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1.
Anaesthesia ; 77(8): 882-891, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35762026

RESUMO

Persistent pain following knee arthroplasty occurs in up to 20% of patients and may require ongoing analgesia, including extended opioid administration. A comprehensive secondary analysis was performed from results of a study that considered persistent postoperative pain in 242 patients who underwent unilateral knee arthroplasty using a standardised enhanced recovery programme. Opioid prescribing for 12 months before and 12 months after surgery was evaluated and converted to oral morphine equivalents. Demographic, functional, psychological and pain questionnaires were completed along with quantitative sensory testing and genetic analysis. Forty-nine percent of patients had at least one opioid prescription in the 12 months before surgery. Opioid prescriptions were filled in 93% of patients from discharge to 3 months and in 27% of patients ≥6 months after surgery. Persistent opioid use ≥6 months after surgery was strongly associated with pre-operative opioid use (RR 3.2, p < 0.001 (95%CI 1.9-5.4)). The median (IQR [range]) oral morphine equivalent daily dose was 3.6 (0.9-10.5 [0-100.0]) mg pre-operatively, 35.0 (22.5-52.5 [4.6-180.0]) mg in hospital, 12.8 (5.1-24.8 [0-57.9]) mg from discharge to 3 months and 5.9 (4.5-12.0 [0-44.5]) mg at ≥6 months following surgery. Predictors of increased daily oral morphine equivalent ≥6 months after surgery included increased average daily oral morphine equivalent dose compared with previous values (lag), increased body mass index and three or more comorbid pain sites. Persistent opioid use was not associated with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (RR 1.003, p = 0.655, 95%CI 0.65-1.002) or WOMAC function (RR 1.001, p = 0.99, 95%CI 0.99-1.03) outcomes 6 months after surgery. There was no association between persistent opioid use and pre-operative quantitative sensory testing results or psychological distress. Pre-operatively, patients with a higher body mass index, more comorbid pain sites and those who had filled an opioid prescription in the last 12 months, were at increased risk of persistent opioid use and a higher oral morphine equivalent daily dose ≥ 6 months after surgery. Strategies need to be developed to limit dose and duration of persistent opioid use in patients following knee arthroplasty surgery.


Assuntos
Artroplastia do Joelho , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides , Artroplastia do Joelho/efeitos adversos , Humanos , Morfina , Transtornos Relacionados ao Uso de Opioides/etiologia , Dor Pós-Operatória/etiologia , Padrões de Prática Médica , Estudos Retrospectivos
2.
Anaesthesia ; 77(2): 164-174, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34555189

RESUMO

The association between intra-operative hypotension and postoperative acute kidney injury, mortality and length of stay has not been comprehensively evaluated in a large single-centre hip fracture population. We analysed electronic anaesthesia records of 1063 patients undergoing unilateral hip fracture surgery, collected from 2015 to 2018. Acute kidney injury, 3-, 30- and 365-day mortality and length of stay were evaluated to assess the relationship between intra-operative hypotension absolute values (≤ 55, 60, 65, 70 and 75 mmHg) and duration of hypotension. The rate of acute kidney injury was 23.7%, mortality at 3-, 30- and 365 days was 3.7%, 8.0% and 25.3%, respectively, and median (IQR [range]) length of stay 8 (6-12 [0-99]) days. Median (IQR [range]) time ≤ MAP 55, 60, 65, 70 and 75 mmHg was 0 (0-0.5[0-72.1]); 0 (0-4.4 [0-104.9]); 2.2 (0-8.7 [0-144.2]); 6.6 (2.2-19.7 [0-198.8]); 17.5 (6.6-37.1 [0-216.3]) minutes, and percentage of surgery time below these thresholds was 1%, 2.5%, 7.9%, 12% and 21% respectively. There were some univariate associations between hypotension and mortality; however, these were no longer evident in multivariable analysis. Multivariable analysis found no association between hypotension and acute kidney injury. Acute kidney injury was associated with male sex, antihypertensive medications and cardiac/renal comorbidities. Three-day mortality was associated with delay to surgery ? 48 hours, whilst 30-day and 365-day mortality was associated with delay to surgery ≥ 48 hours, impaired cognition and cardiac/renal comorbidities. While the rate of acute kidney injury was similar to other studies, use of vasopressors and fluids to reduce the time spent at hypotensive levels failed to reduce this complication. Intra-operative hypotension at the levels observed in this cohort may not be an important determinant of acute kidney injury, postoperative mortality and length of stay.


