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AIMS: There is rising healthcare utilization related to the increasing incidence and prevalence of atrial fibrillation (AF) worldwide. Simplifying therapy and reducing hospital episodes would be a valuable development. The efficacy of a streamlined AF ablation approach was compared to drug therapy and a conventional catheter ablation technique for symptom control in paroxysmal AF. METHODS AND RESULTS: We recruited 321 patients with symptomatic paroxysmal AF to a prospective randomized, multi-centre, open label trial at 13 UK hospitals. Patients were randomized 1:1:1 to cryo-balloon ablation without electrical mapping with patients discharged same day [Ablation Versus Anti-arrhythmic Therapy for Reducing All Hospital Episodes from Recurrent (AVATAR) protocol]; optimization of drug therapy; or cryo-balloon ablation with confirmation of pulmonary vein isolation and overnight hospitalization. The primary endpoint was time to any hospital episode related to treatment for atrial arrhythmia. Secondary endpoints included complications of treatment and quality-of-life measures. The hazard ratio (HR) for a primary endpoint event occurring when comparing AVATAR protocol arm to drug therapy was 0.156 (95% CI, 0.097-0.250; P < 0.0001 by Cox regression). Twenty-three patients (21%) recorded an endpoint event in the AVATAR arm compared to 76 patients (74%) within the drug therapy arm. Comparing AVATAR and conventional ablation arms resulted in a non-significant HR of 1.173 (95% CI, 0.639-2.154; P = 0.61 by Cox regression) with 23 patients (21%) and 19 patients (18%), respectively, recording primary endpoint events (P = 0.61 by log-rank test). CONCLUSION: The AVATAR protocol was superior to drug therapy for avoiding hospital episodes related to AF treatment, but conventional cryoablation was not superior to the AVATAR protocol. This could have wide-ranging implications on how demand for AF symptom control is met. TRIAL REGISTRATION: Clinical Trials Registration: NCT02459574.
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Antiarrítmicos/efeitos adversos , Resultado do Tratamento , Estudos Prospectivos , Hospitais , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , RecidivaRESUMO
OBJECTIVE: The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12âmonths and for 12âmonths after explantation. SUMMARY BACKGROUND DATA: This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery. METHODS: In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12âmonths. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24âmonths. RESULTS: There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12âmonths [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44-2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12âmonths (OR 8.3, 95% CI: 1.8-39; Pâ=â.007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group. CONCLUSIONS: The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions. TRIAL REGISTRATION: ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.
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Diabetes Mellitus Tipo 2/cirurgia , Duodeno/cirurgia , Derivação Jejunoileal , Jejuno/cirurgia , Obesidade/cirurgia , Adulto , Feminino , Humanos , Derivação Jejunoileal/efeitos adversos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Atrial Fibrillation (AF) ablation using the cryoballoon is effective at reducing symptomatic AF episodes. The prevalence of AF is increasing with the aging population and access to such treatment would be enhanced by reducing the resource requirements. Relinquishing electrical mapping of the pulmonary veins (PV) removes the need for PV catheters, electrical recording equipment and staff trained in using this equipment. Moreover, the majority of complications are peri-procedural so overnight hospitalization maybe unnecessary. We tested this streamlined approach to AF ablation against medical therapy using the endpoint of time to all hospital episodes. METHODS: The AVATAR-AF study is a prospective, multicenter, randomized controlled trial testing the primary hypothesis that AF ablation done without PV mapping or overnight hospitalization is more effective than anti-arrhythmic drugs at reducing all hospital episodes related to recurrent atrial arrhythmias. We included a third arm to test a secondary hypothesis that confirming PV entrance block as per consensus guidelines can improve outcomes. Three hundred twenty-one patients with documented paroxysmal AF will be randomized in a 1:1:1 manner to one of three investigation arms: (1) AVATAR protocol cryoballoon ablation without assessment of acute PV isolation or overnight hospitalization; (2) medical therapy with anti-arrhythmic drugs; or (3) conventional cryoballoon ablation with assessment of acute PV isolation. The primary endpoint is defined as the time to all hospital episodes (including outpatient consultation) related to treatment for atrial arrhythmia. CONCLUSION: The AVATAR-AF study will determine whether the resource utilization for AF ablation can be reduced whilst maintaining superiority over medical therapy.
