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BACKGROUND: The multi-centre two-stage SCALOP-2 trial (ISRCTN50083238) assessed whether dose escalation of consolidative chemoradiotherapy (CRT) or concurrent sensitization using the protease inhibitor nelfinavir improve outcomes in locally advanced pancreatic cancer (LAPC) following four cycles of gemcitabine/nab-paclitaxel. METHODS: In stage 1, the maximum tolerated dose (MTD) of nelfinavir concurrent with standard-dose CRT (50.4 Gy in 28 fractions) was identified from a cohort of 27 patients. In stage 2, 159 patients were enrolled in an open-label randomized controlled comparison of standard versus high dose (60 Gy in 30 fractions) CRT, with or without nelfinavir at MTD. Primary outcomes following dose escalation and nelfinavir use were respectively overall survival (OS) and progression free survival (PFS). Secondary endpoints included health-related quality of life (HRQoL). RESULTS: High dose CRT did not improve OS (16.9 (60 % confidence interval, CI 16.2-17.7) vs. 15.6 (60 %CI 14.3-18.2) months; adjusted hazard ratio, HR 1.13 (60 %CI 0.91-1.40; p = 0.68)). Similarly, median PFS was not improved by nelfinavir (10.0 (60 %CI 9.9-10.2) vs. 11.1 (60 %CI 10.3-12.8) months; adjusted HR 1.71 (60 %CI 1.38-2.12; p = 0.98)). Local progression at 12 months was numerically lower with high-dose CRT than with standard dose CRT (n = 11/46 (23.9 %) vs. n = 15/45 (33.3 %)). Neither nelfinavir nor radiotherapy dose escalation impacted on treatment compliance or grade 3/4 adverse event rate. There were no sustained differences in HRQoL scores between treatment groups over 28 weeks post-treatment. CONCLUSIONS: Dose-escalated CRT may improve local tumour control and is well tolerated when used as consolidative treatment in LAPC but does not impact OS. Nelfinavir use does not improve PFS.
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Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia , Nelfinavir , Neoplasias Pancreáticas , Humanos , Nelfinavir/uso terapêutico , Nelfinavir/administração & dosagem , Nelfinavir/efeitos adversos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Dose Máxima Tolerável , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Gencitabina , Idoso de 80 Anos ou mais , Qualidade de Vida , Albuminas/administração & dosagem , Albuminas/uso terapêutico , Albuminas/efeitos adversos , Intervalo Livre de Progressão , Inibidores de Proteases/efeitos adversos , Inibidores de Proteases/uso terapêutico , Inibidores de Proteases/administração & dosagemRESUMO
Workplace wellbeing encompasses all aspects of working life. Peak health organisations recognise that poor workplace wellbeing is costly, both to individuals and to the organisation, and the value in promoting healthy workplaces. Workplace wellbeing improves when its barriers are acknowledged and addressed, and protective factors are promoted. The Emergency Department (ED) is a place of intense and challenging activity, exacerbated by high workloads and overcrowding. This impacts negatively on patient care, staff safety and wellbeing. We held focus groups across four EDs to discuss barriers and enablers to wellbeing and found four core themes: Workplace Satisfaction; Barriers to Wellbeing; Organisational Culture that Prioritises Staff Wellbeing; Self-care and Self Compassion. From this, and existing literature, we collaboratively developed a contextualised staff wellbeing framework titled: 'Staff Wellbeing Good Practice Framework: From Surviving to Thriving, How to Protect your Wellbeing in the Emergency Department' that emphasises their values of Competence, Connection and Control.
