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BACKGROUND: In this study, we identified key discrete clinical and technical factors that may correlate with primary reconstructive success in endoscopic skull base surgery (ESBS). METHODS: ESBS cases with intraoperative cerebrospinal fluid (CSF) leaks at four tertiary academic rhinology programs were retrospectively reviewed. Logistic regression identified factors associated with surgical outcomes by defect subsite (anterior cranial fossa [ACF], suprasellar [SS], purely sellar, posterior cranial fossa [PCF]). RESULTS: Of 706 patients (50.4% female), 61.9% had pituitary adenomas, 73.4% had sellar or SS defects, and 20.5% had high-flow intraoperative CSF leaks. The postoperative CSF leak rate was 7.8%. Larger defect size predicted ACF postoperative leaks; use of rigid reconstruction and older age protected against sellar postoperative leaks; and use of dural sealants compared to fibrin glue protected against PCF postoperative leaks. SS postoperative leaks occurred less frequently with the use of dural onlay. Body-mass index, intraoperative CSF leak flow rate, and the use of lumbar drain were not significantly associated with postoperative CSF leak. Meningitis was associated with larger tumors in ACF defects, nondissolvable nasal packing in SS defects, and high-flow intraoperative leaks in PCF defects. Sinus infections were more common in sellar defects with synthetic grafts and nondissolvable nasal packing. CONCLUSIONS: Depending on defect subsite, reconstructive success following ESBS may be influenced by factors, such as age, defect size, and the use of rigid reconstruction, dural onlay, and tissue sealants.
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Vazamento de Líquido Cefalorraquidiano , Endoscopia , Procedimentos de Cirurgia Plástica , Base do Crânio , Humanos , Feminino , Masculino , Base do Crânio/cirurgia , Vazamento de Líquido Cefalorraquidiano/etiologia , Vazamento de Líquido Cefalorraquidiano/prevenção & controle , Vazamento de Líquido Cefalorraquidiano/epidemiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Endoscopia/métodos , Procedimentos de Cirurgia Plástica/métodos , Adulto , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Idoso , Neoplasias Hipofisárias/cirurgia , Neoplasias da Base do Crânio/cirurgia , Rinorreia de Líquido Cefalorraquidiano/prevenção & controle , Rinorreia de Líquido Cefalorraquidiano/cirurgia , Rinorreia de Líquido Cefalorraquidiano/etiologiaRESUMO
Cancer cells adapt metabolically to proliferate under nutrient limitation. Here we used combined transcriptional-metabolomic network analysis to identify metabolic pathways that support glucose-independent tumor cell proliferation. We found that glucose deprivation stimulated re-wiring of the tricarboxylic acid (TCA) cycle and early steps of gluconeogenesis to promote glucose-independent cell proliferation. Glucose limitation promoted the production of phosphoenolpyruvate (PEP) from glutamine via the activity of mitochondrial PEP-carboxykinase (PCK2). Under these conditions, glutamine-derived PEP was used to fuel biosynthetic pathways normally sustained by glucose, including serine and purine biosynthesis. PCK2 expression was required to maintain tumor cell proliferation under limited-glucose conditions in vitro and tumor growth in vivo. Elevated PCK2 expression is observed in several human tumor types and enriched in tumor tissue from non-small-cell lung cancer (NSCLC) patients. Our results define a role for PCK2 in cancer cell metabolic reprogramming that promotes glucose-independent cell growth and metabolic stress resistance in human tumors.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Regulação Neoplásica da Expressão Gênica , Gluconeogênese/genética , Neoplasias Pulmonares/metabolismo , Neoplasias/metabolismo , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Adaptação Fisiológica/genética , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Ciclo do Ácido Cítrico/genética , Glucose/deficiência , Glutamina/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metabolômica , Camundongos , Camundongos Nus , Mitocôndrias/metabolismo , Neoplasias/genética , Neoplasias/patologia , Fosfoenolpiruvato/metabolismo , Fosfoenolpiruvato Carboxiquinase (ATP)/genética , Purinas/biossíntese , Ácido Pirúvico/metabolismo , Serina/biossínteseRESUMO
This paper uses modal analysis to investigate the effect of manipulating drumhead tension on the modal frequency ratios of a cylindrical drum with two drumheads. This analysis evaluates a drum's free vibration after excitation. It is shown that the frequency of the (01) mode of the drum is the same on both heads, whereas the frequency of each (11) mode has a decreased dependence on that of the opposite drumhead. This allows manipulation of the ratios for the (11) modes of the batter and resonant heads with respect to the overall (01) mode. This manipulation is shown to allow a range of tunings such that the (11) mode of the batter head can be tuned to a ratio of 1.5× that of the (01) mode.
