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1.
Pediatr Transplant ; 28(4): e14784, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38766976

RESUMO

BACKGROUND: The goal of this study was to assess the effect of donor type and pre-transplant immunotherapy (IST) on outcomes of hematopoietic stem cell transplantation (HSCT) for children and young adults with severe aplastic anemia (SAA). METHODS: This retrospective, multi-center study included 52 SAA patients, treated in 5 pediatric transplant programs in Florida, who received HSCT between 2010 and 2020 as the first- or second-line treatment. RESULTS: The median age at HSCT for all 52 patients was 15 years (range 1-25). The 3-year overall survival (OS) by donor type were as follows: 95% [95% CI 85.4-99] for matched related donors (MRD) (N = 24), 84% [95% CI 63.5-99] for haploidentical (N = 13), and 71% [95% CI 36-99] for matched unrelated donors (MUD) (N = 7). The 3-year OS was 81% [95% CI 69.7-99] for all patients, 90.5% [95% CI 79.5-99] for non-IST patients (N = 27), and 70% [95% CI 51-99] for IST patients (N = 24) (log-rank p = .04). Survival of haploidentical HSCT (haplo-HSCT) recipients with post-transplant cyclophosphamide (PTCy) (N = 13) was excellent for both groups: 100% for non-IST patients (N = 3) and 80% for IST patients (N = 10). The 3-year OS for patients with previous IST by donor type in groups where >5 patients were available was 78.8% [95% CI 52.3-99] for haplo-HSCT (N = 10) and 66.7% [95% CI 28.7-99] for MUD (N = 6). Although it appears that patients receiving HSCT ≥6 months after the start of IST had worse survival, the number of patients in each category was small and log-rank was not significant(p = .65). CONCLUSIONS: Patients receiving MUD and haplo-HSCT with PTCy had similar outcomes, suggesting that haplo-HSCT with PTCy could be included in randomized trials of upfront IST versus alternative donor HSCT.


Assuntos
Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Humanos , Anemia Aplástica/terapia , Adolescente , Criança , Estudos Retrospectivos , Masculino , Feminino , Pré-Escolar , Adulto Jovem , Adulto , Lactente , Resultado do Tratamento , Terapia de Imunossupressão/métodos , Doadores de Tecidos , Imunossupressores/uso terapêutico
2.
J Enzyme Inhib Med Chem ; 39(1): 2330907, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38651823

RESUMO

Antimicrobial resistance (AMR) is a pressing global issue exacerbated by the abuse of antibiotics and the formation of bacterial biofilms, which cause up to 80% of human bacterial infections. This study presents a computational strategy to address AMR by developing three novel quantitative structure-activity relationship (QSAR) models based on molecular topology to identify potential anti-biofilm and antibacterial agents. The models aim to determine the chemo-topological pattern of Gram (+) antibacterial, Gram (-) antibacterial, and biofilm formation inhibition activity. The models were applied to the virtual screening of a commercial chemical database, resulting in the selection of 58 compounds. Subsequent in vitro assays showed that three of these compounds exhibited the most promising antibacterial activity, with potential applications in enhancing food and medical device safety.


Assuntos
Antibacterianos , Biofilmes , Desenho de Fármacos , Testes de Sensibilidade Microbiana , Relação Quantitativa Estrutura-Atividade , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Estrutura Molecular , Humanos , Contaminação de Alimentos/prevenção & controle , Relação Dose-Resposta a Droga
3.
J Craniofac Surg ; 33(1): 129-133, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34967520

RESUMO

ABSTRACT: Surgical treatment of craniosynostosis with cranial vault reconstruction in infants is associated with significant blood loss. The optimal blood management approach is an area of active investigation. Thromboelastography (TEG) was used to examine changes in coagulation after surgical blood loss that was managed by transfusion with either whole blood or blood components. Transfusion type was determined by availability of whole blood from the blood bank.This retrospective study examined differences in posttransfusion TEG maximum amplitude (MA), a measure of the maximum clot strength, for patients transfused with whole blood or blood components. We included all patients less than 24 months old who underwent cranial vault remodeling, received intraoperative transfusions with whole blood or blood components, and had baseline and posttransfusion TEG measured. Whole blood was requested for all patients and was preferentially used when it was available from the American Red Cross.Of 48 eligible patients, 30 received whole blood and 18 received blood components. All patients received an intraoperative antifibrinolytic agent. The posttransfusion MA in the whole blood group was 61.8 mm (IQR 59.1, 64.1) compared to 57.9 mm (IQR 50.5, 60.9) in the blood components group (P = 0.010). There was a greater posttransfusion decrease in MA for patients transfused with blood components (median decrease of 7.7 mm [IQR -3.4, 6.3]) compared with whole blood (median decrease of 2.1 mm [IQR -9.6, 7.5] P < 0.001).Transfusion with blood components was associated with a greater decrease in MA that was likely related to decreased postoperative fibrinogen in this group. Patients who received whole blood had higher postoperative fibrinogen levels.


