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1.
JAMA Neurol ; 78(1): 11-20, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33074284

RESUMO

Importance: The reported associations of cerebral microbleeds with recurrent stroke and intracerebral hemorrhage have raised concerns regarding antithrombotic treatment in patients with a history of stroke and microbleeds on magnetic resonance imaging. Objective: To characterize microbleeds in embolic strokes of undetermined source (ESUS) and report interactions between microbleeds and the effects of random assignment to anticoagulant vs antiplatelet therapy. Design, Setting, and Participants: Subgroup analyses of the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs Aspirin to Prevent Embolism in ESUS (NAVIGATE ESUS) international, double-blind, randomized, event-driven phase 3 clinical trial. Participants were enrolled between December 2014 and September 2017 and followed up for a median of 11 months. The study setting included 459 stroke recruitment centers in 31 countries. Patients aged 50 years or older who had neuroimaging-confirmed ESUS between 7 days and 6 months before screening were eligible. Of these 7213 NAVIGATE ESUS participants, 3699 (51%) had information on cerebral microbleeds reported on their baseline clinical magnetic resonance imaging and were eligible for these analyses. Patients with a prior history of symptomatic intracerebral hemorrhage were excluded from the NAVIGATE ESUS trial. Interventions: Rivaroxaban, 15 mg, compared with aspirin, 100 mg, daily. Main Outcomes and Measures: The primary outcome was recurrent stroke. Secondary outcomes were ischemic stroke, intracerebral hemorrhage, and all-cause mortality. Results: Microbleeds were present in 395 of 3699 participants (11%). Of patients with cerebral microbleeds, mean (SD) age was 69.5 (9.4) years, 241 were men (61%), and 201 were White (51%). Advancing age (odds ratio [OR] per year, 1.03; 95% CI, 1.01-1.04), East Asian race/ethnicity (OR, 1.57; 95% CI, 1.04-2.37), hypertension (OR, 2.20; 95% CI, 1.54-3.15), multiterritorial infarcts (OR, 1.95; 95% CI, 1.42-2.67), chronic infarcts (OR, 1.78; 95% CI, 1.42-2.23), and occult intracerebral hemorrhage (OR, 5.23; 95% CI, 2.76-9.90) were independently associated with microbleeds. The presence of microbleeds was associated with a 1.5-fold increased risk of recurrent stroke (hazard ratio [HR], 1.5; 95% CI, 1.0-2.3), a 4-fold risk of intracerebral hemorrhage (HR, 4.2; 95% CI, 1.3-13.9), a 2-fold risk of all-cause mortality (HR, 2.1; 95% CI, 1.1-4.3), and strictly lobar microbleeds with an approximately 2.5-fold risk of ischemic stroke (HR, 2.3; 95% CI, 1.3-4.3). There were no interactions between microbleeds and treatment assignments for recurrent stroke, ischemic stroke, or all-cause mortality. The HR of intracerebral hemorrhage on rivaroxaban was similar between persons with microbleeds (HR, 3.1; 95% CI, 0.3-30.0) and persons without microbleeds (HR, 3.0; 95% CI, 0.6-14.7; interaction P = .97). Conclusions and Relevance: Microbleeds mark an increased risk of recurrent stroke, ischemic stroke, intracerebral hemorrhage, and mortality in ESUS but do not appear to influence effects of rivaroxaban on clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02313909.

