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BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness. The first-line therapy is anti-vascular endothelial growth factor (anti-VEGF) agents delivered by intravitreal injection. Ionising radiation mitigates key pathogenic processes underlying nAMD, and therefore has therapeutic potential. STAR aimed to assess whether stereotactic radiotherapy (SRT) reduces the number of anti-VEGF injections required, without sacrificing visual acuity. METHODS: This pivotal, randomised, double-masked, sham-controlled trial enrolled participants with pretreated chronic active nAMD from 30 UK hospitals. Participants were randomly allocated in a 2:1 ratio to 16-Gray (Gy) SRT delivered using a robotically controlled device or sham SRT, stratified by treatment centre. Eligible participants were aged 50 years or older and had chronic active nAMD, with at least three previous anti-VEGF injections, including at least one in the last 4 months. Participants and all trial and image reading centre staff were masked to treatment allocation, except one unmasked statistician. The primary outcome was the number of intravitreal ranibizumab injections required over 2 years, tested for superiority (fewer injections). The main secondary outcome was Early Treatment Diabetic Retinopathy Study visual acuity at two years, tested for non-inferiority (five-letter margin). The primary analysis used the intention-to-treat principle, and safety was analysed per-protocol on participants with available data. The study is registered with ClinicalTrials.gov (NCT02243878) and is closed for recruitment. FINDINGS: 411 participants enrolled between Jan 1, 2015, and Dec 27, 2019, and 274 were randomly allocated to the 16-Gy SRT group and 137 to the sham SRT group. 240 (58%) of all participants were female, and 171 (42%) of all participants were male. 241 participants in the 16-Gy SRT group and 118 participants in the sham group were included in the final analysis, and 409 patients were treated and formed the safety population, of whom two patients allocated to sham treatment erroneously received 16-Gy SRT. The SRT group received a mean of 10·7 injections (SD 6·3) over 2 years versus 13·3 injections (5·8) with sham, a reduction of 2·9 injections after adjusting for treatment centre (95% CI -4·2 to -1·6, p<0·0001). The SRT group best-corrected visual acuity change was non-inferior to sham (adjusted mean letter loss difference between groups, -1·7 letters [95% CI -4·2 to 0·8]). Adverse event rates were similar across groups, but reading centre-detected microvascular abnormalities occurred in 77 SRT-treated eyes (35%) and 13 (12%) sham-treated eyes. Overall, eyes with microvascular abnormalities tended to have better best-corrected visual acuity than those without. Fewer ranibizumab injections offset the cost of SRT, saving a mean of £565 per participant (95% CI -332 to 1483). INTERPRETATION: SRT can reduce ranibizumab treatment burden without compromising vision. FUNDING: Medical Research Council and National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme.
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Inibidores da Angiogênese , Injeções Intravítreas , Radiocirurgia , Ranibizumab , Acuidade Visual , Humanos , Masculino , Método Duplo-Cego , Feminino , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Ranibizumab/administração & dosagem , Ranibizumab/uso terapêutico , Radiocirurgia/métodos , Pessoa de Meia-Idade , Degeneração Macular , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso de 80 Anos ou maisRESUMO
INTRODUCTION: Current evidence regarding the clinical outcomes of non-vitamin K oral anticoagulants (NOACs) versus warfarin in patients with atrial fibrillation (AF) and previous stroke is inconclusive, especially in patients with previous intracranial haemorrhage (ICrH). We aim to undertake a systematic review and meta-analysis assessing the effectiveness and safety of NOACs versus warfarin in AF patients with a history of stroke. METHODS: We searched studies published up to December 10, 2022, on PubMed, Medline, Embase, and Cochrane Central Register of Controlled Trials. Studies on adults with AF and previous ischaemic stroke (IS) or IrCH receiving either NOACs or warfarin and capturing outcome events (thromboembolic events, ICrH, and all-cause mortality) were eligible for inclusion. RESULTS: Six randomized controlled trials (RCTs) (including 19,489 patients with previous IS) and fifteen observational studies (including 132,575 patients with previous IS and 13,068 patients with previous ICrH) were included. RCT data showed that compared with warfarin, NOACs were associated with a significant reduction in thromboembolic events (odds ratio [OR]: 0.85, 95% confidence interval [CI]: 0.75-0.96), ICrH (OR: 0.57, 95% CI: 0.36-0.90), and all-cause mortality (OR: 0.88, 95% CI: 0.80-0.98). In analysing observational studies, similar results were retrieved. Moreover, patients with previous ICrH had a lower OR on thromboembolic events than those with IS (OR: 0.66, 95% CI: 0.46-0.95 vs. OR: 0.80, 95% CI: 0.70-0.93) in the comparison between NOACs and warfarin. CONCLUSIONS: Observational data showed that in AF patients with previous stroke, NOACs showed better clinical performance compared to warfarin and the benefits of NOACs were more pronounced in patients with previous IrCH versus those with IS. RCT data also showed NOACs are superior to warfarin. However, current RCTs only included AF patients who survived an IS, and further large RCTs focused on patients with previous ICrH are warranted.
