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1.
Infect Control Hosp Epidemiol ; : 1-8, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32183916

RESUMO

OBJECTIVE: Antimicrobial use in the surgical setting is common and frequently inappropriate. Understanding the behavioral context of antimicrobial use is a critical step to developing stewardship programs. DESIGN: In this study, we employed qualitative methodologies to describe the phenomenon of antimicrobial use in 2 surgical units: orthopedic surgery and cardiothoracic surgery. SETTING: This study was conducted at a public, quaternary, university-affiliated hospital. PARTICIPANTS: Healthcare professionals from the 2 surgical unit teams participated in the study. METHODS: We used focused ethnographic and face-to-face semi-structured interviews to observe antimicrobial decision-making behaviors across the patient's journey from the preadmission clinic to the operating room to the postoperative ward. RESULTS: We identified 4 key themes influencing decision making in the surgical setting. Compartmentalized communication (theme 1) was observed with demarcated roles and defined pathways for communication (theme 2). Antimicrobial decisions in the operating room were driven by the most senior members of the team. These decisions, however, were delegated to more junior members of staff in the ward and clinic environment (theme 3). Throughout the patient's journey, communication with the patient about antimicrobial use was limited (theme 4). CONCLUSIONS: Approaches to decision making in surgery are highly structured. Although this structure appears to facilitate smooth flow of responsibility, more junior members of the staff may be disempowered. In addition, opportunities for shared decision making with patients were limited. Antimicrobial stewardship programs need to recognize the hierarchal structure as well as opportunities to engage the patient in shared decision making.

2.
Anesthesiology ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32167984

RESUMO

BACKGROUND: The World Health Organization Disability Assessment Schedule 2.0 has been used to measure postoperative disability in several clinical trials and cohort studies. It is uncertain what the minimal clinically important difference or patient-acceptable symptom state scores are for this scale in patients recovering from surgery. METHODS: The authors analyzed prospectively collected data from three studies that measured disability 3 and 6 months after surgery. Three distribution-based methods (0.3 multiplied by SD, standard error of the measurement, and 5% range) and two anchor-based methods (anchored to two patient-rated health status questions and separately to unplanned hospital readmission) were averaged to estimate the minimal clinically important difference for the World Health Organization Disability Assessment Schedule 2.0 score converted to a percentage scale. Scores consistent with a patient-acceptable symptom state and clinically significant disability were determined by an anchored 75th centile method. RESULTS: Data from 4,361 patients were analyzed. The average minimal clinically important difference estimate for the World Health Organization Disability Assessment Schedule 2.0 was 5%, with similar estimates in patients with or without preoperative disability. The patient-acceptable symptom state score was 16%, and the score consistent with at least moderate clinically significant disability was 35%. Using these estimates, between baseline and 6 months after surgery, 21% of patients had a significant increase in disability, and 73% achieved a patient-acceptable symptom state. CONCLUSIONS: A change in World Health Organization Disability Assessment Schedule 2.0 score of 5% or more after surgery is consistent with a clinically important change in disability. Patients with a score less than 16% after surgery have an acceptable symptom state and can be considered as disability-free, whereas patients with a score of 35% or more can be considered as having at least moderate clinically significant disability. : WHAT WE ALREADY KNOW ABOUT THIS TOPIC: The World Health Organization Disability Assessment Schedule 2.0 is finding widespread adoption as a patient-centered outcome measure in clinical studiesThe minimal clinically important difference and patient-acceptable disability score for patients undergoing surgery remain poorly understood WHAT THIS MANUSCRIPT TELLS US THAT IS NEW: Using previously collected data from three studies across 4,361 patients, a 5% change in score after surgery is clinically importantPatients with a scaled disability score less than 16% after surgery have an acceptable symptom state and can be considered as disability-free.