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OBJECTIVE: YouTube has become the preferred resource for trainees to learn and prepare for surgical cases. This study evaluated the educational quality of YouTube videos detailing thyroidectomy and parathyroidectomy. METHOD: YouTube was systematically searched using 11 terms related to thyroidectomy and parathyroidectomy. Four independent clinical reviewers assessed the videos using Laparoscopic Surgery Video Educational Guidelines as well as modified Laparoscopic Surgery Video Educational Guidelines subgroup tools. RESULTS: Sixty-five videos were identified and evaluated. Overall Laparoscopic Surgery Video Educational Guidelines score was 8.58 ± 3.85 (mean subgroup score, 5.67 ± 2.40). Twenty-eight of 65, 25 of 65 and 12 of 65 videos were deemed medium, low and high quality, respectively. Inter-rater reliability was good for both attending surgeons and residents. Presence of audio or visual commentary had a positive correlation with total Laparoscopic Surgery Video Educational Guidelines scores (R2=0.38). Videos produced by otolaryngologists and US-based physicians scored higher on total scores compared to non-otolaryngology and non-US based physicians. CONCLUSION: Some YouTube videos on thyroidectomy and parathyroidectomy exhibit high educational value. Future efforts should increase the number of high-quality YouTube videos containing both audio and visual commentary or create an online repository of videos for medical students and residents to augment their surgical training.
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Mídias Sociais , Humanos , Paratireoidectomia , Reprodutibilidade dos Testes , Tireoidectomia , Gravação em VídeoRESUMO
BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a helpful adjunct in the control of non-compressible truncal hemorrhage. Concerns regarding ischemia time limits its applicability in transfer. We describe the first reported case of civilian transfer via aeromedical transport to a higher level of care with a zone 3 REBOA catheter deployed. CASE REPORT: We present the case of a patient in hemorrhagic shock with a complex pelvic fracture exceeding the capability of a rural level-two trauma center requiring the use of REBOA catheter to permit aeromedical transport to a level-one trauma center for definitive embolization. CONCLUSION: Deployment of REBOA catheter to facilitate aeromedical transport to an appropriate level of care may be considered if travel times can be kept brief and there is a process and training in place to empower flight medics to consider transporting with a REBOA deployed.
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BACKGROUND: While pediatric trauma centers (PTCs) and adult trauma centers (ATCs) exhibit equivalent trauma mortality, the optimal care environment for traumatically injured adolescents remains controversial. Race has been shown to effect triage within emergency departments (EDs) with people of color receiving lower acuity triage scores. We hypothesized that African-American adolescents were more likely triaged to an ATC than a PTC compared with their White peers. METHODS: Institutional trauma databases from a neighboring, urban Level I PTC and ATC were queried for gunshot wounds in adolescents (15-18 years) presenting to the ED from 2015 to 2017. The PTC and ATC were compared in terms of demographics, services, and outcomes. Results were analyzed using univariate analysis and logistic regression. RESULTS: Among 316 included adolescents, 184 were treated in an ATC versus 132 in a PTC. Patients at the PTC were significantly more likely to be younger (16.1 vs. 17.5 years; p < 0.001), White (16% vs. 5%; p = 0.001), and privately insured (41% vs. 30%; p = 0.002). At each age, the proportion of Whites treated at the PTC exceeded the proportion of African-Americans. At the PTC, patients were more likely to receive inpatient and outpatient social work follow-up (89% vs. 1%, p < 0.001). Adolescents treated at the PTC were less likely to receive opioids (75% vs. 56%, p = 0.001) at discharge and to return to ED within 6 months (25% vs. 11%, p = 0.005). On multivariate logistic regression, African-American adolescents were less likely to be treated at a PTC (odds ratio, 0.30; 95% confidence interval, 0.10-0.85; p = 0.02) after controlling for age and Injury Severity Score. CONCLUSION: Disparities in triage of African-American and White adolescents after bullet injury lead to unequal care. African-Americans were more likely to be treated at the ATC, which was associated with increased opioid prescription, decreased social work support, and increased return to ED. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level IV.