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Serviço Hospitalar de Emergência , Grupos Focais , Satisfação no Emprego , Local de Trabalho , Humanos , Local de Trabalho/psicologia , Local de Trabalho/normas , Masculino , Pesquisa Qualitativa , Cultura Organizacional , Feminino , AdultoRESUMO
Introduction: Whipple's disease is a rare condition that can present with atypical and non-specific features requiring a high index of suspicion for diagnosis. Case Presentation: We present a case of a man in his 40s with peripheral arthritis and bilateral sacro-ileitis for 4-5 years that was treated with an anti-tumour necrosis factor therapy, which led to worsening of his symptoms, elevation of the inflammatory markers, and the development of fever, night sweats, anorexia, and a significant weight loss. The patient had no abdominal pain, diarrhoea, or other gastrointestinal symptoms. An FDG-PET scan showed increased uptake in the stomach and caecum. Endoscopic examination showed inflammatory changes in the stomach and normal mucosa of the duodenum, jejunum, terminal ileum, caecum, and colon. Histopathology was inconclusive, but the diagnosis was confirmed with Tropheryma whipplei PCR testing. He had no neurological symptoms, but cerebrospinal fluid Tropheryma whipplei PCR was positive. He was treated with intravenous ceftriaxone 2 g daily for 4 weeks, followed by trimethoprim/sulfamethoxazole 160/800 mg twice daily for 1 year with close monitoring and follow-up. Conclusion: This case presents an atypical and challenging presentation of Whipple's disease and the importance of proactive testing for neurological involvement.
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INTRODUCTION: Two of the main reasons recent guidelines do not recommend routine population-wide screening programs for asymptomatic carotid artery stenosis (AsxCS) is that screening could lead to an increase of carotid revascularization procedures and that such mass screening programs may not be cost-effective. Nevertheless, selective screening for AsxCS could have several benefits. This article presents the rationale for such a program. AREAS COVERED: The benefits of selective screening for AsxCS include early recognition of AsxCS allowing timely initiation of preventive measures to reduce future myocardial infarction (MI), stroke, cardiac death and cardiovascular (CV) event rates. EXPERT OPINION: Mass screening programs for AsxCS are neither clinically effective nor cost-effective. Nevertheless, targeted screening of populations at high risk for AsxCS provides an opportunity to identify these individuals earlier rather than later and to initiate a number of lifestyle measures, risk factor modifications, and intensive medical therapy in order to prevent future strokes and CV events. For patients at 'higher risk of stroke' on best medical treatment, a prophylactic carotid intervention may be considered.
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Estenose das Carótidas , Análise Custo-Benefício , Programas de Rastreamento , Acidente Vascular Cerebral , Humanos , Estenose das Carótidas/diagnóstico , Programas de Rastreamento/métodos , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/etiologia , Guias de Prática Clínica como Assunto , Fatores de Risco , Doenças Cardiovasculares/prevenção & controle , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/diagnóstico , Doenças Assintomáticas , Estilo de VidaRESUMO
The emerging cost-effective and powerful standalone VR hardware is an increasingly viable supplement to traditional clinical educational modalities. These traditional approaches are effective but can be limited by the cost of simulation infrastructure, the requirement to attend at fixed times and locations and instructor availability present challenges in meeting the needs of clinicians. One barrier facing educators looking to develop bespoke VR-based solutions is the lack of guidelines around their design, development, deployment, and evaluation. Our team has produced and deployed a number of VR-based educational applications. Through reflecting on findings from surveys, interviews, observation, we summarise a range of insights into the complexity and nuances of the clinical VR design and deployment in a framework that can inform and guide educators, clinicians and developers looking to create their own VR applications for use in healthcare.