Assuntos
Injúria Renal Aguda/mortalidade , Tratamento de Emergência/mortalidade , Fraturas do Quadril/mortalidade , Hipotensão/mortalidade , Complicações Intraoperatórias/mortalidade , Complicações Pós-Operatórias/mortalidade , Injúria Renal Aguda/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Tratamento de Emergência/tendências , Feminino , Fraturas do Quadril/cirurgia , Humanos , Hipotensão/diagnóstico , Complicações Intraoperatórias/diagnóstico , Tempo de Internação/tendências , Masculino , Monitorização Intraoperatória/mortalidade , Monitorização Intraoperatória/tendências , Mortalidade/tendências , Complicações Pós-Operatórias/diagnóstico , Estudos Prospectivos , Estudos Retrospectivos
3.
Anaesthesia ; 76(8): 1031-1041, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33899214

RESUMO

Neuro-inflammation may be important in the pathogenesis of postoperative delirium following hip fracture surgery. Studies have suggested a potential role for steroids in reducing postoperative delirium; however, the potential efficacy and safety of pre-operative high-dose dexamethasone in this specific population is largely unknown. Conducting such a study could be challenging, considering the multidisciplinary team involvement and the emergency nature of the surgery. The aim of this study was to assess feasibility and effectiveness of dexamethasone given as early as possible following hospital admission for hip fracture, to inform whether a full-scale trial is warranted. This single-centre, randomised, double-blind, placebo-controlled study randomly allocated 79 participants undergoing hip fracture surgery to dexamethasone 20 mg or placebo pre-operatively. Eligibility and recruitment rates, timing of the intervention and adverse events were recorded. Incidence and severity of postoperative delirium were assessed using the 4AT delirium screening tool and the Memorial Delirium Assessment Scale. Postoperative pain, length of stay and mortality were also assessed. The eligibility rate for inclusion was 178/527 (34%), and 57/178 (32%) of eligible patients presented to hospital when no researcher was available (e.g. after-hours, weekends, public holidays). Recruitment was limited mainly by ethical limitations (not including patients with impaired cognition) and lack of weekend staffing. Median (IQR [range]) time from emergency department admission to drug administration was 13.3 (5.9-17.6 [1.8-139.6]) hours. There was a significant difference in delirium severity scores, favouring the dexamethasone group: median (IQR [range]) 5 (3-6 [3-7]) vs. 9 (6-13 [5-14]) in the placebo group, with the probability of superiority effect size being 0.89, p = 0.010. Delirium incidence did not differ between groups: 6/40 (15%) in the dexamethasone group vs. 9/39 (23%) in the placebo group, relative risk (95%CI) 0.65 (0.22-1.65), p = 0.360). A larger randomised controlled trial is feasible and ideally this should include people with existing cognitive impairment, seven days-a-week cover and a multicentre design.


Assuntos
Dexametasona/uso terapêutico , Delírio do Despertar/prevenção & controle , Avaliação Geriátrica/métodos , Glucocorticoides/uso terapêutico , Fraturas do Quadril/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Humanos , Masculino , Resultado do Tratamento
4.
Br J Surg ; 106(13): 1829-1836, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31441048

RESUMO

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is premalignant pancreatic lesion. International guidelines offer limited predictors of individual risk. A nomogram to predict individual IPMN malignancy risk was released, with good diagnostic performance based on a large cohort of Asian patients with IPMN. The present study validated a nomogram to predict malignancy risk and invasiveness of IPMN using both Eastern and Western cohorts. METHODS: Clinicopathological and radiological data from patients who underwent pancreatic resection for IPMN at four centres each in Eastern and Western countries were collected. After excluding patients with missing data for at least one malignancy predictor in the nomogram (main pancreatic duct diameter, cyst size, presence of mural nodule, serum carcinoembryonic antigen and carbohydrate antigen (CA) 19-9 levels, and age). RESULTS: In total, data from 393 patients who fit the criteria were analysed, of whom 265 were from Eastern and 128 from Western institutions. Although mean age, sex, log value of serum CA19-9 level, tumour location, main duct diameter, cyst size and presence of mural nodule differed between the Korean/Japanese, Eastern and Western cohorts, rates of malignancy and invasive cancer did not differ significantly. Areas under the receiver operating characteristic (ROC) curve values for the nomogram predicting malignancy were 0·745 for Eastern, 0·856 for Western and 0·776 for combined cohorts; respective values for the nomogram predicting invasiveness were 0·736, 0·891 and 0·788. CONCLUSIONS: External validation of the nomogram showed good performance in predicting cancer in both Eastern and Western patients with IPMN lesions.