2.
Heart ; 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33318082

RESUMO

OBJECTIVE: Hypertension is the most important modifiable risk factor for stroke globally. We hypothesised that country-income level variations in knowledge, detection and treatment of hypertension may contribute to variations in the association of blood pressure with stroke. METHODS: We undertook a standardised case-control study in 32 countries (INTERSTROKE). Cases were patients with acute first stroke (n=13 462) who were matched by age, sex and site to controls (n=13 483). We evaluated the associations of knowledge, awareness and treatment of hypertension with risk of stroke and its subtypes and whether this varied by gross national income (GNI) of country. We estimated OR and population attributable risk (PAR) associated with treated and untreated hypertension. RESULTS: Hypertension was associated with a graded increase in OR by reducing GNI, ranging from OR 1.92 (99% CI 1.48 to 2.49) to OR 3.27 (2.72 to 3.93) for highest to lowest country-level GNI (p-heterogeneity<0.0001). Untreated hypertension was associated with a higher OR for stroke (OR 5.25; 4.53 to 6.10) than treated hypertension (OR 2.60; 2.32 to 2.91) and younger age of first stroke (61.4 vs 65.4 years; p<0.01). Untreated hypertension was associated with a greater risk of intracerebral haemorrhage (OR 6.95; 5.61 to 8.60) than ischaemic stroke (OR 4.76; 3.99 to 5.68). The PAR associated with untreated hypertension was higher in lower-income regions, PAR 36.3%, 26.3%, 19.8% to 10.4% by increasing GNI of countries. Lifetime non-measurement of blood pressure was associated with stroke (OR 1.80; 1.32 to 2.46). CONCLUSIONS: Deficits in knowledge, detection and treatment of hypertension contribute to higher risk of stroke, younger age of onset and larger proportion of intracerebral haemorrhage in lower-income countries.

3.
J Natl Compr Canc Netw ; 18(12): 1623-1630, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33285516

RESUMO

BACKGROUND: The NCCN Guidelines for Survivorship recommend dedicated sleep assessment. Reported insomnia prevalence in the general Irish population is 6% to 15%. Reported insomnia prevalence internationally among new/recently diagnosed patients with cancer varies from 30.9% to 54.3%. Insomnia prevalence has not been previously quantified in an Irish oncology cohort. METHODS: A 40-item questionnaire was prospectively administered to ambulatory patients with cancer aged ≥18 years. Prespecified criteria to define insomnia syndrome combined those of the International Classification of Sleep Disorders, version 1, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The Hospital Anxiety and Depression Scale-Depression/Anxiety (HADS-D/A) was used to screen for potential confounding variables. RESULTS: The response rate to the questionnaire was 87% (294/337). The predominant respondent age group was 55 to 64 years (26%; 77/294), 70.7% were female (208/294), and the most common cancer subtypes were breast (37.4%), colorectal (12.9%), and lung (12.2%). A total of 62% (183/294) of patients reported sleep disturbance after diagnosis, 63% (115/183) reported moderate/severe distress related to this disturbance, and 37% (61/183) reported a significant impact on physical function. Although 33% (98/294) met insomnia syndrome criteria, only 34% (33/98) of these patients had a preexisting history of sleep disturbance. Female sex, age <65 years, cancer subtype, alcohol consumption, and HADS-D/A ≥11 were associated with statistically significant higher odds ratios (OR) of insomnia syndrome. Multivariate analysis identified breast cancer (OR, 3.17; P=.01), age <65 years (OR, 1.8; P=.03), and alcohol consumption (OR, 2.3; P=.005) as independent predictors of insomnia syndrome. CONCLUSIONS: Insomnia syndrome prevalence in this cohort is comparable to that reported previously and supports dedicated sleep assessment. This study identifies potentially modifiable risk factors for insomnia and demonstrates additional utility of the HADS score in identifying patients at risk.

4.
ACS Chem Biol ; 15(12): 3187-3196, 2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33242957

RESUMO

New antibiotics are urgently needed to address increasing rates of multidrug resistant infections. Seventy-six diversely functionalized compounds, comprising five structural scaffolds, were synthesized and tested for their ability to inhibit microbial growth. Twenty-six compounds showed activity in the primary phenotypic screen at the Community for Open Antimicrobial Drug Discovery (CO-ADD). Follow-up testing of active molecules confirmed that two unnatural dipeptides inhibit the growth of Cryptococcus neoformans with a minimum inhibitory concentration (MIC) ≤ 8 µg/mL. Syntheses were carried out by undergraduate students at five schools implementing Distributed Drug Discovery (D3) programs. This report showcases that a collaborative research and educational process is a powerful approach to discover new molecules inhibiting microbial growth. Educational gains for students engaged in this project are highlighted in parallel to the research advances. Aspects of D3 that contribute to its success, including an emphasis on reproducibility of procedures, are discussed to underscore the power of this approach to solve important research problems and to inform other coupled chemical biology research and teaching endeavors.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33143153