Assuntos
Craniossinostoses , Tromboelastografia , Transfusão de Componentes Sanguíneos , Perda Sanguínea Cirúrgica/prevenção & controle , Pré-Escolar , Craniossinostoses/cirurgia , Humanos , Lactente , Estudos Retrospectivos
4.
Int J Mol Sci ; 23(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36499384

RESUMO

A method to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC) is developed. A set of structurally heterogeneous agents against MTBC was used to obtain a mathematical model based on topological descriptors. This model was statistically validated through a Leave-n-Out test. It successfully discriminated between active or inactive compounds over 86% in database sets. It was also useful to select new potential antituberculosis compounds in external databases. The selection of new substituted pyrimidines, pyrimidones and triazolo[1,5-a]pyrimidines was particularly interesting because these structures could provide new scaffolds in this field. The seven selected candidates were synthesized and six of them showed activity in vitro.


Assuntos
Antituberculosos , Relação Quantitativa Estrutura-Atividade , Antituberculosos/farmacologia , Antituberculosos/química , Estrutura Molecular , Desenho de Fármacos , Bases de Dados Factuais
5.
Lancet ; 396(10266): 1905-1913, 2020 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-33308472

RESUMO

BACKGROUND: Orotracheal intubation of infants using direct laryngoscopy can be challenging. We aimed to investigate whether video laryngoscopy with a standard blade done by anaesthesia clinicians improves the first-attempt success rate of orotracheal intubation and reduces the risk of complications when compared with direct laryngoscopy. We hypothesised that the first-attempt success rate would be higher with video laryngoscopy than with direct laryngoscopy. METHODS: In this multicentre, parallel group, randomised controlled trial, we recruited infants without difficult airways abnormalities requiring orotracheal intubation in operating theatres at four quaternary children's hospitals in the USA and one in Australia. We randomly assigned patients (1:1) to video laryngoscopy or direct laryngoscopy using random permuted blocks of size 2, 4, and 6, and stratified by site and clinician role. Guardians were masked to group assignment. The primary outcome was the proportion of infants with a successful first attempt at orotracheal intubation. Analysis (modified intention-to-treat [mITT] and per-protocol) used a generalised estimating equation model to account for clustering of patients treated by the same clinician and institution, and adjusted for gestational age, American Society of Anesthesiologists physical status, weight, clinician role, and institution. The trial is registered at ClinicalTrials.gov, NCT03396432. FINDINGS: Between June 4, 2018, and Aug 19, 2019, 564 infants were randomly assigned: 282 (50%) to video laryngoscopy and 282 (50%) to direct laryngoscopy. The mean age of infants was 5·5 months (SD 3·3). 274 infants in the video laryngoscopy group and 278 infants in the direct laryngoscopy group were included in the mITT analysis. In the video laryngoscopy group, 254 (93%) infants were successfully intubated on the first attempt compared with 244 (88%) in the direct laryngoscopy group (adjusted absolute risk difference 5·5% [95% CI 0·7 to 10·3]; p=0·024). Severe complications occurred in four (2%) infants in the video laryngoscopy group compared with 15 (5%) in the direct laryngoscopy group (-3·7% [-6·5 to -0·9]; p=0·0087). Fewer oesophageal intubations occurred in the video laryngoscopy group (n=1 [<1%]) compared with in the direct laryngoscopy group (n=7 [3%]; -2·3 [-4·3 to -0·3]; p=0·028). INTERPRETATION: Among anaesthetised infants, using video laryngoscopy with a standard blade improves the first-attempt success rate and reduces complications. FUNDING: Anaesthesia Patient Safety Foundation, Society for Airway Management, and Karl Storz Endoscopy.


Assuntos
Manuseio das Vias Aéreas/estatística & dados numéricos , Intubação Intratraqueal , Laringoscopia/estatística & dados numéricos , Gravação em Vídeo , Austrália , Esôfago , Feminino , Hospitais Pediátricos , Humanos , Lactente , Análise de Intenção de Tratamento , Masculino , Estados Unidos
6.
J Chem Inf Model ; 61(4): 2016-2025, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33734704

RESUMO

The global pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is threatening the health and economic systems worldwide. Despite the enormous efforts of scientists and clinicians around the world, there is still no drug or vaccine available worldwide for the treatment and prevention of the infection. A rapid strategy for the identification of new treatments is based on repurposing existing clinically approved drugs that show antiviral activity against SARS-CoV-2 infection. In this study, after developing a quantitative structure activity relationship analysis based on molecular topology, several macrolide antibiotics are identified as promising SARS-CoV-2 spike protein inhibitors. To confirm the in silico results, the best candidates were tested against two human coronaviruses (i.e., 229E-GFP and SARS-CoV-2) in cell culture. Time-of-addition experiments and a surrogate model of viral cell entry were used to identify the steps in the virus life cycle inhibited by the compounds. Infection experiments demonstrated that azithromycin, clarithromycin, and lexithromycin reduce the intracellular accumulation of viral RNA and virus spread as well as prevent virus-induced cell death, by inhibiting the SARS-CoV-2 entry into cells. Even though the three macrolide antibiotics display a narrow antiviral activity window against SARS-CoV-2, it may be of interest to further investigate their effect on the viral spike protein and their potential in combination therapies for the coronavirus disease 19 early stage of infection.