ANTECEDENTES: La neoplasia mucinosa papilar intraductal (intraductal papillary mucinous neoplasm, IPMN) es una lesión pancreática premaligna. Las guías internacionales incluyen un número limitado de factores predictivos de riesgo individual. Para predecir el riesgo individual de malignidad del IPMN se ha propuesto un nomograma con un buen rendimiento diagnóstico, basado en una gran cohorte de pacientes asiáticos con IPMN. Este estudio validó el nomograma para predecir el riesgo de cáncer y de invasión de la IPMN utilizando cohortes tanto orientales como occidentales. MÉTODOS: Se recogieron datos clínico-patológicos y radiológicos de pacientes en los que se realizó una resección de páncreas por IPMN en 4 centros en países orientales y en 4 centros de países occidentales. Se excluyeron los pacientes en los que en el nomograma faltaba ≥ 1 factor(es) predictivo(s) de malignidad (diámetro del conducto pancreático principal, tamaño del quiste, presencia de nódulo mural, niveles séricos de CEA y CA19-9, y edad). RESULTADOS: En total, se analizaron datos de 393 pacientes que cumplían con los criterios de inclusión, de los cuales 265 eran de centros orientales y 128 de centros occidentales. Aunque la edad media, el sexo, el valor logarítmico del nivel sérico de CA19-9, la localización del tumor, el diámetro del conducto principal, el tamaño del quiste y la presencia de un nódulo mural difirieron entre las cohortes de Corea/Japón y las cohortes oriental y occidental, las tasas de malignidad y de cáncer invasivo no fueron significativamente diferentes. Las áreas bajo la curva operativa del receptor (area under the receiver operating curve, AUC) que mostró el nomograma para predecir la malignidad fueron: cohorte oriental: 0,745; cohorte occidental: 0,856 y cohortes combinadas: 0,776; y para predecir la invasión tumoral fueron: cohorte oriental: 0,736; cohorte occidental: 0,891, y cohortes combinadas: 0,788. CONCLUSIÓN: La validación externa del nomograma mostró un buen rendimiento en la predicción de cáncer, tanto en pacientes orientales como occidentales con lesiones IPMN.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Nomogramas , Ductos Pancreáticos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma Mucinoso/epidemiologia , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/epidemiologia , Carcinoma Ductal Pancreático/cirurgia , Dilatação Patológica , Endossonografia , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Pancreatectomia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/cirurgia , Valor Preditivo dos Testes , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
5.
Br J Anaesth ; 121(4): 804-812, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30236242

RESUMO

BACKGROUND: Persistent postoperative pain (PPP) is common after total knee arthroplasty (TKA). The primary aim of this prospective cohort study was to identify important predictors of moderate to severe PPP 6 and 12 months after TKA. METHODS: Consenting patients (n=300) undergoing primary unilateral TKA attended a preoperative session to collect clinical information (age, gender, BMI, preoperative knee pain, comorbid pain, likely neuropathic pain) and psychological variables (depression, anxiety, catastrophising, expected pain). Quantitative sensory testing (pressure pain thresholds, temporal summation, conditioned pain modulation) was performed, and blood samples were obtained for subsequent genotyping of OPRM1 and COMT. Acute postoperative pain was measured at rest and during movement. Surgical factors (surgery time, patella resurfacing, anaesthetic type) were collected after operation. Follow-up questionnaires were sent 6 and 12 months after surgery. Multivariate logistic regression was used to identify predictors of PPP. RESULTS: The prevalence of moderate to severe PPP was 21% (n=60) and 16% (n=45) 6 and 12 months after surgery, with 55% (n=33) and 60% (n=31) of PPP likely neuropathic in nature. At 6 months, a combination of preoperative pain intensity, expected pain, trait anxiety, and temporal summation (Akaike information criterion, 309.9; area under receiver operating characteristic (ROC) curve, 0.70) was able to correctly classify 66% of patients into moderate to severe PPP and no to mild PPP groups. At 12 months, preoperative pain intensity, expected pain, and trait anxiety (Akaike information criterion, 286.8; area under ROC curve, 0.66) correctly classified 66% of patients. CONCLUSIONS: Findings from this study highlight several factors that may be targeted in future intervention studies to reduce the development of PPP. TRIAL REGISTRY NUMBER: ACTRN12612001089820.


