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3.
Ann Phys Rehabil Med ; 66(6): 101756, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37276748

RESUMO

BACKGROUND: Objective physical performance-based outcome measures (PerBOMs) are essential tools for the holistic management of people who have had an amputation due to vascular disease. These people are often non-ambulatory, however it is currently unclear which PerBOMs are high quality and appropriate for those who are either ambulatory or non-ambulatory. RESEARCH QUESTION: Which PerBOMs have appropriate clinimetric properties to be recommended for those who have had amputations due to vascular disease ('vascular amputee')? DATA SOURCES: MEDLINE, CINAHL, EMBASE, EMCARE, the Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus databases were searched for the terms: "physical performance" or "function", "clinimetric properties", "reliability", "validity", "amputee" and "peripheral vascular disease" or "diabetes". REVIEW METHODS: A systematic review of PerBOMs for vascular amputees was performed following COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology and PRISMA guidelines. The quality of studies and individual PerBOMs was assessed using COSMIN risk of bias and good measurement properties. Overall PerBOM quality was evaluated with a modified GRADE rating. Key clinimetric properties evaluated were reliability, validity, predictive validity and responsiveness. RESULTS: A total of 15,259 records were screened. Forty-eight studies (2650 participants) were included: 7 exclusively included vascular amputees only, 35 investigated validity, 20 studied predictive validity, 23 investigated reliability or internal consistency and 7 assessed responsiveness. Meta-analysis was neither possible nor appropriate for this systematic review in accordance with COSMIN guidelines, due to heterogeneity of the data. Thirty-four different PerBOMs were identified of which only 4 are suitable for non-ambulatory vascular amputees. The Amputee Mobility Predictor no Prosthesis (AMPnoPro) and Transfemoral Fitting Predictor (TFP) predict prosthesis use only. PerBOMs available for assessing physical performance are the One-Leg Balance Test (OLBT) and Basic Amputee Mobility Score (BAMS). CONCLUSION: At present, few PerBOMs can be recommended for vascular amputees. Only 4 are available for non-ambulatory individuals: AMPnoPro, TFP, OLBT and BAMS.

4.
IEEE Trans Nanobioscience ; 22(4): 933-942, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37030876

RESUMO

The human bacterial pathogen Helicobacter pylori causes a range of gastric diseases. The killing rate of Helicobacter pylori is declining year by year because of high antibiotics resistance. It is urgent to develop new target and novel anti- Helicobacter pylori drugs. As an "energy pump" for bacterial cells, SecA is essential for bacterial growth and drives bacterial protein transmembrane transport, moreover SecA is absent in mammals, all of which nominate SecA as an attractive antimicrobial target. Here, we provided a structure-based virtual screening method to screen the 3D-diversity natural-product-like screening library against SecA for novel anti- Helicobacter pylori inhibitors with novel scaffolds. In this study, homology modeling was used to construct the three-dimensional structure of Helicobacter pylori SecA. Two rounds of molecular docking were then used to find new small-molecule inhibitors of SecA, identifying six lead candidates that maintained key interactions with the binding pocket. After that, molecular dynamics simulations were used to explore more accurate ligand-receptor binding modes in states close to natural conditions. Encouragingly, all six compounds were relatively stable during the simulation. Apart from that the binding free energy calculation based on MM/PBSA demonstrated favorable results of < -13.642 kcal/mol. Finally, ADME-T analysis indicated that these compounds were also sufficiently druggable. All six compounds can be well combined with the crystal structure, which further facilitate the development of SecA inhibitors and lead compounds against Helicobacter pylori.


Assuntos
Anti-Infecciosos , Helicobacter pylori , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Simulação de Dinâmica Molecular
5.
Ann Vasc Surg ; 93: 157-165, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37023916