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Negro ou Afro-Americano/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Centros de Traumatologia , Triagem , População Branca/estatística & dados numéricos , Ferimentos por Arma de Fogo/etnologia , Ferimentos por Arma de Fogo/terapia , Adolescente , Humanos , Masculino , Estados UnidosRESUMO
INTRODUCTION: To determine whether there is a benefit to platelet transfusion in mild traumatic brain injury (MTBI) patients with intracranial hemorrhage (ICH), taking antiplatelet therapy before hospitalization. MATERIALS AND METHODS: The study design retrospectively reviewed patients admitted to a Level I trauma center during a 2-year period with an isolated MTBI (Glasgow Coma Scale score ≥13, ICH seen on a head computed tomographic scan (head computed tomography [HCT]), and taking an antiplatelet agent before hospitalization. HCT's were categorized based on the Marshall Classification, Rotterdam Score, and ICH volume. Hospital records were reviewed noting neurologic, cardiac, respiratory events, and discharge Glasgow Outcome Scale. RESULTS: There were 1,101 patients with TBI hospitalized during the 2-year study period. Three hundred twenty-one of these patients had an MTBI with ICH at the time of admission, and from this group, 113 were taking an antiplatelet agent. Only 4 (1.2%) of the 321 patients suffered a neurologic decline. All were gradual in nature, and none required emergent intervention. An analysis of the 113 patients taking antiplatelet agents, comparing patients who were not given a platelet transfusion with those who received a platelet transfusion, found no significant difference in the rate of HCT progression, neurologic decline, or Glasgow Outcome Scale at hospital discharge between the two groups. There was a trend, which was not significant, toward more medical declines in patients who received a platelet transfusion. A further review, analyzing all 321 patients with ICH showed receiving a transfusion of any type (i.e., platelets, fresh frozen plasma, or blood) was a strong predictor of medical decline (p < 0.0001). The odds ratio of having a medical decline after transfusion was 5.8 (95% confidence interval, 1.2-28.2). CONCLUSIONS: Platelet transfusion did not improve short-term outcomes after MTBI. Further randomized controlled trials need to be done to truly assess if there is no benefit in platelet transfusion in patients taking antiplatelet agents suffering an MTBI. Because the overall outcome in MTBI patients is favorable, platelet transfusion in these patients may not be indicated.
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Lesões Encefálicas/terapia , Hemorragias Intracranianas/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , Transfusão de Plaquetas , Adulto , Progressão da Doença , Feminino , Escala de Coma de Glasgow , Escala de Resultado de Glasgow , Humanos , Tempo de Internação , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To determine a) if a checklist covering a diverse group of intensive care unit protocols and objectives would improve clinician consideration of these domains and b) if improved consideration would change practice patterns. DESIGN: Pre- and post observational study. SETTING: A 24-bed surgical/burn/trauma intensive care unit in a teaching hospital. PATIENTS: A total of 1399 patients admitted between June 2006 and May 2007. INTERVENTIONS: The first component of the study evaluated whether mandating verbal review of a checklist covering 14 intensive care unit best practices altered verbal consideration of these domains. Evaluation was performed using real-time bedside audits on morning rounds. The second component evaluated whether the checklist altered implementation of these domains by changing practice patterns. Evaluation was performed by analyzing data from the Project IMPACT database after patients left the intensive care unit. MEASUREMENTS AND MAIN RESULTS: Verbal consideration of evaluable domains improved from 90.9% (530/583) to 99.7% (669/671, p < .0001) after verbal review of the checklist was mandated. Bedside consideration improved on the use of deep venous thrombosis prophylaxis (p < .05), stress ulcer prophylaxis (p < .01), oral care for ventilated patients (p < 0.01), electrolyte repletion (p < .01), initiation of physical therapy (p < .05), and documentation of restraint orders (p < .0001). Mandatory verbal review of the checklist resulted in a greater than two-fold increase in transferring patients out of the intensive care unit on telemetry (16% vs. 35%, p < .0001) and initiation of physical therapy (28% vs. 42%, p < .0001) compared with baseline practice. CONCLUSIONS: A mandatory verbal review of a checklist covering a wide range of objectives and goals at each patient's bedside is an effective method to improve both consideration and implementation of intensive care unit best practices. A bedside checklist is a simple, cost-effective method to prevent errors of omission in basic domains of intensive care unit management that might otherwise be forgotten in the setting of more urgent care requirements.
