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3.
Reg Anesth Pain Med ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31649029

RESUMO

BACKGROUND AND OBJECTIVES: The serratus plane block (SPB) is a novel chest wall interfascial plane block. Its analgesic efficacy compared with non-block care and paravertebral block (PVB) is unestablished. METHODS: We conducted a random-effects meta-analysis of randomized controlled trials (RCTs) recruiting adult surgical patients that compared a SPB to non-block care or PVB for postoperative analgesia. Visual analog scale pain scores were the primary outcome. Database sources were Medline, Embase, the Cochrane Library, and Google Scholar searched up to July 29, 2019 without language restriction. Risk of bias was assessed using Cochrane methodology. RESULTS: Nineteen RCTs that comprised 1260 patients were included. Six trials involved thoracic surgery patients and 13 studied breast surgery patients. SPB reduced pain scores 0 hour postoperatively (-1.62 cm; 99% CI -2.43 to -0.81; p<0.001; I2=92%), at 2-4 hours (-1.29 cm; 99% CI -2.08 to -0.49; p<0.001; I2=92%), at 6 hours (-1.69 cm; 99% CI -3.19 to -0.20; p=0.004; I2=99%), and up to 24 hours compared with non-block care. SPB also prolonged the time to first analgesic request (193.2 min; 95% CI 7.2 to 379.2 min; p=0.04; I2=99%), reduced 24-hour postoperative opioid consumption (-11.27 mg of IV morphine equivalent; -17.36 to -5.18 mg; p<0.001), and reduced postoperative nausea and vomiting (RR 0.51; 95% CI 0.38 to 0.68; p<0.001; I2=12%). In contrast, no meaningful differences were detected in any of the outcomes for the SPB versus PVB data. CONCLUSIONS: SPB reduced postoperative pain scores (Grading of Recommendations Assessment, Development, and Evaluation rating: low; due to heterogeneity and deficiencies in blinding) in breast and thoracic surgery patients compared with non-block care. Based on five trials only, SPB was not appreciably different from PVB.

4.
Cochrane Database Syst Rev ; 4: CD005351, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30950507

RESUMO

BACKGROUND: Non-invasive positive pressure ventilation (NPPV) has been used to treat respiratory distress due to acute cardiogenic pulmonary oedema (ACPE). We performed a systematic review and meta-analysis update on NPPV for adults presenting with ACPE. OBJECTIVES: To evaluate the safety and effectiveness of NPPV compared to standard medical care (SMC) for adults with ACPE. The primary outcome was hospital mortality. Important secondary outcomes were endotracheal intubation, treatment intolerance, hospital and intensive care unit length of stay, rates of acute myocardial infarction, and adverse event rates. SEARCH METHODS: We searched CENTRAL (CRS Web, 20 September 2018), MEDLINE (Ovid, 1946 to 19 September 2018), Embase (Ovid, 1974 to 19 September 2018), CINAHL Plus (EBSCO, 1937 to 19 September 2018), LILACS, WHO ICTRP, and clinicaltrials.gov. We also reviewed reference lists of included studies. We applied no language restrictions. SELECTION CRITERIA: We included blinded or unblinded randomised controlled trials in adults with ACPE. Participants had to be randomised to NPPV (continuous positive airway pressure (CPAP) or bilevel NPPV) plus standard medical care (SMC) compared with SMC alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected articles for inclusion. We extracted data with a standardised data collection form. We evaluated the risks of bias of each study using the Cochrane 'Risk of bias' tool. We assessed evidence quality for each outcome using the GRADE recommendations. MAIN RESULTS: We included 24 studies (2664 participants) of adult participants (older than 18 years of age) with respiratory distress due to ACPE, not requiring immediate mechanical ventilation. People with ACPE presented either to an Emergency Department or were inpatients. ACPE treatment was provided in an intensive care or Emergency Department setting. There was a median follow-up of 13 days for hospital mortality, one day for endotracheal intubation, and three days for acute myocardial infarction. Compared with SMC, NPPV may reduce hospital mortality (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.51 to 0.82; participants = 2484; studies = 21; I2 = 6%; low quality of evidence) with a number needed to treat for an additional beneficial outcome (NNTB) of 17 (NNTB 12 to 32). NPPV probably reduces endotracheal intubation rates (RR 0.49, 95% CI 0.38 to 0.62; participants = 2449; studies = 20; I2 = 0%; moderate quality of evidence) with a NNTB of 13 (NNTB 11 to 18). There is probably little or no difference in acute myocardial infarction (AMI) incidence with NPPV compared to SMC for ACPE (RR 1.03, 95% CI 0.91 to 1.16; participants = 1313; studies = 5; I2 = 0%; moderate quality of evidence). We are uncertain as to whether NPPV increases hospital length of stay (mean difference (MD) -0.31 days, 95% CI -1.23 to 0.61; participants = 1714; studies = 11; I2 = 55%; very low quality of evidence). Adverse events were generally similar between NPPV and SMC groups, but evidence was of low quality. AUTHORS' CONCLUSIONS: Our review provides support for continued clinical application of NPPV for ACPE, to improve outcomes such as hospital mortality and intubation rates. NPPV is a safe intervention with similar adverse event rates to SMC alone. Additional research is needed to determine if specific subgroups of people with ACPE have greater benefit of NPPV compared to SMC. Future research should explore the benefit of NPPV for ACPE patients with hypercapnia.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Mortalidade Hospitalar , Edema Pulmonar/terapia , Adulto , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal/estatística & dados numéricos , Tempo de Internação , Ventilação não Invasiva , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Can J Cardiol ; 34(9): 1215-1218, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30170676