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Realidade Virtual , Escolaridade , Simulação por Computador , Suplementos Nutricionais , Instalações de SaúdeRESUMO
AIMS: Reducing preventable hospitalization for congestive heart failure (CHF) patients is a challenge for health systems worldwide. CHF patients who also have a recent or ongoing mental disorder may have worse health outcomes compared with CHF patients with no mental disorders. This study examined the impact of mental disorders on 28 day unplanned readmissions of CHF patients. METHODS AND RESULTS: This retrospective cohort study used population-level linked public and private hospitalization and death data of adults aged ≥18 years who had a CHF admission in New South Wales, Australia, between 1 January 2014 and 31 December 2020. Individuals' mental disorder diagnosis and Charlson comorbidity and hospital frailty index scores were derived from admission records. Competing risk and cause-specific risk analyses were conducted to examine the impact of having a mental disorder diagnosis on all-cause hospital readmission. Of the 65 861 adults with index CHF admission discharged alive (mean age: 78.6 ± 12.1; 48% female), 19.2% (12 675) had at least one unplanned readmission within 28 days following discharge. Adults with CHF with a mental disorder diagnosis within 12 months had a higher risk of 28 day all-cause unplanned readmission [hazard ratio (HR): 1.21, 95% confidence interval (CI): 1.15-1.27, P-value < 0.001], particularly those with anxiety disorder (HR: 1.49, 95% CI: 1.35-1.65, P-value < 0.001). CHF patients aged ≥85 years (HR: 1.19, 95% CI: 1.11-1.28), having ≥3 other comorbidities (HR: 1.35, 95% CI: 1.25-1.46), and having an intermediate (HR: 1.34, 95% CI: 1.28-1.40) or high (HR: 1.37, 95% CI: 1.27-1.47) frailty score on admission had a higher risk of unplanned readmission. CHF patients with a mental disorder who have ≥3 other comorbidities and an intermediate frailty score had the highest probability of unplanned readmission (29.84%, 95% CI: 24.68-35.73%) after considering other patient-level factors and competing events. CONCLUSIONS: CHF patients who had a mental disorder diagnosis in the past 12 months are more likely to be readmitted compared with those without a mental disorder diagnosis. CHF patients with frailty and a mental disorder have the highest probability of readmission. Addressing mental health care services in CHF patient's discharge plan could potentially assist reduce unplanned readmissions.
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Fragilidade , Insuficiência Cardíaca , Transtornos Mentais , Adulto , Humanos , Feminino , Adolescente , Idoso , Idoso de 80 Anos ou mais , Masculino , Readmissão do Paciente , Estudos RetrospectivosRESUMO
BACKGROUND: Carotid artery atherosclerosis is highly prevalent in the general population and is a well-established risk factor for acute ischemic stroke. Although the morphological characteristics of vulnerable plaques are well recognized, there is a lack of consensus in reporting and interpreting carotid plaque features. OBJECTIVES: The aim of this paper is to establish a consistent and comprehensive approach for imaging and reporting carotid plaque by introducing the Plaque-RADS (Reporting and Data System) score. METHODS: A panel of experts recognized the necessity to develop a classification system for carotid plaque and its defining characteristics. Using a multimodality analysis approach, the Plaque-RADS categories were established through consensus, drawing on existing published reports. RESULTS: The authors present a universal classification that is applicable to both researchers and clinicians. The Plaque-RADS score offers a morphological assessment in addition to the prevailing quantitative parameter of "stenosis." The Plaque-RADS score spans from grade 1 (indicating complete absence of plaque) to grade 4 (representing complicated plaque). Accompanying visual examples are included to facilitate a clear understanding of the Plaque-RADS categories. CONCLUSIONS: Plaque-RADS is a standardized and reliable system of reporting carotid plaque composition and morphology via different imaging modalities, such as ultrasound, computed tomography, and magnetic resonance imaging. This scoring system has the potential to help in the precise identification of patients who may benefit from exclusive medical intervention and those who require alternative treatments, thereby enhancing patient care. A standardized lexicon and structured reporting promise to enhance communication between radiologists, referring clinicians, and scientists.
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Doenças das Artérias Carótidas , Estenose das Carótidas , AVC Isquêmico , Placa Aterosclerótica , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/complicações , Valor Preditivo dos Testes , Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/terapia , Tomografia Computadorizada por Raios X/efeitos adversos , Imageamento por Ressonância Magnética/efeitos adversos , Estenose das Carótidas/complicações , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/complicaçõesRESUMO
OBJECTIVE: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. METHODS: Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. RESULTS: Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. CONCLUSIONS: The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research.