3.
Br J Anaesth ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32171547

RESUMO

BACKGROUND: The perioperative use of vasoactive drugs is ubiquitous in clinical anaesthesia; yet, the drugs, doses, and haemodynamic targets used are highly variable. Our objectives were to determine whether the perioperative administration of vasoactive drugs reduces mortality, morbidity, and length of stay in adult patients (aged 16 yr or older) undergoing major abdominal surgery. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for peer-reviewed RCTs with no language or date restrictions. Studies that assessed the intraoperative use of vasoactive drugs were included. Title, abstract, and full-text screening was performed. Risk of bias for each outcome measure was conducted. We calculated the risk ratio (RR) using the Mantel-Haenszel random-effects model with corresponding 95% confidence interval (CI) for dichotomous outcomes, and mean difference using the inverse variance random-effects model with corresponding 95% CI for continuous outcomes. RESULTS: Twenty-six studies (5561 participants) were included. There was no difference in mortality at the longest follow-up with an RR of 0.84 (95% CI: 0.63-1.12; P=0.23). The intervention significantly reduced the number of patients with one or more postoperative complications; RR: 0.76 (95% CI: 0.66-0.88; P=0.0002). Hospital length of stay was reduced by 0.91 days in the intervention group. CONCLUSIONS: This review is limited by the quality and sample size of individual studies, and the heterogeneity of the settings, interventions, and outcome measures. Perioperative administration of vasoactive drugs may reduce postoperative complications and hospital length of stay in adult patients having major abdominal surgery.

4.
Br J Anaesth ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32081371
6.
Anesthesiology ; 132(1): 69-81, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31809323

RESUMO

Large randomized trials provide the highest level of clinical evidence. However, enrolling large numbers of randomized patients across numerous study sites is expensive and often takes years. There will never be enough conventional clinical trials to address the important questions in medicine. Efficient alternatives to conventional randomized trials that preserve protections against bias and confounding are thus of considerable interest. A common feature of novel trial designs is that they are pragmatic and facilitate enrollment of large numbers of patients at modest cost. This article presents trial designs including cluster designs, real-time automated enrollment, and practitioner-preference approaches. Then various adaptive designs that improve trial efficiency are presented. And finally, the article discusses the advantages of embedding randomized trials within registries.

7.
Br J Anaesth ; 124(2): 136-145, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31866001

RESUMO

BACKGROUND: The aim of this study was to simulate and compare the healthcare and economic outcomes associated with routine use of intraoperative transoesophageal echocardiography (TOE) in patients undergoing cardiac surgery with those associated with a scenario where TOE is not routinely used. METHODS: The impact of TOE on surgical decision-making was estimated through a systematic literature review. Individual short-term morbidity and mortality estimates were generated by application of the Society of Thoracic Surgeons risk calculator. Long-term event rates, unit costs, and utility weights were sourced from published literature and expert opinion. A discrete-event simulation model was then constructed to simulate both the in-hospital and post-discharge outcomes for patients undergoing cardiac surgery. Robustness of the base case results was examined through deterministic and probabilistic sensitivity analyses. An incremental cost-effectiveness ratio of €30 000 per quality-adjusted life-year gained was assumed to represent acceptable cost-effectiveness. RESULTS: Routine use of intraoperative TOE was associated with lower costs and higher benefits per patient, which indicates that use of TOE is a dominant strategy. The intervention resulted in the avoidance of 299 cardiac complications, 20 strokes, and 11 all-cause deaths per 10 000 patients. Routine intraoperative TOE was associated with an increased occurrence of bleeding owing to more valvular surgery and subsequent long-term anticoagulation. CONCLUSIONS: Routine intraoperative TOE is a cost-effective procedure for patients undergoing cardiac surgery, leading to lower overall costs. It was associated with a decrease in long-term complications including stroke, cardiac complications, and death, although there was a slight increase in extracranial bleeding events.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Análise Custo-Benefício/economia , Ecocardiografia Transesofagiana/economia , Cuidados Intraoperatórios/economia , Cuidados Intraoperatórios/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Análise Custo-Benefício/estatística & dados numéricos , Ecocardiografia Transesofagiana/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Anesthesiology ; 132(1): 44-54, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31789635

RESUMO

There is intense debate around the use of altered and waived consent for pragmatic trials. Those in favor argue that traditional consent compromises the internal and external validity of these trials. Those against, warn that the resultant loss of autonomy compromises respect for persons and could undermine trust in the research enterprise.This article examines whether international ethical guidelines and the policy frameworks in three countries-the United States, England, and Australia-permit altered and waived consent for minimal-risk pragmatic trials conducted outside the emergency setting. Provisions for both are clearly articulated in U.S. regulations, but many countries do not have equivalent frameworks. Investigators should not assume that all consent models permitted in the United States are legal in their jurisdictions, even if they are deemed ethically defensible.The authors summarize ethical and regulatory considerations and present a framework for investigators contemplating trials with altered or waived consent.

9.
Br J Anaesth ; 124(3): 261-270, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31864719

RESUMO

BACKGROUND: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications. METHODS: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes. RESULTS: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05). CONCLUSIONS: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability.