RESUMO

Costs of end of life care for patients who have advanced heart failure (HF) are increasing. There is a perception that many of these patients receive aggressive treatments near the end of life. However, actual patterns of care are unclear. In this article we describe the use of life-sustaining treatments and the timing of goals of care discussions during patients' terminal admission for HF. We conducted a single-centre retrospective cohort study of patients aged 18 years or older with a most responsible discharge diagnosis of HF who died between April 2012 and December 2013. We identified 133 eligible decedents of whom 67 (50%) received some form of life-sustaining treatment, although only 14 (11%) received cardiopulmonary resuscitation (CPR). The first documented orders for scope of treatment were: CPR for 39 (29%), active medical treatment with no CPR for 81 (61%), and comfort care with no CPR for 11 (8%) patients. The last documented orders were for comfort care in 85 (64%) patients. There were 28 (21%) patients who received palliative care consultation. Median time between palliative care consultation and death was 6 days and between orders for comfort care and death was 24 hours. In contrast to the high mortality risk of our study cohort, palliative care consultation was often absent or in the final days of life, with orders for comfort-oriented care being written only 24 hours before death, suggesting there remain opportunities for earlier integration of palliative and goal-directed approaches to therapy for patients who have advanced HF.


Assuntos
Reanimação Cardiopulmonar , Mau Uso de Serviços de Saúde , Insuficiência Cardíaca , Cuidados Paliativos , Assistência Terminal , Canadá/epidemiologia , Reanimação Cardiopulmonar/métodos , Reanimação Cardiopulmonar/estatística & dados numéricos , Estudos de Coortes , Progressão da Doença , Feminino , Mau Uso de Serviços de Saúde/prevenção & controle , Mau Uso de Serviços de Saúde/estatística & dados numéricos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Futilidade Médica , Pessoa de Meia-Idade , Determinação de Necessidades de Cuidados de Saúde , Cuidados Paliativos/métodos , Cuidados Paliativos/estatística & dados numéricos , Estudos Retrospectivos , Assistência Terminal/métodos , Assistência Terminal/estatística & dados numéricos , Fatores de Tempo
6.
Anesth Analg ; 127(2): 520-528, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29596095