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Antiarrítmicos/uso terapêutico , Fibrilação Atrial , Ablação por Cateter/métodos , Criocirurgia/métodos , Hospitalização , Veias Pulmonares/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Ambulatórios/métodos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Estudos Cross-Over , Fenômenos Eletrofisiológicos , Humanos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Veias Pulmonares/fisiopatologia , Recidiva , Avaliação de Sintomas , Resultado do TratamentoRESUMO
INTRODUCTION: The European Medicines Agency (EMA) requires that a specific valved holding chamber (VHC) is designated for use with a given pressurised metered dose inhaler (pMDI). No other regulatory authorities impose similar requirements, implying that VHCs are interchangeable. This in vitro study, employing EMA assessment criteria, assessed the equivalence of four anti-static VHCs (aVHCs) versus the non-conducting VHC most widely referenced in pMDI monographs, the AeroChamber Plus™ (AC+) VHC. MATERIAL & METHODS: The "reference" AC + VHC was prepared by soaking in detergent solution. The four test aVHCs (AeroChamber Plus™ Flow-Vu™ [AC + FV]; Compact Space Chamber Plus [CSC+]; InspiraChamber [IC]; OptiChamber Diamond™ [OCD]) were tested "out-of-packet". Twenty devices of each type were evaluated. A salbutamol pMDI was actuated into each VHC with a 2-s delay between actuation and Andersen Cascade Impactor (ACI) sampling. Drug deposition in four ACI particle size groups was assessed: Group 1, >5.8-10 µm; Group 2, >3.3-5.8 µm; Group 3, >1.1-3.3 µm; Group 4, ≤1.1 µm. Equivalence versus the reference VHC was demonstrated where the 90% confidence interval for the test/reference mass ratio was within 85-118%. RESULTS: The mass retained within the VHC was similar for the AC + VHC and AC + FV aVHC, but was approximately twice as great for the other aVHCs. Salbutamol deposition in all ACI groups with the AC + FV aVHC was equivalent to the reference AC + VHC. By contrast, deposition in ACI groups 1 to 3 with the CSC+, IC and OCD aVHCs was inequivalent to (approximately half that of) the reference VHC. Inter-device variability for each VHC type was greatest for the IC and least for the AC + VHC and AC + FV aVHC. CONCLUSIONS: The performance of VHCs that superficially resemble one another may differ markedly. Thus, as implied by EMA guidelines, VHCs should not automatically be considered to be interchangeable.
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Albuterol/administração & dosagem , Sistemas de Liberação de Medicamentos , Espaçadores de Inalação , Inaladores Dosimetrados , Administração por Inalação , Aerossóis , Broncodilatadores/administração & dosagem , Desenho de Equipamento , Tamanho da PartículaRESUMO
AIMS: The AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK) trial investigated whether ACE-inhibition reduces small abdominal aortic aneurysms (AAA) growth rate, independent of blood pressure (BP) lowering. METHODS AND RESULTS: A three-arm, multi-centre, single-blind, and randomized controlled trial (ISRCTN51383267) was conducted in 14 hospitals in England. Subjects aged ≥55 years with AAA diameter 3.0-5.4 cm were randomized 1:1:1 to receive perindopril arginine 10 mg, or amlodipine 5 mg, or placebo and followed 3-6 monthly over 2 years. The primary outcome was aneurysm growth rate (based on external antero-posterior ultrasound measurements in the longitudinal plane), determined by multi-level modelling to provide maximum likelihood estimates. Two hundred and twenty-four subjects were randomized (2011-2013) to placebo (n = 79), perindopril (n = 73), or amlodipine (n = 72). Mean (SD) changes in mid-trial systolic BP (12 months) were 0.5 (14.3) mmHg, P = 0.78 compared with baseline, -9.5 (13.1) mmHg (P < 0.001), and -6.7 (12.0) mmHg (P < 0.001), respectively. No significant differences in the modelled annual growth rates were apparent [1.68 mm (SE 0.2), 1.77 mm (0.2), and 1.81 mm (0.2), respectively]. The estimated difference in annual growth between the perindopril and placebo groups was 0.08 mm (CI -0.50, 0.65). Similar numbers of AAAs in each group reached 5.5 cm diameter and/or underwent elective surgery: 11 receiving placebo, 10 perindopril, and 11 amlodipine. CONCLUSION: Small AAA growth rates were lower than anticipated, but there was no significant impact of perindopril compared with placebo or placebo and amlodipine, combined despite more effective BP lowering.
