous US, characterizing potential changes in aboveground tree carbon at the county level in response to varying mean annual temperature, precipitation, and N and S deposition. We found that relative to a scenario with N and S deposition reduction and no climate change, greater climate change led generally to decreasing aboveground carbon (mean -7.5% under RCP4.5, -16% under RCP8.5). Keeping climate constant, reduced N deposition tended to lessen aboveground carbon (mean -7%), whereas reduced S deposition tended to increase aboveground carbon (+3%) by 2100. Through mid-century (2050), deposition was more important for predicting carbon responses except under the extreme climate scenarios (RCP8.5); but, by 2100, climate drivers generally outweighed deposition. While more than 70% of counties showed reductions in aboveground carbon relative to the reference scenario, these were not evenly distributed across the US. Counties in the Northwest and Northern Great Plains, and the northern parts of New England and the Midwest, primarily showed positive responses, while counties in the Southeast showed negative responses. Counties with greater initial biomass showed less negative responses to climate change while those which exhibited the greatest change in composition (>15%) had a 95% chance of losing carbon relative to a no-climate change scenario. This analysis highlights that declines in forest growth and survival due to increases in mean temperature and reductions in atmospheric N deposition are likely to outweigh positive impacts of reduced S deposition and potential increases in precipitation. These effects vary at the regional and county level, however, so forest managers must consider local rather than national dynamics to maximize forest carbon sinks in the future.

Emerging Fungal Pathogen Rhodotorula Species Isolated From a Patient With a Lung Malignancy.

Rhodotorula is a genus of ubiquitous pigmented yeast found in the environment and as a commensal of human and animal microbiota. Previously considered nonpathogenic, Rhodotorula has emerged as an important cause of nosocomial and opportunistic infections in susceptible patients. While Rhodotorula spp. are common commensals in healthy individuals, the yeast may overgrow in patients with compromised immune systems causing disease. Herein, we provide a detailed presentation of a rare case involving a 79-year-old Caucasian female with a lung malignancy who developed massive cavitations in her lungs. The patient's lung tissue was cultured and grew an unidentified species of the genus Rhodotorula. The patient's health declined rapidly, and she expired due to hypoxemia. Clinicians must recognize patient groups potentially at risk for infection with Rhodotorula spp. Early identification and initiation of appropriate interventions are crucial in reducing mortality associated with this opportunistic fungal infection.

Climate change could negate U.S. forest ecosystem service benefits gained through reductions in nitrogen and sulfur deposition.

Climate change and atmospheric deposition of nitrogen (N) and sulfur (S) impact the health and productivity of forests. Here, we explored the potential impacts of these environmental stressors on ecosystem services provided by future forests in the contiguous U.S. We found that all stand-level services benefitted (+ 2.6 to 8.1%) from reductions in N+S deposition, largely attributable to positive responses to reduced S that offset the net negative effects of lower N levels. Sawtimber responded positively (+ 0.5 to 0.6%) to some climate change, but negatively (- 2.4 to - 3.8%) to the most extreme scenarios. Aboveground carbon (C) sequestration and forest diversity were negatively impacted by all modelled changes in climate. Notably, the most extreme climate scenario eliminated gains in all three services achieved through reduced deposition. As individual tree species responded differently to climate change and atmospheric deposition, associated services unique to each species increased or decreased under future scenarios. Our results suggest that climate change should be considered when evaluating the benefits of N and S air pollution policies on the services provided by U.S. forests.

Cognitive outcome and its neural correlates after cardiorespiratory arrest in childhood.