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Estenose das Carótidas , Acidente Vascular Cerebral , Humanos , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/diagnóstico por imagem , Consenso , Técnica Delphi , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Constrição PatológicaRESUMO
OBJECTIVE: The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. We updated our 2021 Expert Review and Position Statement, focusing on recent advances in the diagnosis and management of patients with AsxCS. METHODS: A systematic review of the literature was performed up to August 1, 2023, using PubMed/PubMed Central, EMBASE and Scopus. The following keywords were used in various combinations: "asymptomatic carotid stenosis," "carotid endarterectomy" (CEA), "carotid artery stenting" (CAS), and "transcarotid artery revascularization" (TCAR). Areas covered included (i) improvements in best medical treatment (BMT) for patients with AsxCS and declining stroke risk, (ii) technological advances in surgical/endovascular skills/techniques and outcomes, (iii) risk factors, clinical/imaging characteristics and risk prediction models for the identification of high-risk AsxCS patient subgroups, and (iv) the association between cognitive dysfunction and AsxCS. RESULTS: BMT is essential for all patients with AsxCS, regardless of whether they will eventually be offered CEA, CAS, or TCAR. Specific patient subgroups at high risk for stroke despite BMT should be considered for a carotid revascularization procedure. These patients include those with severe (≥80%) AsxCS, transcranial Doppler-detected microemboli, plaque echolucency on Duplex ultrasound examination, silent infarcts on brain computed tomography or magnetic resonance angiography scans, decreased cerebrovascular reserve, increased size of juxtaluminal hypoechoic area, AsxCS progression, carotid plaque ulceration, and intraplaque hemorrhage. Treatment of patients with AsxCS should be individualized, taking into consideration individual patient preferences and needs, clinical and imaging characteristics, and cultural, ethnic, and social factors. Solid evidence supporting or refuting an association between AsxCS and cognitive dysfunction is lacking. CONCLUSIONS: The optimal management of patients with AsxCS should include BMT for all individuals and a prophylactic carotid revascularization procedure (CEA, CAS, or TCAR) for some asymptomatic patient subgroups, additionally taking into consideration individual patient needs and preference, clinical and imaging characteristics, social and cultural factors, and the available stroke risk prediction models. Future studies should investigate the association between AsxCS with cognitive function and the role of carotid revascularization procedures in the progression or reversal of cognitive dysfunction.
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Estenose das Carótidas , Endarterectomia das Carótidas , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Medição de Risco , Resultado do Tratamento , Endarterectomia das Carótidas/efeitos adversos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Procedimentos Endovasculares/efeitos adversos , Stents/efeitos adversos , Estudos RetrospectivosRESUMO
PURPOSE: Carotid intraplaque hemorrhage (IPH) on MRI predicts stroke. Magnetization-prepared rapid acquisition gradient (MP-RAGE) is widely used to detect IPH. CE-MRA is used routinely to assess stenosis. Initial studies indicated that IPH can be identified on mask images of CE-MRA, while Time-of-Flight (TOF) images were reported to have high specificity but lower sensitivity. We investigated the diagnostic accuracy of detecting IPH on mask images of CE-MRA and TOF. METHODS: Thirty-six patients with ≥ 50% stenosis enrolled in the ongoing 2nd European Carotid Surgery Trial underwent carotid MRI. A 5-point quality score was used. Inter-observer agreement between two independent readers was determined. The sensitivity and specificity of IPH detection on mask MRA and TOF were calculated with MP-RAGE as a reference standard. RESULTS: Of the 36 patients included in the current analysis, 66/72 carotid arteries could be scored. The inter-observer agreements for identifying IPH on MP-RAGE, mask, and TOF were outstanding (κ: 0.93, 0.96, and 0.85). The image quality of mask (1.42 ± 0.66) and TOF (2.42 ± 0.66) was significantly lower than MP-RAGE (3.47 ± 0.61). When T1w images were used to delineate the outer carotid wall, very high specificities (>95%) of IPH detection on mask and TOF images were found, while the sensitivity was high for mask images (>81%) and poor for TOF (50-60%). Without these images, the specificity was still high (>97%), while the sensitivity reduced to 62-71%. CONCLUSION: Despite the lower image quality, routinely acquired mask images from CE-MRA, but not TOF, can be used as an alternative to MP-RAGE images to visualize IPH.