RESUMO

Maternal smoking during pregnancy has established associations with poor perinatal outcomes. Among continuing pregnant smokers, harm-reduction strategies have been suggested, including temporary cessation of smoking during pregnancy, also known as partial quitting. Support for this strategy, however, remains limited. Six hundred and ninety-seven women in the Southampton Women's Survey who smoked at their last menstrual period were categorised into sustained quitters, partial quitters (quit in either the first or third trimester but not both) or sustained smokers (continued to smoke throughout pregnancy). In regression models, compared with infants born to sustained smokers, infants born to sustained quitters and partial quitters were heavier at birth by ß = 0.64 standard deviations (SD) (WHO z-score) (95% CI: 0.47-0.80) and 0.48 SD (WHO z-score) (95% CI: 0.24-0.72) respectively, adjusted for confounders, with similar patterns seen for other anthropometric measures (head circumference and crown-heel length). Sustained quitters had longer gestations by ß = 3.5 days (95% CI: 1.8-5.2) compared with sustained smokers, but no difference was seen for partial quitters. While sustained quitting remains the most desired outcome for pregnant smokers, partial quitting should be explored as a strategy to reduce some of the harmful effects of smoking on offspring in those who cannot achieve sustained quitting.


Assuntos
Fumantes/estatística & dados numéricos , Abandono do Hábito de Fumar/estatística & dados numéricos , Fumar/efeitos adversos , Fumar Tabaco/epidemiologia , Adulto , Peso ao Nascer , Feminino , Humanos , Lactente , Cuidado Pré-Concepcional , Gravidez , Fumar/epidemiologia , Inquéritos e Questionários
7.
Am J Hypertens ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33197265

RESUMO

BACKGROUND: Although low sodium intake (<2g/day) and high potassium intake (>3·5g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke and its subtypes. METHODS: We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls (8,761 matched pairs for conditional analysis) from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes. RESULTS: The mean estimated 24-hour sodium and potassium urinary excretion was 3·29g/day and 1·57g/day, with 0·01% of participants having both low sodium (<2·0g/day) and high potassium excretion (>3·5g/day). There was a moderate positive correlation between sodium and potassium excretion (r=0·4435, P<0.001) and between sodium excretion and blood pressure (P<0.001). Compared with an estimated urinary sodium excretion of 2·8-3·5g/day (second quartile, reference), higher (>4·26g/day) (OR 1.81;95%CI,1.65-2.00) and lower (<2·8g/day) sodium excretion (OR 1.39;95%CI,1.26-1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4·26g/day) was significantly greater (P<0.001) for intracerebral haemorrhage (ICH) (OR 2.38;95%CI,1.93-2.92) than for ischemic stroke (OR 1.67;95%CI,1.50-1.87), and greater for large vessel and small vessel ischemic stroke than for cardioembolic ischemic stroke. Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P=0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1·58g/day) and moderate sodium intake (2.8-3.5 g/day) was associated with the lowest risk of stroke. CONCLUSION: The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for intracerebral haemorrhage than ischemic stroke. Our data suggest that moderate sodium intake - rather than low sodium intake - combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.

8.
Eur Heart J ; 41(35): 3363-3373, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-33011774

RESUMO

Several blood pressure guidelines recommend low sodium intake (<2.3 g/day, 100 mmol, 5.8 g/day of salt) for the entire population, on the premise that reductions in sodium intake, irrespective of the levels, will lower blood pressure, and, in turn, reduce cardiovascular disease occurrence. These guidelines have been developed without effective interventions to achieve sustained low sodium intake in free-living individuals, without a feasible method to estimate sodium intake reliably in individuals, and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with moderate intake). In this review, we examine whether the recommendation for low sodium intake, reached by current guideline panels, is supported by robust evidence. Our review provides a counterpoint to the current recommendation for low sodium intake and suggests that a specific low sodium intake target (e.g. <2.3 g/day) for individuals may be unfeasible, of uncertain effect on other dietary factors and of unproven effectiveness in reducing cardiovascular disease. We contend that current evidence, despite methodological limitations, suggests that most of the world's population consume a moderate range of dietary sodium (2.3-4.6g/day; 1-2 teaspoons of salt) that is not associated with increased cardiovascular risk, and that the risk of cardiovascular disease increases when sodium intakes exceed 5 g/day. While current evidence has limitations, and there are differences of opinion in interpretation of existing evidence, it is reasonable, based upon observational studies, to suggest a population-level mean target of <5 g/day in populations with mean sodium intake of >5 g/day, while awaiting the results of large randomized controlled trials of sodium reduction on incidence of cardiovascular events and mortality.

