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OBJECTIVES: To assess the efficacy of a pro-active, absolute cardiovascular risk-guided approach to opportunistically modifying cardiovascular risk factors in patients without coronary ischaemia attending a chest pain clinic. DESIGN: Prospective, randomised, open label, blinded endpoint study. SETTING: The rapid access chest pain clinic of Royal Hobart Hospital, a tertiary hospital. PARTICIPANTS: Patients who presented to the chest pain clinic between 1 July 2014 and 31 December 2017 who had intermediate to high absolute cardiovascular risk scores (5-year risk ≥ 8%). Patients with known cardiac disease or from groups with clinically determined high risk of cardiovascular disease were excluded. MAIN OUTCOME MEASURES: The primary endpoint was change in 5-year absolute risk score (Australian absolute risk calculator) at follow-up (at least 12 months after baseline assessment). Secondary endpoints were changes in lipid profile, blood pressure, smoking status, and body mass index, and major adverse cardiovascular events. RESULTS: The mean change in risk at follow-up was +0.4 percentage points (95% CI, -0.8 to 1.5 percentage points) for the 98 control group patients and -2.4 percentage points (95% CI, -1.5 to -3.4 percentage points) for the 91 intervention group patients; the between-group difference in change was 2.7 percentage points (95% CI, 1.2-4.1 percentage points). Mean changes in lipid profile, systolic blood pressure, and smoking status were larger for the intervention group, but not statistically different from those for the control group. CONCLUSIONS: An absolute cardiovascular risk-guided, pro-active risk factor management strategy employed opportunistically in a chest pain clinic significantly improved 5-year absolute cardiovascular risk scores. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry, ACTRN12617000615381 (retrospective).
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Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Medição de Risco/métodos , Idoso , Dor no Peito , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Clínicas de Dor , Estudos Prospectivos , Gestão de RiscosRESUMO
A generalization of the hybrid scheme for multireference methods as recently put forward by Saitow and Yanai [J. Chem. Phys. 152, 114 111 (2020)] is presented. The hybrid methods are constructed by defining internal and external excitation spaces and evaluating these two subsets of excitations at different levels of theory. New hybrids that use the mix of internally contracted multireference coupled-cluster, unshifted multireference coupled electron pair, and multireference perturbation methods are derived and benchmarked. A new separation of the excitation space, which combines all singles and doubles excitations to the virtual orbitals into the external space, is also presented and tested. In general, the hybrid methods improve upon their non-hybrid parent method and offer a good compromise between computational complexity and numerical accuracy.
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Context: Resilience is the ability to deal with shocks and stresses, including the unknown and previously unimaginable, such as the Covid-19 crisis. Objective: This paper assesses (i) how different farming systems were exposed to the crisis, (ii) which resilience capacities were revealed and (iii) how resilience was enabled or constrained by the farming systems' social and institutional environment. Methods: The 11 farming systems included have been analysed since 2017. This allows a comparison of pre-Covid-19 findings and the Covid-19 crisis. Pre-Covid findings are from the SURE-Farm systematic sustainability and resilience assessment. For Covid-19 a special data collection was carried out during the early stage of lockdowns. Results and conclusions: Our case studies found limited impact of Covid-19 on the production and delivery of food and other agricultural products. This was due to either little exposure or the agile activation of robustness capacities of the farming systems in combination with an enabling institutional environment. Revealed capacities were mainly based on already existing connectedness among farmers and more broadly in value chains. Across cases, the experience of the crisis triggered reflexivity about the operation of the farming systems. Recurring topics were the need for shorter chains, more fairness towards farmers, and less dependence on migrant workers. However, actors in the farming systems and the enabling environment generally focused on the immediate issues and gave little real consideration to long-term implications and challenges. Hence, adaptive or transformative capacities were much less on display than coping capacities. The comparison with pre-Covid findings mostly showed similarities. If challenges, such as shortage of labour, already loomed before, they persisted during the crisis. Furthermore, the eminent role of resilience attributes was confirmed. In cases with high connectedness and diversity we found that these system characteristics contributed significantly to dealing with the crisis. Also the focus on coping capacities was already visible before the crisis. We are not sure yet whether the focus on short-term robustness just reflects the higher visibility and urgency of shocks compared to slow processes that undermine or threaten important system functions, or whether they betray an imbalance in resilience capacities at the expense of adaptability and transformability. Significance: Our analysis indicates that if transformations are required, e.g. to respond to concerns about transnational value chains and future pandemics from zoonosis, the transformative capacity of many farming systems needs to be actively enhanced through an enabling environment.