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Fibrilação Atrial , AVC Isquêmico , Acidente Vascular Cerebral , Tromboembolia , Adulto , Humanos , Varfarina/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Vitamina K , Anticoagulantes/efeitos adversos , Acidente Vascular Cerebral/complicações , Hemorragias Intracranianas , Resultado do TratamentoRESUMO
PURPOSE: The South London Stroke Register (SLSR) is a population-based cohort study, which was established in 1995 to study the causes, incidence, and outcomes of stroke. The SLSR aims to estimate incidence, and acute and long term needs in a multi-ethnic inner-city population, with follow-up durations for some participants exceeding 20 years. PARTICIPANTS: The SLSR aims to recruit residents of a defined area within Lambeth and Southwark who experience a first stroke. More than 7700 people have been registered since inception, and >2750 people continue to be followed up. At the 2011 census, the source population was 357,308. FINDINGS TO DATE: The SLSR was instrumental in highlighting the inequalities in risk and outcomes in the UK, and demonstrating the dramatic improvements in care quality and outcomes in recent decades. Data from the SLSR informed the UK National Audit Office in its 2005 report criticising the poor state of stroke care in England. For people living in the SLSR area the likelihood of being treated in a stroke unit increased from 19% in 1995-7 to 75% in 2007-9. The SLSR has investigated health inequalities in stroke incidence and outcome. SLSR analyses have demonstrated that lower socioeconomic status was associated with poorer outcome, and that Black people and younger people have not experienced the same improvements in stroke incidence as other groups. FUTURE PLANS: As part of an NIHR Programme Grant for Applied Research, from April 2022 the SLSR has expanded to recruit ICD-11 defined stroke (including those with <24 h symptoms where there are neuroimaging findings), and have expanded the follow up interviews to collect more detailed information on quality of life, cognition, and care needs. Additional data items will be added over the Programme based on feedback from patients and other stakeholders.