9.
J Hypertens ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33031177

RESUMO

OBJECTIVE: To investigate the associations of sodium excretion with blood pressure, mortality and cardiovascular diseases in Chinese population. METHODS: We studied 39 366 individuals aged 35-70 years from 115 urban and rural communities in 12 centers across mainland China. Trained research staff conducted face-to-face interview to record baseline information of all participants based on questionnaires, and collected their morning fasting urine samples to estimate 24-h sodium excretion (24hUNaE). Multivariable frailty Cox regression accounting for clustering by centre was performed to examine the association between estimated 24hUNaE and the primary composite outcome of death and major cardiovascular events in a Chinese population. RESULTS: Mean 24hUNaE was 5.68 (SD 1.69) g/day. After a median follow-up of 8.8 years, the composite outcome occurred in 3080 (7.8%) participants, of which 1426 (3.5%) died and 2192 (5.4%) suffered from cardiovascular events. 24hUNaE was positively associated with increased SBP and DBP. Using the 24hUNaE level of 4-4.99 g/day as the reference group, a 24hUNaE of either lower (<3 g/day) or higher (≥7 g/day) was associated with an increased risk of the composite outcome with a hazard ratio of 1.22 (95% confidence interval: 1.01-1.49) and 1.15 (95% confidence interval: 1.01-1.30), respectively. A similar trend was observed between 24hUNaE level and risk of death or major cardiovascular events. CONCLUSION: These findings support a positive association between estimated urinary sodium excretion and blood pressure, and a possible J-shaped pattern of association between sodium excretion and clinical outcomes, with the lowest risk in participants with sodium excretion between 3 and 5 g/day.

10.
Stroke ; 51(10): 2901-2909, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32951537

RESUMO

BACKGROUND AND PURPOSE: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. METHODS: Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. RESULTS: At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38-0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37-1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27-1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. CONCLUSIONS: Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.


Assuntos
Aspirina/uso terapêutico , Infarto Encefálico/prevenção & controle , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Idoso , Infarto Encefálico/complicações , Infarto Encefálico/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Quimioterapia Combinada , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Resultado do Tratamento
11.
Age Ageing ; 49(6): 907-914, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-32821909

RESUMO

BACKGROUND: During the current COVID-19 health crisis virtual geriatric clinics have become increasingly utilised to complete outpatient consultations, although concerns exist about feasibility of such virtual consultations for older people. The aim of this rapid review is to describe the satisfaction, clinic productivity, clinical benefit, and costs associated with the virtual geriatric clinic model of care. METHODS: A rapid review of PubMed, MEDLINE and CINAHL databases was conducted up to April 2020. Two independent reviewers extracted the information. Four subdomains were focused on: satisfaction with the virtual geriatric clinic, clinic productivity, clinical benefit to patients, costs and any challenges associated with the virtual clinic process. RESULTS: Nine studies with 975 patients met our inclusion criteria. All were observational studies. Seven studies reported patients were satisfied with the virtual geriatric clinic model of care. Productivity outcomes included reports of cost-effectiveness, savings on transport, and improved waiting list metrics. Clinical benefits included successful polypharmacy reviews, and reductions in acute hospitalisation rates. Varying challenges were reported for both clinicians and patients in eight of the nine studies. Hearing impairments and difficulty with technology added to anxieties experienced by patients. Physicians missed the added value of a thorough physical examination and had concerns about confidentiality. CONCLUSION: Virtual geriatric clinics demonstrate evidence of productivity, benefit to patients, cost effectiveness and patient satisfaction with the treatment provided. In the current suboptimal pandemic climate, virtual geriatric clinics may allow Geriatricians to continue to provide an outpatient service, despite the encountered inherent challenges.


Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Betacoronavirus , Infecções por Coronavirus/terapia , Transmissão de Doença Infecciosa/prevenção & controle , Pneumonia Viral/terapia , Encaminhamento e Consulta , Telemedicina/métodos , Idoso , Infecções por Coronavirus/epidemiologia , Humanos , Pandemias , Satisfação do Paciente , Pneumonia Viral/epidemiologia
12.
BMJ Open ; 10(8): e036755, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32859663

RESUMO

INTRODUCTION: Adaptive design methods are a potential solution to improve efficiency of clinical trials but their uptake in dialysis is unknown. We aim to investigate the use of adaptive design methods in dialysis clinical trials and to cultivate further adoption of adaptive design methods by the nephrology community. METHODS AND ANALYSIS: We will adhere to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and the Cochrane Collaboration Handbook. We will perform a literature search through MEDLINE (PubMed), EMBASE and CENTRAL, a detailed data extraction of trial characteristics and a narrative synthesis of the data. There will be no language restrictions. We will estimate the percentage of adaptive clinical trials per year in dialysis. Subgroup analysis will be performed by dialysis modality, funder and geographical location. ETHICS AND DISSEMINATION: Ethical approval will not be required for this study as data will be obtained from publicly available clinical trials. We will disseminate our results in a peer-reviewed publication. PROSPERO REGISTRATION NUMBER.

13.
Arch Public Health ; 78: 67, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32704369

RESUMO

Background: In 1995, Eide and Gefeller introduced the concepts of sequential and average attributable fractions as methods to partition the risk of disease among differing exposures. In particular, sequential attributable fractions are interpreted in terms of an incremental reduction in disease prevalence associated with removing a particular risk factor from the population, having removed other risk factors. Clearly, both concepts are causal entities, but are not usually estimated within a causal inference framework. Methods: We propose causal definitions of sequential and average attributable fractions using the potential outcomes framework. To estimate these quantities in practice, we model exposure-exposure and exposure-disease interrelationships using a causal Bayesian network, assuming no unmeasured latent confounders. This allows us to model not only the direct impact of removing a risk factor on disease, but also the indirect impact through the effect on the prevalence of causally downstream risk factors that are typically ignored when calculating sequential and average attributable fractions. The procedure for calculating sequential attributable fractions involves repeated applications of Pearl's do-operator over a fitted Bayesian network, and simulation from the resulting joint probability distributions. Results: The methods are applied to the INTERSTROKE study, which was designed to quantify disease burden attributable to the major risk factors for stroke. The resulting sequential and average attributable fractions are compared with results from a prior estimation approach which uses a single logistic model and which does not properly account for differing causal pathways. Conclusions: In contrast to estimation using a single regression model, the proposed approaches allow consistent estimation of sequential, joint and average attributable fractions under general causal structures.

14.
Stroke ; 51(8): 2454-2463, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32693751

RESUMO

BACKGROUND AND PURPOSE: Stroke is a complex disease with multiple genetic and environmental risk factors. Blacks endure a nearly 2-fold greater risk of stroke and are 2× to 3× more likely to die from stroke than European Americans. METHODS: The COMPASS (Consortium of Minority Population Genome-Wide Association Studies of Stroke) has conducted a genome-wide association meta-analysis of stroke in >22 000 individuals of African ancestry (3734 cases, 18 317 controls) from 13 cohorts. RESULTS: In meta-analyses, we identified one single nucleotide polymorphism (rs55931441) near the HNF1A gene that reached genome-wide significance (P=4.62×10-8) and an additional 29 variants with suggestive evidence of association (P<1×10-6), representing 24 unique loci. For validation, a look-up analysis for a 100 kb region flanking the COMPASS single nucleotide polymorphism was performed in SiGN (Stroke Genetics Network) Europeans, SiGN Hispanics, and METASTROKE (Europeans). Using a stringent Bonferroni correction P value of 2.08×10-3 (0.05/24 unique loci), we were able to validate associations at the HNF1A locus in both SiGN (P=8.18×10-4) and METASTROKE (P=1.72×10-3) European populations. Overall, 16 of 24 loci showed evidence for validation across multiple populations. Previous studies have reported associations between variants in the HNF1A gene and lipids, C-reactive protein, and risk of coronary artery disease and stroke. Suggestive associations with variants in the SFXN4 and TMEM108 genes represent potential novel ischemic stroke loci. CONCLUSIONS: These findings represent the most thorough investigation of genetic determinants of stroke in individuals of African descent, to date.


