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1.
Ann Epidemiol ; 99: 16-23, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39326530

RESUMO

PURPOSE: Research investigating gastrointestinal (GI) symptoms from oil spill-related exposures is sparse. We evaluated prevalent GI symptoms among U.S. Coast Guard responders deployed to the Deepwater Horizon oil spill cleanup. METHODS: Crude oil (via skin contact, inhalation, or ingestion routes), combined crude oil/oil dispersant exposures, other deployment exposures, deployment characteristics, demographics, and acute GI symptoms during deployment (i.e., nausea/vomiting, diarrhea, stomach pain, and constipation) were ascertained cross-sectionally via a post-deployment survey (median time between deployment end and survey completion 185 days) (N = 4885). Log-binomial regression analyses were employed to calculate prevalence ratios (PRs) and 95 % confidence intervals (CI). Effect modification was evaluated. RESULTS: In adjusted models, responders in the highest (versus lowest) tertile of self-reported degree of skin contact to crude oil were more than twice as likely to report nausea/vomiting (PR=2.45; 95 %CI, 1.85-3.23), diarrhea (PR=2.40; 95 %CI, 2.00-2.88), stomach pain (PR=2.51; 95 %CI, 2.01-3.12), and constipation (PR=2.21; 95 %CI, 1.70-2.89). Tests for trend were statistically significant (p < 0.05). Results were similar for crude oil exposure via inhalation and ingestion. Higher PRs for all symptoms were found with combined crude oil/dispersant exposure than with crude oil exposure alone. CONCLUSIONS: These results indicate positive associations between self-reported crude oil and combined crude oil/oil dispersant exposures and acute GI symptoms.

2.
BMJ Open ; 14(8): e080862, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39181551

RESUMO

OBJECTIVES: The Action To promote brain HEalth iN Adults study aimed to determine the feasibility and applicability of recruitment using home blood pressure (BP) monitoring, routine blood biochemistry and videoconference measures of cognition, in adults at high risk of dementia. DESIGN: A decentralised double-blind, placebo-controlled, randomised feasibility trial with a four-stage screening process. SETTING: Conducted with participants online in the state of New South Wales, Australia. PARTICIPANTS: Participants were aged 50-70 years with moderately elevated BP (systolic >120 and <160 mm Hg or diastolic >80 and <95 mm Hg) and ≥1 additional enrichment risk factor of monotherapy treatment of hypertension, diabetes mellitus, elevated low-density lipoprotein cholesterol, obesity, current smoking or a first degree relative with dementia, which indicated an elevated risk for future cognitive decline. INTERVENTION: Triple Pill (active antihypertensive treatment of telmisartan 20 mg, amlodipine 2.5 mg and indapamide 1.25 mg) or placebo Triple Pill (blinded study capsules). PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was feasibility of the study expressed as the percentage of participants randomised from those who were screened. Secondary outcomes were the applicability of videoconference measures of cognition and the overall trial, tolerability of the Triple Pill, safety outcomes and medication adherence. RESULTS: The proportion (95% CI) of patients randomised to those screened was 5% (2%-10%). The applicability of the trial expressed as percentage of those who completed all remote assessments over the number of randomised participants was 67% (95% CI 05 to 22%). There were no serious adverse events or withdrawals from treatment. All participants adhered to study medication, except for one person who had two capsules left at the end of the study period. CONCLUSIONS: The feasibility of this decentralised trial on BP lowering in patients at high risk for dementia is low. However, the applicability of remote assessments of cognitive function is acceptable. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000121864.


Assuntos
Anti-Hipertensivos , Disfunção Cognitiva , Estudos de Viabilidade , Hipertensão , Humanos , Pessoa de Meia-Idade , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Masculino , Feminino , Idoso , Hipertensão/tratamento farmacológico , Método Duplo-Cego , Disfunção Cognitiva/tratamento farmacológico , Telmisartan/uso terapêutico , Telmisartan/administração & dosagem , New South Wales , Anlodipino/administração & dosagem , Anlodipino/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial , Benzimidazóis/uso terapêutico , Benzimidazóis/administração & dosagem , Demência/tratamento farmacológico , Fatores de Risco , Combinação de Medicamentos , Pressão Sanguínea/efeitos dos fármacos
3.
Plant Cell Environ ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38873953

RESUMO

Allotetraploid white clover (Trifolium repens) formed during the last glaciation through hybridisation of two European diploid progenitors from restricted niches: one coastal, the other alpine. Here, we examine which hybridisation-derived molecular events may have underpinned white clover's postglacial niche expansion. We compared the transcriptomic frost responses of white clovers (an inbred line and an alpine-adapted ecotype), extant descendants of its progenitor species and a resynthesised white clover neopolyploid to identify genes that were exclusively frost-induced in the alpine progenitor and its derived subgenomes. From these analyses we identified galactinol synthase, the rate-limiting enzyme in biosynthesis of the cryoprotectant raffinose, and found that the extant descendants of the alpine progenitor as well as the neopolyploid white clover rapidly accumulated significantly more galactinol and raffinose than the coastal progenitor under cold stress. The frost-induced galactinol synthase expression and rapid raffinose accumulation derived from the alpine progenitor likely provided an advantage during early postglacial colonisation for white clover compared to its coastal progenitor.