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Estenose das Carótidas , Humanos , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Constrição Patológica , Angiografia por Ressonância Magnética/métodos , Artérias Carótidas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Hemorragia/diagnóstico por imagemRESUMO
BACKGROUND: The COVID-19 pandemic further exposed the prevalence of existing health disparities in Black communities in the U.S. The current study evaluates COVID-19 data collected in Gary, Indiana, from June 2020 to June 2021. We hypothesized that the number of COVID-19 cases, hospitalizations, and deaths were influenced by race and income. METHODS: In collaboration with the Gary Health Department (GHD), we analyzed demographic data on COVID-19-positive cases. RESULTS: Compared to Gary's non-Black population, age- and population-adjusted rates of hospitalizations and deaths in the Black population were 3-fold (p < 0.0001) and 2-fold (p < 0.05) higher, respectively. This is despite a higher infection rate (p < 0.0001) in the non-Black population. The median household income of a zip code was negatively correlated with COVID-19 hospitalizations (R2 = 0.6345, p = 0.03), but did not correlate with infections and deaths. CONCLUSIONS: The current study demonstrates clear health disparities of income and race in the context of COVID-19-related infections and outcomes in the city of Gary. Indiana University School of Medicine Northwest and GHD officials can collaborate to utilize these data for the reallocation of resources and health education efforts in Gary's highly populated, low-income, and predominantly Black neighborhoods. It should also prompt further investigation into national health resource allocation.
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Background: Cardiovascular disease (CVD) and cancer are leading causes of death and people with cancer are at higher risk of developing CVD than the general population. Many cancer medicines have cardiotoxic effects but the size of the population exposed to these potentially cardiotoxic medicines is not known. We aimed to determine the prevalence of exposure to potentially cardiotoxic cancer medicines in Australia. Methods: We identified potentially cardiotoxic systemic cancer medicines through searching the literature and registered product information documents. We conducted a retrospective cohort study of Australians dispensed potentially cardiotoxic cancer medicines between 2005 and 2021, calculating age-standardised annual prevalence rates of people alive with exposure to a potentially cardiotoxic medicine during or prior to each year of the study period. Findings: We identified 108,175 people dispensed at least one potentially cardiotoxic cancer medicine; median age, 64 (IQR: 52-74); 57% female. Overall prevalence increased from 49 (95%CI: 48.7-49.3)/10,000 to 232 (95%CI: 231.4-232.6)/10,000 over the study period; 61 (95%CI: 60.5-61.5)/10,000 to 293 (95%CI: 292.1-293.9)/10,000 for females; and 39 (95%CI: 38.6-39.4)/10,000 to 169 (95%CI: 168.3-169.7)/10,000 for males. People alive five years following first exposure increased from 29 (95%CI: 28.8-29.2)/10,000 to 134 (95%CI: 133.6-134.4)/10,000; and from 22 (95%CI: 21.8-22.2)/10,000 to 76 (95%CI: 75.7-76.3)/10,000 for those alive at least 10 years following first exposure. Most people were exposed to only one potentially cardiotoxic medicine, rates of which increased from 39 (95%CI: 38.7-39.3)/10,000 in 2005 to 131 (95%CI: 130.6-131.4)/10,000 in 2021. Interpretation: The number of people exposed to efficacious yet potentially cardiotoxic cancer medicines in Australia is growing. Our findings can support the development of service planning and create awareness about the magnitude of cancer treatment-related cardiotoxicities. Funding: NHMRC Centre for Research Excellence in Medicines Intelligence, Cancer Institute NSW Early Career Fellowship.