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Qualidade de Vida , Acidente Vascular Cerebral , Humanos , Estudos de Coortes , Londres/epidemiologia , Incidência , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapiaRESUMO
BACKGROUND AND PURPOSE: Prediction of stroke impact provides essential information for healthcare planning and priority setting. We aim to estimate 30-year projections of stroke epidemiology in the European Union using multiple modeling approaches. METHODS: Data on stroke incidence, prevalence, deaths, and disability-adjusted life years in the European Union between 1990 and 2017 were obtained from the global burden of disease study. Their trends over time were modeled using 3 modeling strategies: linear, Poisson, and exponential regressions-adjusted for the gross domestic product per capita, which reflects the impact of economic development on health status. We used the Akaike information criterion for model selection. The 30-year projections up to 2047 were estimated using the best fitting models, with inputs on population projections from the United Nations and gross domestic product per capita prospects from the World Bank. The technique was applied separately by age-sex-country groups for each stroke measure. RESULTS: In 2017, there were 1.12 million incident strokes in the European Union, 9.53 million stroke survivors, 0.46 million deaths, and 7.06 million disability-adjusted life years lost because of stroke. By 2047, we estimated an additional 40 000 incident strokes (+3%) and 2.58 million prevalent cases (+27%). Conversely, 80 000 fewer deaths (-17%) and 2.31 million fewer disability-adjusted life years lost (-33%) are projected. The largest increase in the age-adjusted incidence and prevalence rates are expected in Lithuania (average annual percentage change, 0.48% and 0.7% respectively), and the greatest reductions in Portugal (-1.57% and -1.3%). Average annual percentage change in mortality rates will range from -2.86% (Estonia) to -0.08% (Lithuania), and disability-adjusted life years' from -2.77% (Estonia) to -0.23% (Romania). CONCLUSIONS: The number of people living with stroke is estimated to increase by 27% between 2017 and 2047 in the European Union, mainly because of population ageing and improved survival rates. Variations are expected to persist between countries showing opportunities for improvements in prevention and case management particularly in Eastern Europe.
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Efeitos Psicossociais da Doença , Pessoas com Deficiência , Anos de Vida Ajustados por Qualidade de Vida , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Europa (Continente)/epidemiologia , Feminino , Previsões , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: There have been reductions in stroke mortality over recent decades, but estimates by aetiological subtypes are limited. This study estimates time trends in mortality and functional dependence by ischaemic stroke (IS) aetiological subtype over a 16-year period. METHODS AND FINDINGS: The study population was 357,308 in 2011; 50.4% were males, 56% were white, and 25% were of black ethnic backgrounds. Population-based case ascertainment of stroke was conducted, and all participants who had their first-ever IS between 2000 and 2015 were identified. Further classification was concluded according to the underlying mechanism into large-artery atherosclerosis (LAA), cardio-embolism (CE), small-vessel occlusion (SVO), other determined aetiologies (OTH), and undetermined aetiologies (UND). Temporal trends in survival rates were examined using proportional-hazards survival modelling, adjusted for demography, prestroke risk factors, case mix variables, and processes of care. We carried out additional regression analyses to explore patterns in case-fatality rates (CFRs) at 30 days and 1 year and to explore whether these trends occurred at the expense of greater functional dependence (Barthel Index [BI] < 15) among survivors. A total of 3,128 patients with first-ever ISs were registered. The median age was 70.7 years; 50.9% were males; and 66.2% were white, 25.5% were black, and 8.3% were of other ethnic groups. Between 2000-2003 and 2012-2015, the adjusted overall mortality decreased by 24% (hazard ratio [HR] per year 0.976; 95% confidence interval [CI] 0.959-0.993). Mortality reductions were equally noted in both sexes and in the white and black populations but were only significant in CE strokes (HR per year 0.972; 95% CI 0.945â0.998) and in patients aged ≥55 years (HR per year 0.975; 95% CI 0.959â0.992). CFRs within 30 days and 1 year after an IS declined by 38% (rate ratio [RR] per year 0.962; 95% CI 0.941â0.984) and 37% (RR per year 0.963; 95% CI 0.949â0.976), respectively. Recent IS was independently associated with a 23% reduced risk of functional dependence at 3 months after onset (RR per year 0.983; 95% CI 0.968-0.998; p = 0.002 for trend). The study is limited by small number of events in certain subgroups (e.g., LAA), which could have led to insufficient power to detect significant trends. CONCLUSIONS: Both mortality and 3-month functional dependence after IS decreased by an annual average of around 2.4% and 1.7%, respectively, during 2000â2015. Such reductions were particularly evident in strokes of CE origins and in those aged ≥55 years.