Assuntos
COVID-19 , Preparações Farmacêuticas , Antibacterianos , Antivirais/farmacologia , Humanos , Macrolídeos/farmacologia , Relação Quantitativa Estrutura-Atividade , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
7.
Anesth Analg ; 132(2): 493-499, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32149758

RESUMO

BACKGROUND: Moyamoya disease is a condition with potentially devastating and permanent neurological sequelae. Adequate volume status and blood pressure, tight control of carbon dioxide to achieve normocarbia, and providing postoperative analgesia to prevent hyperventilation are typical goals that are used during anesthetic care in these patients. The purpose of this study was to assess postanesthesia neurological complications in moyamoya patients undergoing general anesthesia for imaging studies and surgical procedures excluding neurosurgical revascularization. METHODS: We performed a retrospective cohort study examining moyamoya patients who received general anesthesia for imaging studies and nonneurosurgical-revascularization procedures between January 1, 2001 and December 1, 2016 at our quaternary care pediatric hospital. A general anesthetic encounter was excluded if it occurred within 30 days after a revascularization surgery. The electronic medical records of study patients were analyzed for perioperative management, and neurological outcomes within 30 days of an anesthetic were assessed. RESULTS: A total of 58 patients undergoing 351 anesthesia exposures were included in the study. Three patients experienced neurological complications, which included focal neurological weakness, seizure, and altered mental status. The incidence of complications during anesthesia encounters was 0.85% (3/351) with a 95% confidence interval of 0.28-2.62. CONCLUSIONS: Over a 16-year period at our hospital, 3 children with moyamoya disease who underwent anesthesia for nonneurosurgical-revascularization purposes demonstrated postanesthesia neurological symptoms. The symptoms were consistent with transient ischemic attacks and all resolved without long-term sequelae.


Assuntos
Anestesia Geral/efeitos adversos , Ataque Isquêmico Transitório/etiologia , Transtornos Mentais/etiologia , Doença de Moyamoya/complicações , Convulsões/etiologia , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Ataque Isquêmico Transitório/fisiopatologia , Ataque Isquêmico Transitório/psicologia , Masculino , Transtornos Mentais/psicologia , Doença de Moyamoya/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Convulsões/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
8.
Paediatr Anaesth ; 31(2): 186-196, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33190350

RESUMO

BACKGROUND: Blood product utilization in injured children is poorly characterized; the decision to prepare products or transfuse patients can be difficult due to a lack of reliable evidence of transfusion needs across pediatric age-groups and injury types. We conducted an audit of transfusion practices in pediatric trauma based on age, injuries, and mechanism of injury. METHODS: We reviewed and cross-referenced blood product transfusion practice data from the trauma registry and the anesthesia transfusion record database at a level 1 pediatric trauma center over a 10-year period. Demographic data, injury severity scores, and survival statistics were obtained from the trauma registry. Transfusion rates are reported separately for hospital admission and for intraoperative transfusions for procedures performed during the first two hospital days. Descriptive statistical analysis was used to compare specific groups based on age, injury type, and mechanism of injury. RESULTS: We report 14 569 trauma admissions of 14 606 patients. The transfusion rate during the admission was 1.56% (227/14 569). 4591 (30.9%) admissions had surgical interventions in first two days of hospitalization with an intraoperative transfusion rate of 2.98%. Patients younger than one year had the highest transfusion rate during admission (2.8%), and the highest transfusion rate during surgical procedures performed in the first two days of the admission (18.87%). Admissions due to vascular injuries had the highest transfusion rates in infancy followed by hollow visceral injuries in adolescents (71.4% and 25%, respectively). Vascular injuries in most age-groups also had high transfusion rates ranging from 11% in 5- to 9-year age-group to 71% in infants. Mechanisms with the highest transfusion rates were firearm wounds in patients older than one year and vehicular accidents for patients younger than one year. CONCLUSIONS: The overall blood product needs in the pediatric trauma population are low (1.56%). Selected populations requiring higher rates of need include infants younger than one year, and children with thoracic and vascular injuries. Understanding transfusion patterns is important to optimize resource allocation.