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Cuidados Críticos/normas , Medicina Baseada em Evidências/normas , Fidelidade a Diretrizes/normas , Implementação de Plano de Saúde , Programas Obrigatórios , Análise Custo-Benefício/normas , Cuidados Críticos/economia , Medicina Baseada em Evidências/economia , Feminino , Fidelidade a Diretrizes/economia , Implementação de Plano de Saúde/economia , Mortalidade Hospitalar , Hospitais de Ensino/economia , Hospitais Universitários , Humanos , Unidades de Terapia Intensiva/economia , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/economia , Masculino , Programas Obrigatórios/economia , Programas Obrigatórios/estatística & dados numéricos , Erros Médicos/prevenção & controle , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde/estatística & dados numéricos , Transferência de Pacientes/economia , Transferência de Pacientes/normas , Garantia da Qualidade dos Cuidados de Saúde/economia , Garantia da Qualidade dos Cuidados de Saúde/normas , Resultado do Tratamento , WashingtonRESUMO
OBJECTIVES: To examine the feasibility and potential utility of a tracheostomy protocol based on a standardized approach to ventilator weaning. DESIGN: Prospective, observational data collection. SETTING: Academic medical center. PATIENTS: Surgical intensive care unit patients requiring mechanical ventilatory support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Tracheostomy practice in 200 patients was analyzed in relation to spontaneous breathing trial (SBT) weaning. Decision for, and performance of, tracheostomy occurred (median [interquartile range]) 5.0 (3.75-8.0) and 7.0 (5.0-10.0) days following initiation of mechanical ventilation, respectively. Duration of mechanical ventilation was greater in tracheostomy compared with nontracheostomy patients (15.0 [11.0-19.0] vs. 6.0 [4.0-8.0], p < .001). For patients requiring ventilatory support for > or = 20 days, 100% of patients were maintained via tracheostomy. A protocol based on weaning performance, which included technical considerations, was developed. Individuals who failed preliminary weaning assessment or SBT for 3 successive days following 5 days (nonreintubated patients) or 3 days (reintubated patients) of ventilatory support met tracheostomy criteria. The protocol was implemented on a pilot basis in 125 individuals. Of the 55 (44.0%) patients undergoing tracheostomy, 25 (45.5%) did so consistent with criteria. Eighteen patients (32.7%) underwent tracheostomy before the time interval of data collection targeting weaning protocol performance, and 12 patients (21.8%) passed SBT on one or more occasions, were not extubated, and proceeded to tracheostomy. CONCLUSIONS: A standardized approach in which the decision for tracheostomy is based on objective measures of weaning performance may be a means of using this procedure more consistently and effectively.
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Cuidados Críticos/normas , Procedimentos Clínicos/normas , Traqueostomia/normas , Desmame do Respirador/normas , Centros Médicos Acadêmicos , Algoritmos , Benchmarking/normas , Técnicas de Apoio para a Decisão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Missouri , Projetos Piloto , Estudos Prospectivos , Garantia da Qualidade dos Cuidados de Saúde/normasRESUMO
Extracorporeal membrane oxygenation (ECMO) is a technique for providing life support for patients experiencing both pulmonary and cardiac failure by maintaining oxygenation and perfusion until native organ function is restored. ECMO is used routinely at many specialized hospitals for infants and less commonly for children with respiratory or cardiac failure from a variety of causes. Its usage is more controversial in adults, but select medical centers have reported favorable findings in patients with ARDS and other causes of severe pulmonary failure. ECMO is also rarely used as a rescue therapy in a small subset of adult patients with cardiac failure. This article will review the current uses and techniques of ECMO in the critical care setting as well as the evidence supporting its usage. In addition, current practice management related to coding and reimbursement for this intensive therapy will be discussed.