Assuntos
Artroplastia do Joelho/efeitos adversos , Dor Pós-Operatória/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Ansiedade/psicologia , Catecol O-Metiltransferase/sangue , Dor Crônica , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/epidemiologia , Neuralgia/etiologia , Medição da Dor , Dor Pós-Operatória/psicologia , Dor Pós-Operatória/terapia , Prevalência , Estudos Prospectivos , Receptores Opioides mu/sangue , Fatores de Risco , Resultado do Tratamento
7.
Eur J Pain ; 22(7): 1312-1320, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29577496

RESUMO

BACKGROUND: While promising, there are mixed findings for the efficacy of transcranial direct current stimulation (tDCS) for the management of chronic pain. The goal of this study was to evaluate the effect of anodal tDCS on pain and function in people with upper limb neuropathic pain. METHODS: The study was a double-blinded, randomized controlled trial. Thirty participants were randomly allocated into active and sham tDCS groups. Baseline assessments of pain and function, as well as quantitative sensory testing (QST) to probe the function of the nociceptive system, were undertaken prior to participants receiving 5 days of active or sham anodal tDCS (1 mA) over the primary motor cortex. The outcome measures were re-assessed 1, 3 and 8 weeks following the intervention. RESULTS: Group analyses revealed no significant improvement in pain, function, or QST measures over time in either group. However, there were significantly more individual responders (≥30% change in pain) in the active compared to the sham tDCS group at the final follow-up. In the active group, there was a significant correlation indicating those with higher baseline pain had greater pain relief. CONCLUSIONS: On group analyses, no evidence was provided that 1 mA tDCS is beneficial for people with upper limb neuropathic pain, although it may provide lasting pain relief for some individuals. SIGNIFICANCE: At the group level, we found no evidence that 5 days of active 1 mA tDCS is effective for people with upper limb neuropathic pain. However, there were more individual responders in the active tDCS group compared to sham, and those who responded early after treatment experienced sustained pain relief.


Assuntos
Dor Crônica/terapia , Neuralgia/terapia , Estimulação Transcraniana por Corrente Contínua , Adulto , Idoso , Dor Crônica/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Neuralgia/fisiopatologia , Manejo da Dor , Extremidade Superior/fisiopatologia
8.
Clin Exp Immunol ; 188(1): 63-78, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27880975

RESUMO

Systemic lupus erythematosus (SLE) is a common autoimmune disorder with a complex and poorly understood immunopathogenesis. However, a pathogenic role for the T helper type 17 (Th17) axis was demonstrated by many studies, while regulatory T cells (Tregs ) were shown to mediate protection. Recently, we and others characterized a novel and independent T cell population expressing both the Treg characteristic transcription factor forkhead box protein 3 (FoxP3) and the Th17-defining retinoic acid receptor-related orphan nuclear receptor γt (RORγt). Studies in a model of acute glomerulonephritis unveiled potent regulatory, but also proinflammatory, functions of RORγt+ FoxP3+ Tregs . This bi-functional nature prompted us to suggest the name 'biTregs '. Importantly, the pathogenic biTreg effects were dependent upon expression of RORγt. We thus aimed to evaluate the contribution of RORγt+ FoxP3+ biTregs to pristane-induced SLE and explored the therapeutic potential of interference with RORγt activation. Our analyses revealed expansion of IL-17 producing biTregs in a distinctive time-course and organ-specific pattern, coincident with the development of autoimmunity and tissue injury. Importantly, specific ablation of RORγt activation in endogenous biTregs resulted in significant amelioration of pristane-induced pulmonary vasculitis and lupus nephritis. As potential mechanisms underlying the observed protection, we found that secretion of IL-17 by biTregs was abrogated completely in FoxP3Cre  × RORCfl/fl mice. Furthermore, Tregs showed a more activated phenotype after cell-specific inactivation of RORγt signalling. Finally, and remarkably, biTregs were found to potently suppress anti-inflammatory Th2 immunity in a RORγt-dependent manner. Our study thus identifies biTregs as novel players in SLE and advocates RORγt-directed interventions as promising therapeutic strategies.


Assuntos
Expressão Gênica , Interleucina-17/metabolismo , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Animais , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Imunidade Humoral , Imunomodulação , Imunofenotipagem , Pulmão/metabolismo , Pulmão/patologia , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/etiologia , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Contagem de Linfócitos , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Fenótipo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Células Th2/imunologia , Células Th2/metabolismo
9.
Anaesth Intensive Care ; 44(6): 742-744, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27832562

RESUMO

Tramadol is used in children aged <12 years for analgesia, particularly for those at risk of obstructive sleep apnoea undergoing adenotonsillectomy. The Australian Therapeutic Goods Administration have strongly recommended that oral tramadol drops (100 mg/ml) not be used in children <12 years because of the risk of inadvertent overdose. The total mass of drug in a 10 ml bottle is 1000 mg. The only alternative preparation available is a 50 mg capsule that requires dispersion of a capsule's contents should smaller doses be required. The accuracy of this preparation has not been assessed. Twenty surgical ward nurses were asked to prepare a 15 mg dose of tramadol from a 50 mg capsule. The dose was within ±5% of 15 mg in 13 cases (65%) and within ±10% in 19 cases (95%) (range 13.9-17.1 mg). Despite the dose variability of this method of preparing tramadol, we consider it sufficiently accurate for clinical use. We also consider it safe, as even at the highest dose prepared, the variability would be unlikely to contribute to clinically significant side-effects or toxicity. Moreover, the maximal dose that could be administered is limited to the size of the capsule (50 mg).