Assuntos
Tolerância ao Exercício/fisiologia , Indicadores Básicos de Saúde , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Biomarcadores/sangue , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Complicações Pós-Operatórias/mortalidade , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Autorrelato , Inquéritos e Questionários
10.
JAMA Netw Open ; 2(11): e1916345, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774526

RESUMO

Importance: Body mass index (BMI) has been the most common obesity measure to assess perioperative risk; however, cardiometabolic risk is associated with the burden of visceral fat. Definitive evidence on the association of visceral fat measures, such as waist circumference and waist-to-hip ratio (WHR), with postoperative complications is lacking. Objective: To compare the value of waist circumference with the value WHR and BMI in predicting adverse outcomes, including major septic complications and persistent disability, following major abdominal surgery. Design, Setting, and Participants: This planned secondary analysis of the Restrictive vs Liberal Fluid Therapy for Major Abdominal Surgery (RELIEF) randomized clinical trial took place at 47 centers in 7 countries between October 2013 and September 2016, with 90-day follow-up. A total of 2954 adult RELIEF participants were coenrolled in this secondary analysis. Data analysis took place from December 2018 to September 2019. Exposures: Waist circumference, WHR, and BMI measurements. Main Outcomes and Measures: The primary outcomes were 30-day major septic complications and 90-day persistent disability or death. Results: Of 2954 eligible participants, 2755 were included (mean [SD] age, 65.9 [12.9] years; 1426 [51.8%] men) in the final analysis. A total of 564 participants (20.6%) experienced at least 1 major septic complication within 30 days after surgery (sepsis, 265 [9.7%]; surgical site infection, 409 [14.9%]; anastomotic leak, 78 [2.8%]; pneumonia, 104 [3.8%]). Waist circumference had a statistically significantly larger odds ratio (OR) and discrimination indices as well as a smaller prediction error than WHR or BMI for 30-day major septic complications or death (waist circumference: OR, 1.44; 95% CI, 1.28-1.62; P < .001; area under the receiver operating characteristic curve, 0.641; net reclassification index, 0.266; integrated discrimination improvement [score × 104], 152.98; Brier score, 0.162; WHR: OR, 1.15; 95% CI, 1.03-1.28; P = .01; area under the receiver operating characteristic curve, 0.621; net classification index, 0.199; integrated discrimination improvement [score × 104], 28.47; Brier score, 0.164; BMI: OR, 1.33; 95% CI, 1.17-1.50; P < .001; area under the receiver operating characteristic curve, 0.629; net reclassification index, 0.205; integrated discrimination improvement [score × 104], 85.61; Brier score, 0.163) but not for any other outcomes. Conclusions and Relevance: In this secondary analysis of the RELIEF randomized clinical trial, waist circumference was observed to be superior to other adiposity indices in predicting 30-day major septic complications alone or in conjunction with death following elective major abdominal surgery. Findings suggest that waist circumference is a useful adiposity measure that should be incorporated in preoperative risk assessment for such complications. Trial Registration: ClinicalTrials.gov identifier: NCT01424150.

11.
Clin Cancer Res ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754048

RESUMO

PURPOSE: The majority of deaths from breast cancer occur following the development of metastatic disease, a process inhibited by ß-blockers in preclinical studies. This phase II randomized controlled trial evaluated the effect of preoperative ß-blockade with propranolol on biomarkers of metastatic potential and the immune cell profile within the primary tumor of patients with breast cancer. PATIENTS AND METHODS: In this triple-blind placebo-controlled clinical trial, 60 patients were randomly assigned to receive an escalating dose of oral propranolol (n = 30; 80-160 mg daily) or placebo (n = 30) for 7 days prior to surgery. The primary endpoint investigated the effect of propranolol on prometastatic and proinflammatory gene expression within the primary tumor. RESULTS: Propranolol downregulated primary tumor expression of mesenchymal genes (P = 0.002) without affecting epithelial gene expression (P = 0.21). Bioinformatic analyses implicated downregulation of Snail/Slug (P = 0.03), NF-κB/Rel (P < 0.01), and AP-1 (P < 0.01) transcription factors in structuring the observed transcriptome alterations, and identified changes in intratumoral neutrophil, natural killer cell, and dendritic cell recruitment (all P < 0.01). Patients with clinical evidence of drug response (lowered heart rate and blood pressure) demonstrated elevated tumor infiltration of CD68+ macrophages and CD8+ T cells. CONCLUSIONS: One week of ß-blockade with propranolol reduced intratumoral mesenchymal polarization and promoted immune cell infiltration in early-stage surgically-resectable breast cancer. These results show that ß-blockade reduces biomarkers associated with metastatic potential, and support the need for larger phase III clinical trials powered to detect the impact of ß-blockade on cancer recurrence and survival.