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Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/etnologia , Isquemia Encefálica/fisiopatologia , Causas de Morte/tendências , Avaliação da Deficiência , Feminino , Nível de Saúde , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/fisiopatologia , Fatores de TempoRESUMO
BACKGROUND: As the average life expectancy increases, more people are predicted to have strokes. Recent studies have shown an increasing incidence in certain types of cerebral infarction. We aimed to estimate time trends in incidence, prior risk factors, and use of preventive treatments for ischaemic stroke (IS) aetiological subtypes and to ascertain any demographic disparities. METHODS AND FINDINGS: Population-based data from the South London Stroke Register (SLSR) between 2000 and 2015 were studied. IS was classified, based on the underlying mechanism, into large-artery atherosclerosis (LAA), cardio-embolism (CE), small-vessel occlusion (SVO), other determined aetiologies (OTH), and undetermined aetiologies (UND). After calculation of age-, sex-, and ethnicity-specific incidence rates by subtype for the 16-year period, we analysed trends using Cochran-Armitage tests, Poisson regression models, and locally estimated scatterplot smoothers (loess). A total of 3,088 patients with first IS were registered. Between 2000-2003 and 2012-2015, the age-adjusted incidence of IS decreased by 43% from 137.3 to 78.4/100,000/year (incidence rate ratio [IRR] 0.57, 95% CI 0.5-0.64). Significant declines were observed in all subtypes, particularly in SVO (37.4-18; p < 0.0001) and less in CE (39.3-25; p < 0.0001). Reductions were recorded in males and females, younger (<55 years old) and older (≥55 years old) individuals, and white and black ethnic groups, though not significantly in the latter (144.6-116.2; p = 0.31 for IS). A 4-fold increase in prior-to-stroke use of statins was found (adjusted odds ratio [OR] 4.39, 95% CI 3.29-5.86), and despite the increasing prevalence of hypertension (OR 1.54, 95% CI 1.21-1.96) and atrial fibrillation (OR 1.7, 95% CI 1.22-2.36), preventive use of antihypertensive and antiplatelet drugs was declining. A smaller number of participants in certain subgroup-specific analyses (e.g., black ethnicity and LAA subtype) could have limited the power to identify significant trends. CONCLUSIONS: The incidence of ISs has been declining since 2000 in all age groups but to a lesser extent in the black population. The reported changes in medication use are unlikely to fully explain the reduction in stroke incidence; however, innovative prevention strategies and better management of risk factors may contribute further reduction.
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Arteriopatias Oclusivas/epidemiologia , Infarto Cerebral/epidemiologia , Arteriosclerose Intracraniana/epidemiologia , Embolia Intracraniana/epidemiologia , Londres/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Arteriopatias Oclusivas/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , População Negra/estatística & dados numéricos , Infarto Cerebral/etnologia , Infarto Cerebral/etiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Incidência , Arteriosclerose Intracraniana/complicações , Embolia Intracraniana/complicações , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Prevalência , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: Postoperative pain is one of the most important problems that confront surgical patients. The aim of this work is to compare pain control using intravenous patient controlled analgesia (PCA) and patient controlled epidural analgesia (PCEA) in cirrhotic patients undergoing elective hepatic resection. METHODS: Thirty four adult patients ASAI and II scheduled for liver resection were randomly allocated into two groups-Group (P) with I.V (PCA) with fentanyl and Group (E) (PCEA) via epidural catheter using Bubivacaine 0.125% plus 2 microgram per ml fentanyl. Coagulation changes were followed and pain score was compared in both groups. RESULTS: 34 child A cirrhotic patients, undergoing liver resection were studied. The demographic data were comparable in both groups. There was a significant decrease in pain score in both groups during the follow up period when compared to their initial score. When comparing average pain score between both groups, the PCEA group had significantly lower values. The changes in prothrombin time (PT), INR, and hemoglobin (Hb), were significant all over the follow up period compared to their corresponding base line values. 2 cases needed FFP to normalize the INR for epidural removal. There was no significant difference regarding postoperative nausea and vomiting (PONV) in both groups, no clinical manifestation suggesting epidural hematoma, and no cases were recorded to have respiratory depression. There were no significant differences in patient satisfaction and ICU stay. CONCLUSION: The two modalities of pain control seems to be nearly equivalent, but considering the risk of epidural catheter insertion and removal in cirrhotic patients who are further exposed to hepatectomy with subsequent additional coagulopathy, it may be wise to consider IVPCA technique as a policy for pain management in cirrhotic patient undergoing hepatectomy.