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BACKGROUND: Intracerebral haemorrhage (ICH) is a severe clinical consequence of cerebral small vessel disease (SVD), but associations between renal impairment and SVD in patients with ICH have not been fully characterised. METHODS: Using data from the CROMIS-2 ICH observational study, we compared SVD neuroimaging markers and total burden (score 0-3) identified using CT brain imaging in patients with and without renal impairment (estimated glomerular filtration rate, eGFR<60). We assessed functional outcome at 6-month follow-up using the modified Rankin scale. RESULTS: 1027 participants were included (mean age 72.8, 57.1% male); 274 with and 753 without renal impairment. 18.7% of the eGFR<60 group had moderate-to-severe SVD burden (score 2-3), compared with 14.0% of those with eGFR>60 (p = 0.039). SVD burden was associated with renal impairment after adjusting for hypertension (OR 1.36, 95% CI 1.04-1.77, p = 0.023), but not after adjusting for age. Cerebral atrophy was more prevalent in patients with eGFR<60 (81.2% vs. 72.0%, p = 0.002), as were WMH (45.6% vs. 36.6%, p = 0.026). Neither was associated with renal function after adjusting for age and vascular risk factors. Renal impairment was associated with functional outcome (OR 0.65, 95% CI 0.47-0.89, p = 0.007), but not after adjusting for age, pre-morbid function and comorbidities (OR 0.95, 95% CI 0.65-1.38, p = 0.774). CONCLUSION: In acute ICH, renal impairment is associated with a higher cerebral SVD burden independent of hypertension, but not age. Reduced eGFR is associated with worse functional outcome, but not independent of age and comorbidities. Since CT has limited sensitivity to detect SVD severity and distribution, further studies including MRI are needed.
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Doenças de Pequenos Vasos Cerebrais , Hipertensão , Humanos , Masculino , Feminino , Estudos Prospectivos , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Hipertensão/complicações , Rim/diagnóstico por imagem , Rim/fisiologiaRESUMO
BACKGROUND: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases. METHODS: Urinary 11-dehydro-thromboxane B2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values. RESULTS: In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg. CONCLUSIONS: Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin.
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Aspirina , Neoplasias Colorretais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores , Neoplasias Colorretais/tratamento farmacológico , Creatinina , Tromboxanos/uso terapêuticoRESUMO
SARS-CoV-2 has been associated with multiple disease processes and chronic sequela. Much less understood are the neurological effects, ranging from headaches, pro-thrombotic state, encephalitis, and myopathic processes. Many case reports have documented post-SARS-CoV-2 virus effects; however, this case highlights the possibility of a less commonly described neurological manifestation possibly related to the BNT162b2 mRNA Pfizer vaccine. There is scant literature on immune-mediated necrotizing myopathy (IMNM) triggered after COVID-19 vaccination. The BNT162b2 mRNA COVID-19 vaccine (Pfizer, BioNTech) has proven to be safe and effective in reducing transmission of COVID-19, but post-vaccination neurological events, including venous sinus thrombosis, transverse myelitis, and immune-mediated diseases, such as Guillain-Barré syndrome, have been reported. We report a case of IMNM with HMG-CoA reductase antibody positivity in the setting of BNT162b2 vaccination. The patient presented with progressive muscle weakness with rhabdomyolysis and necrotizing autoimmune myopathy proven on muscle biopsy after the second dose of the BNT162b2 vaccine. Ultimately, this case report highlights the importance of clinical suspicion for early diagnosis and initiation of treatment after symptoms concerning necrotizing myopathy.
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Monitoring Consumption Switzerland is a public-private partnership between the University of St. Gallen and the payment companies Worldline and SIX that processes and publishes payment data on transactions in Switzerland processed by Wordline/SIX in real time. This paper provides background information on this novel source of data and presents their attributes, aggregation and granularity, and their interpretability. The paper presents several use cases that show the strengths of the data, and it alerts future users of the data to possible challenges. The paper also discusses the project's impact and provides an outlook.
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BACKGROUND: Atrial fibrillation (AF) known before ischemic stroke (KAF) has been postulated to be an independent category with a recurrence risk higher than that of AF detected after stroke (AFDAS). However, it is unknown whether this risk difference is confounded by pre-existing anticoagulation, which is most common in KAF and also indicates a high ischemic stroke recurrence risk. METHODS: Individual patient data analysis from 5 prospective cohorts of anticoagulated patients following AF-associated ischemic stroke. We compared the primary (ischemic stroke recurrence) and secondary outcome (all-cause death) among patients with AFDAS versus KAF and among anticoagulation-naïve versus previously anticoagulated patients using multivariable Cox, Fine-Gray models, and goodness-of-fit statistics to investigate the relative independent prognostic importance of AF-category and pre-existing anticoagulation. RESULTS: Of 4,357 patients, 1,889 (43%) had AFDAS and 2,468 (57%) had KAF, while 3,105 (71%) were anticoagulation-naïve before stroke and 1,252 (29%) were previously anticoagulated. During 6,071 patient-years of follow-up, we observed 244 recurrent strokes and 661 deaths. Only pre-existing anticoagulation (but not KAF) was independently associated with a higher hazard for stroke recurrence in both Cox and Fine-Gray models. Models incorporating pre-existing anticoagulation showed better fit than those with AF category; adding AF-category did not result in better model fit. Neither pre-existing anticoagulation nor KAF were independently associated with death. CONCLUSION: Our findings challenge the notion that KAF and AFDAS are clinically relevant and distinct prognostic entities. Instead of attributing an independently high stroke recurrence risk to KAF, future research should focus on the causes of stroke despite anticoagulation to develop improved preventive treatments. ANN NEUROL 2023;94:43-54.