Hypoxia-ischaemia (HI) can result in structural brain abnormalities, which in turn can lead to behavioural deficits in various cognitive and motor domains, in both adult and paediatric populations. Cardiorespiratory arrest (CA) is a major cause of hypoxia-ischaemia in adults, but it is relatively rare in infants and children. While the effects of adult CA on brain and cognition have been widely studied, to date, there are no studies examining the neurodevelopmental outcome of children who suffered CA early in life. Here, we studied the long-term outcome of 28 children who suffered early CA (i.e., before age 16). They were compared to a group of control participants (n = 28) matched for age, sex and socio-economic status. The patient group had impairments in the domains of memory, language and academic attainment (measured using standardised tests). Individual scores within the impaired range were most commonly found within the memory domain (79%), followed by academic attainment (50%), and language (36%). The patient group also had reduced whole brain grey matter volume, and reduced volume and fractional anisotropy of the white matter. In addition, lower performance on memory tests was correlated with bilaterally reduced volume of the hippocampi, thalami, and striatum, while lower attainment scores were correlated with bilateral reduction of fractional anisotropy in the superior cerebellar peduncle, the main output tract of the cerebellum. We conclude that patients who suffered early CA are at risk of developing specific cognitive deficits associated with structural brain abnormalities. RESEARCH HIGHLIGHTS: Our data shed light on the long-term outcome and associated neural mechanisms after paediatric hypoxia-ischaemia as a result of cardiorespiratory arrest. Patients had impaired scores on memory, language and academic attainment. Memory impairments were associated with smaller hippocampi, thalami, and striatum. Lower academic attainment correlated with reduced fractional anisotropy of the superior cerebellar peduncle.

Quantitative Foot Muscle Magnetic Resonance Imaging Reliably Measures Disease Progression in Children and Adolescents with Charcot-Marie-Tooth Disease Type 1A.

Quantitative muscle fat fraction (FF) responsiveness is lower in younger Charcot-Marie-Tooth disease type 1A (CMT1A) patients with lower baseline calf-level FF. We investigated the practicality, validity, and responsiveness of foot-level FF in this cohort involving 22 CMT1A patients and 14 controls. The mean baseline foot-level FF was 25.9 ± 20.3% in CMT1A patients, and the 365-day FF (n = 15) increased by 2.0 ± 2.4% (p < 0.001 vs controls). Intrinsic foot-level FF demonstrated large responsiveness (12-month standardized response mean (SRM) of 0.86) and correlated with the CMT examination score (ρ = 0.58, P = 0.01). Intrinsic foot-level FF has the potential to be used as a biomarker in future clinical trials involving younger CMT1A patients. ANN NEUROL 2024;96:170-174.

Plasma neurofilament light, glial fibrillary acid protein, and phosphorylated tau 181 as biomarkers for neuropsychiatric symptoms and related clinical disease progression.

BACKGROUND: Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer's disease (AD) pathology and cognitive decline. METHODS: One hundred and fifty-one participants with normal cognition (n=76) or mild cognitive impairment (n=75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Linear regression and ROC analyses were used to address the associations of interest. RESULTS: Higher GFAP levels were associated with NPS at baseline (ß=0.23, p=.008). Higher NfL and GFAP levels were associated with the presence of NPS at follow-up (ß=0.29, p=.007 and ß=0.28, p=.007, respectively) and with an increase in the NPI-Q severity score over time (ß=0.23, p=.035 and ß=0.27, p=.011, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.73 to 0.84, p=.007) and AD pathology (AUC 0.79 to 0.86, p=.006), but not of cognitive decline (AUC 0.79 to 0.84, p=.068). CONCLUSION: Plasma GFAP is associated with NPS while NfL and GFAP are both associated with future NPS and NPS severity. Considering the presence of NPS along with blood-based AD-biomarkers may improve diagnosis and prediction of clinical progression of NPS and inform clinical decision-making in non-demented older people.

'Legacy publication of a 2009 validation of the Riester Big Ben Square Desk aneroid device for blood pressure measurement according to the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults (2002)'.