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OBJECTIVE. The purpose of this study is to evaluate the association of common clinical variables with small-bore tunneled central venous catheter (CVC) infection. MATERIALS AND METHODS. Retrospective data were collected from all small-bore (6-French) tunneled CVCs placed by the interventional radiology service between 2012 and 2015. Only patients who had a documented reason for tunneled CVC removal were included in the analysis to capture all events. Transfemoral, transhepatic, and translumbar placements were excluded to reduce cohort heterogeneity. Multiple clinical variables were collected from a review of the medical record. The t test and Fisher exact test were used for two-group comparisons for continuous variables and categoric variables, respectively. Logistic regression analyses were further used to identify variables that were associated with catheter infection. RESULTS. One hundred eighty-two patients (105 women [57.7%] and 77 men [42.3%]) with a mean (± SD) age of 49.7 ± 16 years were included. Thirty-two catheters (17.6%) were removed because of infection. Noninfected lines were removed at a mean of 39 (SD, 57.3) days, whereas infected lines were removed at a mean of 95.9 (SD, 113.4) days after placement (p < 0.001). There was a statistically significant difference in the number of tunneled CVCs removed for infection when the indication for tunneled CVC placement was the administration of IV antibiotics (p = 0.04). By multivariate analysis, only time to removal (p = 0.002; odds ratio, 0.992; 95% CI, 0.986-0.998) and a history of tunneled CVC (p = 0.01; odds ratio, 0.306; 95% CI, 0.121-0.772) were associated with catheter removal for infection. CONCLUSION. Time to catheter removal and history of tunneled CVC were associated with an increased risk of tunneled CVC removal because of infection.
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Infecções Relacionadas a Cateter/diagnóstico , Cateteres Venosos Centrais , Adulto , Idoso , Remoção de Dispositivo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia Intervencionista , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: There is limited research on the dietary behaviours of Canadian children at school, including where students obtain food from during school hours or whether lunch-time food source influences diet quality. METHODS: Nationally representative cross-sectional data from 24-h dietary recalls were analysed from the 2004 Canadian Community Health Survey (n = 4589). Dietary outcomes included school hour and school day dietary intakes and School Healthy Eating Index (S-HEI) scores. Survey-weighted covariate-adjusted linear regression models examined differences in dietary outcomes across lunch-time food source groups. RESULTS: The majority of children (72.8%) reported bringing lunch from home, whereas fewer students obtained lunch from off-campus locations (11.6%), schools (9.6%) or skipped lunch (5.9%). Compared to off-campus lunches, home-packed lunches were significantly higher in fibre, vitamins A, D and C, thiamin, magnesium, iron, grains, vegetables and fruit, but lower in total calories, fat and calories from minimally nutritious foods. Average school hour diet quality required improvement for all age groups, although S-HEI scores did not differ significantly by lunch-time food source among 6-8-year-old children. However, for children age 9-17 years, bringing a home-packed lunch was associated with significantly higher S-HEI scores compared to students obtaining lunch from off-campus locations. After adjusting for age and sex, lunch-time food source was also significantly associated with whole day dietary quality. CONCLUSIONS: Although the nutritional quality of off-campus lunches was lower than home-packed lunches, the quality of foods was suboptimal, regardless of food source. Strategies are needed to enhance access to nutritious foods on campus and improve the nutritional quality of packed lunches, which supply the majority of lunch-time foods consumed by Canadian children.