Assuntos
Analgésicos Opioides/administração & dosagem , Tramadol/administração & dosagem , Administração Oral , Cápsulas , Criança , Pré-Escolar , Humanos , Lactente
11.
Br J Anaesth ; 114(4): 551-61, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25542191

RESUMO

BACKGROUND: Several studies have identified clinical, psychosocial, patient characteristic, and perioperative variables that are associated with persistent postsurgical pain; however, the relative effect of these variables has yet to be quantified. The aim of the study was to provide a systematic review and meta-analysis of predictor variables associated with persistent pain after total knee arthroplasty (TKA). METHODS: Included studies were required to measure predictor variables prior to or at the time of surgery, include a pain outcome measure at least 3 months post-TKA, and include a statistical analysis of the effect of the predictor variable(s) on the outcome measure. Counts were undertaken of the number of times each predictor was analysed and the number of times it was found to have a significant relationship with persistent pain. Separate meta-analyses were performed to determine the effect size of each predictor on persistent pain. Outcomes from studies implementing uni- and multivariable statistical models were analysed separately. RESULTS: Thirty-two studies involving almost 30 000 patients were included in the review. Preoperative pain was the predictor that most commonly demonstrated a significant relationship with persistent pain across uni- and multivariable analyses. In the meta-analyses of data from univariate models, the largest effect sizes were found for: other pain sites, catastrophizing, and depression. For data from multivariate models, significant effects were evident for: catastrophizing, preoperative pain, mental health, and comorbidities. CONCLUSIONS: Catastrophizing, mental health, preoperative knee pain, and pain at other sites are the strongest independent predictors of persistent pain after TKA.


Assuntos
Artroplastia do Joelho/efeitos adversos , Dor Pós-Operatória/etiologia , Viés , Feminino , Humanos , Masculino
12.
Br J Anaesth ; 112(4): 675-80, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24322572

RESUMO

BACKGROUND: Our hypothesis was that deep anaesthesia, as estimated by a low target bispectral index (BIS) of 30-40, would result in less postoperative pain than that achieved at a conventional depth of anaesthesia. METHODS: We undertook a randomized double-blind controlled study at two tertiary teaching hospitals in New Zealand (2010-1) recruiting 135 adult patients ASA I-II presenting for non-emergent surgery under general anaesthesia requiring tracheal intubation. Anaesthesia was maintained with desflurane and a multimodal analgesia regimen comprising fentanyl infusion, i.v. paracetamol, and parecoxib. Patients were randomly assigned to either a low BIS (30-40) group or a high BIS (45-60) group. Desflurane concentrations were titrated to achieve these targets. Postoperative pain was assessed by: the pain on awakening (0-10, verbal rating scale, VRS(awake)) in the post-anaesthetic care unit; pain on activity at 20-24 h after operation (VRS(d1A)); and the rate of morphine patient-controlled analgesia (PCA) usage over the first 24 h. RESULTS: There was no statistically significant difference between the two groups for any of the pain scores. The median [inter-quartile range (IQR)] VRS(awake) was 4.0 (0-8) for the low and 4.0 (0-8) for the high BIS groups (P=0.56). The median (IQR) VRS(d1A) was 3.0 (1-5) for the low and 3.0 (1.5-4.5) for the high BIS groups (P=0.83). The median PCA morphine consumption in the low BIS group was 0.61 mg h(-1) (0.04-1.5) vs 0.43 mg h(-1) (0-1.59) in the high BIS group (P=0.98). CONCLUSIONS: We conclude that there is no clinically useful analgesic effect of a deep anaesthesia regimen.