Assuntos
Afro-Americanos/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/genética , Afro-Americanos/etnologia , Estudos de Coortes , Predisposição Genética para Doença/etnologia , Humanos , Acidente Vascular Cerebral/etnologia
15.
Am J Med ; 133(12): 1471-1478.e4, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32603788

RESUMO

BACKGROUND: Guidelines recommend increased salt intake as a first-line recommendation in the management of symptomatic orthostatic hypotension and recurrent syncope. There have been no systematic reviews of this intervention. We sought to summarize the evidence for increased salt intake in patients with orthostatic intolerance syndromes. METHODS: We conducted a systematic review and meta-analysis of studies in PubMed, EMBASE, and CINAHL. Interventional studies that increased salt intake in individuals with orthostatic intolerance syndromes were included. Primary outcome measures included incidence of falls and injuries, and rates of syncope and presyncope. Secondary outcome measures included other orthostatic intolerance symptoms, blood pressure, and heart rate. RESULTS: A total of 14 studies were eligible, including participants with orthostatic hypotension, syncope, postural orthostatic tachycardia syndrome, and idiopathic orthostatic tachycardia (n = 391). Mean age was 35.6 (± 15) years. All studies were small and short-term (<60 mins-90 days). No study reported on the effect of increased salt intake on falls or injuries. Meta-analysis demonstrated that during head-up tilt, mean time to presyncope with salt intake increased by 1.57 minutes (95% confidence interval [CI], 1.26-1.88), mean systolic blood pressure increased by 12.27 mm Hg (95% CI, 10.86-13.68), and mean heart rate decreased by -3.97 beats per minute (95% CI, -4.08 to -3.86), compared with control. Increased salt increased supine blood pressure by 1.03 mm Hg (95% CI, 0.81 to 1.25). Increased salt intake resulted in an improvement or resolution of symptoms in 62.3% (95% CI, 51.6 to 72.6) of participants in short-term follow-up studies (mean follow-up of 44.3 days, 6 studies; n=91). Methodological quality of studies were low with high statistical heterogeneity in all meta-analyses. CONCLUSIONS: Our meta-analysis provides low-quality evidence of a short-term improvement in orthostatic intolerance with increased salt intake. There were no clinical trials demonstrating the efficacy and safety of increased salt intake on long-term clinical outcomes. Overall, there is a paucity of clinical trial evidence to support a cornerstone recommendation in the management of orthostatic intolerance syndromes.


Assuntos
Intolerância Ortostática/dietoterapia , Cloreto de Sódio na Dieta/administração & dosagem , Adulto , Humanos , Pessoa de Meia-Idade , Adulto Jovem
16.
JAMA ; 323(19): 1934-1944, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32427305

RESUMO

Importance: The benefit of blood pressure lowering for the prevention of dementia or cognitive impairment is unclear. Objective: To determine the association of blood pressure lowering with dementia or cognitive impairment. Data Sources and Study Selection: Search of PubMed, EMBASE, and CENTRAL for randomized clinical trials published from database inception through December 31, 2019, that evaluated the association of blood pressure lowering on cognitive outcomes. The control groups consisted of either placebo, alternative antihypertensive agents, or higher blood pressure targets. Data Extraction and Synthesis: Data were screened and extracted independently by 2 authors. Random-effects meta-analysis models were used to report pooled treatment effects and CIs. Main Outcomes and Measures: The primary outcome was dementia or cognitive impairment. The secondary outcomes were cognitive decline and changes in cognitive test scores. Results: Fourteen randomized clinical trials were eligible for inclusion (96 158 participants), of which 12 reported the incidence of dementia (or composite of dementia and cognitive impairment [3 trials]) on follow-up and were included in the primary meta-analysis, 8 reported cognitive decline, and 8 reported changes in cognitive test scores. The mean (SD) age of trial participants was 69 (5.4) years and 40 617 (42.2%) were women. The mean systolic baseline blood pressure was 154 (14.9) mm Hg and the mean diastolic blood pressure was 83.3 (9.9) mm Hg. The mean duration of follow-up was 49.2 months. Blood pressure lowering with antihypertensive agents compared with control was significantly associated with a reduced risk of dementia or cognitive impairment (12 trials; 92 135 participants) (7.0% vs 7.5% of patients over a mean trial follow-up of 4.1 years; odds ratio [OR], 0.93 [95% CI, 0.88-0.98]; absolute risk reduction, 0.39% [95% CI, 0.09%-0.68%]; I2 = 0.0%) and cognitive decline (8 trials) (20.2% vs 21.1% of participants over a mean trial follow-up of 4.1 years; OR, 0.93 [95% CI, 0.88-0.99]; absolute risk reduction, 0.71% [95% CI, 0.19%-1.2%]; I2 = 36.1%). Blood pressure lowering was not significantly associated with a change in cognitive test scores. Conclusions and Relevance: In this meta-analysis of randomized clinical trials, blood pressure lowering with antihypertensive agents compared with control was significantly associated with a lower risk of incident dementia or cognitive impairment.