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Oxigenação por Membrana Extracorpórea/tendências , Controle de Formulários e Registros/tendências , Reembolso de Seguro de Saúde/tendências , Administração da Prática Médica/tendências , Oxigenação por Membrana Extracorpórea/economia , Oxigenação por Membrana Extracorpórea/métodos , Controle de Formulários e Registros/economia , Insuficiência Cardíaca/terapia , Humanos , Reembolso de Seguro de Saúde/economia , Administração da Prática Médica/economia , Insuficiência Respiratória/terapiaRESUMO
PURPOSE OF REVIEW: Appropriate measurements of success in trauma systems are evolving. We review the rationale behind prior trauma and rehabilitation outcomes measures, and how they have led to the current rehabilitation tools in use today. In addition, we review the difficulties with current methods and future improvements that need to occur. RECENT FINDINGS: As medicine marches toward improved used of clinical evidence, trauma practitioners have worked for improved outcomes research. A major part of this is that outcomes such as functional status and quality of life are as important as mortality statistics. Trauma rehabilitation outcomes are thus more important, yet in the past all such tools have had major impediments to implementation across a heterogeneous trauma population. Newly recognized major domains such as quality of life, preinjury status, patient perceptions, and actual function at work have not been adequately addressed with current rehabilitation measures. At this time, no clinically applicable trauma rehabilitation score exists. SUMMARY: Trauma rehabilitation outcomes are an important measurement of trauma system effectiveness. A more effective, easily applied rehabilitation score is needed to adequately assess all appropriate domains of clinical improvement in the injured patient.
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Avaliação de Resultados em Cuidados de Saúde/normas , Ferimentos e Lesões/reabilitação , Determinação de Ponto Final , Humanos , Avaliação de Resultados em Cuidados de Saúde/métodos , Qualidade de VidaRESUMO
BACKGROUND: Current guidelines recommend using antiseptic- or antibiotic-impregnated central venous catheters (CVCs) if, following a comprehensive strategy to prevent catheter-related blood stream infection (CR-BSI), infection rates remain above institutional goals based on benchmark values. The purpose of this study was to determine if chlorhexidine/silver sulfadiazine-impregnated CVCs could decrease the CR-BSI rate in an intensive care unit (ICU) with a low baseline infection rate. METHODS: Pre-intervention and post-intervention observational study in a 24-bed surgical/trauma/burn ICU from October, 2002 to August, 2005. All patients requiring CVC placement after March, 2004 had a chlorhexidine/silver sulfadiazine-impregnated catheter inserted (post-intervention period). RESULTS: Twenty-three CR-BSIs occurred in 6,960 catheter days (3.3 per 1,000 catheter days)during the 17-month control period. After introduction of chlorhexidine/silver sulfadiazine-impregnated catheters, 16 CR-BSIs occurred in 7,732 catheter days (2.1 per 1,000 catheter days; p = 0.16). The average length of time required for an infection to become established after catheterization was similar in the two groups (8.4 vs. 8.6 days; p = 0.85). Chlorhexidine/silver sulfadiazine-impregnated catheters did not result in a statistically significant change in the microbiological profile of CR-BSIs, nor did they increase the incidence of resistant organisms. CONCLUSIONS: Although chlorhexidine/silver sulfadiazine-impregnated catheters are useful in specific patient populations, they did not result in a statistically significant decrease in the CR-BSI rate in this study, beyond what was achieved with education alone.