12.
Anesthesiology ; 131(6): 1368-1369, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31644436
13.
Lancet ; 394(10212): 1907-1914, 2019 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645286

RESUMO

BACKGROUND: An association between increasing anaesthetic depth and decreased postoperative survival has been shown in observational studies; however, evidence from randomised controlled trials is lacking. Our aim was to compare all-cause 1-year mortality in older patients having major surgery and randomly assigned to light or deep general anaesthesia. METHODS: In an international trial, we recruited patients from 73 centres in seven countries who were aged 60 years and older, with significant comorbidity, having surgery with expected duration of more than 2 h, and an anticipated hospital stay of at least 2 days. We randomly assigned patients who had increased risk of complications after major surgery to receive light general anaesthesia (bispectral index [BIS] target 50) or deep general anaesthesia (BIS target 35). Anaesthetists also nominated an appropriate range for mean arterial pressure for each patient during surgery. Patients were randomly assigned in permuted blocks by region immediately before surgery, with the patient and assessors masked to group allocation. The primary outcome was 1-year all-cause mortality. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000632897, and is closed to accrual. FINDINGS: Patients were enrolled between Dec 19, 2012, and Dec 12, 2017. Of the 18 026 patients screened as eligible, 6644 were enrolled, randomly assigned to treatment or control, and formed the intention-to-treat population (3316 in the BIS 50 group and 3328 in the BIS 35 group). The median BIS was 47·2 (IQR 43·7 to 50·5) in the BIS 50 group and 38·8 (36·3 to 42·4) in the BIS 35 group. Mean arterial pressure was 3·5 mm Hg (4%) higher (median 84·5 [IQR 78·0 to 91·3] and 81·0 [75·4 to 87·6], respectively) and volatile anaesthetic use was 0·26 minimum alveolar concentration (30%) lower (0·62 [0·52 to 0·73] and 0·88 [0·74 to 1·04], respectively) in the BIS 50 than the BIS 35 group. 1-year mortality was 6·5% (212 patients) in the BIS 50 group and 7·2% (238 patients) in the BIS 35 group (hazard ratio 0·88, 95% CI 0·73 to 1·07, absolute risk reduction 0·8%, 95% CI -0·5 to 2·0). Grade 3 adverse events occurred in 954 (29%) patients in the BIS 50 group and 909 (27%) patients in the BIS 35 group; and grade 4 adverse events in 265 (8%) and 259 (8%) patients, respectively. The most commonly reported adverse events were infections, vascular disorders, cardiac disorders, and neoplasms. INTERPRETATION: Among patients at increased risk of complications after major surgery, light general anaesthesia was not associated with lower 1-year mortality than deep general anaesthesia. Our trial defines a broad range of anaesthetic depth over which anaesthesia may be safely delivered when titrating volatile anaesthetic concentrations using a processed electroencephalographic monitor. FUNDING: Health Research Council of New Zealand; National Health and Medical Research Council, Australia; Research Grant Council of Hong Kong; National Institute for Health and Research, UK; and National Institutes of Health, USA.


Assuntos
Anestesia Geral/efeitos adversos , Anestesia Geral/mortalidade , Anestésicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Idoso , Anestesia Geral/métodos , Anestésicos/farmacologia , Pressão Arterial , Monitores de Consciência , Feminino , Humanos , Masculino , Período Pós-Operatório
14.
BMJ Open ; 9(9): e030402, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31494615

RESUMO

INTRODUCTION: The intraoperative administration of dexamethasone for prophylaxis against postoperative nausea and vomiting is a common and recommended practice. The safety of the administration of this immunosuppressive agent at a time of significant immunological disruption has not been rigorously evaluated in terms of infective complications. METHODS/ANALYSIS: This is a pragmatic, multicentre, randomised, controlled, non-inferiority trial. A total of 8880 patients undergoing elective major surgery will be enrolled. Participants will be randomly allocated to receive either dexamethasone 8 mg or placebo intravenously following the induction of anaesthesia in a 1:1 ratio, stratified by centre and diabetes status. Patient enrolment into the trial is ongoing. The primary outcome is surgical site infection at 30 days following surgery, defined according to the Centre for Disease Control criteria. ETHICS/DISSEMINATION: The PADDI trial has been approved by the ethics committees of over 45 participating sites in Australia, New Zealand, Hong Kong, South Africa and the Netherlands. The trial has been endorsed by the Australia and New Zealand College of Anaesthetists Clinical Trials Network and the Australian Society for Infectious Diseases Clinical Research Network. Participant recruitment began in March 2016 and is expected to be complete in mid-2019. Publication of the results of the PADDI trial is anticipated to occur in early 2020. TRIAL REGISTRATION NUMBER: ACTRN12614001226695.