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Dieta , Comportamento Alimentar , Abastecimento de Alimentos , Almoço , Valor Nutritivo , Instituições Acadêmicas , Estudantes , Adolescente , Canadá , Criança , Estudos Transversais , Registros de Dieta , Feminino , Serviços de Alimentação , Humanos , MasculinoRESUMO
BACKGROUND: Asthma affects 300 million people worldwide. In asthma, the major cause of morbidity and mortality is acute airway narrowing, due to airway smooth muscle (ASM) hypercontraction, associated with airway remodelling. However, little is known about the transcriptional differences between healthy and asthmatic ASM cells. OBJECTIVES: To investigate the transcriptional differences between asthmatic and healthy airway smooth muscle cells (ASMC) in culture and investigate the identified targets using in vitro and ex vivo techniques. METHODS: Human asthmatic and healthy ASMC grown in culture were run on Affymetrix_Hugene_1.0_ST microarrays. Identified candidates were confirmed by PCR, and immunohistochemistry. Functional analysis was conducted using in vitro ASMC proliferation, attachment and contraction assays and ex vivo contraction of mouse airways. RESULTS: We suggest a novel role for latrophilin (LPHN) receptors, finding increased expression on ASMC from asthmatics, compared with non-asthmatics in vivo and in vitro, suggesting a role in mediating airway function. A single nucleotide polymorphism in LPHN1 was associated with asthma and with increased LPHN1 expression in lung tissue. When activated, LPHNs regulated ASMC adhesion and proliferation in vitro, and promoted contraction of mouse airways and ASMC. CONCLUSIONS: Given the need for novel inhibitors of airway remodelling and bronchodilators in asthma, the LPHN family may represent promising novel targets for future dual therapeutic intervention.
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Asma/genética , Asma/metabolismo , Miócitos de Músculo Liso/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores de Peptídeos/genética , Acetilcolina/farmacologia , Animais , Estudos de Casos e Controles , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Masculino , Glicoproteínas de Membrana , Proteínas de Membrana/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Contração Muscular/efeitos dos fármacos , Miócitos de Músculo Liso/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Peptídeos/metabolismo , Sistema Respiratório/citologia , Venenos de Aranha/farmacologia , Transcrição GênicaRESUMO
Efficient reduction of CCl4 took place upon exposure to 350-nm photons of aqueous solutions containing sulfonated poly(ether etherketone) (SPEEK) as a sensitizer and either poly(vinyl alcohol) (PVA) or HCO2H/HCO2- buffer. The photoreaction formed chloride ions whose concentration increased linearly with time in solutions free of O2, whereas slower reductions occurred in the presence of air. Utilization of formate buffer as the H-atom donor yielded photoreactions at least 10 times faster than those in the presence of PVA and generated CHCl3 as another reaction product. The quantum yield of chloride ion formation, ø(Cl-), was found to be a function of both the SPEEK concentration and concentration of formate buffer. Whereas the quantum efficiency increased steadily with decreasing solution acidity, a drastic surge in the reaction rate occurred in neutral solutions. ø(Cl-) first increased rapidly to a maximum value exceeding 1 at pH 7.3 and then decreased thereafter. The dependence of r(Cl-) on (I0)1/2, where I0 is the light intensity, and the occurrence of postirradiation formation of Cl- through the reduction of CCl4 in the dark are further evidence that the photoreaction proceeded by a chain process. Several of the kinetic features were rationalized by means of a mechanism involving the α-hydroxy radicals of SPEEK and â¢CCl3 as chain carriers.
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Three-dimensional printing has rapidly become an easily accessible, innovative and versatile technology, with a vast range of applications across a wide range of industries. There has been a recent emergence in the scientific literature relating to its potential application across a multitude of fields within medicine and surgery; however, its use within anaesthesia has yet to be formally explored. We undertook a systematic review using MEDLINE and EMBASE databases of three-dimensional printing in anaesthesia. We identified eight relevant articles. Due to the paucity of studies, we also completed a narrative review of the applications of three-dimensional printing pertinent to anaesthetic practice that our department are currently exploring, and suggest potential future uses for this technology relevant to our speciality.