Assuntos
Anestesia Geral/métodos , Dor Pós-Operatória/prevenção & controle , Adolescente , Adulto , Idoso , Analgesia Controlada pelo Paciente/métodos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/sangue , Anestésicos Inalatórios/administração & dosagem , Desflurano , Método Duplo-Cego , Esquema de Medicação , Eletroencefalografia/métodos , Feminino , Fentanila/administração & dosagem , Fentanila/sangue , Humanos , Isoflurano/administração & dosagem , Isoflurano/análogos & derivados , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Morfina/administração & dosagem , Medição da Dor/métodos , Adulto Jovem
13.
J Vasc Res ; 50(4): 324-31, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23860328

RESUMO

We describe a method for coculture of macro- or microvascular human endothelial cells (ECs) and pericytes (PCs) within a 3-dimensional (3-D) protein matrix resulting in lumenized EC cords invested by PCs. To prevent apoptotic cell death of ECs in 3-D culture, human umbilical vein or dermal microvascular ECs were transduced to express the antiapoptotic protein Bcl-2. To prevent PC-mediated gel contraction, the collagen-fibronectin gel was polymerized within a polyglycolic acid nonwoven matrix. Over the first 24-48 h, EC-only gels spontaneously formed cords that developed lumens via vacuolization; such vascular networks were maintained for up to 7 days. In EC-PC cocultures, PCs were recruited to the EC networks. PC investment of EC cords both limited the lumen diameter and increased the degree of vascular network arborization. Peg and socket junctions formed between ECs and PCs in this system, but dye transfer, indicative of gap junction formation, was not observed. This simple system can be used to analyze bidirectional signals between ECs and PCs in a 3-D geometry.


Assuntos
Comunicação Celular , Células Endoteliais/fisiologia , Células Endoteliais da Veia Umbilical Humana/fisiologia , Microvasos/fisiologia , Neovascularização Fisiológica , Pericitos/fisiologia , Apoptose , Movimento Celular , Células Cultivadas , Técnicas de Cocultura , Colágeno/metabolismo , Células Endoteliais/metabolismo , Fibronectinas/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Junções Intercelulares/fisiologia , Microvasos/metabolismo , Pericitos/metabolismo , Ácido Poliglicólico/química , Polimerização , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fatores de Tempo , Transdução Genética , Transfecção
14.
Eur J Surg Oncol ; 39(8): 850-7, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23726257

RESUMO

BACKGROUND AND AIMS: The aim was to externally validate the capability of a simplified Barcelona Clinic Liver Cancer (s-BCLC) staging system in allocating patients to hepatic resection (HR) and the effect on survival: S-BCLC was defined by only 2 groups: AA included BCLC A1 + A2 classes with alpha-fetoprotein (AFP) ≤ 20 ng/ml and AB included A1 + A2 with AFP > 20 ng/ml plus A3 + A4 subgroups. METHODS: This study compared a training group (TG) with hepatocellular carcinoma (HCC) submitted to hepatic resection (HR) in Milan with another group of patients, the validation group (VG) in Creteil. All patients underwent ultrasound-guided anatomical resection (<3 segments). RESULTS: Overall survival got worse from A1 to A4 (p = 0.0271) in TG (n = 132), as well as in VG (n = 100) (p = 0.0044) with a more important overlapping of each curves. According s-BCLC classification, the survival curves of TG (p = 0.0001) and VG (p = 0.0250) showed a definitive separation in two different staging groups. The s-BCLC provided the best predictive accuracy and it also presented the highest separability index and C-statistics in both TG and VG. On the other hand, in the evaluation of discriminatory ability for death, measured by ROC curve areas, the s-BCLC system gave better results than the others. CONCLUSION: This experience stressed the high value of BCLC system in staging of HCC, but the s-BCLC system seems to be more useful for therapeutic decision making.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Análise de Variância , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/cirurgia , Bases de Dados Factuais , Intervalo Livre de Doença , Detecção Precoce de Câncer , Feminino , Seguimentos , Hepatectomia/métodos , Humanos , Itália , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Curva ROC , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida
15.
Eur J Surg Oncol ; 36(10): 997-1003, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20674253