4.
Nature ; 630(8017): 744-751, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38867042

RESUMO

DNA base damage is a major source of oncogenic mutations1. Such damage can produce strand-phased mutation patterns and multiallelic variation through the process of lesion segregation2. Here we exploited these properties to reveal how strand-asymmetric processes, such as replication and transcription, shape DNA damage and repair. Despite distinct mechanisms of leading and lagging strand replication3,4, we observe identical fidelity and damage tolerance for both strands. For small alkylation adducts of DNA, our results support a model in which the same translesion polymerase is recruited on-the-fly to both replication strands, starkly contrasting the strand asymmetric tolerance of bulky UV-induced adducts5. The accumulation of multiple distinct mutations at the site of persistent lesions provides the means to quantify the relative efficiency of repair processes genome wide and at single-base resolution. At multiple scales, we show DNA damage-induced mutations are largely shaped by the influence of DNA accessibility on repair efficiency, rather than gradients of DNA damage. Finally, we reveal specific genomic conditions that can actively drive oncogenic mutagenesis by corrupting the fidelity of nucleotide excision repair. These results provide insight into how strand-asymmetric mechanisms underlie the formation, tolerance and repair of DNA damage, thereby shaping cancer genome evolution.


Assuntos
Dano ao DNA , Reparo do DNA , DNA Polimerase Dirigida por DNA , DNA , Mutagênese , Mutação , Animais , Humanos , Camundongos , Alquilação/efeitos da radiação , Linhagem Celular , DNA/química , DNA/genética , DNA/metabolismo , DNA/efeitos da radiação , Adutos de DNA/química , Adutos de DNA/genética , Adutos de DNA/metabolismo , Adutos de DNA/efeitos da radiação , Dano ao DNA/genética , Dano ao DNA/efeitos da radiação , Reparo do DNA/genética , Reparo do DNA/fisiologia , Replicação do DNA , DNA Polimerase Dirigida por DNA/metabolismo , Mutagênese/genética , Mutagênese/efeitos da radiação , Mutação/genética , Mutação/efeitos da radiação , Neoplasias/genética , Transcrição Gênica , Raios Ultravioleta/efeitos adversos
5.
Int J Stroke ; 19(5): 482-489, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38803115

RESUMO

Intracerebral hemorrhage (ICH) is a devastating disease, causing high rates of death, disability, and suffering across the world. For decades, its treatment has been shrouded by the lack of reliable evidence, and consequently, the presumption that an effective treatment is unlikely to be found. Neutral results arising from several major randomized controlled trials had established a negative spirit within and outside the stroke community. Frustration among researchers and a sense of nihilism in clinicians has created the general perception that patients presenting with ICH have a poor prognosis irrespective of them receiving any form of active management. All this changed in 2023 with the positive results on the primary outcome in randomized controlled trials showing treatment benefits for a hyperacute care bundle approach (INTERACT3), early minimal invasive hematoma evacuation (ENRICH), and use of factor Xa-inhibitor anticoagulation reversal with andexanet alfa (ANNEXa-I). These advances have now been extended in 2024 by confirmation that intensive blood pressure lowering initiated within the first few hours of the onset of symptoms can substantially improve outcome in ICH (INTERACT4) and that decompressive hemicraniectomy is a viable treatment strategy in patients with large deep ICH (SWITCH). This evidence will spearhead a change in the perception of ICH, to revolutionize the care of these patients to ultimately improve their outcomes. We review these and other recent developments in the hyperacute management of ICH. We summarize the results of randomized controlled trials and discuss related original research papers published in this issue of the International Journal of Stroke. These exciting advances demonstrate how we are now at the dawn of a new, exciting, and brighter era of ICH management.


Assuntos
Hemorragia Cerebral , Humanos , Hemorragia Cerebral/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Proc Natl Acad Sci U S A ; 121(20): e2403871121, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38717857

RESUMO

DNA base damage is a major source of oncogenic mutations and disruption to gene expression. The stalling of RNA polymerase II (RNAP) at sites of DNA damage and the subsequent triggering of repair processes have major roles in shaping the genome-wide distribution of mutations, clearing barriers to transcription, and minimizing the production of miscoded gene products. Despite its importance for genetic integrity, key mechanistic features of this transcription-coupled repair (TCR) process are controversial or unknown. Here, we exploited a well-powered in vivo mammalian model system to explore the mechanistic properties and parameters of TCR for alkylation damage at fine spatial resolution and with discrimination of the damaged DNA strand. For rigorous interpretation, a generalizable mathematical model of DNA damage and TCR was developed. Fitting experimental data to the model and simulation revealed that RNA polymerases frequently bypass lesions without triggering repair, indicating that small alkylation adducts are unlikely to be an efficient barrier to gene expression. Following a burst of damage, the efficiency of transcription-coupled repair gradually decays through gene bodies with implications for the occurrence and accurate inference of driver mutations in cancer. The reinitation of transcription from the repair site is not a general feature of transcription-coupled repair, and the observed data is consistent with reinitiation never taking place. Collectively, these results reveal how the directional but stochastic activity of TCR shapes the distribution of mutations following DNA damage.