Assuntos
Anti-Hipertensivos/uso terapêutico , Disfunção Cognitiva/prevenção & controle , Demência/prevenção & controle , Hipertensão/tratamento farmacológico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco
17.
Cochrane Database Syst Rev ; 5: CD012825, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32392374

RESUMO

BACKGROUND: An increasing body of evidence suggests that inflammation plays a key role in stroke, in particular stroke of atherosclerotic origin. Anti-inflammatory medications are a widely heterogeneous group of drugs that are used to suppress the innate inflammatory pathway and thus prevent persistent or recurrent inflammation. Anti-inflammatory agents have the potential to stabilise atherosclerotic plaques by impeding the inflammatory pathway. By targeting specific cytokines, the inflammatory pathway may be interrupted at various stages. OBJECTIVES: To assess the benefits and harms of anti-inflammatory medications plus standard care versus standard care with or without placebo for prevention of vascular events (stroke, myocardial infarction (MI), non-fatal cardiac arrest, unstable angina requiring revascularisation, vascular death) and all-cause mortality in people with a prior history of ischaemic stroke or transient ischaemic attack (TIA). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; last searched 29 May 2019); MEDLINE (1948 to 29 May 2019); Embase (1980 to 29 May 2019); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 29 May 2019); and Scopus (1995 to 29 May 2019). In an effort to identify additional published, unpublished, and ongoing trials, we searched several grey literature sources (last searched 30 May 2019). We incorporated all identified studies into the results section. We applied no restrictions with respect to language, date of publication, or study setting. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) and cluster-randomised controlled trials that evaluated anti-inflammatory medications for prevention of major cardiovascular events following ischaemic stroke or TIA. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed for inclusion titles and abstracts of studies identified by the search. Two review authors independently reviewed full-text articles for inclusion in this review. We planned to assess risk of bias and to apply the GRADE method. MAIN RESULTS: We identified no studies that met the inclusion criteria. AUTHORS' CONCLUSIONS: There is currently a paucity of evidence on the use of anti-inflammatory medications for prevention of major cardiovascular events following ischaemic stroke or TIA. RCTs are needed to assess whether use of anti-inflammatory medications in this setting is beneficial.


Assuntos
Angina Instável/prevenção & controle , Anti-Inflamatórios/uso terapêutico , Parada Cardíaca/prevenção & controle , Ataque Isquêmico Transitório/complicações , Infarto do Miocárdio/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Humanos , Placa Aterosclerótica/complicações , Placa Aterosclerótica/tratamento farmacológico , Prevenção Secundária/métodos , Acidente Vascular Cerebral/etiologia
18.
Cardiovasc Res ; 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32289159

RESUMO

AIMS: The COMPASS trial demonstrated that the combination of rivaroxaban 2.5mg twice-daily and aspirin 100mg once daily compared with aspirin 100 mg once daily reduced major adverse cardiovascular events (MACE) in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD) by 24% during a mean follow-up of 23 months. We explored whether this effect varies by sex. METHODS AND RESULTS: The effects were examined in women and men using log-rank tests and Kaplan-Meier curve. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were obtained from stratified Cox proportional hazards models to explore subgroup effects including subgroup of women and men according to baseline modified REACH risk score. Of 27,395 patients randomized, 18,278 were allocated to receive rivaroxaban plus aspirin (n = 9,152) or aspirin alone (n = 9,126), and of these 22.1% were women. Women compared with men had similar incidence rates for MACE and major bleeding but borderline lower rates for MI (1.7% vs. 2.2%, p = 0.05). The effect of combination therapy compared with aspirin in women and men were consistent for MACE (women: 3.8% vs. 5.2%, HR 0.72, 95% CI 0.54-0.97; men: 4.2% vs. 5.5%, HR 0.76, 95% CI 0.66-0.89; p interaction 0.75) and major bleeding (women: 3.1% vs. 1.4%, HR 2.22, 95% CI 1.42-3.46; men: 3.2% vs. 2.0%, HR 1.60, 95% CI 1.29-1.97; p interaction 0.19). There was no significant interaction between randomized treatment and baseline modified REACH score above or below the median for MACE or major bleeding. CONCLUSIONS: In patients with stable CAD or PAD, the combination of rivaroxaban (2x2.5mg twice-daily) and aspirin compared with aspirin alone appears to produce consistent benefits in women and men, independent of baseline cardiovascular risk.