RESUMO

BACKGROUND: Vascular Emergency Clinics (VEC) improve patient outcomes in chronic limb-threatening ischemia (CLTI). They provide a "1 stop" open access policy, whereby "suspicion of CLTI" by a healthcare professional or patient leads to a direct review. We assessed the resilience of the outpatient VEC model to the first year of the coronavirus disease (COVID-19) pandemic. METHODS: A retrospective review of a prospectively maintained database of all patients assessed in our VEC for lower limb pathologies between March 2020 and April 2021 was performed. This was cross-referenced to national and loco-regional Governmental COVID-19 data. Individuals with CLTI were further analysed to determine Peripheral Arterial Disease-Quality Improvement Framework compliance. RESULTS: Seven hundred and ninety one patients attended for 1,084 assessments (Male n = 484, 61%; Age 72.5 ± standard deviation 12.2 years; White British n = 645, 81.7%). In total, 322 patients were diagnosed with CLTI (40.7%). A total of 188 individuals (58.6%) underwent a first revascularization strategy (Endovascular n = 128, 39.8%; Hybrid n = 41, 12.7%; Open surgery n = 19, 5.9%; Conservative n = 134, 41.6%). Major lower limb amputation rate was 10.9% (n = 35) and mortality rate was 25.8% (n = 83) at 12 months of follow-up. Median referral to assessment time was 3 days (interquartile range: 1-5). For the nonadmitted patient with CLTI, the median assessment to intervention was 8 days (interquartile range: 6-15) and median referral to intervention time of 11 days (11-18). CONCLUSIONS: The VEC model has demonstrated strong resilience to the COVID-19 pandemic with rapid treatment timelines maintained for patients with CLTI.


Assuntos
COVID-19 , Infecções por Coronavirus , Coronavirus , Procedimentos Endovasculares , Doença Arterial Periférica , Humanos , Masculino , Idoso , Feminino , Pandemias , Fatores de Risco , Procedimentos Endovasculares/efeitos adversos , Isquemia , Resultado do Tratamento , Salvamento de Membro , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/cirurgia , Isquemia Crônica Crítica de Membro , Estudos Retrospectivos , Doença Crônica
6.
Eur J Vasc Endovasc Surg ; 65(2): 271, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36265557
7.
Br J Surg ; 109(8): 686-694, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35552376

RESUMO

BACKGROUND: The aim was to determine the comparative benefits of structured high-pain exercise, structured low-pain exercise, and usual-care control, to identify which has the largest effect on walking ability in people with intermittent claudication (IC). METHODS: A network meta-analysis was undertaken to assess two outcomes: pain-free walking ability (PFWA) and maximal walking ability (MWA). Nine electronic databases were searched. Trials were included if they were: RCTS; involved adults with IC; had at least two of the following arms-structured low-pain exercise, structured high--pain exercise or usual-care control; and a maximal or pain-free treadmill walking outcome. RESULTS: Some 14 trials were included; results were pooled using the standardized mean difference (MD). Structured low-pain exercise had a significant large positive effect on MWA (MD 2.23, 95 percent c.i. 1.11 to 3.35) and PFWA (MD 2.26, 1.26 to 3.26) compared with usual-care control. Structured high-pain exercise had a significant large positive effect on MWA (MD 0.95, 0.20 to 1.70) and a moderate positive effect on PFWA (0.77, 0.01 to 1.53) compared with usual-care control. In an analysis of structured low- versus high pain exercise, there was a large positive effect in favour of low-pain exercise on MWA (MD 1.28, -0.07 to 2.62) and PFWA (1.50, 0.24 to 2.75); however, this was significant only for PFWA. CONCLUSION: There is strong evidence in support of use of structured high-pain exercise, and some evidence in support of structured low-pain exercise, to improve walking ability in people with IC compared with usual-care control (unstructured exercise advice).


Assuntos
Terapia por Exercício , Claudicação Intermitente , Adulto , Exercício Físico , Teste de Esforço , Terapia por Exercício/métodos , Humanos , Claudicação Intermitente/terapia , Dor , Caminhada
8.
N Engl J Med ; 386(17): 1615-1626, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35476650