Assuntos
Dano ao DNA , RNA Polimerase II , Transcrição Gênica , Animais , Humanos , Camundongos , Alquilação , DNA/metabolismo , DNA/genética , Reparo por Excisão , Mutação , RNA Polimerase II/metabolismo , RNA Polimerase II/genética , Processos Estocásticos
7.
Drug Alcohol Depend ; 250: 109944, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37316389

RESUMO

BACKGROUND: Identifying young people who are susceptible to e-cigarettes is important for developing interventions designed to discourage uptake. Current evidence in a broader range of national contexts is needed given recent surges in youth e-cigarette use in many countries and the constantly evolving nature of vaping products and the promotional strategies used by the industry to increase their appeal. METHODS: A cross-sectional online survey was administered to around 1000 15-30 year olds in each of four countries: Australia, China, India, and the United Kingdom (total n = 4007). The survey assessed demographic characteristics, e-cigarette and tobacco use, exposure to e-cigarette advertising, and number of friends and family members who vape. Those who had never used e-cigarettes (n = 1589) were assessed for susceptibility (curiosity about e-cigarettes, intentions to use in the next 12 months, and likely use if offered by a friend). Mixed effects logistic regression analysis was used to identify factors associated with susceptibility to e-cigarette use. RESULTS: Susceptibility to e-cigarette use was apparent among 54% of respondents from Australia, 61% from India, 62% from the UK, and 82% from China. Factors positively associated with susceptibility were tobacco use, exposure to advertising, higher income, and having friends and family members who vape. Factors negatively associated with susceptibility were perceptions of harmfulness and education. CONCLUSION: The results indicate the need across a diverse range of countries for interventions designed to address substantial proportions of young people who are likely to be susceptible to e-cigarette use.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Vaping , Adolescente , Humanos , Estudos Transversais , Uso de Tabaco , Inquéritos e Questionários
8.
EClinicalMedicine ; 59: 101977, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37152361

RESUMO

Background: We aimed to develop and validate a prognostic model for predicting malignant brain oedema in patients with acute ischaemic stroke in a real-world setting of practice. Methods: A prospective multicentre study enrolled adult patients with acute ischaemic stroke with brain CT < 24 h of onset of symptoms admitted to nine tertiary-level hospitals in China between September 2017 and December 2019. Malignant brain oedema was defined as any patient who had decompressive craniectomy, discharge in coma, or in-hospital death attributed to symptomatic brain swelling. The derivation cohort was a consecutive cohort of patients from one centre and the validation cohort was non-consecutive patients from the other centres. Multivariable logistic regression was used to define independent predictors from baseline clinical characteristics, imaging features, complications, and management. A web-based nomogram and a risk score were developed based on the final model. Model performance was assessed for discrimination and calibration in both derivation and validation cohorts. The study is registered, NCT03222024. Findings: Based on the derivation cohort (n = 1627), the model was developed with seven variables including large infarct (adjusted odds ratio [OR] 40.90, 95% CI 20.20-82.80), National Institutes of Health Stroke Scale (NIHSS) score (OR 1.09, 1.06-1.12), thrombolysis (OR 2.11, 1.18-3.78), endovascular treatment (OR 2.87, 1.47-5.59), pneumonia (OR 2.47, 1.53-3.97), brain atrophy (OR 0.57, 0.37-0.86), and recanalisation (OR 0.36, 0.17-0.75). The classification threshold of a predicted probability ≥0.14 showed good discrimination and calibration in both derivation cohort (area under the receiver-operating curve [AUC] 0.90, 0.87-0.92; sensitivity 0.95, 0.92-0.98) and validation cohort (n = 556, AUC 0.88, 0.82-0.95; sensitivity 0.84, 0.73-0.95). The risk score based on this model had a total point that ranged from -1 to 20, with an optimal score of ≥10 showing good discrimination and calibration in both derivation (AUC 0.89, 0.87-0.92; sensitivity 0.95, 0.92-0.98) and validation (AUC 0.88, 0.82-0.95; sensitivity 0.84, 0.73-0.95) cohorts. Interpretation: The INTEP-AR model (i.e. large Infarct, NIHSS score, Thrombolysis, Endovascular treatment, Pneumonia, brain Atrophy, and Recanalisation) incorporating multiple clinical and radiological characteristics has shown good prognostic value for predicting malignant brain oedema after acute ischaemic stroke. Funding: National Natural Science Foundation of China; Science and Technology Department of Sichuan Province; West China Hospital.