15.
EClinicalMedicine ; 11: 18-26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31317130

RESUMO

Background: Surgical audit, sometimes including public reporting, is an important foundation of high quality health care. We aimed to assess the validity of a novel outcome metric, days at home up to 30 days after surgery, as a surgical outcome measure in clinical trials and quality assurance. Methods: This was a multicentre, registry-based cohort study. We used prospectively collected hospital and national healthcare registry data obtained from patients aged 18 years or older undergoing a broad range of surgeries in Sweden over a 10-year period. The association between days at home up to 30 days after surgery and patient (older age, poorer physical status, comorbidity) and surgical (elective or non-elective, complexity, duration) risk factors, process of care outcomes (re-admissions, discharge destination), clinical outcomes (major complications, 30-day mortality) and death up to 1 year after surgery were measured. Findings: From January, 2005, to December, 2014, we obtained demographic and perioperative data on 636,885 patients from 21 Swedish hospitals. Mortality at 30 days and one year was 1.8% and 7.3%, respectively. The median (IQR) days at home up to 30 days after surgery was 27 (23-29), being significantly lower among high-risk patients, those recovering from more complex surgical procedures, and suffering serious postoperative complications (all p < 0.0001). Patients with 8 days or less at home up to 30 days after surgery had a nearly 7-fold higher risk of death up to 1 year postoperatively when compared with those with 29 or 30 days at home (adjusted HR 6.78 [95% CI: 6.44-7.13]). Interpretation: Days at home up to 30 days after surgery is a valid, easy to measure patient-centred outcome metric. It is highly sensitive to changes in surgical risk and impact of complications, and has prognostic importance; it is therefore a valuable endpoint for perioperative clinical trials and quality assurance. Funding: Swedish National Research Council Medicine and Stockholm County Council ALF-project grant (LE), and the Australian National Health and Medical Research Council (PM).

17.
Pain Rep ; 4(2): e719, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31041421

RESUMO

Introduction: Seizure-related protein 6 (Sez6) contributes to chronic pain development as sez6 knockout mice show attenuated pain behaviours after peripheral nerve injury, compared with control mice. The type I transmembrane isoform of Sez6 is cleaved by the ß-amyloid precursor protein cleavage enzyme 1 (BACE1), resulting in Sez6 extracellular domain shedding from the neuron surface. Objectives: To determine whether this BACE1-shed form of Sez6 can be detected in the cerebrospinal fluid (CSF) and whether Sez6 levels in the CSF are altered in neuropathic pain or chronic inflammatory pain (IP). Methods: We analysed the CSF samples collected during surgery from patients with chronic neuropathic pain (n = 8) or IP (n = 33), comparing them to the CSF samples from patients with suspected subarachnoid haemorrhage that was subsequently excluded (nonsurgical group, n = 5). Western blots were used to determine the relative Sez6 levels in the CSF from the different patient and nonsurgical comparison groups. Results: The results show that BACE1-shed Sez6 can be readily detected in the CSF by Western blot and that the levels of Sez6 are significantly higher in the IP group than in the nonsurgical comparison group. Conclusion: The association between elevated Sez6 levels in the CSF and IP is further evidence for persistent alterations in central nervous system activity in chronic IP conditions.