Assuntos
Transfusão de Sangue , Centros de Traumatologia , Adolescente , Criança , Humanos , Incidência , Lactente , Escala de Gravidade do Ferimento , Estudos Retrospectivos
9.
Transfusion ; 60(12): 2787-2792, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32860229

RESUMO

BACKGROUND: The AABB (American Association of Blood Banks) and the College of American Pathologists (CAP) regulations call on blood banks to address the risk of misidentification of a patient's blood type, which can result in transfusion of a mismatched product. Transfusion of mismatched blood product is potentially fatal due to acute hemolytic transfusion reaction and is considered a preventable event. CAP regulations outline options to reduce risk of mistransfusion by either documenting the ABO group of the intended recipient on a second sample collected at a separate phlebotomy, or utilizing a mechanical barrier system or electronic identification verification system that ensures the patient from whom the pretransfusion specimen was collected is the same patient who is about to be transfused. STUDY DESIGN AND METHODS: An electronic or barrier system was not available for implementation at our institution, therefore we developed a protocol for a two-sample verification system. The first determination is performed on a current sample and the second by one of the following methods: (a) comparison with previous laboratory records, (b) testing a second sample collected at a time different from the first sample (i.e., laboratory specimen available with a different timestamp, or a new blood sample). RESULTS: We improved our transfusion process and implemented a policy to require a second sample to confirm a patient's blood type. We also implemented workflows to obtain blood type confirmation from history of a second blood type result from previous laboratory records, including a policy to accept previous blood type records from an outside laboratory. CONCLUSIONS: We describe a practice change for two-sample verification for type and screen in a large-scale pediatric hospital. We outline specific workflows for pre-operative and emergency transfusion scenarios, and pediatric-specific challenges.


Assuntos
Bancos de Sangue , Incompatibilidade de Grupos Sanguíneos , Tipagem e Reações Cruzadas Sanguíneas , Transfusão de Sangue , Hospitais Pediátricos , Reação Transfusional/prevenção & controle , Criança , Humanos
10.
Anesthesiology ; 133(3): 523-533, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32433278

RESUMO

BACKGROUND: Children are required to fast before elective general anesthesia. This study hypothesized that prolonged fasting causes volume depletion that manifests as low blood pressure. This study aimed to assess the association between fluid fasting duration and postinduction low blood pressure. METHODS: A retrospective cohort study was performed of 15,543 anesthetized children without preinduction venous access who underwent elective surgery from 2016 to 2017 at Children's Hospital of Philadelphia. Low blood pressure was defined as systolic blood pressure lower than 2 standard deviations below the mean (approximately the 2.5th percentile) for sex- and age-specific reference values. Two epochs were assessed: epoch 1 was from induction to completion of anesthesia preparation, and epoch 2 was during surgical preparation. RESULTS: In epoch 1, the incidence of low systolic blood pressure was 5.2% (697 of 13,497), and no association was observed with the fluid fasting time groups: less than 4 h (4.6%, 141 of 3,081), 4 to 8 h (6.0%, 219 of 3,652), 8 to 12 h (4.9%, 124 of 2,526), and more than 12 h (5.0%, 213 of 4,238). In epoch 2, the incidence of low systolic blood pressure was 6.9% (889 of 12,917) and varied across the fasting groups: less than 4 h (5.6%, 162 of 2,918), 4 to 8 h (8.1%, 285 of 3,531), 8 to 12 h (5.9%, 143 of 2,423), and more than 12 h (7.4%, 299 of 4,045); after adjusting for confounders, fasting 4 to 8 h (adjusted odds ratio, 1.33; 95% CI, 1.07 to 1.64; P = 0.009) and greater than 12 h (adjusted odds ratio, 1.28; 95% CI, 1.04 to 1.57; P = 0.018) were associated with significantly higher odds of low systolic blood pressure compared with the group who fasted less than 4 h, whereas the increased odds of low systolic blood pressure associated with fasting 8 to 12 h (adjusted odds ratio, 1.11; 95% CI, 0.87 to 1.42; P = 0.391) was nonsignificant. CONCLUSIONS: Longer durations of clear fluid fasting in anesthetized children were associated with increased risk of postinduction low blood pressure during surgical preparation, although this association appeared nonlinear.


Assuntos
Jejum/efeitos adversos , Hipotensão/etiologia , Hipotensão/fisiopatologia , Cuidados Pré-Operatórios/métodos , Pressão Sanguínea , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Tempo
11.
J Chem Inf Model ; 60(6): 2819-2829, 2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32460488