9.
Lancet Glob Health ; 11(6): e942-e952, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37119831

RESUMO

BACKGROUND: In the absence of reliable data to quantify the burden of stroke, we aimed to determine the incidence and outcome of stroke through the conduct of a prospective population-based study in Ulaanbaatar, Mongolia, during 2019-21. METHODS: All cases of stroke were identified through surveillance of multiple overlapping sources of hospitalised, ambulatory, and deceased individuals, using standardised diagnostic criteria in adult (aged ≥16 years) residents of the six urban districts of Ulaanbaatar, Mongolia (population person-years, N=1 896 965) between Jan 1, 2019, and Dec 31, 2020. Data on sociodemography, medical history, and management were collected. Crude and standardised incidence were calculated for first-ever stroke and its major pathological subtypes, and reported with 95% CIs. Outcomes were 28-day case fatality ratios and functional recovery on the modified Rankin scale at 90 days and 1 year. FINDINGS: 3803 strokes in 3738 patients were identified, of which 2962 were first-ever incident cases (mean age 59 years [SD 13], 1161 [39·2%] females). Annual incidence of first-ever stroke (per 100 000) was 156·1 (95% CI 150·5-161·8) on a crude basis, 171·6 (157·5-185·6) when age-adjusted to the Mongolian population, and 140·3 (136·7-143·9) when age-adjusted to the world population. World-adjusted incidence of pathological subtypes were 66·6 (95% CI 64·8-68·3) for ischaemic stroke, 54·5 (53·0-56·1) for intracerebral haemorrhage, and 18·7 (18·3-19·1) for subarachnoid haemorrhage. Men were twice as likely to suffer ischaemic stroke and intracerebral haemorrhage as women, but the risks were similar for subarachnoid haemorrhage; these patterns were consistent across age-groups. The predominant risk factors were hypertension seen in 1363 (63·1%) of 2161, smoking in 596 (26·8%) of 2220, regular alcohol consumption in 533 (24·0%) of 2220, obesity in 342 (16·1%) of 2125, and diabetes in 282 (12·7%) of 2220. There was little use (0·9%) of thrombolysis for acute ischaemic stroke, partly due to delays in presentation after the onset of symptoms (median 16·0 h [IQR 3·0-48·0]). The 28-day case-fatality rate was 36·1% (95% CI 34·3-37·9) overall, and 14·8% (12·8-16·7) for ischaemic stroke, 52·9% (49·9-55·8) for intracerebral haemorrhage, and 54·3% (49·4-59·1) for subarachnoid haemorrhage. Corresponding figures for poor functional outcome at 1-year, defined by scores of 3-6 for death or dependency on the mRS, were 61·6% (95% CI 59·8-63·4), 47·5% (44·7-50·3), 77·0% (74·5-79·5), and 61·8% (57·0-66·5), respectively. INTERPRETATION: The urban population of Ulaanbaatar, Mongolia, has a high incidence of stroke, particularly for intracerebral haemorrhage and subarachnoid haemorrhage, from which half of patients die within 1 month and more than two-thirds are either dead or dependent at 90 days. Although the overall incidence of stroke is similar to other countries, it occurs at a mean age of 60 years, which is at least 10 years younger than in high-income countries. These epidemiological data can inform the implementation of future programmes and scale-up activities for the primary and secondary prevention of stroke, and in the organisation of systems of care. FUNDING: Science and Technology Foundation of the Ministry of Education, Culture, and Science of Mongolia and The George Institute for Global Health.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/epidemiologia , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico , Estudos Prospectivos , Incidência , Mongólia/epidemiologia , Hemorragia Cerebral/epidemiologia
10.
Tob Induc Dis ; 21: 09, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36741540

RESUMO

INTRODUCTION: China has recently introduced a range of e-cigarette control policies with a focus on addressing an increase in youth vaping. This study aimed to investigate a wide range of e-cigarette-related attitudes and behaviors in a national sample of Chinese adolescents and young adults to obtain insights into their exposure to, experiences with, and attitudes to e-cigarettes on the cusp of new regulations coming into force. METHODS: An online survey was administered to a sample of 1062 adolescents and young adults (aged 15-30 years) in China in November-December 2021. Quotas were applied to achieve an approximately equal gender split, representation across age sub-groups (15-17, 18-20, 21-23, 24-26, and 27-30 years), and approximately two-thirds representing low- and middle-income groups. Adjusted odds ratios (AORs) were also calculated. RESULTS: Just under half (47%) reported no knowledge of e-cigarettes and/or vaping. One in five reported ever using e-cigarettes ('even once or twice'), 8% reported being current users, and 3% reported being daily users. Around twothirds of those who had heard of e-cigarettes/vaping had friends who vaped and had seen e-cigarette advertising. Fruit flavors were most popular, and the most frequently nominated reasons for vaping were to cut down on cigarette smoking and because a friend used them. The factors positively associated with ever use of e-cigarettes were current tobacco smoking (AOR=68.26) or previous tobacco smoking (AOR=39.15) and having friends who vape (AOR=1.76). Perceptions of addictiveness were negatively associated with ever use (AOR=0.47). Strong support was evident for most assessed e-cigarette control policies. CONCLUSIONS: The results indicate that young people in China have been able to access and use e-cigarettes, although rates of regular use are low. Generally, high levels of expressed support for a range of e-cigarette control policies among members of this age group suggest the new regulatory environment is consistent with their policy preferences.