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Aneurisma da Aorta Abdominal , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos , Pressão Sanguínea , Método Duplo-Cego , Inglaterra , Humanos , Hipertensão , Funções Verossimilhança , Pessoa de Meia-Idade , Método Simples-CegoRESUMO
BACKGROUND AND PURPOSE: Abnormalities of the retinal circulation may be associated with cerebrovascular disease. We investigated associations between retinal microvascular abnormalities and (1) strokes and subclinical cerebral infarcts and (2) cerebral white matter lesions in a UK-based triethnic population-based cohort. METHODS: A total of 1185 participants (age, 68.8±6.1 years; 77% men) underwent retinal imaging and cerebral magnetic resonance imaging. Cerebral infarcts and white matter hyperintensities were identified on magnetic resonance imaging, retinopathy was graded, and retinal vessels were measured. RESULTS: Higher retinopathy grade (odds ratio [OR], 1.40 [95% confidence interval (95% CI), 1.16-1.70]), narrower arteriolar diameter (OR, 0.98 [95% CI, 0.97-0.99]), fewer symmetrical arteriolar bifurcations (OR, 0.84 [95% CI, 0.75-0.95]), higher arteriolar optimality deviation (OR, 1.16 [95% CI, 1.00-1.34]), and more tortuous venules (OR, 1.20 [95% CI, 1.09-1.32]) were associated with strokes/infarcts and white matter hyperintensities. Associations with quantitative retinal microvascular measures were independent of retinopathy. CONCLUSIONS: Abnormalities of the retinal microvasculature are independently associated with stroke, cerebral infarcts, and white matter lesions.
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Infarto Cerebral/diagnóstico por imagem , Leucoaraiose/diagnóstico por imagem , Doenças Retinianas/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Idoso , Arteríolas/diagnóstico por imagem , Infarto Cerebral/epidemiologia , Comorbidade , Feminino , Humanos , Leucoaraiose/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/epidemiologia , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND: Hypertension is the leading risk factor contributing to the global burden of disease. We aimed to assess the change in blood pressure management between 1994 and 2011 in England with a series of annual surveys. METHODS: We did a serial cross-sectional study of five Health Survey for England surveys based on nationally representative samples of non-institutionalised adults (aged ≥16 years). Mean blood pressure levels and rates of awareness, treatment, and control of hypertension were assessed. Hypertension was defined as systolic blood pressure 140 mm Hg or higher, diastolic blood pressure 90 mm Hg or higher, or receiving treatment for high blood pressure. FINDINGS: The mean blood pressure levels of men and women in the general population and among patients with treated hypertension progressively improved between 1994 and 2011. In patients with treated hypertension, blood pressure improved from 150·0 (SE 0·59)/80·2 (0·27) mm Hg to 135·4 (0·58)/73·5 (0·41) mm Hg. Awareness, treatment, and control rates among men and women combined also improved significantly across each stage of this 17-year period, with the prevalence of control among treated patients almost doubling from 33% (SE 1·4) in 1994 to 63% (1·7) in 2011. Nevertheless, of all adults with survey-defined hypertension in 2011, hypertension was controlled in only 37%. INTERPRETATION: If the same systematic improvement in all aspects of hypertension management continues until 2022, 80% of patients with treated hypertension will have controlled blood pressure levels with a potential annual saving of about 50,000 major cardiovascular events. FUNDING: None.
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Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Estudos Transversais , Quimioterapia Combinada , Uso de Medicamentos/estatística & dados numéricos , Inglaterra/epidemiologia , Feminino , Pesquisas sobre Atenção à Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Distribuição por Sexo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Treatment for hypertension with antihypertensive medication has been shown to reduce stroke, cardiovascular events, and mortality in older adults, but there is concern that such treatment may not be appropriate in frailer older adults. To investigate whether there is an interaction between effect of treatment for hypertension and frailty in older adults, we calculated the frailty index (FI) for all available participants from the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over, and obtained frailty adjusted estimates of the effect of treatment with antihypertensive medication on risk of stroke, cardiovascular events, and mortality. METHODS: Participants in HYVET were randomised 1:1 to active treatment with indapamide sustained release 1.5 mg ± perindopril 2 to 4 mg or to matching placebo. Data relating to blood pressure, comorbidities, cognitive function, depression, and quality of life were collected at entry into the study and at subsequent follow-up visits. The FI was calculated at entry, based on 60 potential deficits. The distribution of FI was similar to that seen in population studies of adults aged 80 years and above (median FI, 0.17; IQR, 0.11-0.24). Cox regression was used to assess the impact of FI at entry to the study on subsequent risk of stroke, total mortality, and cardiovascular events. Models were stratified by region of recruitment and adjusted for sex and age at entry. Extending these models to include a term for a possible interaction between treatment for hypertension and FI provided a formula for the treatment effect as a function of FI. For all three models, the point estimates of the hazard ratios for the treatment effect decreased as FI increased, although to varying degrees and with varying certainty. RESULTS: We found no evidence of an interaction between effect of treatment for hypertension and frailty as measured by the FI. Both the frailer and the fitter older adults with hypertension appeared to gain from treatment. CONCLUSIONS: Further work to examine whether antihypertensive treatment modifies frailty as measured by the FI should be explored. TRIAL REGISTRATION: ClinicalTrials.gov NCT00122811 (July 2005).