19.
Diabetes Metab Syndr Obes ; 13: 197-205, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32158243

RESUMO

Objective: Low energy meal replacement regimens can induce short-term weight loss in patients with severe obesity, but usually require specially formulated dietary supplements. We sought to determine the effects of a milk-based meal replacement program on anthropometric and metabolic characteristics in adults with severe obesity. Methods: We conducted a retrospective cohort study of patients attending our hospital-based bariatric medicine service who completed a 24-week program consisting of eight weeks of milk-based meal replacement followed by weight stabilisation and maintenance phases. Patients were seen fortnightly by the bariatric physician, nurse and dietitian. We assessed changes in anthropometric and metabolic outcomes in completers at 0, 8, 16 and 24 weeks. Results: Of 105 program completers available for follow-up, 53.3% were female. Mean age was 51.1±11.2 years. Body weight decreased from 144.0±27.6 kg at baseline to 121.1±25.0 kg at 24 weeks (P<0.001), a mean total body weight loss of 15.9±6.0%, with a reduction in body mass index from 50.6±8.0 to 42.6±7.6 kg m-2 (P<0.001). In patients with diabetes, haemoglobin A1c decreased from 66.3±13.0 to 48.3±13.5 mmol/mol (P<0.001) and diabetes medication use decreased significantly. There were significant improvements also in lipid profiles and reductions in antihypertensive medication use. Conclusion: These preliminary findings suggest that completion of a 24-week milk-based meal replacement program has large effects on important outcomes in adults with severe obesity. However, attrition was high. Prospective assessment of the efficacy, safety, durability and cost-effectiveness of this intervention seems warranted.

20.
BMC Res Notes ; 13(1): 156, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32178726

RESUMO

OBJECTIVE: Skin tags are associated with an insulin resistant phenotype but studies in White Europeans with morbid obesity are lacking. We sought to determine whether the presence of cervical or axillary skin tags was associated with increased cardiovascular risk in Irish adults with morbid obesity. We conducted a cross-sectional study of patients attending our Irish regional bariatric centre with a BMI ≥ 40 kg m-2 (or ≥ 35 kg m-2 with co-morbidities). We compared anthropometric and metabolic characteristics in those with versus without skin tags. RESULTS: Of 164 patients, 100 (31 male, 37 with type 2 diabetes, 36 on lipid lowering therapy, 41 on antihypertensive therapy) participated. Mean age was 53.7 ± 11.3 (range 31.1-80) years. Cervical or axillary tags were present in 85 patients. Those with tags had higher systolic blood pressure 138.0 ± 16.0 versus 125.1 ± 8.3 mmHg, p = 0.003) and HbA1c (46.5 ± 13.2 versus 36.8 ± 3.5 mmol/mol, p = 0.017). Tags were present in 94.6% of patients with diabetes, compared to 79.4% of those without diabetes (p = 0.039). Antihypertensive therapy was used by 45.8% of patients with skin tags compared to 13.3% without tags (p = 0.018). In bariatric clinic attenders skin tags were associated with higher SBP and HbA1c and a higher prevalence of diabetes and hypertension, consistent with increased vascular risk, but lipid profiles were similar.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Hipertensão/epidemiologia , Obesidade Mórbida/complicações , Neoplasias Cutâneas/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Bariatria , Determinação da Pressão Arterial , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/fisiopatologia , Prevalência , Fatores de Risco , Adulto Jovem
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