11.
BMC Med ; 20(1): 420, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36320059

RESUMO

BACKGROUND: Multimorbidity (the presence of two or more chronic conditions) is common amongst people with chronic kidney disease, but it is unclear which conditions cluster together and if this changes as kidney function declines. We explored which clusters of conditions are associated with different estimated glomerular filtration rates (eGFRs) and studied associations between these clusters and adverse outcomes. METHODS: Two population-based cohort studies were used: the Stockholm Creatinine Measurements project (SCREAM, Sweden, 2006-2018) and the Secure Anonymised Information Linkage Databank (SAIL, Wales, 2006-2021). We studied participants in SCREAM (404,681 adults) and SAIL (533,362) whose eGFR declined lower than thresholds (90, 75, 60, 45, 30 and 15 mL/min/1.73m2). Clusters based on 27 chronic conditions were identified. We described the most common chronic condition(s) in each cluster and studied their association with adverse outcomes using Cox proportional hazards models (all-cause mortality (ACM) and major adverse cardiovascular events (MACE)). RESULTS: Chronic conditions became more common and clustered differently across lower eGFR categories. At eGFR 90, 75, and 60 mL/min/1.73m2, most participants were in large clusters with no prominent conditions. At eGFR 15 and 30 mL/min/1.73m2, clusters involving cardiovascular conditions were larger and were at the highest risk of adverse outcomes. At eGFR 30 mL/min/1.73m2, in the heart failure, peripheral vascular disease and diabetes cluster in SCREAM, ACM hazard ratio (HR) is 2.66 (95% confidence interval (CI) 2.31-3.07) and MACE HR is 4.18 (CI 3.65-4.78); in the heart failure and atrial fibrillation cluster in SAIL, ACM HR is 2.23 (CI 2.04 to 2.44) and MACE HR is 3.43 (CI 3.22-3.64). Chronic pain and depression were common and associated with adverse outcomes when combined with physical conditions. At eGFR 30 mL/min/1.73m2, in the chronic pain, heart failure and myocardial infarction cluster in SCREAM, ACM HR is 2.00 (CI 1.62-2.46) and MACE HR is 4.09 (CI 3.39-4.93); in the depression, chronic pain and stroke cluster in SAIL, ACM HR is 1.38 (CI 1.18-1.61) and MACE HR is 1.58 (CI 1.42-1.76). CONCLUSIONS: Patterns of multimorbidity and corresponding risk of adverse outcomes varied with declining eGFR. While diabetes and cardiovascular disease are known high-risk conditions, chronic pain and depression emerged as important conditions and associated with adverse outcomes when combined with physical conditions.


Assuntos
Fibrilação Atrial , Dor Crônica , Insuficiência Cardíaca , Insuficiência Renal Crônica , Adulto , Humanos , Multimorbidade , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/complicações , Fibrilação Atrial/complicações , Insuficiência Cardíaca/complicações , Rim
12.
World Neurosurg ; 161: 367-375, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35505556

RESUMO

In this narrative review, we discuss aspects of study design for research in the surgical treatment of patients with spontaneous acute intracerebral hemorrhage (ICH). We emphasize the importance of carefully defining the primary end point relevant to the intervention under investigation, whether this is technical (i.e., residual hematoma volume) or clinical (i.e., mortality or functional outcome), and the timing of its assessment. Compared with patients with acute ischemic stroke, patients with spontaneous acute ICH may take longer to fully recover. Efficient patient recruitment is essential for all research studies and deferred consent is an option to allow disabled and critically ill patients to be included. Although central concealment of the randomization process, often with a method of stratification to ensure that prognostic variables are balanced between groups, it is often appropriate to undertake analysis of the treatment effect adjusted for various predefined covariables. The definition of minimally invasive surgery, and its use and timing in relation to ICH, requires urgent assessment. Future studies could be better designed and executed as part of a large (inter)national ICH trials consortium, consisting of dedicated interdisciplinary teams of neurologists, neurosurgeons, intensivists, and epidemiologists. We advocate studies to be pragmatic and adhere to the IDEAL recommendations and CONSORT guidelines.