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Anti-Hipertensivos/uso terapêutico , Idoso Fragilizado , Hipertensão/tratamento farmacológico , Idoso de 80 Anos ou mais , Pressão Sanguínea/efeitos dos fármacos , Comorbidade , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/epidemiologia , Incidência , Indapamida/uso terapêutico , Masculino , Perindopril/uso terapêutico , Qualidade de Vida , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND: Combining multimodal lifestyle interventions and disease-modifying drugs (novel or repurposed) could provide novel precision approaches to prevent cognitive impairment. Metformin is a promising candidate in view of the well-established link between type 2 diabetes (T2D) and Alzheimer's Disease and emerging evidence of its potential neuro-protective effects (e.g. vascular, metabolic, anti-senescence). MET-FINGER aims to test a FINGER 2.0 multimodal intervention, combining an updated FINGER multidomain lifestyle intervention with metformin, where appropriate, in an APOE ε4-enriched population of older adults (60-79 years) at increased risk of dementia. METHODS: MET-FINGER is an international randomised, controlled, parallel-group, phase-IIb proof-of-concept clinical trial, where metformin is included through a trial-within-trial design. 600 participants will be recruited at three sites (UK, Finland, Sweden). Participants at increased risk of dementia based on vascular risk factors and cognitive screening, will be first randomised to the FINGER 2.0 intervention (lifestyle + metformin if eligible; active arm) or to receive regular health advice (control arm). Participants allocated to the FINGER 2.0 intervention group at risk indicators of T2D will be additionally randomised to receive metformin (2000 mg/day or 1000 mg/day) or placebo. The study duration is 2 years. The changes in global cognition (primary outcome, using a Neuropsychological Test Battery), memory, executive function, and processing speed cognitive domains; functional status; lifestyle, vascular, metabolic, and other dementia-related risk factors (secondary outcomes), will be compared between the FINGER 2.0 intervention and the control arm. The feasibility, potential interaction (between-groups differences in healthy lifestyle changes), and disease-modifying effects of the lifestyle-metformin combination will be exploratory outcomes. The lifestyle intervention is adapted from the original FINGER trial (diet, physical activity, cognitive training, monitoring of cardiovascular/metabolic risk factors, social interaction) to be consistently delivered in three countries. Metformin is administered as Glucophage®XR/SR 500, (500 mg oral tablets). The metformin/placebo treatment will be double blinded. CONCLUSION: MET-FINGER is the first trial combining a multimodal lifestyle intervention with a putative repurposed disease-modifying drug for cognitive impairment prevention. Although preliminary, its findings will provide crucial information for innovative precision prevention strategies and form the basis for a larger phase-III trial design and future research in this field. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05109169).
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Doença de Alzheimer , Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Metformina , Idoso , Humanos , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Reposicionamento de Medicamentos , Estilo de Vida , Metformina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Pessoa de Meia-IdadeRESUMO
AIMS: The randomized, double-blind, placebo-controlled HOPE-HF trial assessed the benefit of atrio-ventricular (AV) delay optimization delivered using His bundle pacing. It recruited patients with left ventricular ejection fraction ≤40%, PR interval ≥200 ms, and baseline QRS ≤140 ms or right bundle branch block. Overall, there was no significant increase in peak oxygen uptake (VO2max) but there was significant improvement in heart failure specific quality of life. In this pre-specified secondary analysis, we evaluated the impact of baseline PR interval, echocardiographic E-A fusion, and the magnitude of acute high-precision haemodynamic response to pacing, on outcomes. METHODS AND RESULTS: All 167 randomized participants underwent measurement of PR interval, acute haemodynamic response at optimized AV delay, and assessment of presence of E-A fusion. We tested the impact of these baseline parameters using a Bayesian ordinal model on VO2max, quality of life and activity measures. There was strong evidence of a beneficial interaction between the baseline acute haemodynamic response and the blinded benefit of pacing for VO2 (Pr 99.9%), Minnesota Living With Heart Failure (MLWHF) (Pr 99.8%), MLWHF physical limitation score (Pr 98.9%), EQ-5D visual analogue scale (Pr 99.6%), and exercise time (Pr 99.4%). The baseline PR interval and the presence of baseline E-A fusion did not have this reliable ability to predict the clinical benefit of pacing over placebo across multiple endpoints. CONCLUSIONS: In the HOPE-HF trial, the acute haemodynamic response to pacing reliably identified patients who obtained clinical benefit. Patients with a long PR interval (≥200 ms) and left ventricular impairment who obtained acute haemodynamic improvement with AV-optimized His bundle pacing were likely to obtain clinical benefit, consistent across multiple endpoints. Importantly, this gradation can be reliably tested for before randomization, but does require high-precision AV-optimized haemodynamic assessment to be performed.