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Analgesia Epidural/métodos , Analgesia Controlada pelo Paciente/métodos , Anestesia Intravenosa/métodos , Hepatectomia , Cirrose Hepática/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Analgésicos Opioides , Anestésicos Locais , Bupivacaína , Feminino , Fentanila , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor/métodos , Medição da Dor/métodos , Satisfação do Paciente/estatística & dados numéricos , Resultado do TratamentoRESUMO
OBJECTIVE: This study aims to conduct a systematic review and meta-analysis of the diagnostic accuracy of deep learning (DL) using speech samples in depression. MATERIALS AND METHODS: This review included studies reporting diagnostic results of DL algorithms in depression using speech data, published from inception to January 31, 2024, on PubMed, Medline, Embase, PsycINFO, Scopus, IEEE, and Web of Science databases. Pooled accuracy, sensitivity, and specificity were obtained by random-effect models. The diagnostic Precision Study Quality Assessment Tool (QUADAS-2) was used to assess the risk of bias. RESULTS: A total of 25 studies met the inclusion criteria and 8 of them were used in the meta-analysis. The pooled estimates of accuracy, specificity, and sensitivity for depression detection models were 0.87 (95% CI, 0.81-0.93), 0.85 (95% CI, 0.78-0.91), and 0.82 (95% CI, 0.71-0.94), respectively. When stratified by model structure, the highest pooled diagnostic accuracy was 0.89 (95% CI, 0.81-0.97) in the handcrafted group. DISCUSSION: To our knowledge, our study is the first meta-analysis on the diagnostic performance of DL for depression detection from speech samples. All studies included in the meta-analysis used convolutional neural network (CNN) models, posing problems in deciphering the performance of other DL algorithms. The handcrafted model performed better than the end-to-end model in speech depression detection. CONCLUSIONS: The application of DL in speech provided a useful tool for depression detection. CNN models with handcrafted acoustic features could help to improve the diagnostic performance. PROTOCOL REGISTRATION: The study protocol was registered on PROSPERO (CRD42023423603).
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BACKGROUND: Endovascular repair of aortic aneurysmal disease is established due to perceived advantages in patient survival, reduced postoperative complications, and shorter hospital lengths of stay. High spatial and contrast resolution 3D CT angiography images are used to plan the procedures and inform device selection and manufacture, but in standard care, the surgery is performed using image-guidance from 2D X-ray fluoroscopy with injection of nephrotoxic contrast material to visualise the blood vessels. This study aims to assess the benefit to patients, practitioners, and the health service of a novel image fusion medical device (Cydar EV), which allows this high-resolution 3D information to be available to operators at the time of surgery. METHODS: The trial is a multi-centre, open label, two-armed randomised controlled clinical trial of 340 patient, randomised 1:1 to either standard treatment in endovascular aneurysm repair or treatment using Cydar EV, a CE-marked medical device comprising of cloud computing, augmented intelligence, and computer vision. The primary outcome is procedural time, with secondary outcomes of procedural efficiency, technical effectiveness, patient outcomes, and cost-effectiveness. Patients with a clinical diagnosis of AAA or TAAA suitable for endovascular repair and able to provide written informed consent will be invited to participate. DISCUSSION: This trial is the first randomised controlled trial evaluating advanced image fusion technology in endovascular aortic surgery and is well placed to evaluate the effect of this technology on patient outcomes and cost to the NHS. TRIAL REGISTRATION: ISRCTN13832085. Dec. 3, 2021.