Assuntos
AVC Isquêmico , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Hematoma/cirurgia , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Neurocirurgiões
13.
Cerebrovasc Dis ; 51(3): 384-393, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34879381

RESUMO

BACKGROUND: Health care quality and insurance coverage have improved with economic development in China, but the burden of cardiovascular diseases (CVDs) continues to increase with ongoing gaps in prevention. We aimed to compare the uptake of secondary CVD prevention between stroke and coronary heart disease (CHD) patients in China. METHODS: In a cross-sectional community-based survey of 47,841 adults (age ≥45 years) in 7 regions of China between 2014 and 2016, we identified those with a history of stroke or CHD to quantify disparities in conventional secondary CVD prevention strategies in multivariable logistic regression models. RESULTS: There were 4,105 and 1,022 participants with a history of stroke and CHD, respectively. Compared to participants with CHD, those with a history of stroke were significantly less likely to be taking blood-pressure-lowering (39.7% vs. 53%), lipid-lowering (13.7% vs. 36.8%), and antiplatelet (20.8% vs. 50.6%) agents, at least one (48.9% vs. 70.8%) or all 3 recommended medicines (6.1% vs. 24.0%), and were less likely to achieve a lipid-cholesterol target (30.3% vs. 44.0%). Participants with a history of stroke achieved less optimal secondary prevention goals for medication use, either from any (adjusted odds ratio [aOR] 0.54, 95% confidence interval [CI] 0.44-0.66) or all 3 medications (aOR 0.27, 95% CI 0.20-0.36), as well as better blood pressure (aOR 0.81, 95% CI 0.66-0.98) and low-density lipoprotein cholesterol (aOR 0.34, 95% CI 0.27-0.43) levels of control. There were no significant differences in weight, smoking, or physical activity between the groups. CONCLUSION: Stroke patients had lower use of secondary CVD-preventive medication and achieved lower levels of risk factor control than those of CHD patients in China. Nationwide disease-specific strategies, and better education of participants and health care providers, may narrow these gaps.


Assuntos
Doenças Cardiovasculares , Doença das Coronárias , Acidente Vascular Cerebral , China/epidemiologia , Colesterol , LDL-Colesterol , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Doença das Coronárias/prevenção & controle , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Prevenção Secundária , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle
14.
Trials ; 22(1): 905, 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34895306

RESUMO

BACKGROUND: Chronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH. METHODS: The second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-centre, randomized, placebo-controlled, double-blind trial which aims to enrol 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition and reduction in haematoma volumes at 14, 28 and 90 days. DISCUSSION: This multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH. TRIAL REGISTRATION: ChiCTR, ChiCTR1900021659 . Registered on 3 March 2019, http://www.chictr.org.cn/showproj.aspx?proj=36157 .


Assuntos
Hematoma Subdural Crônico , Adulto , Idoso , Atorvastatina/efeitos adversos , Dexametasona/efeitos adversos , Método Duplo-Cego , Hematoma Subdural Crônico/diagnóstico por imagem , Hematoma Subdural Crônico/tratamento farmacológico , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
J Pediatr Surg ; 56(12): 2348-2353, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33836845

RESUMO

BACKGROUND: Trauma patients undergo a standardized history and physical, however identification of mental health risk factors is not typically included. We aimed to assess the feasibility of using a modified version of Psychological Simple Triage and Rapid Treatment (PsySTART) to identify post-traumatic stress disorder (PTSD) risk factors in pediatric trauma patients. We hypothesized that PsySTART could identify risk factors and be integrated into the electronic medical record (EMR). METHODS: Trauma patients 10-17 years old at a level II pediatric trauma center from 2014 to 2015 were screened. PsySTART was used on a pilot cohort to determine if risk factors were present. PsySTART was then integrated into an automated EMR workflow and completion rates were evaluated. RESULTS: PsySTART was completed in a pilot cohort of 63 patients with the following findings: 33.3% (n = 21) with 1 risk factor, 22.2% (n = 14) with 2 risk factors, and 19.1% (n = 12) with ≥3 risk factors. The most commonly identified risk factor was, "felt or expressed extreme fear or panic" (n = 27, 43.0%). After EMR integration, PsySTART was successfully completed with automatic consults in 156 of 198 patients (78.8%). CONCLUSIONS: PsySTART identified risk factors in pediatric trauma patients. EMR integration was feasible and led to proactive psychological management and intervention. LEVEL OF EVIDENCE: IV.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Adolescente , Criança , Estudos de Viabilidade , Humanos , Saúde Mental , Projetos Piloto , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Triagem
16.
Stroke Vasc Neurol ; 6(3): 395-401, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33526633