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV), a major cause of illness and death in infants worldwide, could be prevented by vaccination during pregnancy. The efficacy, immunogenicity, and safety of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine in pregnant women and their infants are uncertain. METHODS: In a phase 2b trial, we randomly assigned pregnant women, at 24 through 36 weeks' gestation, to receive either 120 or 240 µg of RSVpreF vaccine (with or without aluminum hydroxide) or placebo. The trial included safety end points and immunogenicity end points that, in this interim analysis, included 50% titers of RSV A, B, and combined A/B neutralizing antibodies in maternal serum at delivery and in umbilical-cord blood, as well as maternal-to-infant transplacental transfer ratios. RESULTS: This planned interim analysis included 406 women and 403 infants; 327 women (80.5%) received RSVpreF vaccine. Most postvaccination reactions were mild to moderate; the incidence of local reactions was higher among women who received RSVpreF vaccine containing aluminum hydroxide than among those who received RSVpreF vaccine without aluminum hydroxide. The incidences of adverse events in the women and infants were similar in the vaccine and placebo groups; the type and frequency of these events were consistent with the background incidences among pregnant women and infants. The geometric mean ratios of 50% neutralizing titers between the infants of vaccine recipients and those of placebo recipients ranged from 9.7 to 11.7 among those with RSV A neutralizing antibodies and from 13.6 to 16.8 among those with RSV B neutralizing antibodies. Transplacental neutralizing antibody transfer ratios ranged from 1.41 to 2.10 and were higher with nonaluminum formulations than with aluminum formulations. Across the range of assessed gestational ages, infants of women who were immunized had similar titers in umbilical-cord blood and similar transplacental transfer ratios. CONCLUSIONS: RSVpreF vaccine elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns. (Funded by Pfizer; ClinicalTrials.gov number, NCT04032093.).


Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Proteínas Virais de Fusão , Hidróxido de Alumínio/efeitos adversos , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Feminino , Humanos , Lactente , Gravidez , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/efeitos adversos , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vacinas contra Vírus Sincicial Respiratório/uso terapêutico , Vírus Sincicial Respiratório Humano/imunologia , Vacinação , Proteínas Virais de Fusão/imunologia
10.
BMJ Open ; 11(10): e053599, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615685

RESUMO

OBJECTIVE: Estimate the prevalence/incidence/number of major lower extremity amputations (MLEAs) in the UK; identify sources of routinely collected electronic health data used; assess time trends and regional variation; and identify reasons for variation in reported incidence/prevalence of MLEA. DESIGN: Systematic review and narrative synthesis. DATA SOURCES: Medline, Embase, EMcare, CINAHL, The Cochrane Library, AMED, Scopus and grey literature sources searched from 1 January 2009 to 1 August 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Reports that provided population-based statistics, used routinely collected electronic health data, gave a measure of MLEA in adults in the general population or those with diabetes in the UK or constituent countries were included. DATA EXTRACTION AND SYNTHESIS: Data extraction and quality assessment using the Joanna Briggs Institute Critical Appraisal Instruments were performed by two reviewers independently. Due to considerable differences in study populations and methodology, data pooling was not possible; data were tabulated and narratively synthesised, and study differences were discussed. RESULTS: Twenty-seven reports were included. Incidence proportion for the general population ranged from 8.2 to 51.1 per 100 000 and from 70 to 291 per 100 000 for the population with diabetes. Evidence for trends over time was mixed, but there was no evidence of increasing incidence. Reports consistently found regional variation in England with incidence higher in the north. No studies reported prevalence. Differences in database use, MLEA definition, calculation methods and multiple procedure inclusion which, together with identified inaccuracies, may account for the variation in incidence. CONCLUSIONS: UK incidence and trends in MLEA remain unclear; estimates vary widely due to differences in methodology and inaccuracies. Reasons for regional variation also remain unexplained and prevalence uninvestigated. International consensus on the definition of MLEA and medical code list is needed. Future research should recommend standards for the reporting of such outcomes and investigate further the potential to use primary care data in MLEA epidemiology. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020165592.


Assuntos
Amputação Cirúrgica , Extremidade Inferior , Adulto , Humanos , Incidência , Extremidade Inferior/cirurgia , Prevalência , Reino Unido/epidemiologia
11.
Clin J Am Soc Nephrol ; 16(8): 1190-1200, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34362786