RESUMO

The presence of organic structure directing agents (templates) in the synthesis of zeolites allows the synthesis to be directed, in many cases, toward structures in which there is a large stabilization between the template and the zeolite micropore due to dispersion interactions. Although other factors are also important (temperature, pH, Si/Al ratio, etc.), systems with strong zeolite-template interactions are good candidates for an application of new computational algorithms, for instance those based in molecular topology (MT), that can be used in combination with large databases of organic molecules. Computational design of new templates allows the synthesis of existing and new zeolites to be expanded and refined. Three zeolites with similar 3-D large pore systems, BEA, BEC, and ISV, were selected with the aim of finding new templates for their selective syntheses. Using a training set of active and inactive templates (obtained from the literature) for the synthesis of target zeolites, it was possible to select chemical descriptors related to activity, meaning a good candidate template. With a discriminant function defined upon MT, the screening through a database of organic molecules led to a small subset (preselection) of candidate templates for the synthesis of BEA, BEC, and ISV. As far as we know, this is the first time that topological/topochemical descriptors, which do not consider 3-D information on the molecules, have been used to predict the activity of zeolite structure directing agents (SDAs). Following the prediction of SDAs using MT, an automated approach of sequential template filling of micropores based on a combination of Monte Carlo and lattice energy minimization was applied for all the candidate templates in the three zeolites. Two results can be obtained from this: an evaluation of the quality of the molecular topology QSAR models leading to the preselection of templates, and a final selection of candidate templates for the selective synthesis of BEA, BEC, and ISV. Regarding the latter, a good template will be that which maximizes the zeolite-template dispersion interactions with one, and only one, of the three zeolites. The presented methodology can be used to find alternative (maybe cheaper or perhaps more selective) templates than those already known.


Assuntos
Zeolitas , Modelos Moleculares , Método de Monte Carlo
12.
Anesth Analg ; 130(3): 730-739, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31082971

RESUMO

BACKGROUND: Prophylactic analgesic administration reduces pain behavior after pediatric bilateral myringotomy and pressure equalization tube placement (BMT). We hypothesized that postoperative pain in children treated with intraoperative ketorolac would, among several exposures of interest, be strongly associated with ear condition. METHODS: We conducted a retrospective cohort study of healthy children (9 months to 7 years) who underwent BMT at the Children's Hospital of Philadelphia or its ambulatory surgery centers from 2013 to 2016. Anesthetic care included preoperative oral midazolam, sevoflurane/nitrous oxide (N2O)/air/oxygen (O2) by mask, and intramuscular ketorolac. Demographic and procedural information included left and right tympanic membrane (normal, retracted, or bulging) and middle ear (normal/no, serous, mucoid, or purulent effusion) conditions. Because tympanic membrane and middle ear conditions were highly concordant and mean maximum Face, Legs, Activity, Cry and Consolability (FLACC) scores (0-10) were not different across the array of abnormal findings, we categorized each ear as normal or abnormal based on middle ear effusion alone. We then defined the ear condition of each child (primary exposure) using bilateral findings: normal/normal, normal/abnormal, and abnormal/abnormal. Secondary exposures included age, BMT history, procedure duration, facility location, and attending surgeon/anesthesiologist pair. The primary outcome was maximum postanesthesia care unit FLACC score: 4-10 (moderate-to-severe pain) versus 0-3 (no-to-low pain). Rescue oxycodone, acetaminophen administration, and emergence agitation were secondary outcomes. Statistical analysis incorporated generalized linear mixed models with random intercepts accounting for the clustering effect of provider pairs. Adjusting for multiple comparisons, significance level was set at P = .004. RESULTS: Excluding recurrent cases, 1922 unique evaluable subjects remained. The probability of moderate-to-severe pain behavior (FLACC, 4-10) was 52.4% (95% confidence interval [CI], 50.2-54.6) overall. In a confounder-adjusted model, ear condition was significantly associated with moderate-to-severe pain: compared to bilateral abnormal (effusions), odds ratio (OR) (95% CI) for bilateral normal was 2.2 (1.6-2.9), P < .0001. Younger age (OR, 1.1 [1.1-1.2] per year; P = .001) and longer procedure duration (OR, 1.1 [1.0-1.2] per minute; P = .0008) were likewise related to higher pain. With surgeon added to the model, variance explained by provider pairs decreased from 9.60% to 1.05%. Two secondary outcome associations also emerged: comparing bilateral normal to abnormal ears, ORs were 1.7 (1.3-2.2), P = .0001, for rescue oxycodone and 2.0 (1.2-3.3), P = .008, for emergence agitation. CONCLUSIONS: Pain behavior after BMT varies by surgeon and is strongly associated with ear condition. Ketorolac as a single prophylactic analgesic appears less effective in younger children with normal middle ear findings.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Resistência a Medicamentos , Cetorolaco/administração & dosagem , Ventilação da Orelha Média/efeitos adversos , Dor Pós-Operatória/prevenção & controle , Membrana Timpânica/cirurgia , Fatores Etários , Anti-Inflamatórios não Esteroides/efeitos adversos , Comportamento Infantil , Pré-Escolar , Esquema de Medicação , Feminino , Hospitais Pediátricos , Humanos , Lactente , Cetorolaco/efeitos adversos , Masculino , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/fisiopatologia , Dor Pós-Operatória/psicologia , Philadelphia , Pressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
13.
Anesth Analg ; 131(1): 61-73, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32287142