RESUMO

AIMS: The standard of care for diffuse malignant peritoneal mesothelioma involves operative cytoreduction and intraperitoneal chemotherapy. Most centers favor aggressive operative cytoreduction, accepting high morbidity and mortality. In our trials, patients underwent less extensive cytoreduction followed by prolonged intraperitoneal chemotherapy. Patients underwent a second cytoreduction with heated intraperitoneal chemotherapy. We hypothesized this would result in lower operative morbidity and mortality with similar survival. METHODS: Hospital records, discharge summaries, microbiology, radiography, and office records were retrospectively reviewed to supplement a prospective database. 30-day morbidity and mortality were categorized, and classified according to the Clavien methodology. RESULTS: 47 first and 39 second operations were performed with 13% and 26% morbidity, respectively. Mortality was 2%. Infections comprised 59% of the morbidity. Inclusive of both operations, formal peritonectomy was performed in 16% of patients, resection of isolated lesions in less than half, and only 19% had a visceral organs other than the spleen resected. At the completion of the protocol, only 3% of patients had visible intraperitoneal disease. The mean total length of stay for both operations combined was 16 ± 23 days. Overall median survival was 54.9 months, and median survival for the epithelioid subtype was 70.2 months. CONCLUSIONS: A two-stage cytoreduction with intraperitoneal chemotherapy offers median survival comparable to one-stage protocols, with relatively low morbidity, mortality, visceral resections and length of stay despite two operations. This series supports that our protocol is a feasible and safe approach.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Laparotomia/métodos , Mesotelioma/mortalidade , Mesotelioma/terapia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/terapia , Centros Médicos Acadêmicos , Adulto , Biópsia por Agulha , Causas de Morte , Terapia Combinada , Bases de Dados Factuais , Feminino , Humanos , Imuno-Histoquímica , Injeções Intraperitoneais , Estimativa de Kaplan-Meier , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Cidade de Nova Iorque , Neoplasias Peritoneais/patologia , Prognóstico , Estudos Prospectivos , Reoperação/métodos , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida , Resultado do Tratamento
16.
J Inherit Metab Dis ; 31(2): 281-8, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18415697

RESUMO

Apolipoprotein A-V (apoA-V) was discovered in 2001 both by comparative sequencing and as a liver regeneration protein. The gene is a located at the APOA1/C3/A4/A5 gene cluster on chromosome 11q23, a locus well known for playing a major role in regulating plasma cholesterol and triglyceride (TG) levels. ApoA-V is produced in the liver and has very low plasma concentrations (0.1-0.4 mug/ml). Mice lacking apoA-V have 4-fold increased TG levels, whereas apoA-V overexpression leads to 40% plasma TG reduction. Based on metabolic studies in vivo, apoA-V enhances the catabolism of TG rich lipoproteins rather than affecting their intestinal or hepatic production. By activating proteoglycans-bound lipoprotein lipase (LPL), apoA-V can accelerate TG hydrolysis from VLDL and chylomicrons independent from other apoproteins. Several variants at the APOA5 gene locus have been detected in humans. Some single nucleotide polymorphisms (SNPs) are associated with significantly higher plasma TG levels in patients (e.g., -1131T > C, S19W, G185C). In addition, these SNPs may affect fibrate response and obesity. However, data for a possible association of APOA5 variants with coronary heart disease are not consistent. Severe structural mutations (Q139X, Q148X, IVS3 + 3G > C) predispose to familial hypertriglyceridaemia and late-onset chylomicronaemia. Thus, despite its low plasma concentration, apoA-V is a major regulator of plasma TG metabolism in humans. However, the precise mechanism of its function is not yet clear.


Assuntos
Apolipoproteínas A/metabolismo , Erros Inatos do Metabolismo Lipídico/metabolismo , Fígado/metabolismo , Triglicerídeos/metabolismo , Animais , Apolipoproteína A-V , Apolipoproteínas/genética , Apolipoproteínas/metabolismo , Apolipoproteínas A/sangue , Apolipoproteínas A/genética , Modelos Animais de Doenças , Predisposição Genética para Doença , Humanos , Erros Inatos do Metabolismo Lipídico/sangue , Erros Inatos do Metabolismo Lipídico/genética , Lipólise , Camundongos , Mutação , Fenótipo
17.
Anaesth Intensive Care ; 36(2): 214-21, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18361013

RESUMO

Anaesthetic technicians play a key role in the operating room, yet little is known about their levels of job satisfaction or workplace stress. A blinded, confidential single mail-out survey was posted to anaesthetic technicians in New Zealand. The survey consisted of demographic information, a job satisfaction survey, the Maslach Burnout Inventory and the Short Form 12. At total of 154 forms were returned (51% response rate). Respondents worked predominantly in public hospitals and many had duties outside the operating room. Job satisfaction was related to teamwork, practical nature of work and patient contact, while dissatisfaction was related to lack of respect from nurses and limited career pathway. High to moderate levels of emotional exhaustion (48%), depersonalisation (39%) and low levels of personal accomplishment (58%) were indicators of burnout. The Short Form 12 revealed high levels of physical impairment in 24% and emotional impairment in 35% of respondents. These data suggest that work is needed to evaluate anaesthetic assistants' job structure and actively manage their important physical and emotional sequelae.