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Anestesia/métodos , Anestesiologia/métodos , Impressão Tridimensional , Humanos , Modelos AnatômicosRESUMO
Tramadol is administered to dogs for analgesia but has variability in its extent of absorption, which may hinder its efficacy. Additionally, the active opioid metabolite (M1) occurs in low concentrations. The purpose of this study was to determine if administration of oral tramadol with suspected metabolism inhibitors (ketoconazole, cimetidine) would lead to improved bioavailability of tramadol and M1. Six healthy Greyhounds were included. They were administered tramadol orally and intravenously, M1 intravenously, oral tramadol with oral ketoconazole and oral tramadol with oral cimetidine. Oral tramadol bioavailability was low (2.6%). Ketoconazole and cimetidine significantly increased tramadol bioavailability to 18.2% and 20.3%, respectively. The mean maximum plasma concentration of tramadol alone was 22.9 ng/ml, and increased to 109.9 and 143.2 µg/ml with ketoconazole and cimetidine, respectively. However, measured tramadol plasma concentrations were below the minimum concentration considered effective in humans (228 µg/ml). In all treatment groups, measured M1 concentrations (<7 µg/ml) were below concentrations associated with efficacy in humans. To conclude, tramadol and M1 concentrations were low and variable in dogs after oral dosing of tramadol, even in combination with cimetidine or ketoconazole, but effective concentrations in dogs have not been defined.
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Analgésicos Opioides/farmacocinética , Antifúngicos/farmacologia , Cimetidina/farmacologia , Antagonistas dos Receptores H2 da Histamina/farmacologia , Cetoconazol/farmacologia , Tramadol/farmacocinética , Administração Oral , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/sangue , Animais , Disponibilidade Biológica , Cães/metabolismo , Interações Medicamentosas , Feminino , Masculino , Tramadol/administração & dosagem , Tramadol/sangueRESUMO
Dietary n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation has previously been shown to modify joint-related inflammation in several species, although information in the horse is lacking. We investigated whether dietary supplementation with n-3 LCPUFA would modify experimentally induced synovitis in horses. Twelve, skeletally mature, non-pregnant mares were randomly assigned to either a control diet (CONT) or an n-3 long-chain fatty acid-enriched treatment diet (N3FA) containing 40 g/day of n-3 LCPUFA for 91 days. Blood samples taken on days 0, 30, 60 and 90, and synovial fluid collected on days 0 and 90 were processed for lipid composition. On day 91, joint inflammation was stimulated using an intra-articular (IA) injection of 100 ng of recombinant equine IL-1beta (reIL-1ß). Synovial fluid samples taken at post-injection hours (PIH) 0, 4, 8 and 24 were analysed for prostaglandin E2 (PGE2 ), matrix metalloproteinase (MMP) activity and routine cytology. Synovium and articular cartilage samples collected at PIH 8 were analysed for gene expression of MMP 1 and MMP 13, interleukin-1beta (IL-1ß), cyclooxygenase 2 (COX-2), tumour necrosis factor-alpha and the aggrecanases, a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5. A 90-day feeding period of n-3 LCPUFA increased serum phospholipid and synovial fluid lipid compositions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) compared to CONT horses. The reIL-1ß injection caused an inflammatory response; however, there was no effect of dietary treatment on synovial fluid PGE2 content and MMP activity. Synovial tissue collected from N3FA horses exhibited lower expression of ADAMTS-4 compared to CONT horses. Despite the presence of EPA and DHA in the synovial fluid of N3FA horses, dietary n-3 LCPUFA supplementation did not modify synovial fluid biomarkers compared to CONT horses; however, the lower ADAMTS-4 mRNA expression in N3FA synovium warrants further investigation of n-3 LCPUFA as a joint therapy.