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Anti-Infecciosos Locais/administração & dosagem , Bacteriemia/prevenção & controle , Cateterismo Venoso Central/instrumentação , Cateteres de Demora/microbiologia , Infecção Hospitalar/prevenção & controle , Adulto , Idoso , Bacteriemia/etiologia , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Clorexidina/administração & dosagem , Feminino , Fungemia/etiologia , Fungemia/prevenção & controle , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Sulfadiazina de Prata/administração & dosagemRESUMO
BACKGROUND: In the United States, there is a perceived divide regarding the benefits and risks of firearm ownership. The American College of Surgeons Committee on Trauma Injury Prevention and Control Committee designed a survey to evaluate Committee on Trauma (COT) member attitudes about firearm ownership, freedom, responsibility, physician-patient freedom and policy, with the objective of using survey results to inform firearm injury prevention policy development. METHODS: A 32-question survey was sent to 254 current U.S. COT members by email using Qualtrics. SPSS was used for χ exact tests and nonparametric tests, with statistical significance being less than 0.05. RESULTS: Our response rate was 93%, 43% of COT members have firearm(s) in their home, 88% believe that the American College of Surgeons should give the highest or a high priority to reducing firearm-related injuries, 86% believe health care professionals should be allowed to counsel patients on firearms safety, 94% support federal funding for firearms injury prevention research. The COT participants were asked to provide their opinion on the American College of Surgeons initiating advocacy efforts and there was 90% or greater agreement on 7 of 15 and 80% or greater on 10 of 15 initiatives. CONCLUSION: The COT surgeons agree on: (1) the importance of formally addressing firearm injury prevention, (2) allowing federal funds to support research on firearms injury prevention, (3) retaining the ability of health care professionals to counsel patients on firearms-related injury prevention, and (4) the majority of policy initiatives targeted to reduce interpersonal violence and firearm injury. It is incumbent on trauma and injury prevention organizations to leverage these consensus-based results to initiate prevention, advocacy, and other efforts to decrease firearms injury and death. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level I; therapeutic care, level II.
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Ferimentos por Arma de Fogo/prevenção & controle , Consenso , Feminino , Armas de Fogo/estatística & dados numéricos , Humanos , Masculino , Propriedade/estatística & dados numéricos , Política Pública , Segurança , Sociedades Médicas , Inquéritos e Questionários , Traumatologia/estatística & dados numéricos , Estados UnidosRESUMO
BACKGROUND: Medical errors are common, and physicians have notably been poor medical error reporters. In the SICU, reporting was generally poor and reporting by physicians was virtually nonexistent. This study was designed to observe changes in error reporting in an SICU when a new card-based system (SAFE) was introduced. STUDY DESIGN: Before implementation of the SAFE reporting system, education was given to all SICU healthcare providers. The SAFE system was introduced into the SICU for a 9-month period from March 2003 through November 2003, to replace an underused online system. Data were collected from the SAFE card reports and the online reporting systems during introduction, removal, and reimplementation of these cards. Reporting rates were calculated as number of reported events per 1,000 patient days. RESULTS: Reporting rates increased from 19 to 51 reports per 1,000 patient days after the SAFE cards were introduced into the ICU (p= 0.001). Physician reporting increased most, rising from 0.3 to 5.8 reports per 1,000 patient days; nursing reporting also increased from 18 to 39 reports per 1,000 patient days (both p=0.001). When the SAFE cards were removed, physician reporting declined to 0 reports per 1,000 patient days (p=0.01) and rose to 8.1 (p=0.001) when the cards were returned, similar to nursing results. A higher proportion of physician reports were events that caused harm compared with no effect (p < 0.05). CONCLUSIONS: A card reporting system, combined with appropriate education, improved overall reporting in the SICU, especially among physician providers. Nurses were more likely to use reporting systems than were physicians. Physician reports were more likely to be of events that caused harm.