RESUMO

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) pandemic has challenged medical systems and clinicians globally to unforeseen levels. Rapid spread of COVID-19 has forced clinicians to care for patients with a highly contagious disease without evidence-based guidelines. Using a virtual modified nominal group technique, the Pediatric Difficult Intubation Collaborative (PeDI-C), which currently includes 35 hospitals from 6 countries, generated consensus guidelines on airway management in pediatric anesthesia based on expert opinion and early data about the disease. PeDI-C identified overarching goals during care, including minimizing aerosolized respiratory secretions, minimizing the number of clinicians in contact with a patient, and recognizing that undiagnosed asymptomatic patients may shed the virus and infect health care workers. Recommendations include administering anxiolytic medications, intravenous anesthetic inductions, tracheal intubation using video laryngoscopes and cuffed tracheal tubes, use of in-line suction catheters, and modifying workflow to recover patients from anesthesia in the operating room. Importantly, PeDI-C recommends that anesthesiologists consider using appropriate personal protective equipment when performing aerosol-generating medical procedures in asymptomatic children, in addition to known or suspected children with COVID-19. Airway procedures should be done in negative pressure rooms when available. Adequate time should be allowed for operating room cleaning and air filtration between surgical cases. Research using rigorous study designs is urgently needed to inform safe practices during the COVID-19 pandemic. Until further information is available, PeDI-C advises that clinicians consider these guidelines to enhance the safety of health care workers during airway management when performing aerosol-generating medical procedures. These guidelines have been endorsed by the Society for Pediatric Anesthesia and the Canadian Pediatric Anesthesia Society.


Assuntos
Manuseio das Vias Aéreas/métodos , Anestesiologia/métodos , Infecções por Coronavirus/terapia , Intubação Intratraqueal/métodos , Pediatria/métodos , Pneumonia Viral/terapia , Adolescente , Anestesia/métodos , Anestesiologia/normas , COVID-19 , Criança , Pré-Escolar , Consenso , Guias como Assunto , Humanos , Lactente , Recém-Nascido , Controle de Infecções , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Intubação Intratraqueal/normas , Pandemias , Pediatria/normas
14.
Paediatr Anaesth ; 30(9): 1027-1032, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32478969

RESUMO

BACKGROUND: Exhaled nitric oxide (eNO) is a known biomarker for the diagnosis and monitoring of bronchial hyperreactivity in adults and children. AIMS: To investigate the potential role of eNO measurement for predicting perioperative respiratory adverse events in children, we sought to determine its feasibility and acceptability before adenotonsillectomy. METHODS: We attempted eNO testing in children, 4-12 years of age, immediately prior to admission for outpatient adenotonsillectomy. We used correlations between eNO levels and postoperative adverse respiratory events to make sample size predictions for future studies that address the predictability of the device. RESULTS: One hundred and three (53%) of 192 children were able to provide an eNO sample. The success rate increased with age from 23% (9%-38%) at age 4 to over 85% (54%-98%) after age 9. Using the eNO normal value (<20 ppb) as a cutoff, an expected sample size to detect a significant difference between children with and without adverse events is 868, assuming that respiratory adverse events occur in 29% of children. CONCLUSIONS: eNO testing on the day of surgery has limited feasibility in children younger than 7 years of age. The most common reason for failure was inadequate physical performance while interacting with the testing device. The role of this respiratory biomarker in the context of perioperative outcomes for pediatric adenotonsillectomy remains unknown and should be further studied with improved technologies.


Assuntos
Testes Respiratórios , Óxido Nítrico , Adulto , Biomarcadores , Criança , Pré-Escolar , Expiração , Estudos de Viabilidade , Humanos
15.
Paediatr Anaesth ; 30(4): 446-454, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31894609