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AIMS: Excessive prolongation of PR interval impairs coupling of atrio-ventricular (AV) contraction, which reduces left ventricular pre-load and stroke volume, and worsens symptoms. His bundle pacing allows AV delay shortening while maintaining normal ventricular activation. HOPE-HF evaluated whether AV optimized His pacing is preferable to no-pacing, in a double-blind cross-over fashion, in patients with heart failure, left ventricular ejection fraction (LVEF) ≤40%, PR interval ≥200 ms and either QRS ≤140 ms or right bundle branch block. METHODS AND RESULTS: Patients had atrial and His bundle leads implanted (and an implantable cardioverter-defibrillator lead if clinically indicated) and were randomized to 6 months of pacing and 6 months of no-pacing utilizing a cross-over design. The primary outcome was peak oxygen uptake during symptom-limited exercise. Quality of life, LVEF and patients' holistic symptomatic preference between arms were secondary outcomes. Overall, 167 patients were randomized: 90% men, 69 ± 10 years, QRS duration 124 ± 26 ms, PR interval 249 ± 59 ms, LVEF 33 ± 9%. Neither peak oxygen uptake (+0.25 ml/kg/min, 95% confidence interval [CI] -0.23 to +0.73, p = 0.3) nor LVEF (+0.5%, 95% CI -0.7 to 1.6, p = 0.4) changed with pacing but Minnesota Living with Heart Failure quality of life improved significantly (-3.7, 95% CI -7.1 to -0.3, p = 0.03). Seventy-six percent of patients preferred His bundle pacing-on and 24% pacing-off (p < 0.0001). CONCLUSION: His bundle pacing did not increase peak oxygen uptake but, under double-blind conditions, significantly improved quality of life and was symptomatically preferred by the clear majority of patients. Ventricular pacing delivered via the His bundle did not adversely impact ventricular function during the 6 months.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Masculino , Humanos , Feminino , Fascículo Atrioventricular , Estudos Cross-Over , Volume Sistólico , Qualidade de Vida , Tolerância ao Exercício , Função Ventricular Esquerda , Oxigênio , Resultado do Tratamento , Estimulação Cardíaca Artificial/métodos , Terapia de Ressincronização Cardíaca/métodos , Eletrocardiografia/métodosRESUMO
OBJECTIVES: to compare walking speed in the UK older population with the speed required to utilise pedestrian crossings (≥1.2 m/s), and determine health and socio-demographic associations with walking impairment. DESIGN: cross-sectional study using Health Survey for England 2005 data. SETTING: private households in England. PARTICIPANTS: random population sample of 3,145 adults (1,444 men) aged ≥65 years. MAIN OUTCOME MEASURES: walking speed was assessed by timing a walk of 8 feet at normal pace. Walking impairment was defined as walking speed <1.2 m/s or non-participation in the test due to being unsafe or unable. RESULTS: the mean walking speed was 0.9 m/s in men and 0.8 m/s in women; 84% of men and 93% of women ≥65 years had walking impairment. Female gender, increasing age, lower socio-economic status, poorer health and lower grip strength were predictors of walking impairment. CONCLUSION: most older adults either cannot walk 8 feet safely or cannot walk fast enough to use a pedestrian crossing in the UK. The health impacts on older adults include limited independence and reduced opportunities for physical activity and social interaction. An assumed normal walking speed for pedestrian crossings of 1.2 m/s is inappropriate for older adults and revision of these timings should be considered.
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Acidentes de Trânsito/estatística & dados numéricos , Limitação da Mobilidade , Caminhada/fisiologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Classe Social , Fatores de Tempo , Reino UnidoRESUMO
BACKGROUND: The acute respiratory distress syndrome (ARDS) occurs in response to a variety of insults, and mechanical ventilation is life-saving in this setting, but ventilator-induced lung injury can also contribute to the morbidity and mortality in the condition. The Beacon Caresystem is a model-based bedside decision support system using mathematical models tuned to the individual patient's physiology to advise on appropriate ventilator settings. Personalised approaches using individual patient description may be particularly advantageous in complex patients, including those who are difficult to mechanically ventilate and wean, in particular ARDS. METHODS: We will conduct a multi-centre international randomised, controlled, allocation concealed, open, pragmatic clinical trial to compare mechanical ventilation in ARDS patients following application of the Beacon Caresystem to that of standard routine care to investigate whether use of the system results in a reduction in driving pressure across all severities and phases of ARDS. DISCUSSION: Despite 20 years of clinical trial data showing significant improvements in ARDS mortality through mitigation of ventilator-induced lung injury, there remains a gap in its personalised application at the bedside. Importantly, the protective effects of higher positive end-expiratory pressure (PEEP) were noted only when there were associated decreases in driving pressure. Hence, the pressures set on the ventilator should be determined by the diseased lungs' pressure-volume relationship which is often unknown or difficult to determine. Knowledge of extent of recruitable lung could improve the ventilator driving pressure. Hence, personalised management demands the application of mechanical ventilation according to the physiological state of the diseased lung at that time. Hence, there is significant rationale for the development of point-of-care clinical decision support systems which help personalise ventilatory strategy according to the current physiology. Furthermore, the potential for the application of the Beacon Caresystem to facilitate local and remote management of large numbers of ventilated patients (as seen during this COVID-19 pandemic) could change the outcome of mechanically ventilated patients during the course of this and future pandemics. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04115709. Registered on 4 October 2019, version 4.0.