RESUMO

BACKGROUND AND OBJECTIVES: We evaluated the efficacy and cardiovascular safety of roxadustat versus placebo by analyzing data pooled from three phase 3 studies of roxadustat in patients with non-dialysis-dependent CKD and CKD-related anemia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In the three phase 3, double-blind studies of roxadustat versus placebo evaluating the treatment of CKD-related anemia in patients not requiring dialysis, the primary efficacy end point was mean change from baseline in hemoglobin averaged over weeks 28-52, regardless of rescue therapy. The primary cardiovascular safety end point was a composite measure of major adverse cardiovascular events (MACE; all-cause mortality, myocardial infarction, stroke). MACE plus (MACE+; MACE plus unstable angina and heart failure requiring hospitalization) and all-cause mortality were key secondary safety end points. These safety end points were adjudicated. RESULTS: A total of 4277 patients with non-dialysis-dependent CKD were randomized (roxadustat, n=2391; placebo, n=1886). Baseline characteristics were comparable between groups; the mean (SD) hemoglobin was 9.1 (0.7) g/dl and mean eGFR was 20 (12) ml/min per 1.73 m2. Patients treated with roxadustat versus those treated with placebo showed a mean change from baseline in hemoglobin averaged over weeks 28-52, regardless of rescue therapy, of 1.9 versus 0.2 g/dl, a treatment difference of 1.7 (95% confidence interval [95% CI], 1.7 to 1.8). Roxadustat reduced the need for red blood cell transfusion in the first 52 weeks versus placebo (6.1 versus 20.4 per 100 patient-exposure years, respectively; hazard ratio [HR], 0.26; 95% CI, 0.21 to 0.32). There were no increased risks of MACE (HR, 1.10; 95% CI, 0.96 to 1.27), MACE+ (HR, 1.07; 95% CI, 0.94 to 1.21), all-cause mortality (HR, 1.08; 95% CI, 0.93 to 1.26), or individual MACE+ components in patients treated with roxadustat versus those treated with placebo. CONCLUSIONS: Roxadustat was more effective than placebo at increasing hemoglobin in patients with non-dialysis-dependent CKD and anemia, while decreasing transfusion rate and being noninferior to placebo with respect to risk of MACE. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: A Study of FG-4592 for the Treatment of Anemia in Chronic Kidney Disease Patients Not Receiving Dialysis, NCT01750190; Roxadustat in the Treatment of Anemia in Chronic Kidney Disease Patients Not Requiring Dialysis (ALPS), NCT01887600; Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease (CKD), Not on Dialysis, NCT02174627.


Assuntos
Anemia/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Inibidores Enzimáticos/uso terapêutico , Glicina/análogos & derivados , Isoquinolinas/uso terapêutico , Insuficiência Renal Crônica/complicações , Idoso , Anemia/sangue , Anemia/etiologia , Ensaios Clínicos Fase III como Assunto , Inibidores Enzimáticos/efeitos adversos , Transfusão de Eritrócitos , Feminino , Glicina/efeitos adversos , Glicina/uso terapêutico , Hemoglobinas/metabolismo , Humanos , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Isoquinolinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Exp Eye Res ; 209: 108651, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34097907

RESUMO

Pyroptosis is a caspase-dependent programmed cell death pathway that initiates and sustains inflammation through release of pro-inflammatory cytokines interleukin (IL)-1ß and IL-18 following formation of gasdermin D (GSDMD)-mediated membrane pores. To determine the possible pathogenic contributions of pyroptosis toward development of full-thickness retinal necrosis during AIDS-related human cytomegalovirus retinitis, we performed a series of studies using an established model of experimental murine cytomegalovirus (MCMV) retinitis in mice with retrovirus-induced immunosuppression (MAIDS). Initial investigations demonstrated significant transcription and translation of key pyroptosis-associated genes within the ocular compartments of MCMV-infected eyes of mice with MAIDS. Subsequent investigations compared MCMV-infected eyes of groups of wildtype MAIDS mice with MCMV-infected eyes of groups of caspase-1-/- MAIDS mice, GSDMD-/- MAIDS mice, or IL-18-/- MAIDS mice to explore a possible contribution of pyroptosis towards the pathogenesis of MAIDS-related MCMV retinitis. Histopathologic analysis revealed typical full-thickness retinal necrosis in 100% of MCMV-infected eyes of wildtype MAIDS mice. In sharp contrast, none (0%) of MCMV-infected eyes of MAIDS mice that were deficient in either caspase-1, GSDMD, or IL-18 developed full-thickness retinal necrosis but instead exhibited an atypical pattern of retinal disease characterized by thickening and proliferation of the retinal pigmented epithelium layer with relative sparing of the neurosensory retina. Surprisingly, MCMV-infected eyes of all groups of deficient MAIDS mice harbored equivalent intraocular amounts of infectious virus as seen in MCMV-infected eyes of groups of wildtype MAIDS mice despite failure to develop full-thickness retinal necrosis. We conclude that pyroptosis plays a significant role in the development of full-thickness retinal necrosis during the pathogenesis of MAIDS-related MCMV retinitis. This observation may extend to the pathogenesis of AIDS-related HCMV retinitis and other AIDS-related opportunistic virus infections.