RESUMO

BACKGROUND: Postoperative nausea and vomiting after elective outpatient surgery can complicate discharge and increase patient suffering. Within our hospital system, there was variability in the use of postoperative nausea and vomiting prophylaxis for patients undergoing anterior cruciate ligament reconstruction, which resulted in variable outcomes. To address this variability, we designed and implemented a standardized postoperative nausea and vomiting prophylaxis guideline for the care of this surgical population. AIM: We sought to develop and implement a standardized postoperative nausea and vomiting prophylaxis guideline for all patients presenting for elective ambulatory anterior cruciate ligament reconstruction with the goal of reducing the rate of emesis to ≤5%. METHODS: We convened a multidisciplinary team to develop a postoperative nausea and vomiting prophylaxis guideline which included administration of dexamethasone, ondansetron, and a low-dose propofol infusion in addition to a femoral and sciatic nerve block and routine ketorolac administration for pain control. Our primary outcome, emesis rate, was tracked using a P-chart. Process measures included use of guideline medications and balancing measures included opioid administration, pain scores, and emergence time. RESULTS: We analyzed postoperative nausea and vomiting outcomes for 817 patients from January 1, 2014, to December 31, 2018. The baseline postoperative emesis rate for all anesthetizing locations was 17%. Following, guideline implementation, the emesis rate decreased to 5%. Opioid administration was decreased following guideline implementation. The percentage of patients managed without any perioperative opioids increased from 16% in the baseline group to 38% following guideline implementation. The P-chart suggests that the observed reduction in emesis rate represents special cause variation and this reduction was sustained over a two-year period. CONCLUSIONS: Implementation of standard postoperative nausea and vomiting guidelines for adolescents undergoing outpatient anterior cruciate ligament reconstruction was associated with lower emesis rates. This reduction in emesis rate may have been due to the concurrent reduction in opioids we observed following guideline implementation.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Antieméticos/uso terapêutico , Dexametasona/uso terapêutico , Ondansetron/uso terapêutico , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Adolescente , Anti-Inflamatórios não Esteroides/uso terapêutico , Feminino , Humanos , Hipnóticos e Sedativos/uso terapêutico , Cetorolaco/uso terapêutico , Masculino , Bloqueio Nervoso/métodos , Propofol/uso terapêutico , Resultado do Tratamento
16.
Paediatr Anaesth ; 30(2): 137-146, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31785039

RESUMO

BACKGROUND: Children routinely undergo inhalational induction of general anesthesia. Intravenous line placement typically occurs after induction of anesthesia and can be challenging, particularly in infants and young children. AIMS: We conducted a retrospective observational study to determine whether there was an association between clear liquid fasting time and the number of peripheral intravenous catheter insertion attempts in anesthetized children. The secondary aim was to identify factors associated with multiple attempts to insert intravenous lines. METHODS: After institutional research board approval, we retrieved a data set of all children between 0 months and 18 years who received general anesthesia at our hospital between January 1, 2016, and September 30, 2017. Data included age, gender, weight, race, ASA status, gestational age, number of peripheral intravenous catheter insertion attempts, any assistive device for insertion, and insertion site. Inclusion criteria were mask induction, ASA status 1 or 2, nonemergency, ambulatory surgical procedures, and placement of a single intravenous line during the anesthetic. RESULTS: A total of 9693 patients were included in the study. Of which 8869 patients required one insertion attempt and 824 underwent multiple insertion attempts. 50% of patients in the single insertion attempt group had clear liquid fasting time <6.9 hours compared to 51.8% of patients requiring multiple attempts. Logistic regression model adjusted for age, ASA status, gender, and BMI did not find an association between duration of clear liquid fasting time and rate of multiple insertion attempts for intravenous catheters (OR: 0.99, 95% CI: 0.98-1.01, P = .47). CONCLUSION: Clear liquid fasting time was not associated with multiple insertion attempts for intravenous line insertion in children receiving general anesthesia. Factors such as patient age, ethnicity, time of day of induction of anesthesia, and American Society of Anesthesiologists Physical Status classification show a greater association with the risk of multiple intravenous line insertion attempts.


Assuntos
Cateterismo Periférico/métodos , Jejum , Cuidados Pré-Operatórios/métodos , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Tempo
17.
Anesthesiology ; 131(4): 830-839, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31335549

RESUMO

BACKGROUND: The infant airway is particularly vulnerable to trauma from repeated laryngoscopy attempts. Complications associated with elective tracheal intubations in anesthetized infants may be underappreciated. We conducted this study of anesthetized infants to determine the incidence of multiple laryngoscopy attempts during routine tracheal intubation and assess the association of laryngoscopy attempts with hypoxemia and bradycardia. METHODS: We conducted a retrospective cross-sectional cohort study of anesthetized infants (age less than or equal to 12 months) who underwent direct laryngoscopy for oral endotracheal intubation between January 24, 2015, and August 1, 2016. We excluded patients with a history of difficult intubation and emergency procedures. Our primary outcome was the incidence of hypoxemia or bradycardia during induction of anesthesia. We evaluated the relationship between laryngoscopy attempts and our primary outcome, adjusting for age, weight, American Society of Anesthesiologists status, staffing model, and encounter location. RESULTS: A total of 1,341 patients met our inclusion criteria, and 16% (n = 208) had multiple laryngoscopy attempts. The incidence of hypoxemia was 35% (n = 469) and bradycardia was 8.9% (n = 119). Hypoxemia and bradycardia occurred in 3.7% (n = 50) of patients. Multiple laryngoscopy attempts were associated with an increased risk of hypoxemia (adjusted odds ratio: 1.78, 95% CI: 1.30 to 2.43, P < 0.001). There was no association between multiple laryngoscopy attempts and bradycardia (adjusted odds ratio: 1.23, 95% CI: 0.74 to 2.03, P = 0.255). CONCLUSIONS: In a quaternary academic center, healthy infants undergoing routine tracheal intubations had a high incidence of multiple laryngoscopy attempts and associated hypoxemia episodes.