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Unidades de Terapia Intensiva/estatística & dados numéricos , Sistemas Computadorizados de Registros Médicos/tendências , Médicos , Gestão de Riscos/métodos , Procedimentos Cirúrgicos Operatórios , Adulto , Controle de Formulários e Registros , Humanos , Erros Médicos/prevenção & controle , Erros Médicos/estatística & dados numéricos , Gestão de Riscos/tendênciasRESUMO
Many of the effects of ANP are mediated through the elevation of cellular cGMP levels by the activation of particulate guanylate cyclase. While the stimulation of this enzyme is receptor-mediated, the molecular mechanism of activation remains unknown. In this study we present evidence that ATP as well as its analogues adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S) and adenylylimidophosphate (AMPPNP) activates guanylate cyclase from rat lung membranes and markedly potentiates the effect of ANP on the enzyme. The order of potency is ATP gamma S greater than ATP greater than AMPPNP. The enzyme activation by adenine nucleotide and ANP together is much more than the sum of the individual activations, suggesting that ATP may be the physiological component essential for the ANP-stimulated guanylate cyclase activation. The ATP gamma S-stimulated guanylate cyclase activity diminishes in the presence of various kinds of detergents, suggesting either that the conformation of an ATP binding site in guanylate cyclase is altered by detergents or that protein-protein interaction may be involved in the activation of guanylate cyclase by ATP. Guanylate cyclase from rat lung membranes is poorly activated by ANP and/or ATP gamma S after removing the cytosolic and weakly membrane-associated proteins or factors by centrifugation. Pre-incubation of the membranes with ATP gamma S retains enzyme activation after membrane washing. These results suggest either that ATP gamma S stabilizes the conformation of nucleotide binding site in guanylate cyclase from denaturation by membrane washing, or that the stimulatory effect of ATP on guanylate cyclase activity may be mediated by accessory proteins or non-protein cofactors which are lost during membrane washing, but remain bound to membranes by ATP gamma S pretreatment.
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Trifosfato de Adenosina/farmacologia , Guanilato Ciclase/metabolismo , Pulmão/enzimologia , Trifosfato de Adenosina/análogos & derivados , Adenilil Imidodifosfato/farmacologia , Animais , Fator Natriurético Atrial/farmacologia , Membrana Celular/enzimologia , Ativação Enzimática , Guanosina 5'-O-(3-Tiotrifosfato) , Guanosina Trifosfato/análogos & derivados , Guanosina Trifosfato/farmacologia , Guanilil Imidodifosfato/farmacologia , Cinética , Ratos , Tionucleotídeos/farmacologiaRESUMO
PURPOSE: We investigated the potential of cyclooxygenase (COX)-2 as anappropriate chemopreventive and/or therapeutic target for oral cancer. EXPERIMENTAL DESIGN: Immunohistochemical analysis of COX-2 expression was carried out on 37 oral squamous cell carcinomas (OSCCs) and 23 normal oral epithelium samples. We investigated whether the COX-2-selective inhibitor NS398 induced growth inhibition in four human OSCC cell lines and whether this was COX-2 dependent. RESULTS: COX-2 staining was more intense in the carcinomas compared with normal epithelium (P < 0.001). Early-stage tumors (stages I and II) had significantly higher epithelial COX-2 staining than late-stage tumors (stages III and IV; P = 0.034), and overexpression of COX-2 was detected in hyperplastic and dysplastic epithelium. Treatment of OSCC cells with NS398 for 72 h at concentrations of 50 micro M and above resulted in growth inhibition accompanied by a reversible G(0)-G(1) arrest, but no apoptosis or terminal differentiation. However, a concentration of 10 micro M was sufficient to abolish secreted prostaglandin E(2) (PGE(2)) production. Over a longer treatment time, lower concentrations of NS398 were growth inhibitory. Growth inhibition of the OSCC cell line H357 was detected after treatment with 5 micro M NS398 as well as 100 micro M NS398 for 6-12 days. In cultures treated with 5 micro M NS398, but not in those treated with 100 micro M NS398, restoration of PGE(2) to control levels abrogated growth inhibition. CONCLUSIONS: NS398 inhibits the growth of OSCC cells by mechanisms that are dependent and independent of suppression of PGE(2) synthesis. Molecular targeting of COX-2, PGE(2) synthase, or PGE(2) receptors may be useful as a chemopreventive or therapeutic strategy for oral cancer.