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COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Pulmão , Estudos Multicêntricos como Assunto , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial/efeitos adversos , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/terapia , SARS-CoV-2RESUMO
BACKGROUND: Antiretroviral therapy (ART) has led to dramatic improvements in survival for people living with HIV, but is unable to cure infection, or induce viral control off therapy. Designing intervention trials with novel agents with the potential to confer a period of HIV remission without ART remains a key scientific and community goal. We detail the rationale, design, and outcomes of a randomised, placebo-controlled trial of two HIV-specific long-acting broadly neutralising antibodies (bNAbs): 3BNC117-LS and 10-1074-LS, which target CD4 binding site and V3 loop respectively, on post-treatment viral control. METHODS: RIO is a randomised, placebo-controlled, double-blinded prospective phase II study. Eligible individuals will have started ART within 3 months of primary HIV infection and have viral sequences that appear to be sensitive to both bNAbs. It will randomise 72 eligible participants 1:1 to the following arms via a two-stage design. In Stage 1, arm A participants are given dual long-acting (LS-variants) bNAbs infusions, followed by intensively monitored Analytical Treatment Interruption (ATI) (n = 36); in arm B, participants receive placebo infusions followed by ATI. The primary endpoint will be time to viral rebound within 36 weeks after ATI. Upon viral rebound, the participant and researcher are unblinded. Participants in arm A recommence ART and complete the study. Participants in arm B are invited to restart ART and enroll into Stage 2 where they will receive open-label LS bNAbs, followed by a second ATI 24 weeks after. Secondary and exploratory endpoints include adverse events, time to undetectable viraemia after restarting ART, immunological markers, HIV proviral DNA, serum bNAb concentrations in blood, bNAb resistance at viral rebound, and quality of life measures. DISCUSSION: The two-stage design was determined in collaboration with community involvement. This design allows all participants the option to receive bNAbs. It also tests the hypothesis that bNAbs may drive sustained HIV control beyond the duration of detectable bNAb concentrations. Community representatives were involved at all stages. This included the two-stage design, discussion on the criteria to restart ART, frequency of monitoring visits off ART, and reducing the risk of onward transmission to HIV-negative partners. It also included responding to the challenges of COVID-19. TRIAL REGISTRATION: The protocol is registered on Clinical. TRIALS: gov and EudraCT and has approval from UK Ethics and MHRA.
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COVID-19 , Infecções por HIV , HIV-1 , Anticorpos Amplamente Neutralizantes , Ensaios Clínicos Fase II como Assunto , Participação da Comunidade , Anticorpos Anti-HIV , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate blood lipid levels in the adult English population in 2006 and to report change in the use and efficacy of lipid-lowering treatment since 2003 after which time the general practitioner contract introduced a 'pay-per-performance' approach. DESIGN: Cross-sectional surveys. PARTICIPANTS: Nationally representative sample of 14,142 noninstitutionalized adults (>16 years) living in England, partaking in the Health Survey for England 2006. MEASUREMENTS: Mean levels of total, HDL, non-HDL and total/HDL cholesterol ratio, prevalence of hypercholesterolaemia, use of lipid lowering agents and lipid levels and control rates among those on treatment. RESULTS: Age-standardized mean cholesterol levels fell from 5·49 mM in men and 5·56 mM in women in 2003 to 5·26 and 5·37 mM, respectively, in 2006. In 2006, 59% of adults had a total cholesterol ≥ 5·0 mM and 11% reported lipid-lowering treatment, of whom 66% had a total cholesterol < 5·0 mM and 22% were < 4·0 mM. The majority of those with established coronary heart disease, stroke or diabetes but fewer than one quarter of those with hypertension or ≥ 20% estimated 10-year cardiovascular risk and no established CVD took lipid-lowering drugs. Lipid lowering treatment rates increased fivefold and control rates among the treated (to < 5·0 mM) more than doubled between 1998 and 2006. About one-third of those with established CVD or diabetes had cholesterol levels of < 4·0 mM. CONCLUSIONS: Previously reported improvements in treatment and control rates between 1998 and 2003 continued between 2003 and 2006, with the biggest increases among those with established CVD and diabetes.