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Ração Animal/análise , Dieta/veterinária , Ácidos Graxos Ômega-3/farmacologia , Doenças dos Cavalos/induzido quimicamente , Sinovite/veterinária , Fenômenos Fisiológicos da Nutrição Animal , Animais , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Doenças dos Cavalos/dietoterapia , Cavalos , Interleucina-1beta/administração & dosagem , Interleucina-1beta/toxicidade , Proteínas Recombinantes , Sinovite/induzido quimicamente , Sinovite/dietoterapiaRESUMO
Gain-of-function missense mutations in voltage-gated sodium channel Nav1.7 have been linked to small-fiber neuropathy, which is characterized by burning pain, dysautonomia and a loss of intraepidermal nerve fibers. However, the mechanistic cascades linking Nav1.7 mutations to axonal degeneration are incompletely understood. The G856D mutation in Nav1.7 produces robust changes in channel biophysical properties, including hyperpolarized activation, depolarized inactivation, and enhanced ramp and persistent currents, which contribute to the hyperexcitability exhibited by neurons containing Nav1.8. We report here that cell bodies and neurites of dorsal root ganglion (DRG) neurons transfected with G856D display increased levels of intracellular Na(+) concentration ([Na(+)]) and intracellular [Ca(2+)] following stimulation with high [K(+)] compared with wild-type (WT) Nav1.7-expressing neurons. Blockade of reverse mode of the sodium/calcium exchanger (NCX) or of sodium channels attenuates [Ca(2+)] transients evoked by high [K(+)] in G856D-expressing DRG cell bodies and neurites. We also show that treatment of WT or G856D-expressing neurites with high [K(+)] or 2-deoxyglucose (2-DG) does not elicit degeneration of these neurites, but that high [K(+)] and 2-DG in combination evokes degeneration of G856D neurites but not WT neurites. Our results also demonstrate that 0 Ca(2+) or blockade of reverse mode of NCX protects G856D-expressing neurites from degeneration when exposed to high [K(+)] and 2-DG. These results point to [Na(+)] overload in DRG neurons expressing mutant G856D Nav1.7, which triggers reverse mode of NCX and contributes to Ca(2+) toxicity, and suggest subtype-specific blockade of Nav1.7 or inhibition of reverse NCX as strategies that might slow or prevent axon degeneration in small-fiber neuropathy.
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Cálcio/metabolismo , Eritromelalgia/metabolismo , Gânglios Espinais/metabolismo , Mutação de Sentido Incorreto , Canal de Sódio Disparado por Voltagem NAV1.3/metabolismo , Neuritos/metabolismo , Canais de Sódio/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Animais , Cálcio/toxicidade , Células Cultivadas , Gânglios Espinais/citologia , Humanos , Canal de Sódio Disparado por Voltagem NAV1.3/genética , Neuritos/patologia , Potássio/metabolismo , Ratos , Ratos Sprague-Dawley , Sódio/metabolismo , Canais de Sódio/genética , Trocador de Sódio e Cálcio/antagonistas & inibidoresRESUMO
AIMS: Little is known about the long-term effects of intensive multifactorial treatment early in the diabetes disease trajectory. In the absence of long-term data on hard outcomes, we described change in 10-year modelled cardiovascular risk in the 5 years following diagnosis, and quantified the impact of intensive treatment on 10-year modelled cardiovascular risk at 5 years. METHODS: In a pragmatic, cluster-randomized, parallel-group trial in Denmark, the Netherlands and the UK, 3057 people with screen-detected Type 2 diabetes were randomized by general practice to receive (1) routine care of diabetes according to national guidelines (1379 patients) or (2) intensive multifactorial target-driven management (1678 patients). Ten-year modelled cardiovascular disease risk was calculated at baseline and 5 years using the UK Prospective Diabetes Study Risk Engine (version 3ß). RESULTS: Among 2101 individuals with complete data at follow up (73.4%), 10-year modelled cardiovascular disease risk was 27.3% (sd 13.9) at baseline and 21.3% (sd 13.8) at 5-year follow-up (intensive treatment group difference -6.9, sd 9.0; routine care group difference -5.0, sd 12.2). Modelled 10-year cardiovascular disease risk was lower in the intensive treatment group compared with the routine care group at 5 years, after adjustment for baseline cardiovascular disease risk and clustering (-2.0; 95% CI -3.1 to -0.9). CONCLUSIONS: Despite increasing age and diabetes duration, there was a decline in modelled cardiovascular disease risk in the 5 years following diagnosis. Compared with routine care, 10-year modelled cardiovascular disease risk was lower in the intensive treatment group at 5 years. Our results suggest that patients benefit from intensive treatment early in the diabetes disease trajectory, where the rate of cardiovascular disease risk progression may be slowed.