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Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Análise Custo-Benefício , Computação em Nuvem , Procedimentos Endovasculares/métodos , Implante de Prótese Vascular/efeitos adversos , Resultado do Tratamento , Estudos Retrospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Background: Anticipating the burden of intracerebral haemorrhage is crucial for proactive management and building resilience against future health challenges. Prior forecasts are based on population demography and to a lesser extent epidemiological trends. This study aims to utilise selected modifiable risk factors and socio-demographic indicators to forecast the incidence and mortality of intracerebral haemorrhage in Europe between 2019 and 2050. Methods: Three intracerebral haemorrhage risk factors identified in the Global Burden of Diseases, Injuries, and Risk Factors study (GBD 2019)-high systolic blood pressure, high fasting plasma glucose, and high body mass index-were utilised to predict the risk-attributable fractions between 2019 and 2050. Disease burden not attributable to these risk factors was then forecasted using time series models (autoregressive integrated moving average [ARIMA]), incorporating the Socio-demographic Index (SDI) as an external predictor. The optimal parameters of ARIMA models were selected for each age-sex-country group based on the Akaike Information Criterion (AIC). Different health scenarios were constructed by extending the past 85th and 15th percentiles of annualised rates of change in risk factors and SDI across all location-years, stratified by age and sex groups. A decomposition analysis was performed to assess the relative contributions of population size, age composition, and intracerebral haemorrhage risk on the projected changes. Findings: Compared with observed figures in 2019, our analysis predicts an increase in the burden of intracerebral haemorrhage in Europe in 2050, with a marginal rise of 0.6% (95% uncertainty interval [UI], -7.4% to 9.6%) in incident cases and an 8.9% (-2.8% to 23.6%) increase in mortality, reaching 141.2 (120.6-166.5) thousand and 144.2 (122.9-172.2) thousand respectively. These projections may fluctuate depending on trajectories of the risk factors and SDI; worsened trends could result in increases of 16.7% (8.7%-25.3%) in incidence and 31.2% (17.7%-48%) in mortality, while better trajectories may lead to a 10% (16.4%-2.3%) decrease in intracerebral haemorrhage cases with stabilised mortality. Individuals aged ≥80 years are expected to contribute significantly to the burden, comprising 62.7% of the cases in 2050, up from 40% in 2019, and 72.5% of deaths, up from 50.5%. Country-wide variations were noted in the projected changes, with decreases in the standardised rates across all nations but varying crude rates. The largest relative reductions in counts for both incidence and mortality are expected in Latvia, Bulgaria, and Hungary-ranging from -38.2% to -32.4% and -37.3% to -30.2% respectively. In contrast, the greatest increases for both measures were forecasted in Ireland (45.7% and 74.4%), Luxembourg (45% and 70.7%), and Cyprus (44.5% and 74.2%). The modelled increase in the burden of intracerebral haemorrhage could largely be attributed to population ageing. Interpretation: This study provides a comprehensive forecast of intracerebral haemorrhage in Europe until 2050, presenting different trajectories. The potential increase in the number of people experiencing and dying from intracerebral haemorrhage could have profound implications for both caregiving responsibilities and associated costs. However, forecasts were divergent between different scenarios and among EU countries, signalling the pivotal role of public health initiatives in steering the trajectories. Funding: The European Union's Horizon 2020 Research and Innovation Programme under grant agreement No. 754517. The National Institute for Health and Care Research (NIHR) under its Programme Grants for Applied Research (NIHR202339).