Assuntos
Córnea/patologia , Retinite por Citomegalovirus/patologia , Síndrome de Imunodeficiência Adquirida Murina/complicações , Muromegalovirus/isolamento & purificação , Piroptose , Animais , Córnea/virologia , Retinite por Citomegalovirus/complicações , Retinite por Citomegalovirus/virologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Síndrome de Imunodeficiência Adquirida Murina/virologia
13.
Eur J Vasc Endovasc Surg ; 62(2): 294, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34183249

Assuntos
Aneurisma , Humanos
14.
Ann Vasc Surg ; 76: 406-416, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33951523

RESUMO

OBJECTIVE: Investigate the relationship of frailty and severity of chronic limb-threatening ischaemia (CLTI), and their comparative associations with one-year outcomes, in patients presenting to a vascular limb salvage (VaLS) clinic. METHODS: This retrospective cohort study utilised data collected from a prospectively maintained VaLS clinic database. Patients aged ≥50 presenting to the VaLS clinic with CLTI between February 2018 and April 2019 were included. Frailty was measured using the Clinical Frailty Scale (CFS) and limb threat severity by the Wound, Ischaemia, and foot Infection (WIfI) score. Excessive polypharmacy was defined as ≥10 medications. Anticholinergic burden (ACB) score and Charlson comorbidity index (CCI) were calculated for all patients. The primary outcome measure was a composite endpoint of death or amputation at one-year. Associations with outcome were assessed using Cox regression and reported as hazards ratios (HR) with 95% confidence intervals (CI). RESULTS: A total of 198 patients were included, with CFS scores available for 190 patients. 98 patients (52%) were frail (CFS ≥5). 127 patients (67%) initially underwent endovascular revascularisation. Excessive polypharmacy was common (55 patients; 28%). Frailty was associated with increased WIfI stage (P = 0.025) as well as age, female sex, CCI score, number of medications, excessive polypharmacy but not ACB score. Frail patients were more frequently managed non-operatively (P = 0.017). Frailty (HR 1.91; 95% CI 1.09, 3.34; P = 0.024) and WIfI stage 4 (HR 3.29; 95%CI 1.23, 8.80; P = 0.018) were associated with death or amputation on univariable analysis. WIfI stage 4 (HR 2.80; 95%CI 1.04, 7.57; P = 0.042) and CCI score (HR 1.21; 95%CI 1.03, 1.41; P = 0.015), but not frailty (HR 1.25; 95%CI 0.67, 2.33; P = 0.474), were independently associated with death or amputation on multivariable analysis. CONCLUSIONS: Frailty is highly prevalent among CLTI patients and related to severity of limb threat. The CFS may be a useful adjunct to patient risk assessment in CLTI.


Assuntos
Procedimentos Endovasculares , Idoso Fragilizado , Fragilidade/epidemiologia , Isquemia/terapia , Doença Arterial Periférica/terapia , Procedimentos Cirúrgicos Vasculares , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Doença Crônica , Tomada de Decisão Clínica , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Fragilidade/diagnóstico , Fragilidade/mortalidade , Estado Funcional , Humanos , Isquemia/diagnóstico , Isquemia/mortalidade , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Valor Preditivo dos Testes , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade
15.
Kidney Int Rep ; 6(3): 613-623, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33732976