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Diabetes Mellitus Tipo 2/prevenção & controle , Angiopatias Diabéticas/prevenção & controle , Adulto , Idoso , Terapia Combinada/estatística & dados numéricos , Diagnóstico Precoce , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Resultado do TratamentoRESUMO
Tuberculosis (TB) remains an important issue in Australia with more than 85% of active cases contributed by overseas-born persons. Other risk groups include older Australians who acquired TB in the past and indigenous people. Immune suppression is an emerging risk factor for TB, particularly due to the expanding group of conditions for which potent immunosuppressive therapies is now used. Screening for latent TB is recommended in many risk groups including recent contacts of those with transmissible TB, those undergoing immune suppressive therapy, recently arrived refugees or migrants from high-risk countries and indigenous people with high rates of TB in the local community. Interferon-gamma release assay (IGRA) has now been available for several years for the diagnosis of latent TB. It is now used in many clinical situations, and despite the rapid rate of new publications, there are still gaps in our knowledge. This paper reviews the current role of interferon-gamma release assay in various situations, to determine its place in current practice and to explore where uncertainties exist.
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Testes de Liberação de Interferon-gama/métodos , Tuberculose/diagnóstico , Tuberculose/imunologia , Austrália/epidemiologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Tuberculose Latente/imunologia , Tuberculose/epidemiologiaRESUMO
Aspirin is a foundation drug of the pharmaceutical industry originally derived as an analgesic/anti-inflammatory agent but serendipitously discovered to have use as a prophylactic drug for major adverse cardiovascular events (MACE). Its modern-day utility in this latter role relies on its efficacy/safety balance in a contemporary population where, at least in high-income countries, age-standardised incident rates for MACE are falling, and where there are now competing therapeutic agents. Its future may be determined by its potential role as a chemoprophylactic or adjunct agent for cancer or other disease states. It therefore will continue to be the subject of further clinical research.
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Aspirina , Doenças Cardiovasculares , Humanos , Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversosRESUMO
Clinic blood pressure (BP) is recommended for absolute cardiovascular disease (CVD) risk assessment. However, in 'real-world' settings, clinic BP measurement is unstandardised and less reliable compared to more rigorous methods but the impact for absolute CVD risk assessment is unknown. This study aimed to determine the difference in absolute CVD risk assessment using real-world clinic BP compared to standardised BP methods. Participants were patients (n = 226, 59 ± 15 years; 58% female) with hypertension referred to a BP clinic for assessment. 'Real-world' clinic BP was provided by the referring doctor. All participants had unobserved automated office BP (AOBP) and 24-h ambulatory BP monitoring (ABPM) measured at the clinic. Absolute CVD risk was calculated (Framingham) using systolic BP from the referring doctor (clinic BP), AOBP and ABPM, with agreement assessed by Kappa statistic. Clinic systolic BP was 18 mmHg than AOBP and daytime ABPM and 22 mmHg higher than 24-h ABPM (p < 0.001). Subsequently, absolute CVD risk scores using clinic BP were higher compared to AOBP, daytime ABPM and 24-h ABPM (10.4 ± 8.1%, 7.8 ± 6.4%, 7.8 ± 6.3%, and 7.3 ± 6.1%, respectively, P < 0.001). As a result, more participants were classified as high CVD risk using clinic BP (n = 89, 40%) compared with AOBP (n = 44, 20%) daytime ABPM (n = 38, 17%) and 24-h ABPM (n = 38, 17%) (p < 0.001) with weak agreement in risk classification (κ = 0.57[0.45-0.69], κ = 0.52[0.41-0.64] and κ = 0.55[0.43-0.66], respectively). Real-world clinic BP was higher and classified twice as many participants at high CVD risk compared to AOBP or ABPM. Given the challenges to high-quality BP measurement in clinic, more rigorous BP measurement methods are needed for absolute CVD risk assessment.