RESUMO

BACKGROUND: Caudal block is commonly used to provide postoperative analgesia after pediatric surgery in the lower abdomen. Typically administered as a single-shot technique, 1 limitation of this block is the short duration of analgesia. To overcome this, dexamethasone has been used as an adjuvant to prolong block duration. However, there are concerns about steroid-related morbidity and the optimal route of dexamethasone administration (eg, caudal or intravenous) is unknown. METHODS: We conducted a systematic review and random-effects meta-analysis of randomized controlled trials recruiting pediatric surgical patients receiving a caudal block for surgical anesthesia or postoperative analgesia. Included studies compared dexamethasone (caudal, intravenous, or both) to control. Duration of analgesia was the primary outcome. Database sources were Medline, Embase, the Cochrane Library, and Google Scholar searched up to August 18, 2017, without language restriction. Screening of studies, data extraction, and risk of bias assessment were performed independently and in duplicate by 2 authors. Risk of bias was assessed using Cochrane methodology and the strength of evidence was scored using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: The initial search retrieved 93 articles. Fourteen randomized controlled trials that comprised 1315 pediatric patients met the inclusion criteria. All but 1 study involved lower abdominal operations (orchidopexy, inguinal hernia repair, and hypospadias repair). The caudal and intravenous dose of dexamethasone ranged from 0.1 to 0.2 mg/kg and 0.5 to 1.5 mg/kg, respectively, and all studies were pooled in the main analysis. Dexamethasone prolonged the duration of analgesia by both the caudal route (5.43 hours, 95% confidence interval [CI], 3.52-7.35; P < .001; I = 99.3%; N = 9; n = 620; GRADE quality = moderate) and intravenous route (5.51 hours; 95% CI, 3.56-7.46; P < .001; I = 98.9%; N = 5; n = 364; GRADE quality = moderate) versus control. Secondary benefits of dexamethasone included reduced narcotic rescue analgesia requirement in the postanesthetic care unit (relative risk [RR], 0.30; 95% CI, 0.18-0.51; P < .001; I = 0.0%; N = 5; number needed to treat for benefit [NNTB] = 5; 95% CI, 4-7), less subsequent postoperative rescue analgesia requirement (RR, 0.46; 95% CI, 0.23-0.92; P = .03; I = 96.0%; N = 9; n = 629; NNTB = 3; 95% CI, 2-20; n = 310), and lower rates of postoperative nausea and vomiting (RR, 0.47; 95% CI, 0.30-0.73; P = .001; I = 0.0%; NNTB = 11; 95% CI, 8-21; N = 9; n = 628). Adverse events linked to the dexamethasone were rare. CONCLUSIONS: Caudal and intravenous dexamethasone are similarly effective for prolonging the duration of analgesia from caudal blockade, resulting in a doubled to tripled duration. Given the off-label status of caudal dexamethasone, intravenous administration is recommended-although only high intravenous doses (0.5 mg/kg up to 10 mg) have been studied.


Assuntos
Analgesia/métodos , Dexametasona/uso terapêutico , Cirurgia Geral/métodos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Pediatria/métodos , Administração Intravenosa , Adolescente , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Dexametasona/efeitos adversos , Hérnia Inguinal , Humanos , Lactente , Infusões Intravenosas , Náusea e Vômito Pós-Operatórios/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Esteroides/efeitos adversos
7.
Eur J Anaesthesiol ; 35(7): 469-483, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29369117

RESUMO

BACKGROUND: Much uncertainty exists as to whether peri-operative goal-directed therapy is of benefit. OBJECTIVES: To discover if peri-operative goal-directed therapy decreases mortality and morbidity in adult surgical patients. DESIGN: An updated systematic review and random effects meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase and the Cochrane Library were searched up to 31 December 2016. ELIGIBILITY CRITERIA: Randomised controlled trials enrolling adult surgical patients allocated to receive goal-directed therapy or standard care were eligible for inclusion. Trauma patients and parturients were excluded. Goal-directed therapy was defined as fluid and/or vasopressor therapy titrated to haemodynamic goals [e.g. cardiac output (CO)]. Outcomes included mortality, morbidity and hospital length of stay. Risk of bias was assessed using Cochrane methodology. RESULTS: Ninety-five randomised trials (11 659 patients) were included. Only four studies were at low risk of bias. Modern goal-directed therapy reduced mortality compared with standard care [odds ratio (OR) 0.66; 95% confidence interval (CI) 0.50 to 0.87; number needed to treat = 59; N = 52; I = 0.0%]. In subgroup analysis, there was no mortality benefit for fluid-only goal-directed therapy, cardiac surgery patients or nonelective surgery. Contemporary goal-directed therapy also reduced pneumonia (OR 0.69; 95% CI, 0.51 to 0. 92; number needed to treat = 38), acute kidney injury (OR 0. 73; 95% CI, 0.58 to 0.92; number needed to treat = 29), wound infection (OR 0.48; 95% CI, 0.37 to 0.63; number needed to treat = 19) and hospital length of stay (days) (-0.90; 95% CI, -1.32 to -0.48; I = 81. 2%). No important differences in outcomes were found for the pulmonary artery catheter studies, after accounting for advances in the standard of care. CONCLUSION: Peri-operative modern goal-directed therapy reduces morbidity and mortality. Importantly, the quality of evidence was low to very low (e.g. Grading of Recommendations, Assessment, Development and Evaluation scoring), and there was much clinical heterogeneity among the goal-directed therapy devices and protocols. Additional well designed and adequately powered trials on peri-operative goal-directed therapy are necessary.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Hidratação/métodos , Procedimentos Cirúrgicos Operatórios/métodos , Adulto , Débito Cardíaco/fisiologia , Metas , Hemodinâmica/fisiologia , Humanos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Reg Anesth Pain Med ; 42(3): 319-326, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28252523