RESUMO

BACKGROUND AND PURPOSE: As studies vary in defining the prognostic significance of smoking in acute ischaemic stroke (AIS), we aimed to determine the relation of smoking and key outcomes in patient participants who had thrombolysed AIS of the international quasi-factorial randomised Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: Post-hoc analyses of ENCHANTED, an international quasi-factorial randomised evaluation of intravenous alteplase-dose comparison and levels of blood pressure control in patients who had thrombolysed AIS. Multivariable logistic regression models with inverse probability of treatment weighting (IPTW) propensity scores were used to determine associations of self-reported smoking status and clinical outcomes, according to 90-day modified Rankin Scale (mRS) scores and symptomatic intracerebral haemorrhage (sICH). RESULTS: Of 4540 patients who had an AIS, there were 1008 (22.2%) current smokers who were younger and predominantly male, with more comorbidities of hypertension, coronary artery disease, atrial fibrillation and diabetes mellitus, and greater baseline neurological impairment, compared with non-smokers. In univariate analysis, current smokers had a higher likelihood of a favourable shift in mRS scores (OR 0.88, 95% CI 0.77 to 0.99; p=0.038) but this association reversed in a fully adjusted model with IPTW (adjusted OR 1.15, 95% CI 1.04 to 1.28; p=0.009). A similar trend was also apparent for dichotomised poor outcome (mRS scores 2-6: OR 1.18, 95% CI 1.05 to 1.33; p=0.007), but not with the risk of sICH across standard criteria. CONCLUSION: Smoking predicts poor functional recovery in patients who had thrombolysed AIS. TRIAL REGISTRATION NUMBER: NCT01422616.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamento farmacológico , Feminino , Fibrinolíticos , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , Masculino , Fumar/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento
17.
Eur J Trauma Emerg Surg ; 47(4): 939-947, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31384999

RESUMO

PURPOSE: Whole-body computed tomography (CT) for blunt trauma patients is common. Chest CT (CCT) identifies "occult" pneumo- (PTX) and hemothorax (HTX) not seen on chest radiograph (CXR), one-third of whom get chest tubes, while CXR identifies "non-occult" PTX/HTX. To assess chest tube value for occult injury vs. expectant management, we compared output, duration, and length of stay (LOS) for chest tubes placed for occult vs. non-occult (CXR-visible) injury. METHODS: We compared chest tube output and duration, and patient length of stay for occult vs. non-occult PTX/HTX. This was a retrospective analysis of 5451 consecutive Level I blunt trauma patients, from 2010 to 2013. RESULTS: Of these blunt trauma patients, 402 patients (7.4%) had PTX, HTX or both, and both CXR and CCT. One third (n = 136, 33.8%) had chest tubes placed in 163 hemithoraces (27 bilateral). Non-occult chest tube output for all patients was 1558 ± 1919 cc (n = 54), similar to occult at 1123 ± 1076 cc (n = 109, p = 0.126). Outputs were similar for HTX-only patients, with non-occult (n = 34) at 1917 ± 2130 cc, vs. occult (n = 54) at 1449 ± 1131 cc (p = 0.24). Chest tube duration for all patients was 6.3 ± 4.9 days for non-occult vs. 5.0 ± 3.3 for occult (p = 0.096). LOS was similar between all occult injury patients (n = 46) and non-occult (n = 90, 17.0 ± 15.8 vs. 13.7 ± 11.9 days, p = 0.23). CONCLUSION: Mature clinical judgment may dictate which patients need chest tubes and explain the similarity between groups.


Assuntos
Pneumotórax , Traumatismos Torácicos , Ferimentos não Penetrantes , Tubos Torácicos , Hemotórax/diagnóstico por imagem , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação , Pneumotórax/diagnóstico por imagem , Estudos Retrospectivos , Traumatismos Torácicos/complicações , Traumatismos Torácicos/diagnóstico por imagem , Toracostomia , Tomografia Computadorizada por Raios X , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/diagnóstico por imagem
18.
J Womens Health (Larchmt) ; 30(3): 314-323, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33227218

RESUMO

Background: We examined sex differences in cause of death and cause-specific excess mortality after stroke. Materials and Methods: First-ever strokes (2010-2013; 35 hospitals) participating in the Australian Stroke Clinical Registry were linked to national death registrations and other administrative datasets. One-year cause-specific mortality was categorized as stroke, ischemic heart disease, other cardiovascular disease (CVD; e.g., hypertension), cancer, and other. Specific hazard ratios (sHRs) of death for women compared to men were estimated using competing risk models, with adjustment for factors differing by sex (e.g., age and stroke severity). Age- and sex-specific mortality rates expected in the general population were derived from national data. Standardized mortality ratios (SMRs; observed/expected deaths) were estimated for cause-specific mortality by sex after age standardization. Results: Among 9,441 cases (46% women), women were 7 years older than men, had more severe strokes, and received similar patterns of suboptimal secondary prevention medications at discharge. Women had greater mortality associated with stroke (sHRunadjusted 1.65) and other CVD (sHRunadjusted 1.65), which was related to age and stroke severity rather than other factors. Compared to population norms, those surviving to 30 days had eight-fold increased mortality from stroke (primary/recurrent) events irrespective of sex (SMRage-standardised women 8.8; men 8.3). Excess mortality from other CVD was greater in women (SMRage-standardised 3.6 vs. men 2.8; p = 0.026). Conclusions: Cause-specific mortality after first-ever stroke differs by sex. The greater death rate attributed to stroke/other CVD in women was mostly explained by age and stroke severity. Greater implementation of secondary stroke prevention is relevant to both sexes.