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BACKGROUND: We studied the genetic fingerprints of ovarian cancer and validated the potential of Mammaglobin b (SCGB2A1), one of the top differentially expressed genes found in our analysis, as a novel ovarian tumour rejection antigen. METHODS: We profiled 70 ovarian carcinomas including 24 serous (OSPC), 15 clear-cell (CC), 24 endometrioid (EAC) and 7 poorly differentiated tumours, and 14 normal human ovarian surface epithelial (HOSE) control cell lines using the Human HG-U133 Plus 2.0 chip (Affymetrix). Quantitative real-time PCR and immunohistochemistry staining techniques were used to validate microarray data at RNA and protein levels for SCGB2A1. Full-length human-recombinant SCGB2A1 was used to pulse monocyte-derived dendritic cells (DCs) to stimulate autologous SCGB2A1-specific cytotoxic T-lymphocyte (CTL) responses against chemo-naive and chemo-resistant autologous ovarian tumours. RESULTS: Gene expression profiling identified SCGB2A1 as a top differentially expressed gene in all histological ovarian cancer types tested. The CD8+ CTL populations generated against SCGB2A1 were able to consistently induce lysis of autologous primary (chemo-naive) and metastatic/recurrent (chemo-resistant) target tumour cells expressing SCGB2A1, whereas autologous HLA-identical noncancerous cells were not lysed. Cytotoxicity against autologous tumour cells was significantly inhibited by anti-HLA-class I (W6/32) monoclonal antibody. Intracellular cytokine expression measured by flow cytometry showed a striking type 1 cytokine profile (i.e., high IFN-γ secretion) in SCGB2A1-specific CTLs. CONCLUSION: SCGB2A1 is a top differentially expressed gene in all major histological types of ovarian cancers and may represent a novel and attractive target for the immunotherapy of patients harbouring recurrent disease resistant to chemotherapy.
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Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Mamoglobina B/metabolismo , Neoplasias Ovarianas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/genética , Biomarcadores Tumorais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoterapia , Mamoglobina B/genética , Análise em Microsséries , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Transcriptoma , Estudos de Validação como AssuntoRESUMO
Automated cuff measured blood pressure (BP) is the global standard used for diagnosing hypertension, but there are concerns regarding the accuracy of the method. Individual variability in systolic BP (SBP) amplification from central (aorta) to peripheral (brachial) arteries could be related to the accuracy of cuff BP, but this has never been determined and was the aim of this study. Automated cuff BP and invasive brachial BP were recorded in 795 participants (74% male, aged 64 ± 11 years) receiving coronary angiography at five independent research sites (using seven different automated cuff BP devices). SBP amplification was recorded invasively by catheter and defined as brachial SBP minus aortic SBP. Compared with invasive brachial SBP, cuff SBP was significantly underestimated (130 ± 18 mmHg vs. 138 ± 22 mmHg, p < 0.001). The level of SBP amplification varied significantly among individuals (mean ± SD, 7.3 ± 9.1 mmHg) and was similar to level of difference between cuff and invasive brachial SBP (mean difference -7.6 ± 11.9 mmHg). SBP amplification explained most of the variance in accuracy of cuff SBP (R2 = 19%). The accuracy of cuff SBP was greatest among participants with the lowest SBP amplification (ptrend < 0.001). After cuff BP values were corrected for SBP amplification, there was a significant improvement in the mean difference from the intra-arterial standard (p < 0.0001) and in the accuracy of hypertension classification according to 2017 ACC/AHA guideline thresholds (p = 0.005). The level of SBP amplification is a critical factor associated with the accuracy of conventional automated cuff measured BP.