RESUMO

INTRODUCTION: Erythropoiesis-stimulating agents are associated with increased cardiovascular risk when higher doses are used toward higher hematocrit targets. Patients new to dialysis are at higher risk for morbidity and mortality. Systematic evaluation of this population was predefined in the roxadustat clinical development program. Roxadustat is a hypoxia-inducible prolyl hydroxylase inhibitor. METHODS: Data were pooled from 3 phase 3, randomized, open-label, active-controlled trials. Eligible adults had kidney failure and initiated dialysis for 2 weeks to ≤ 4 months prior to randomization to roxadustat or epoetin alfa. Efficacy was assessed as mean change in hemoglobin from baseline averaged over weeks 28 to 52, regardless of rescue therapy. Key cardiovascular safety endpoints were major adverse cardiovascular events (MACE; all-cause mortality [ACM], myocardial infarction, and stroke), and MACE+ (MACE plus unstable angina or congestive heart failure requiring hospitalization), and ACM. RESULTS: This study included 1530 patients with kidney failure incident to dialysis. Mean (SD) changes in hemoglobin from baseline averaged over weeks 28 to 52, regardless of rescue therapy, were 2.12 (1.45) versus 1.91 (1.42) g/dl in the roxadustat and epoetin alfa groups (least-squares mean difference: 0.22; 95% CI, 0.05 to 0.40; P = 0.0130). Risks of MACE and MACE+ were lower in the roxadustat group (hazard ratio [HR], 0.70; 95% CI, 0.51 to 0.96) than the epoetin alfa group (HR, 0.66; 95% CI, 0.50 to 0.89); the HR for ACM was 0.76 (95% CI, 0.52 to 1.11). CONCLUSION: Roxadustat was at least as efficacious as epoetin alfa. Roxadustat had a lower risk of MACE/MACE+ in patients new to dialysis.

16.
Eur J Vasc Endovasc Surg ; 61(4): 612-619, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33583708

RESUMO

OBJECTIVE: Vascular limb salvage services are recommended by the Global Vascular Guidelines to help improve outcomes for patients with chronic limb-threatening ischaemia (CLTI), although their description within the literature is limited. This study reports the 12 month outcomes for an outpatient based vascular limb salvage (VaLS) clinic. METHODS: An analysis of a prospectively maintained database, involving all consecutive patients diagnosed with CLTI within the VaLS clinic from February 2018-February 2019, was undertaken. Data were compared with two comparator cohorts, identified from coding data: 1) patients managed prior to the clinic, between May 2017 and February 2018 (Pre-Clinic [PC]); and 2) patients managed outside of clinic, between February 2018 and February 2019 (Alternative Pathways [AP]). Freedom from major amputation at 12 months was the primary outcome. Kaplan-Meier plots and adjusted Cox's proportional hazard models (aHR) were used to compare outcomes. RESULTS: Five hundred and sixty-six patients (VaLS 158, AP 173, PC 235) were included (median age 74 years). Patients managed within the VaLS cohort were statistically significantly more likely to be free from major amputation (90.5%) compared with both the AP (82.1%, aHR 0.52, 95% confidence interval [CI] 0.28 - 0.98, p = .041) and the PC (80.0%; aHR 0.50, 95% CI 0.28 - 0.91, p = .022) cohorts at 12 months, after adjustment for age, disease severity, and presence of diabetes. CONCLUSION: This study supports the recommendations of the Global Vascular Guidelines that vascular limb salvage clinics may improve the rate of major amputation. Furthermore, the study provides a reproducible service model that delivers timely vascular assessment in an ambulatory setting. Further evaluation is required to assess longer term outcomes.


Assuntos
Amputação Cirúrgica , Procedimentos Endovasculares , Isquemia/terapia , Salvamento de Membro , Doença Arterial Periférica/terapia , Melhoria de Qualidade , Indicadores de Qualidade em Assistência à Saúde , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Inglaterra , Feminino , Humanos , Isquemia/diagnóstico por imagem , Isquemia/fisiopatologia , Salvamento de Membro/efeitos adversos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
17.
BMC Rheumatol ; 5(1): 3, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33536080

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that causes chronic synovitis, resulting in progressive joint destruction and functional disability and affects approximately 400,000 people in the UK. This real-world study aimed to describe the characteristics, treatment patterns and clinical outcomes of patients who received abatacept in UK clinical practice. METHODS: This was a multi-centre, retrospective, observational study of patients with RA treated with abatacept at four UK centres between 01 January 2013 and 31 December 2017. Data were collected from medical records of each patient from the index date (date of first bDMARD initiation) until the most recent visit, death or end of study (31 December 2017). RESULTS: In total, 213 patients were included in the study. Patients received up to eight lines of therapy (LOTs). Treatment with abatacept, or any other bDMARD, was associated with reductions in DAS28-ESR and DAS28-CRP scores at 6 and 12 months. The distribution of EULAR responses (good/moderate/no response) tended to be more favourable for patients when receiving abatacept than when receiving other bDMARDs (22.8%/41.3%/35.9% versus 16.6%/41.4%/42.1% at 6 months, and 27.9%/36.1%/36.1% versus 21.2%/34.5%/44.2% at 12 months). Patients receiving abatacept at LOT1 (n = 68) spent significantly longer on treatment compared with patients receiving other bDMARDs (53.4 vs. 17.4 months; p< 0.01); a similar trend was observed for LOT2. Among patients who discontinued after 6 months, a greater proportion experienced infection requiring antibiotics when receiving other bDMARDs compared to those receiving abatacept. CONCLUSIONS: RA patients who received bDMARDs, including abatacept, experienced reduced disease activity. When receiving abatacept as first or second line of therapy, patients persisted with treatment significantly longer than those receiving other bDMARDs.