RESUMO

BACKGROUND AND OBJECTIVES: Dexamethasone is a useful adjuvant in regional anesthesia that is used to prolong the duration of analgesia for peripheral nerve blocks. Recent randomized controlled trials (RCTs) have demonstrated conflicting results as to whether perineural versus intravenous (IV) administration is superior in this regard, and the perineural use of dexamethasone remains off-label. Therefore, we sought to perform a systematic review and meta-analysis of RCTs. METHODS: In accordance with PRISMA guidelines, we performed a random-effects meta-analysis of RCTs comparing perineural versus IV dexamethasone with duration of analgesia as the primary outcome. RESULTS: Eleven RCTs met the inclusion criteria with a total of 1076 subjects. Perineural dexamethasone prolonged the duration of analgesia by 3.77 hours (95% confidence interval [CI], 1.87-5.68 hours; P < 0.001) compared to IV dexamethasone, with high statistical heterogeneity. For secondary outcomes, perineural dexamethasone prolonged the duration of both motor (3.47 hours [95% CI, 1.49-5.45]; P < 0.001) and sensory (2.28 hours [95% CI, 0.38-4.17]; P = 0.019) block compared to IV administration. Furthermore, perineural dexamethasone patients consumed slightly less oral opioids at 24 hours than IV dexamethasone patients (7.1 mg of oral morphine equivalents [95% CI, 0.74-13.5 mg]; P = 0.029), and there were no statistically significant differences in the other secondary outcomes. Notably, no increase in adverse events was detected. CONCLUSIONS: Perineural dexamethasone prolongs the duration of analgesia across the RCTs included in our meta-analysis. The magnitude of effect of 3.77 hours raises the question as to whether perineural dexamethasone should be administered routinely over its IV counterpart-or reserved for selected patients where such prolongation would be clinically important.


Assuntos
Anti-Inflamatórios/administração & dosagem , Bloqueio Nervoso Autônomo/métodos , Dexametasona/administração & dosagem , Administração Intravenosa , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
10.
BMC Cardiovasc Disord ; 16(1): 246, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27905877

RESUMO

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) have been associated with improved patient outcomes in patients with heart failure with reduced ejection fraction (HFrEF) but not preserved ejection fraction (HFpEF). We conducted a systematic review and meta-analysis of selective and nonselective MRAs in HFrEF and HFpEF. METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE. We included randomized controlled trials (RCT) of MRAs in adults with HFpEF or HFrEF if they reported data on major adverse cardiac events or drug safety. RESULTS: We identified 15 studies representing 16321 patients. MRAs were associated with a reduced risk of cardiovascular death (RR 0.81 [0.75-0.87], I2 0%), all-cause mortality (RR 0.83 [0.77-0.88], I2 0%), and cardiac hospitalizations (RR 0.80 [0.70-0.92], I2 58.4%). However, an a-priori specified subgroup analysis demonstrated that these benefits were limited to HFrEF (cardiovascular death RR 0.79 [0.73-0.86], I2 0%; all-cause mortality RR 0.81 [0.75-0.87], I2 0%; cardiac hospitalizations RR 0.76 [0.64-0.90], I2 68%), but not HFpEF (all-cause mortality RR 0.92 [0.79-1.08], I2 0%; cardiac hospitalizations RR 0.91 [0.67-1.24], I2 17%). MRAs increased the risk of hyperkalemia (RR 2.03 [1.78-2.31], I2 0%). Nonselective MRAs, but not selective MRAs increased the risk of gynecomastia (RR 7.37 [4.42-12.30], I2 0% vs. RR 0.74 [0.43-1.27], I2 0%). Evidence was of moderate quality for cardiovascular death, all-cause mortality and cardiovascular hospitalizations; and high-quality for hyperkalemia and gynecomastia. CONCLUSIONS: MRAs reduce the risk of adverse cardiac events in HFrEF but not HFpEF. MRA use in HFpEF increases the risk of harm from hyperkalemia and gynecomastia. Selective MRAs are equally effective as nonselective MRAs, without a risk of gynecomastia.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Insuficiência Cardíaca/fisiopatologia , Hospitalização/tendências , Humanos
11.
PLoS Genet ; 6(9): e1001092, 2010 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-20824081