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Pressão Arterial , Hipertensão , Feminino , Humanos , Masculino , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial/métodos , Artéria Braquial/fisiologia , Hipertensão/diagnóstico , Pessoa de Meia-Idade , IdosoRESUMO
OBJECTIVE: Hypertension management is directed by cuff blood pressure (BP), but this may be inaccurate, potentially influencing cardiovascular disease (CVD) events and health costs. This study aimed to determine the impact on CVD events and related costs of the differences between cuff and invasive SBP. METHODS: Microsimulations based on Markov modelling over one year were used to determine the differences in the number of CVD events (myocardial infarction or coronary death, stroke, atrial fibrillation or heart failure) predicted by Framingham risk and total CVD health costs based on cuff SBP compared with invasive (aortic) SBP. Modelling was based on international consortium data from 1678 participants undergoing cardiac catheterization and 30 separate studies. Cuff underestimation and overestimation were defined as cuff SBP less than invasive SBP and cuff SBP greater than invasive SBP, respectively. RESULTS: The proportion of people with cuff SBP underestimation versus overestimation progressively increased as SBP increased. This reached a maximum ratio of 16â:â1 in people with hypertension grades II and III. Both the number of CVD events missed (predominantly stroke, coronary death and myocardial infarction) and associated health costs increased stepwise across levels of SBP control, as cuff SBP underestimation increased. The maximum number of CVD events potentially missed (11.8/1000 patients) and highest costs ($241â300âUSD/1000 patients) were seen in people with hypertension grades II and III and with at least 15âmmHg of cuff SBP underestimation. CONCLUSION: Cuff SBP underestimation can result in potentially preventable CVD events being missed and major increases in health costs. These issues could be remedied with improved cuff SBP accuracy.
Assuntos
Doenças Cardiovasculares , Hipertensão , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Pressão Sanguínea/fisiologia , Aorta , Custos de Cuidados de Saúde , Fatores de RiscoRESUMO
BACKGROUND: Accurate blood pressure (BP) measurement is critical for optimal cardiovascular risk management. Age-related trajectories for cuff-measured BP accelerate faster in women compared with men, but whether cuff BP represents the intraarterial (invasive) aortic BP is unknown. This study aimed to determine the sex differences between cuff BP, invasive aortic BP, and the difference between the 2 measurements. METHODS: Upper-arm cuff BP and invasive aortic BP were measured during coronary angiography in 1615 subjects from the Invasive Blood Pressure Consortium Database. This analysis comprised 22 different cuff BP devices from 28 studies. RESULTS: Subjects were 64±11 years (range 40-89) and 32% women. For the same cuff systolic BP (SBP), invasive aortic SBP was 4.4 mm Hg higher in women compared with men. Cuff and invasive aortic SBP were higher in women compared with men, but the sex difference was more pronounced from invasive aortic SBP, was the lowest in younger ages, and the highest in older ages. Cuff diastolic blood pressure overestimated invasive diastolic blood pressure in both sexes. For cuff and invasive diastolic blood pressure separately, there were sex*age interactions in which diastolic blood pressure was higher in younger men and lower in older men, compared with women. Cuff pulse pressure underestimated invasive aortic pulse pressure in excess of 10 mm Hg for both sexes in older age. CONCLUSIONS: For the same cuff SBP, invasive aortic SBP was higher in women compared with men. How this translates to cardiovascular risk prediction needs to be determined, but women may be at higher BP-related risk than estimated by cuff measurements.