Assuntos
Anestesiologia , Esgotamento Profissional/epidemiologia , Satisfação no Emprego , Auxiliares de Cirurgia/psicologia , Estresse Psicológico/epidemiologia , Adulto , Esgotamento Profissional/psicologia , Mobilidade Ocupacional , Feminino , Humanos , Descrição de Cargo , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Enfermeiros Anestesistas , Auxiliares de Cirurgia/educação , Auxiliares de Cirurgia/estatística & dados numéricos , Estresse Psicológico/psicologia , Inquéritos e Questionários , Recursos Humanos
18.
Anaesthesia ; 62(9): 907-12, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17697217

RESUMO

The interaction of many poorly defined, physiological, pharmacological, and pathological factors make titration of general anaesthesia in the elderly difficult. There may be a potential clinical benefit using the processed electroencephalogram (EEG) to monitor hypnotic level in this population. We prospectively studied 16 patients aged over 65 years having hip fractures repaired under general anaesthesia by experienced anaesthetists blinded to Bispectral Index (BIS(XP)) and Entropy values. Pre-induction EEG indices did not correlate with age or mini-mental state examination (MMSE). During maintenance of anaesthesia, BIS(XP) and Response Entropy (RE) values were within the recommended range of 40-60, 45% and 32% of the total time, respectively. BIS(XP) and Response Entropy (RE) values were above 60 for 11% and 13% of the total time, respectively, and below 40 for 44% and 55% of the total time, respectively. BIS(XP) correlated well with RE in 12 patients, but in the other four patients there was a difference of more than 20 points between BIS(XP) and RE.


Assuntos
Eletroencefalografia/métodos , Entropia , Monitorização Intraoperatória/métodos , Fatores Etários , Idoso , Anestesia Geral , Métodos Epidemiológicos , Feminino , Fraturas do Quadril/cirurgia , Humanos , Masculino , Psicometria , Processamento de Sinais Assistido por Computador
20.
Qual Saf Health Care ; 14(3): e1, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15933282

RESUMO

BACKGROUND: All anaesthetists have to handle life threatening crises with little or no warning. However, some cognitive strategies and work practices that are appropriate for speed and efficiency under normal circumstances may become maladaptive in a crisis. It was judged in a previous study that the use of a structured "core" algorithm (based on the mnemonic COVER ABCD-A SWIFT CHECK) would diagnose and correct the problem in 60% of cases and provide a functional diagnosis in virtually all of the remaining 40%. It was recommended that specific sub-algorithms be developed for managing the problems underlying the remaining 40% of crises and assembled in an easy-to-use manual. Sub-algorithms were therefore developed for these problems so that they could be checked for applicability and validity against the first 4000 anaesthesia incidents reported to the Australian Incident Monitoring Study (AIMS). METHODS: The need for 24 specific sub-algorithms was identified. Teams of practising anaesthetists were assembled and sets of incidents relevant to each sub-algorithm were identified from the first 4000 reported to AIMS. Based largely on successful strategies identified in these reports, a set of 24 specific sub-algorithms was developed for trial against the 4000 AIMS reports and assembled into an easy-to-use manual. A process was developed for applying each component of the core algorithm COVER at one of four levels (scan-check-alert/ready-emergency) according to the degree of perceived urgency, and incorporated into the manual. The manual was disseminated at a World Congress and feedback was obtained. RESULTS: Each of the 24 specific crisis management sub-algorithms was tested against the relevant incidents among the first 4000 reported to AIMS and compared with the actual management by the anaesthetist at the time. It was judged that, if the core algorithm had been correctly applied, the appropriate sub-algorithm would have been resolved better and/or faster in one in eight of all incidents, and would have been unlikely to have caused harm to any patient. The descriptions of the validation of each of the 24 sub-algorithms constitute the remaining 24 papers in this set. Feedback from five meetings each attended by 60-100 anaesthetists was then collated and is included. CONCLUSION: The 24 sub-algorithms developed form the basis for developing a rational evidence-based approach to crisis management during anaesthesia. The COVER component has been found to be satisfactory in real life resuscitation situations and the sub-algorithms have been used successfully for several years. It would now be desirable for carefully designed simulator based studies, using naive trainees at the start of their training, to systematically examine the merits and demerits of various aspects of the sub-algorithms. It would seem prudent that these sub-algorithms be regarded, for the moment, as decision aids to support and back up clinicians' natural responses to a crisis when all is not progressing as expected.


Assuntos
Anestesiologia/normas , Emergências , Complicações Intraoperatórias/terapia , Manuais como Assunto , Guias de Prática Clínica como Assunto , Ressuscitação/normas , Algoritmos , Austrália , Consenso , Humanos , Monitorização Intraoperatória , Gestão de Riscos , Análise e Desempenho de Tarefas
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