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BACKGROUND: There is limited information on long-term outcomes after stroke in sub-Saharan Africa (SSA). Current estimates of case fatality rate (CFR) in SSA are based on small sample sizes with varying study design and report heterogeneous results. AIMS: We report CFR and functional outcomes from a large, prospective, longitudinal cohort of stroke patients in Sierra Leone and describe factors associated with mortality and functional outcome. METHODS: A prospective longitudinal stroke register was established at both adult tertiary government hospitals in Freetown, Sierra Leone. It recruited all patients ⩾ 18 years with stroke, using the World Health Organization definition, from May 2019 until October 2021. To reduce selection bias onto the register, all investigations were paid by the funder and outreach conducted to raise awareness of the study. Sociodemographic data, National Institute of Health Stroke Scale (NIHSS), and Barthel Index (BI) were collected on all patients on admission, at 7 days, 90 days, 1 year, and 2 years post stroke. Cox proportional hazards models were constructed to identify factors associated with all-cause mortality. A binomial logistic regression model reports odds ratio (OR) for functional independence at 1 year. RESULTS: A total of 986 patients with stroke were included, of which 857 (87%) received neuroimaging. Follow-up rate was 82% at 1 year, missing item data were <1% for most variables. Stroke cases were equally split by sex and mean age was 58.9 (SD: 14.0) years. About 625 (63%) were ischemic, 206 (21%) primary intracerebral hemorrhage, 25 (3%) subarachnoid hemorrhage, and 130 (13%) were of undetermined stroke type. Median NIHSS was 16 (9-24). CFR at 30 days, 90 days, 1 year, and 2 years was 37%, 44%, 49%, and 53%, respectively. Factors associated with increased fatality at any timepoint were male sex (hazard ratio (HR): 1.28 (1.05-1.56)), previous stroke (HR: 1.34 (1.04-1.71)), atrial fibrillation (HR: 1.58(1.06-2.34)), subarachnoid hemorrhage (HR: 2.31 (1.40-3.81)), undetermined stroke type (HR: 3.18 (2.44-4.14)), and in-hospital complications (HR: 1.65 (1.36-1.98)). About 93% of patients were completely independent prior to their stroke, declining to 19% at 1 year after stroke. Functional improvement was most likely to occur between 7 and 90 days post stroke with 35% patients improving, and 13% improving between 90 days to 1 year. Increasing age (OR: 0.97 (0.95-0.99)), previous stroke (OR: 0.50 (0.26-0.98)), NIHSS (OR: 0.89 (0.86-0.91)), undetermined stroke type (OR: 0.18 (0.05-0.62)), and ⩾1 in-hospital complication (OR: 0.52 (0.34-0.80)) were associated with lower OR of functional independence at 1 year. Hypertension (OR: 1.98 (1.14-3.44)) and being the primary breadwinner of the household (OR: 1.59 (1.01-2.49)) were associated with functional independence at 1 year. CONCLUSION: Stroke affected younger people and resulted in high rates of fatality and functional impairment relative to global averages. Key clinical priorities for reducing fatality include preventing stroke-related complications through evidence-based stroke care, improved detection and management of atrial fibrillation, and increasing coverage of secondary prevention. Further research into care pathways and interventions to encourage care seeking for less severe strokes should be prioritized, including reducing the cost barrier for stroke investigations and care.
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Fibrilação Atrial , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Acidente Vascular Cerebral/diagnóstico , Hemorragia Subaracnóidea/complicações , Estudos Prospectivos , Fibrilação Atrial/complicações , Serra Leoa/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Neovascular (wet) age-related macular degeneration (AMD) can be associated with large submacular haemorrhage (SMH). The natural history of SMH is very poor, with typically marked and permanent loss of central vision in the affected eye. Practice surveys indicate varied management approaches including observation, intravitreal anti-vascular endothelial growth factor therapy, intravitreal gas to pneumatically displace SMH, intravitreal alteplase (tissue plasminogen activator, TPA) to dissolve the clot, subretinal TPA via vitrectomy, and varying combinations thereof. No large, published, randomised controlled trials have compared these management options. METHODS: TIGER is a phase 3, pan-European, two-group, active-control, observer-masked, superiority, randomised controlled surgical trial. Eligible participants have large, fovea-involving SMH of no more than 15 days duration due to treatment-naïve or previously treated neovascular AMD, including idiopathic polypoidal choroidal vasculopathy and retinal angiomatous proliferation. A total of 210 participants are randomised in a 1:1 ratio to pars plana vitrectomy, off-label subretinal TPA up to 25 µg in 0.25 ml, intravitreal 20% sulfahexafluoride gas and intravitreal aflibercept, or intravitreal aflibercept monotherapy. Aflibercept 2 mg is administered to both groups monthly for 3 doses, then 2-monthly to month 12. The primary efficacy outcome is the proportion of participants with best-corrected visual acuity (BCVA) gain of ≥ 10 Early Treatment Diabetic Retinopathy (ETDRS) letters in the study eye at month 12. Secondary efficacy outcomes (at 6 and 12 months unless noted otherwise) are proportion of participants with a BCVA gain of ≥ 10 ETDRS letters at 6 months, mean ETDRS BCVA, Radner maximum reading speed, National Eye Institute 25-item Visual Function Questionnaire composite score, EQ-5D-5L with vision bolt-on score, Short Warwick and Edinburgh Mental Wellbeing score, scotoma size on Humphrey field analyser, and presence/absence of subfoveal fibrosis and/or atrophy and area of fibrosis/atrophy using independent reading centre multimodal image analysis (12 months only). Key safety outcomes are adverse events, serious adverse events, and important medical events, coded using the Medical Dictionary for Regulatory Activities Preferred Terms. DISCUSSION: The best management of SMH is unknown. TIGER aims to establish if the benefits of SMH surgery outweigh the risks, relative to aflibercept monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663750 ; EudraCT: 2020-004917-10.