Assuntos
Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Adulto , Idoso , HDL-Colesterol/sangue , Estudos Transversais , Inglaterra , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Lipoproteínas HDL/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
AIMS: To assess the feasibility and reproducibility of non-invasive vascular assessment in a childhood population setting and identify the determinants of vascular phenotype in early life. METHODS AND RESULTS: We studied 7557 children (age 9.8-12.3 years) participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Six research technicians underwent a 5-month training protocol to enable study of brachial artery endothelial function by flow-mediated dilatation (FMD) and arterial stiffness by carotid to radial pulse wave velocity (PWV) and brachial distensibility [distensibility coefficient (DC)]. Reproducibility studies were performed at the beginning, the middle, and the end of the study. A blinded repeat evaluation of a random selection of 3% of the cohort was also undertaken throughout the study. The effect of anthropometric and environmental factors on each measure was examined. Successful measures were obtained in 88, 95, and 87% of the studied children for FMD, PWV, and DC, respectively. The coefficients of variation between technicians for FMD, PWV, and DC were 10.5, 4.6, and 6.6% at the beginning of the study and reached 7.7, 4.1, and 10% at the end. Baseline vessel diameter and gender were important determinants of all the vascular measures, with a small effect of room and skin temperatures on FMD and PWV. Boys consistently had lower FMD and DC and higher PWV measures (P < 0.01 for all). CONCLUSION: Reproducible, high-quality assessments of vascular structure and function in children can be made on a large scale in field studies by suitably trained non-specialist operators. This study provides an invaluable resource for assessing the impact of early influences, genetic, and environmental factors on arterial phenotype.
Assuntos
Endotélio Vascular/fisiologia , Hemodinâmica/genética , Fenótipo , Antropometria , Aterosclerose/genética , Aterosclerose/fisiopatologia , Aterosclerose/prevenção & controle , Velocidade do Fluxo Sanguíneo/genética , Pressão Sanguínea/genética , Artéria Braquial/fisiologia , Artérias Carótidas/fisiologia , Criança , Meio Ambiente , Estudos de Viabilidade , Feminino , Humanos , Estudos Longitudinais , Masculino , Resistência Vascular/genética , Vasodilatação/genéticaRESUMO
AIMS: to examine the associations of several markers of adiposity and a wide range of cardiovascular risk factors and biomarkers in pre-pubertal children. METHODS AND RESULTS: four measures of adiposity,body mass index (BMI), waist circumference, dual-energy X-ray absorptiometry (DXA)-determined fat mass, and leptin concentration, were available in up to 7589 children aged 8.8-11.7 (9.9 mean) years from the Avon Longitudinal Study of Parents and Children (ALSPAC). Thirteen per cent of boys and 18.8% of girls were overweight, and 5.3% of boys and 5% of girls were obese. Body mass index was highly correlated with waist circumference (r = 0.91), DXA fat mass (r = 0.87), and leptin concentration (r = 0.75), and all had similar associations with cardiovascular risk factors. A 1 kg/m(2) greater BMI was associated with 1.4 mmHg (95% CI 1.25-1.44) higher systolic blood pressure (BP). In 5002 children, a 1 kg/m(2) greater BMI was associated with a 0.05 mmol/L (95% CI 0.036-0.055) higher non-high-density lipoprotein (HDL) cholesterol and 0.03 mmol/L (95% CI -0.034 to -0.025) lower HDL cholesterol. There were also graded associations with apolipoproteins A1 and B, interleukin-6, and C-reactive protein. Comparing children who were obese with those who were normal weight, the odds ratio for hypertension was 10.7 (95% CI 7.2-15.9) for boys and 13.5 (95% CI 9.4-19.5) for girls. CONCLUSION: in pre-pubertal UK children, overweight/obesity is common and has broadly similar associations with BP, HDL cholesterol, and non-HDL cholesterol to those observed in adults. Future research should evaluate whether effective interventions to maintain healthy weight in childhood could have important benefits for adult cardiovascular risk.