Assuntos
Carcinoma de Células Escamosas/patologia , Inibidores de Ciclo-Oxigenase/farmacologia , Dinoprostona/biossíntese , Isoenzimas/antagonistas & inibidores , Neoplasias Bucais/patologia , Nitrobenzenos/farmacologia , Sulfonamidas/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Isoenzimas/metabolismo , Queratinócitos/enzimologia , Queratinócitos/patologia , Proteínas de Membrana , Neoplasias Bucais/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Transfecção , Células Tumorais CultivadasRESUMO
BACKGROUND: Use of chlorhexidine and silver sulfadiazine-impregnated (CSS) central venous catheters (CVCs) has not been shown to decrease the catheter-related bloodstream infection rate in an ICU. The purpose of this study was to determine if use of minocycline and rifampin-impregnated (MR) CVCs would decrease central line-associated bloodstream infection (CLABSI) rates compared with those observed with use of CSS-impregnated CVCs. STUDY DESIGN: A total of 7,181 patients were admitted to a 24-bed university hospital surgical ICU: 2,551 between March 2004 and August 2005 (period 1) and 4,630 between April 2006 and July 2008 (period 2). All patients requiring CVC placement in period 1 had a CSS catheter inserted, and in period 2 all patients had MR CVCs placed. RESULTS: Twenty-two CLABSIs occurred during 7,732 catheter days (2.7 per 1,000 catheter days) in the 18-month period when CSS lines were used. After the introduction of MR CVCs, 21 catheter-related bloodstream infections occurred during 15,722 catheter days (1.4 per 1,000 catheter days). This represents a significant (p < 0.05) decrease in the CLABSI rate after introduction of MR CVCs. Mean length of time to infection developing after catheterization (8.6 days for CSS vs 6.1 days for MR) was also different (p = 0.04). The presence of MR did not alter the microbiologic profile of catheter-related infections, and it did not increase the incidence of resistant organisms. CONCLUSIONS: The CLABSI rate decreased more with the use of MR CVCs compared with CSS CVCs in an ICU where the CLABSI rate was already low. The types of organisms causing infection were similar. With continued use of MR-impregnated CVCs in our ICU in the subsequent 5 years, we have seen sustained low rates of CLABSIs.
Assuntos
Anti-Infecciosos/administração & dosagem , Bacteriemia/prevenção & controle , Infecções Relacionadas a Cateter/prevenção & controle , Minociclina/administração & dosagem , Rifampina/administração & dosagem , Centros Médicos Acadêmicos , Bacteriemia/etiologia , Infecções Relacionadas a Cateter/etiologia , Cateteres Venosos Centrais/efeitos adversos , Clorexidina/administração & dosagem , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Sulfadiazina de Prata/administração & dosagem , Resultado do TratamentoRESUMO
This study analyzes data pertaining to 12 rapes and rape-murders committed by one male adolescent offender over a 4-year period. All offenses except the first were committed while the offender was under psychiatric and probationary supervision. The use or relinquishment of violence by the offender was found to be dependent on subtle interpersonal factors. The authors stress the importance of the use of crime scene data and interviews of patients who have committed sex crimes, the role of psychological profiles in apprehension of suspects, and the contribution of law enforcement as a data resource.
Assuntos
Psicologia Criminal , Homicídio , Estupro , Adolescente , Adulto , Coleta de Dados , Feminino , Psiquiatria Legal , Humanos , Entrevista Psicológica , Masculino , Transtornos Mentais/psicologia , Controle Social Formal , ViolênciaRESUMO
We conducted a prospective study to determine the role of the esophagus in causing chest pain in patients with established CAD on optimum therapy. Thirty-two men with documented CAD who complained of frequent and usually daily retrosternal chest pain were evaluated. Following a standard esophageal manometry and acid perfusion test, simultaneous two-channel ambulatory Holter monitor and esophageal pH record tests were performed for 24 hours. Fifty-three episodes of chest pain were documented in 20 patients; 11 patients were free of pain. Of the 20 patients who complained of chest pains, 17 (85 percent) demonstrated at least one episode of PPR, defined as a drop in distal esophageal pH to less than 4 within ten minutes before or after the onset chest pain. Episodes of asymptomatic GER were common. The correlation of PPR with chest pain was 70 percent (37/53 episodes) and of ischemic ECG changes with chest pain 13 percent (7/53); in the remaining, there was no correlation with either. Two patients demonstrated simultaneous PPR and ischemic ECG changes. Seventeen esophageal motility abnormalities were observed in 14 patients (45 percent). It is our conclusion that esophageal disorders contribute to chest pain in patients with documented CAD. In this group, GER plays a greater role than in those with normal coronary arteries. In addition, esophageal motility disorders are common in these patients. Esophageal testing can be undertaken safely in these patients.