Assuntos
Ativador de Plasminogênio Tecidual , Degeneração Macular Exsudativa , Inibidores da Angiogênese/efeitos adversos , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Ensaios Clínicos Controlados Aleatórios como Assunto , Hemorragia Retiniana/diagnóstico , Hemorragia Retiniana/tratamento farmacológico , Hemorragia Retiniana/etiologia , Ativador de Plasminogênio Tecidual/efeitos adversos , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual , VitrectomiaRESUMO
Introduction: Stroke is the second most common cause of adult death in Africa. This study reports the demographics, stroke types, stroke care and hospital outcomes for stroke in Freetown, Sierra Leone. Methods: A prospective observational register recorded all patients 18 years and over with stroke between May 2019 and April 2020. Stroke was defined according to the WHO criteria. Pearson's chi-squared test was used to examine associations between categorical variables and unpaired t-tests for continuous variables. Multivariable logistic regression, to explain in-hospital death, was reported as odds ratios (ORs) and 95% confidence intervals. Results: Three hundred eighty-five strokes were registered, and 315 (81.8%) were first-in-a-lifetime events. Mean age was 59.2 (SD 13.8), and 187 (48.6%) were male. Of the strokes, 327 (84.9%) were confirmed by CT scan. Two hundred thirty-one (60.0%) were ischaemic, 85 (22.1%) intracerebral haemorrhage, 11 (2.9%) subarachnoid haemorrhage and 58 (15.1%) undetermined stroke type. The median National Institutes of Health Stroke Scale on presentation was 17 [interquartile range (IQR) 9-25]. Haemorrhagic strokes compared with ischaemic strokes were more severe, 20 (IQR 12-26) vs. 13 (IQR 7-22) (p < 0.001), and occurred in a younger population, mean age 52.3 (SD 12.0) vs. 61.6 (SD 13.8) (p < 0.001), with a lower level of educational attainment of 28.2 vs. 40.7% (p = 0.04). The median time from stroke onset to arrival at the principal referral hospital was 25 hours (IQR 6-73). Half of the patients (50.4%) sought care at another health provider prior to arrival. One hundred fifty-one patients died in the hospital (39.5%). Forty-three deaths occurred within 48 hours of arriving at the hospital, with median time to death of 4 days (IQR 0-7 days). Of the patients, 49.6% had ≥1 complication, 98 (25.5%) pneumonia and 33 (8.6%) urinary tract infection. Male gender (OR 3.33, 1.65-6.75), pneumonia (OR 3.75, 1.82-7.76), subarachnoid haemorrhage (OR 43.1, 6.70-277.4) and undetermined stroke types (OR 6.35, 2.17-18.60) were associated with higher risk of in-hospital death. Discussion: We observed severe strokes occurring in a young population with high in-hospital mortality. Further work to deliver evidence-based stroke care is essential to reduce stroke mortality in Sierra Leone.