18.
Eur J Vasc Endovasc Surg ; 61(4): 664-674, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33573912

RESUMO

OBJECTIVE: A significant proportion of vascular surgery patients may have undiagnosed cognitive impairment; however, its true prevalence and impact on outcomes are unknown. The aim of this review was to estimate the prevalence of cognitive impairment among individuals with clinically significant vascular surgical pathology and investigate its associations with post-operative outcomes in those undergoing vascular surgery. METHODS: MEDLINE, EMBASE, EMCare, CINAHL, PsycINFO, and Scopus were searched for relevant studies. Included studies assessed cognitive function among individuals with either symptomatic vascular surgical pathology, or disease above threshold for intervention, using a validated cognitive assessment tool. The primary outcome measure was prevalence of cognitive impairment. Secondary outcomes included incidence of post-operative delirium (POD). Two reviewers independently extracted relevant study data and assessed risk of bias (ROBINS-E or RoB 2 tool). Prevalence (%) of cognitive impairment was calculated for individual studies and presented with 95% confidence intervals (CI). Prevalence data from comparable studies were pooled using the Mantel-Haenszel method (random effects model) for separate vascular disease types. Certainty of effect estimates was assessed using the GRADE criteria. RESULTS: Twenty-four studies (2 564 participants) were included in the systematic review, and nine studies (1 310 participants) were included in the meta-analyses. The prevalence of cognitive impairment was 61% (95% CI 48 - 74; 391 participants; low certainty) in studies including multiple vascular surgical pathologies, 38% (95% CI 32 - 44; 278 participants; very low certainty) in carotid artery disease, and 19% (95% CI 10 - 33; 641 participants; low certainty) in those with intermittent claudication. Lower cognitive assessment scores were associated with POD (five studies; 841 participants), but data were not suitable for pooling. CONCLUSION: Screening elective vascular surgery patients for cognitive impairment may be appropriate given its high prevalence, and the association of worse cognition with POD, among individuals with clinically significant vascular surgical pathology.


Assuntos
Cognição , Disfunção Cognitiva/epidemiologia , Complicações Cognitivas Pós-Operatórias/epidemiologia , Doenças Vasculares/cirurgia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Comorbidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Cognitivas Pós-Operatórias/diagnóstico , Complicações Cognitivas Pós-Operatórias/psicologia , Prevalência , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Doenças Vasculares/epidemiologia , Doenças Vasculares/patologia
20.
MedEdPublish (2016) ; 10: 62, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-38486550

RESUMO

This article was migrated. The article was marked as recommended. Introduction As traditional clinical teaching faces major obstacles during the COVID-19 pandemic, medical educators look toward remote teaching methods to provide solutions to allow continuation of teaching. Remote methods, teaching delivered other than face-to-face, align with the transformation seen within pedagogy over the last 20 years. Aim The aim of this scoping review was to i) identify existing teaching methods available to remotely teach cardiovascular knowledge or skills and ii) identify if they have been evaluated. Methods A scoping review of the literature was undertaken to synthesise available evidence and examine remote teaching methods for application to undergraduate medical education. Results Forty-two articles were identified which presented remote teaching methods using either teaching based online, computer-programs, digital resources, mobile-phone technology, podcasts, serious gaming, social media or resources to aid self-directed learning. Although results were heterogenous, they gave an indication of the method's usefulness. However, evaluations were not consistent and if they were, would have strengthened the value of the findings. Conclusion Various remote teaching methods are available to replace face-to-face cardiovascular teaching where this is not possible. Evidence for effectiveness and engagement of individual platforms are variable. Given the ongoing COVID-19 pandemic, medical educators should prioritise ongoing evaluation of remote teaching methods and share best practice.

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