RESUMO

Eukaryotic DNA replication origins differ both in their efficiency and in the characteristic time during S phase when they become active. The biological basis for these differences remains unknown, but they could be a consequence of chromatin structure. The availability of genome-wide maps of nucleosome positions has led to an explosion of information about how nucleosomes are assembled at transcription start sites, but no similar maps exist for DNA replication origins. Here we combine high-resolution genome-wide nucleosome maps with comprehensive annotations of DNA replication origins to identify patterns of nucleosome occupancy at eukaryotic replication origins. On average, replication origins contain a nucleosome depleted region centered next to the ACS element, flanked on both sides by arrays of well-positioned nucleosomes. Our analysis identified DNA sequence properties that correlate with nucleosome occupancy at replication origins genome-wide and that are correlated with the nucleosome-depleted region. Clustering analysis of all annotated replication origins revealed a surprising diversity of nucleosome occupancy patterns. We provide evidence that the origin recognition complex, which binds to the origin, acts as a barrier element to position and phase nucleosomes on both sides of the origin. Finally, analysis of chromatin reconstituted in vitro reveals that origins are inherently nucleosome depleted. Together our data provide a comprehensive, genome-wide view of chromatin structure at replication origins and suggest a model of nucleosome positioning at replication origins in which the underlying sequence occludes nucleosomes to permit binding of the origin recognition complex, which then (likely in concert with nucleosome modifiers and remodelers) positions nucleosomes adjacent to the origin to promote replication origin function.


Assuntos
Cromatina/química , Replicação do DNA/genética , Células Eucarióticas/metabolismo , Variação Genética , Genoma Fúngico/genética , Origem de Replicação/genética , Saccharomyces cerevisiae/genética , Sequência de Bases , Sequência Consenso/genética , Período de Replicação do DNA/genética , Genes Fúngicos/genética , Nucleossomos/metabolismo , Complexo de Reconhecimento de Origem/metabolismo , Ligação Proteica , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Sítio de Iniciação de Transcrição
12.
Genetics ; 182(2): 623-6, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19332878

RESUMO

Modulating gene dose is an effective way to alter protein levels and modify phenotypes to understand gene function. In addition, combining gene-dose alleles with chemical perturbation can provide insight into drug-gene interactions. Here, we present a strategy that combines diverse loss-of-function alleles to systematically modulate gene dose in Saccharomyces cerevisiae. The generated gene dosage allele set expands the genetic toolkit for uncovering novel phenotypes.


Assuntos
Alelos , Dosagem de Genes/efeitos dos fármacos , Dosagem de Genes/genética , Metotrexato/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Regulação Fúngica da Expressão Gênica/genética , Fenótipo , RNA Fúngico/análise , RNA Fúngico/genética , Sensibilidade e Especificidade
13.
Nucleic Acids Res ; 36(7): 2123-35, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18187505

RESUMO

Lsr2 is a small, basic protein present in Mycobacterium and related actinomycetes. Recent studies suggest that Lsr2 is a regulatory protein involved in multiple cellular processes including cell wall biosynthesis and antibiotic resistance. However, the underlying molecular mechanisms remain unknown. In this article, we performed biochemical studies of Lsr2-DNA interactions and structure-function analysis of Lsr2. Analysis by atomic force microscopy revealed that Lsr2 has the ability to bridge distant DNA segments, suggesting that Lsr2 plays a role in the overall organization and compactness of the nucleoid. Mutational analysis identified critical residues and selection of dominant negative mutants demonstrated that both DNA binding and protein oligomerization are essential for the normal functions of Lsr2 in vivo. These results provide strong evidence that Lsr2 is a DNA bridging protein, which represents the first identification of such proteins in bacteria phylogenetically distant from the Enterobacteriaceae. DNA bridging by Lsr2 also provides a mechanism of transcriptional regulation by Lsr2.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/metabolismo , Mycobacterium tuberculosis/genética , Sequência Rica em At , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , DNA Bacteriano/química , DNA Bacteriano/metabolismo , DNA Bacteriano/ultraestrutura , DNA Circular/química , DNA Circular/metabolismo , DNA Circular/ultraestrutura , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Microscopia de Força Atômica , Mutação
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