Assuntos
Doenças Cardiovasculares , Acidente Vascular Cerebral , Austrália/epidemiologia , Causas de Morte , Feminino , Humanos , Masculino , Sistema de Registros , Fatores de Risco , Caracteres Sexuais , Fatores Sexuais
19.
Neurology ; 96(1): e30-e41, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33093227

RESUMO

OBJECTIVE: To investigate whether certain patient, acute care, or primary care factors are associated with medication initiation and discontinuation in the community after stroke or TIA. METHODS: This is a retrospective cohort study using prospective data on adult patients with first-ever acute stroke/TIA from the Australian Stroke Clinical Registry (April 2010 to June 2014), linked with nationwide medication dispensing and Medicare claims data. Medication users were those with ≥1 dispensing in the year postdischarge. Discontinuation was assessed among medication users and defined as having no medication supply for ≥90 days in the year postdischarge. Multivariable competing risks regression, accounting for death during the observation period, was conducted to investigate factors associated with time to medication discontinuation. RESULTS: Among 17,980 registry patients with stroke/TIA, 91.4% were linked to administrative datasets. Of these, 9,817 adults with first-ever stroke/TIA were included (45.4% female, 47.6% aged ≥75 years, and 11.4% intracerebral hemorrhage). While most patients received secondary prevention medications (79.3% antihypertensive, 81.8% antithrombotic, and 82.7% lipid-lowering medication), between one-fifth and one-third discontinued treatment over the subsequent year postdischarge (20.9% antihypertensive, 34.1% antithrombotic, and 28.5% lipid-lowering medications). Prescription at hospital discharge (sub-hazard ratio [SHR] 0.70; 95% confidence interval [CI] 0.62-0.79), quarterly contact with a primary care physician (SHR 0.62; 95% CI 0.57-0.67), and prescription by a specialist physician (SHR 0.87; 95% CI 0.77-0.98) were all inversely associated with antihypertensive discontinuation. CONCLUSIONS: Patterns of use of secondary prevention medications after stroke/TIA are not optimal, with many survivors discontinuing treatment within 1 year postdischarge. Improving postdischarge care for patients with stroke/TIA is needed to minimize unwarranted discontinuation.


Assuntos
Adesão à Medicação/estatística & dados numéricos , Prevenção Secundária/métodos , Prevenção Secundária/estatística & dados numéricos , Acidente Vascular Cerebral/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Austrália , Quimioprevenção/métodos , Quimioprevenção/estatística & dados numéricos , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Retrospectivos
20.
Stroke Vasc Neurol ; 5(4): 323-330, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32989012

RESUMO

BACKGROUND: The COVID-19 pandemic and physical distancing guidelines have compelled stroke practices worldwide to reshape their delivery of care significantly. We aimed to illustrate how the stroke services were interrupted during the pandemic in China. METHODS: A 61-item questionnaire designed on Wenjuanxing Form was completed by doctors or nurses who were involved in treating patients with stroke from 1 February to 31 March 2020. RESULTS: A total of 415 respondents completed the online survey after informed consent was obtained. Of the respondents, 37.8%, 35.2% and 27.0% were from mild, moderate and severe epidemic areas, respectively. Overall, the proportion of severe impact (reduction >50%) on the admission of transient ischaemic stroke, acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH) was 45.0%, 32.0% and 27.5%, respectively. Those numbers were 36.9%, 27.9% and 22.3%; 36.5%, 22.1% and 22.6%; and 66.4%, 47.5% and 41.1% in mild, moderate and severe epidemic areas, respectively (all p<0.0001). For AIS, thrombolysis was moderate (20%-50% reduction) or severely impacted (>50%), as reported by 54.4% of the respondents, while thrombectomy was 39.3%. These were 44.4%, 26.3%; 44.2%, 39.4%; and 78.2%, 56.5%, in mild, moderate and severe epidemic areas, respectively (all p<0.0001). For patients with acute ICH, 39.8% reported the impact was severe or moderate for those eligible for surgery who had surgery. Those numbers were 27.4%, 39.0% and 58.1% in mild, moderate and severe epidemic areas, respectively. For staff resources, about 20% (overall) to 55% (severe epidemic) of the respondents reported moderate or severe impact on the on-duty doctors and nurses. CONCLUSION: We found a significant reduction of admission for all types of patients with stroke during the pandemic. Patients were less likely to receive appropriate care, for example, thrombolysis/thrombectomy, after being admitted to the hospital. Stroke service in severe COVID-19 epidemic areas, for example, Wuhan, was much more severely impacted compared with other regions in China.


Assuntos
COVID-19/epidemiologia , Serviços de Saúde/estatística & dados numéricos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Hemorragia Cerebral/epidemiologia , China/epidemiologia , Estudos Transversais , Humanos , Ataque Isquêmico Transitório/epidemiologia , AVC Isquêmico/epidemiologia , Neurocirurgia/estatística & dados numéricos , Pandemias , Admissão do Paciente/estatística & dados numéricos , Administração dos Cuidados ao Paciente , Acidente Vascular Cerebral/cirurgia , Inquéritos e Questionários , Terapia Trombolítica/estatística & dados numéricos
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