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Fibrilação Atrial , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , AVC Isquêmico/complicações , Anticoagulantes/uso terapêuticoRESUMO
Moyamoya Disease (MMD) is a rare cerebrovascular disorder which can have significant cognitive consequences. The aim of the current study was to describe comprehensively the domain-specific cognitive profile of adult patients with MMD and to assess whether this changes in the absence of recurrent stroke over long-term follow-up. Comprehensive neuropsychological assessment covering seven cognitive domains was conducted on 61 adult patients with MMD at baseline and then at up to 3 further time points during follow up (median=2.31, 4.87 and 7.12 years). Although 27 patients had had prior surgical revasculariation, none had surgery between neuropsychological assessments. Cognitive impairment was common. At baseline, impairment in executive functions was most frequent (57%), followed by performance IQ (36%), speed of information processing (31%) and visual memory (30%). We found that the neuropsychological profile remains broadly stable over long-term follow-up with no clear indication of improvement or significant decline. The pattern of impairment also did not differ depending on age of onset or whether there was a history of either prior stroke at presentation or revascularisation surgery at presentation.
Assuntos
Doença de Moyamoya , Acidente Vascular Cerebral , Humanos , Adulto , Doença de Moyamoya/complicações , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/psicologia , Cognição , Função Executiva , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Testes NeuropsicológicosRESUMO
BACKGROUND: Cerebral amyloid angiopathy (CAA), a common cause of intracerebral hemorrhage (ICH), is diagnosed using the Boston criteria including magnetic resonance imaging (MRI) biomarkers (cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS). The simplified Edinburgh criteria include computed tomography (CT) biomarkers (subarachnoid extension (SAE) and finger-like projections (FLPs)). The underlying mechanisms and diagnostic accuracy of CT compared to MRI biomarkers of CAA are unknown. METHODS: We included 140 survivors of spontaneous lobar supratentorial ICH with both acute CT and MRI. We assessed associations between MRI and CT biomarkers and the diagnostic accuracy of CT- compared to MRI-based criteria. RESULTS: FLPs were more common in patients with strictly lobar CMB (44.7% vs 23.5%; p = 0.014) and SAE was more common in patients with cSS (61.3% vs 31.2%; p = 0.002). The high probability of the CAA category of the simplified Edinburgh criteria showed 87.2% (95% confidence interval (CI): 78.3-93.4) specificity, 29.6% (95% CI: 18.0-43.6) sensitivity, 59.3% (95% CI: 38.8-77.6) positive predictive value, and 66.4% (95%: CI 56.9-75.0) negative predictive value, 2.3 (95% CI: 1.2-4.6) positive likelihood ratio and 0.8 (95% CI 0.7-1.0) negative likelihood ratio for probable CAA (vs non-probable CAA), defined by the modified Boston criteria; the area under the receiver operating characteristic curve (AUROC) was 0.62 (95% CI: 0.54-0.71). CONCLUSION: In lobar ICH survivors, we found associations between putative biomarkers of parenchymal CAA (FLP and strictly lobar CMBs) and putative biomarkers of leptomeningeal CAA (SAE and cSS). In a hospital population, CT biomarkers might help rule-in probable CAA (diagnosed using the Boston criteria), but their absence is probably not as useful to rule it out, suggesting an important continued role for MRI in ICH survivors with suspected CAA.