OBJECTIVE: To report a validation of the Riester Big Ben Square Desk Aneroid Sphygmomanometer according to the international protocol developed by the Working Group on Blood Pressure Monitoring of the European Society of Hypertension 2002 (ESH-IP 2002) in the interest of transparency. This legacy publication is intended to assure users that the device satisfied the requirements in place at that time. METHODS: Performance of the device was assessed by participants' age, sex, arm circumference and entry SBP/DBP. Validation was performed in 33 participants. The sphygmomanometer was assessed according to the ESH-IP, which defines zones of accuracy compared to the mercury standard as ≤5, ≤10, ≤15 mmHg or more. RESULTS: The mean (± SD) age was 50.5 ±â€…13.0 years, range 29-71 years, entry SBP 142.6 ±â€…23.7 mmHg, entry DBP 89.0 ±â€…17.8 mmHg. The device passed all the requirements listed and the validation protocol. The Riester Big Ben Square Desk aneroid sphygmomanometer slightly underestimated the observer-measured SBP, yet slightly overestimated DBP. The observer-device disagreement was -0.8 ±â€…6.4 mmHg SBP and +0.6 ±â€…4.0 mmHg DBP. CONCLUSION: These data show that the Riester Big Ben Square Desk aneroid sphygmomanometer fulfilled the ESH-IP 2002 requirements for the validation of BP monitors. It was on this basis that the British and Irish Hypertension Society recommended it for clinical use in the adult population.

Peripheral artery disease recognition, diagnosis, and management in general practice in the Republic of Ireland and England: an online survey.

BACKGROUND: Peripheral artery disease (PAD) is common and associated with future cardiovascular events. PAD is underdiagnosed, which limits opportunities to address secondary prevention of cardiovascular disease. It is unknown how closely guidelines for detection of PAD are followed in primary care. AIM: To survey GPs' attitudes to diagnosis and follow-up of patients with PAD. DESIGN & SETTING: Online survey of GPs in England and the Republic of Ireland (RoI). METHOD: GPs' approaches to management of PAD were assessed using likelihood ratings (scales of 0-10) and discrete questions. Findings were summarised as proportions, or median and interquartile ranges (IQR). RESULTS: In total, 111 responses were analysed; 68 (61%) from England and 43 (39%) from the RoI. Considering a hypothetical patient at risk of PAD, likelihood of GPs enquiring about PAD symptoms (leg pains: 3/10 or erectile dysfunction: 2/10) was low. GPs in the RoI compared with GPs in England more often examined the heart (10/10 versus 7/10) or carotid vessels (5/10 versus 1/10). Lower limb pulses were palpated in response to symptoms or signs of PAD. In England 25% of practitioners, and in the RoI 55% of practitioners, reported that they do not measure ankle-brachial index (ABI). CONCLUSION: Currently, detection of PAD is generally triggered by 'classical' leg claudication symptoms, while known vascular risk factors appear to elicit little consideration. ABI measurement is not performed by many practitioners, suggesting that a proportion of vascular referrals must be based on history and examination findings alone. Opportunities to recognise PAD are missed.

Cholesterol-metabolism, plant sterols, and long-term cognitive decline in older people - Effects of sex and APOEe4.

Neurodegenerative, vascular, and dementia diseases are linked to dysregulations in cholesterol metabolism. Dietary plant sterols, or phytosterols, may interfere to neurodegeneration and cognitive decline, and have cholesterol-lowering, anti-inflammatory, and antioxidant qualities. Here, we investigated the potential associations between circulating cholesterol precursors and metabolites, triglycerides, and phytosterols with cognitive decline in older people by performing multivariate analysis on 246 participants engaged in a population-based prospective study. In our analysis we considered the potential effect of sex and APOEe4. We reveal particular dysregulations of diet-derived phytosterols and endogenous cholesterol synthesis and metabolism, and their variations over time linked to cognitive decline in the general population. These results are significant to the development of interventions to avoid cognitive decline in older adults and suggest that levels of circulating sterols should be taken into account when evaluating risk.

Characterisation of paediatric brain tumours by their MRS metabolite profiles.