18.
Blood Adv ; 3(10): 1598-1609, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31126915

RESUMO

Tranexamic acid (TXA) is an antifibrinolytic agent that blocks plasmin formation. Because plasmin is known to promote inflammatory and immunosuppressive responses, we explored the possibility that plasmin-mediated immunosuppression in patients undergoing cardiac surgery can be directly reversed by TXA and decrease postoperative infection rates. The modulatory effect of TXA on inflammatory cytokine levels and on innate immune cell activation were evaluated with multiplex enzyme-linked immunosorbent assay and flow cytometry, respectively. Postoperative infection rates were determined in patients undergoing cardiac surgery and randomized to TXA (ACTRN12605000557639; http://www.anzca.edu.au). We demonstrate that TXA-mediated plasmin blockade modulates the immune system and reduces surgery-induced immunosuppression in patients following cardiac surgery. TXA enhanced the expression of immune-activating markers while reducing the expression of immunosuppressive markers on multiple myeloid and lymphoid cell populations in peripheral blood. TXA administration significantly reduced postoperative infection rates, despite the fact that patients were being administered prophylactic antibiotics. This effect was independent of the effect of TXA at reducing blood loss. TXA was also shown to exert an immune-modulatory effect in healthy volunteers, further supporting the fibrin-independent effect of TXA on immune function and indicating that baseline plasmin levels contribute to the regulation of the immune system in the absence of any comorbidity or surgical trauma. Finally, the capacity of TXA to reduce infection rates, modulate the innate immune cell profile, and generate an antifibrinolytic effect overall was markedly reduced in patients with diabetes, demonstrating for the first time that the diabetic condition renders patients partially refractory to TXA.

19.
Br J Anaesth ; 123(2): 228-237, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31128879

RESUMO

BACKGROUND: Clinical indicators are powerful tools to quantify the safety and quality of patient care. Their validity is often unclear and definitions extremely heterogeneous. As part of the International Standardised Endpoints in Perioperative Medicine (StEP) initiative, this study aimed to derive a set of standardised and valid clinical outcome indicators for use in perioperative clinical trials. METHODS: We identified clinical indicators via a systematic review of the anaesthesia and perioperative medicine literature (PubMed/OVID, EMBASE, and Cochrane Library). We performed a three-stage Delphi consensus-gaining process that involved 54 clinician-researchers worldwide. Indicators were first shortlisted and the most suitable definitions for evaluation of quality and safety interventions determined. Indicators were then assessed for validity, reliability, feasibility, and clarity. RESULTS: We identified 167 clinical outcome indicators. Participation in the three Delphi rounds was 100% (n=13), 68% (n=54), and 85% (n= 6), respectively. A final list of eight outcome indicators was generated: surgical site infection at 30 days, stroke within 30 days of surgery, death within 30 days of coronary artery bypass grafting, death within 30 days of surgery, admission to the intensive care unit within 14 days of surgery, readmission to hospital within 30 days of surgery, and length of hospital stay (with or without in-hospital mortality). They were rated by the majority of experts as valid, reliable, easy to use, and clearly defined. CONCLUSIONS: These clinical indicators can be confidently used as endpoints in clinical trials measuring quality, safety, and improvement in perioperative care. REGISTRATION: PROSPERO 2016 CRD42016042102 (http://www.crd.york.ac.uk/PROSPERO/display_record.php? ID=CRD42016042102).


Assuntos
Consenso , Segurança do Paciente/normas , Assistência Perioperatória/normas , Qualidade da Assistência à Saúde/normas , Ensaios Clínicos como Assunto , Humanos , Padrões de Referência , Reprodutibilidade dos Testes
20.
Lancet ; 393(10180): 1537-1546, 2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-30983589

RESUMO

Over the past decade there has been an increasing reliance on strong opioids to treat acute and chronic pain, which has been associated with a rising epidemic of prescription opioid misuse, abuse, and overdose-related deaths. Deaths from prescription opioids have more than quadrupled in the USA since 1999, and this pattern is now occurring globally. Inappropriate opioid prescribing after surgery, particularly after discharge, is a major cause of this problem. Chronic postsurgical pain, occurring in approximately 10% of patients who have surgery, typically begins as acute postoperative pain that is difficult to control, but soon transitions into a persistent pain condition with neuropathic features that are unresponsive to opioids. Research into how and why this transition occurs has led to a stronger appreciation of opioid-induced hyperalgesia, use of more effective and safer opioid-sparing analgesic regimens, and non-pharmacological interventions for pain management. This Series provides an overview of the epidemiology and societal effect, basic science, and current recommendations for managing persistent postsurgical pain. We discuss the advances in the prevention of this transitional pain state, with the aim to promote safer analgesic regimens to better manage patients with acute and chronic pain.


Assuntos
Dor Aguda/terapia , Dor Crônica/terapia , Dor Pós-Operatória/terapia , Dor Aguda/diagnóstico , Dor Aguda/etiologia , Analgésicos Opioides/uso terapêutico , Dor Crônica/diagnóstico , Dor Crônica/etiologia , Humanos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia
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