Assuntos
Anestesia/métodos , Bradicardia/epidemiologia , Hipóxia/epidemiologia , Laringoscopia/estatística & dados numéricos , Estudos de Coortes , Estudos Transversais , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos
18.
Anesth Analg ; 129(2): 477-481, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-29481434

RESUMO

BACKGROUND: The migration of pediatric thoracic epidural catheters via a thoracic insertion site has been described. We assessed the migration of caudally threaded thoracic epidural catheters in neonates and infants at our institution. METHODS: The anesthesia records and diagnostic imaging studies of neonates and infants who had caudal epidural catheters placed during a 26-month period at our hospital were analyzed. Imaging studies were reviewed for changes in epidural catheter tip position. RESULTS: Eighty-five patients 1-325 days of age (median, 51 days; interquartile range, 39-78 days) and weights of 2.5-9.5 kg (median, 5 kg; interquartile range, 4.3-5.8 kg) met the study criteria. Fifty-four (64%) of the patients (95% CI, 52%-73%) experienced catheter migration of 1 or more vertebral levels (range, 3 levels caudad [outward] to 3 levels cephalad [inward]), and 23 (27%) of the patients (95% CI, 18%-38%) experienced catheter migration to the T4 level or higher. Migration of 2 or more vertebral levels occurred only in children who weighed <6 kg and were under 73 days of age. CONCLUSIONS: Epidural catheter migration occurs commonly in neonates and infants. Postoperative imaging is crucial to confirm catheter tip location after epidural catheter placement, as failure to assess catheter migration might result in suboptimal analgesia or other undesirable outcomes.


Assuntos
Analgesia Epidural/instrumentação , Anestesia Epidural/instrumentação , Cateteres de Demora , Migração de Corpo Estranho/etiologia , Fatores Etários , Analgesia Epidural/efeitos adversos , Anestesia Epidural/efeitos adversos , Desenho de Equipamento , Migração de Corpo Estranho/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
19.
Anesth Analg ; 129(6): 1635-1644, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31743185

RESUMO

When life-threatening, critical events occur in the operating room, the fast-paced, high-distraction atmosphere often leaves little time to think or deliberate about management options. Success depends on applying a team approach to quickly implement well-rehearsed, systematic, evidence-based assessment and treatment protocols. Mobile devices offer resources for readily accessible, easily updatable information that can be invaluable during perioperative critical events. We developed a mobile device version of the Society for Pediatric Anesthesia 26 Pediatric Crisis paper checklists-the Pedi Crisis 2.0 application-as a resource to support clinician responses to pediatric perioperative life-threatening critical events. Human factors expertise and principles were applied to maximize usability, such as by clustering information into themes that clinicians utilize when accessing cognitive aids during critical events. The electronic environment allowed us to feature optional diagnostic support, optimized navigation, weight-based dosing, critical institution-specific phone numbers pertinent to emergency response, and accessibility for those who want larger font sizes. The design and functionality of the application were optimized for clinician use in real time during actual critical events, and it can also be used for self-study or review. Beta usability testing of the application was conducted with a convenience sample of clinicians at 9 institutions in 2 countries and showed that participants were able to find information quickly and as expected. In addition, clinicians rated the application as slightly above "excellent" overall on an established measure, the Systems Usability Scale, which is a 10-item, widely used and validated Likert scale created to assess usability for a variety of situations. The application can be downloaded, at no cost, for iOS devices from the Apple App Store and for Android devices from the Google Play Store. The processes and principles used in its development are readily applicable to the development of future mobile and electronic applications for the field of anesthesiology.


Assuntos
Anestesia/normas , Lista de Checagem/normas , Aplicativos Móveis/normas , Pediatria/normas , Sociedades Médicas/normas , Anestesia/tendências , Lista de Checagem/métodos , Lista de Checagem/tendências , Criança , Humanos , Aplicativos Móveis/tendências , Pediatria/tendências , Sociedades Médicas/tendências
20.
Mol Divers ; 23(2): 371-379, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30284694

RESUMO

The aim of the present study is to show how molecular topology can be a powerful in silico tool for the prediction of the fungicidal activity of several diphenylamine derivatives against three fungal species (cucumber downy mildew, rice blast and cucumber gray mold). A multi-target QSAR model was developed, and two strategies were followed. First is the construction of a virtual library of molecules using DesMol2 program and a subsequent selection of potential active ones. Second is the selection of molecules from the literature on the basis of molecular scaffolds. More than 700 diphenylamine derivatives designed and other 60 fluazinam's derivatives with structural similarity higher than 80% were studied. Almost twenty percent of the molecules analyzed show potential activity against the three fungal species.


Assuntos
Fungicidas Industriais/química , Modelos Moleculares , Química Agrícola , Simulação por Computador , Relação Quantitativa Estrutura-Atividade , Pesquisa
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