1H-magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single-voxel MRS (point-resolved single-voxel spectroscopy sequence, 1.5 T: echo time [TE] 23-37 ms/135-144 ms, repetition time [TR] 1500 ms; 3 T: TE 37-41 ms/135-144 ms, TR 2000 ms) was performed from 2003 to 2012 during routine magnetic resonance imaging for a suspected brain tumour on 340 children from five hospitals with 464 spectra being available for analysis and 281 meeting quality control. Mean spectra were generated for 13 tumour types. Mann-Whitney U-tests and Kruskal-Wallis tests were used to compare mean metabolite concentrations. Receiver operator characteristic curves were used to determine the potential for individual metabolites to discriminate between specific tumour types. Principal component analysis followed by linear discriminant analysis was used to construct a classifier to discriminate the three main central nervous system tumour types in paediatrics. Mean concentrations of metabolites were shown to differ significantly between tumour types. Large variability existed across each tumour type, but individual metabolites were able to aid discrimination between some tumour types of importance. Complete metabolite profiles were found to be strongly characteristic of tumour type and, when combined with the machine learning methods, demonstrated a diagnostic accuracy of 93% for distinguishing between the three main tumour groups (medulloblastoma, pilocytic astrocytoma and ependymoma). The accuracy of this approach was similar even when data of marginal quality were included, greatly reducing the proportion of MRS excluded for poor quality. Children's brain tumours are strongly characterised by MRS metabolite profiles readily acquired during routine clinical practice, and this information can be used to support noninvasive diagnosis. This study provides both key evidence and an important resource for the future use of MRS in the diagnosis of children's brain tumours.

Cost Effectiveness of Endovascular Ultrasound Renal Denervation in Patients with Resistant Hypertension.

BACKGROUND: Resistant hypertension (rHTN) is defined as blood pressure (BP) of ≥ 140/90 mmHg despite treatment with at least three antihypertensive medications, including a diuretic. Endovascular ultrasound renal denervation (uRDN) aims to control BP alongside conventional BP treatment with antihypertensive medication. This analysis assesses the cost effectiveness of the addition of the Paradise uRDN System compared with standard of care alone in patients with rHTN from the perspective of the United Kingdom (UK) health care system. METHODS: Using RADIANCE-HTN TRIO trial data, we developed a state-transition model. Baseline risk was calculated using Framingham and Prospective Cardiovascular Münster (PROCAM) risk equations to estimate the long-term cardiovascular risks in patients treated with the Paradise uRDN System, based on the observed systolic BP (SBP) reduction following uRDN. Relative risks sourced from a meta-analysis of randomised controlled trials were then used to project cardiovascular events in patients with baseline SBP ('control' patients); utility and mortality inputs and costs were derived from UK data. Costs and outcomes were discounted at 3.5% per annum. Modelled outcomes were validated against trial meta-analyses and the QRISK3 algorithm and real-world evidence of RDN effectiveness. One-way and probabilistic sensitivity analyses were conducted to assess the uncertainty surrounding the model inputs and sensitivity of the model results to changes in parameter inputs. Results were reported as incremental cost-effectiveness ratios (ICERs). RESULTS: A mean reduction in office SBP of 8.5 mmHg with uRDN resulted in an average improvement in both absolute life-years (LYs) and quality-adjusted life-years (QALYs) gained compared with standard of care alone (0.73 LYs and 0.67 QALYs). The overall base-case ICER with uRDN was estimated at £5600 (€6500) per QALY gained (95% confidence interval £5463-£5739 [€6341-€6661]); modelling demonstrated > 99% probability that the ICER is below the £20,000-£30,000 (€23,214-€34,821) per QALYs gained willingness-to-pay threshold in the UK. Results were consistent across sensitivity analyses and validation checks. CONCLUSIONS: Endovascular ultrasound RDN with the Paradise system offers patients with rHTN, clinicians, and healthcare systems a cost-effective treatment option alongside antihypertensive medication.