Assuntos
Adiposidade/fisiologia , LDL-Colesterol/sangue , Hipertensão/etiologia , Hipertrigliceridemia/etiologia , Leptina/metabolismo , Sobrepeso/patologia , Absorciometria de Fóton , Tecido Adiposo/patologia , Índice de Massa Corporal , Criança , Feminino , Humanos , Hipertensão/patologia , Hipertrigliceridemia/patologia , Estudos Longitudinais , Masculino , Obesidade/patologia , Fatores de Risco , Circunferência da Cintura/fisiologiaRESUMO
PURPOSE: To explore age-trajectories of quality of life (QoL) and influences on them in a 4-year period among older adults living in England. METHODS: Data come from three waves (2002-2003 and 2006-2007) of the English Longitudinal Study of Ageing, a large panel study of 11,392 individuals aged 50 and over. We used Latent Growth Curve models and ageing-vector graphs to describe both individual differences and average population age-trajectories in QoL (measured by the CASP19 questionnaire). RESULTS: QoL at baseline was poorer for older than younger respondents, with the differences widening with age. QoL also declined more rapidly for older individuals. Gender, education, depression, limiting long-standing illness, difficulty with ADL-s, lack of wealth, non-employment, decreased number of friends and low positive support had a negative impact on QoL. Living with a partner had a positive effect on the QoL of men but not of women. The ageing-vector graphs revealed a clear gradient in age-trajectories of QoL for those in the best to the worst psychosocial, socioeconomic and health conditions. CONCLUSIONS: Younger old adults can be prepared for further ageing by increasing their network of friends and engaging with the wider community while they are able.
Assuntos
Envelhecimento , Qualidade de Vida , Idoso , Inglaterra , Feminino , Humanos , Entrevistas como Assunto , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
Some data suggest that nocturnal dosing of antihypertensive agents may reduce cardiovascular outcomes more than daytime dosing. This trial was designed to evaluate whether ambulatory blood pressure monitoring levels differ by timing of drug dosing. Patients aged 18 to 80 years with reasonably controlled hypertension (≤150/≤90 mm Hg) on stable therapy of ≥1 antihypertensive agent were recruited from 2 centers in London and Thessaloniki. Patients were randomized to receive usual therapy either in the morning (6 am-11 am) or evening (6 pm-11 pm) for 12 weeks when participants crossed over to the alternative timing for a further 12 weeks. Clinic blood pressures and a 24-hour recording were taken at baseline, 12, and 24 weeks and routine blood tests were taken at baseline. The study had 80% power to detect 3 mm Hg difference in mean 24-hour systolic blood pressure (α=0.05) by time of dosing. A 2-level hierarchical regression model adjusted for center, period, and sequence was used. Of 103 recruited patients (mean age, 62; 44% female), 95 patients (92%) completed all three 24-hour recordings. Mean 24-hour systolic and diastolic blood pressures did not differ between daytime and evening dosing. Similarly, morning and evening dosing had no differential impact on mean daytime (7 am-10 pm) and nighttime (10 pm-7 am) blood pressure levels nor on clinic levels. Stratification by age (≤65/≥65 years) or sex did not affect results. In summary, among hypertensive patients with reasonably well-controlled blood pressure, the timing of antihypertensive drug administration (morning or evening) did not affect mean 24-hour or clinic blood pressure levels. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT01669928.
Assuntos
Anti-Hipertensivos , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Esquema de Medicação , Hipertensão , Idoso , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial/métodos , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
AIMS: In patients with heart failure and a pathologically prolonged PR interval, left ventricular (LV) filling can be improved by shortening atrioventricular delay using His-bundle pacing. His-bundle pacing delivers physiological ventricular activation and has been shown to improve acute haemodynamic function in this group of patients. In the HOPE-HF (His Optimized Pacing Evaluated for Heart Failure) trial, we are investigating whether these acute haemodynamic improvements translate into improvements in exercise capacity and heart failure symptoms. METHODS AND RESULTS: This multicentre, double-blind, randomized, crossover study aims to randomize 160 patients with PR prolongation (≥200 ms), LV impairment (EF ≤ 40%), and either narrow QRS (≤140 ms) or right bundle branch block. All patients receive a cardiac device with leads positioned in the right atrium and the His bundle. Eligible patients also receive a defibrillator lead. Those not eligible for implantable cardioverter defibrillator have a backup pacing lead positioned in an LV branch of the coronary sinus. Patients are allocated in random order to 6 months of (i) haemodynamically optimized dual chamber His-bundle pacing and (ii) backup pacing only, using the non-His ventricular lead. The primary endpoint is change in exercise capacity assessed by peak oxygen uptake. Secondary endpoints include change in ejection fraction, quality of life scores, B-type natriuretic peptide, daily patient activity levels, and safety and feasibility assessments of His-bundle pacing. CONCLUSIONS: Hope-HF aims to determine whether correcting PR prolongation in patients with heart failure and narrow QRS or right bundle branch block using haemodynamically optimized dual chamber His-bundle pacing improves exercise capacity and symptoms. We aim to complete recruitment by the end of 2018 and report in 2020.