RESUMEN
BACKGROUND: With a median age at diagnosis of 70, lung cancer remains a significant public health challenge for older Americans. Surgery is a key component in treating most patients with non-metastatic lung cancer. These patients experience postoperative pain, fatigue, loss of respiratory capacity, and decreased physical function. Data on quality of life (QOL) in older adults undergoing lung cancer surgery is limited, and few interventions are designed to target the needs of older adults and their family caregivers (FCGs). The primary aim of this comparative effectiveness trial is to determine whether telephone-based physical activity coaching before and after surgery will be more beneficial than physical activity self-monitoring alone for older adults and their FCGs. METHODS: In this multicenter comparative effectiveness trial, 382 older adults (≥ 65 years) with lung cancer and their FCGs will be recruited before surgery and randomized to either telephone-based physical activity coaching or physical activity self-monitoring alone. Participants allocated to the telephone-based coaching comparator will receive five telephone sessions with coaches (1 pre and 4 post surgery), an intervention resource manual, and a wristband pedometer. Participants in the self-monitoring only arm will receive American Society of Clinical Oncology (ASCO) physical activity information and wristband pedometers. All participants will be assessed at before surgery (baseline), at discharge, and at days 30, 60, and 180 post-discharge. The primary endpoint is the 6-minute walk test (6MWT) at 30 days post-discharge. Geriatric assessment, lower extremity function, self-reported physical function, self-efficacy, and QOL will also be assessed. DISCUSSION: The trial will determine whether this telephone-based physical activity coaching approach can enhance postoperative functional capacity and QOL outcomes for older adults with lung cancer and their FCGs. Trial results will provide critical findings to inform models of postoperative care for older adults with cancer and their FCGs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06196008.
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Cuidadores , Ejercicio Físico , Neoplasias Pulmonares , Calidad de Vida , Humanos , Anciano , Neoplasias Pulmonares/cirugía , Masculino , Femenino , Teléfono , Atención Perioperativa/métodosRESUMEN
Aim: Stakeholder engagement is central to comparative effectiveness research yet there are gaps in definitions of success. We used a framework developed by Lavallee et al. defining effective engagement criteria to evaluate stakeholder engagement during a pragmatic cluster-randomized trial. Methods: Semi-structured interviews were developed from the framework and completed to learn about members' experiences. Interviews were analyzed in a deductive approach for themes related to the effective engagement criteria. Results: Thirteen members participated and described: respect for ideas, time to achieve consensus, access to information and continuous feedback as areas of effective engagement. The primary criticism was lack of diversity. Discussion: Feedback was positive, particularly among themes of respect, trust and competence, and led to development of a list of best practices for engagement. The framework was successful for evaluating engagement. Conclusion: Standardized frameworks allow studies to formally evaluate their stakeholder engagement approach and develop best practices for future research.
What is this article about? This article is about the evaluation of how effective the stakeholder engagement was in a comparative effectiveness research (CER) study funded by the Patient Centered Outcomes Research Institute (PCORI). The research team found a framework (developed by Lavalle et al.) that defined six different criteria for effective stakeholder engagement, and used that criteria to complete semi-structured interviews with the stakeholders involved with our study. These interviews were reviewed to determine what stakeholder engagement processes were successful and helped provide a list of best practices for stakeholder engagement for other researchers doing CER. What were the results? Stakeholders highlighted respect for their ideas, time to achieve consensus, easy access to information and a continuous feedback loop between study team and stakeholders as effective engagement processes. What do the results mean? These results can help other researchers doing CER learn best practices to implement from the outset of a study to best engage stakeholders in their research. The results also show that having a standardized framework to evaluate stakeholder engagement is important and allows for research teams to formally evaluate their engagement approach and learn what was successful and where there are areas for improvement in future studies.
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Investigación sobre la Eficacia Comparativa , Participación de los Interesados , Humanos , Investigación sobre la Eficacia Comparativa/métodos , Evaluación del Resultado de la Atención al PacienteRESUMEN
PURPOSE: Biomarker-driven master protocols represent a new paradigm in oncology clinical trials, but their complex designs and wide-ranging genomic results returned can be difficult to communicate to participants. The objective of this pilot study was to evaluate patient knowledge and expectations related to return of genomic results in the Lung Cancer Master Protocol (Lung-MAP). METHODS: Eligible participants with previously treated advanced non-small-cell lung cancer were recruited from patients enrolled in Lung-MAP. Participants completed a 38-item telephone survey ≤ 30 days from Lung-MAP consent. The survey assessed understanding about the benefits and risks of Lung-MAP participation and knowledge of the potential uses of somatic testing results returned. Descriptive statistics and odds ratios for associations between demographic factors and correct responses to survey items were assessed. RESULTS: From August 1, 2017, to June 30, 2019, we recruited 207 participants with a median age of 67, 57.3% male, and 94.2% White. Most participants "strongly/somewhat agreed" with statements that they "received enough information to understand" Lung-MAP benefits (82.6%) and risks (69.5%). In items asking about potential uses of Lung-MAP genomic results, 87.0% correctly indicated that the results help to select cancer treatment, but < 20% correctly indicated that the results are not used to confirm cancer diagnosis, would not reveal risk of developing diseases besides cancer, and would not indicate if family members had increased cancer risk. There were no associations between sociodemographic factors and proportions providing correct responses. CONCLUSION: In a large National Clinical Trials Network biomarker-driven master protocol, most participants demonstrated incorrect knowledge and expectations about the uses of genomic results provided in the study despite most indicating that they had enough information to understand benefits and risks.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Biomarcadores , Carcinoma de Pulmón de Células no Pequeñas/genética , Femenino , Genómica , Humanos , Neoplasias Pulmonares/genética , Masculino , Motivación , Proyectos Piloto , Factores SociodemográficosAsunto(s)
Ensayos Clínicos como Asunto/métodos , Alfabetización en Salud/métodos , National Cancer Institute (U.S.)/organización & administración , Neoplasias/terapia , Selección de Paciente/ética , Medios de Comunicación Sociales/normas , Participación de los Interesados/psicología , Alfabetización Digital , Humanos , Estados UnidosRESUMEN
BACKGROUND: The Fred Hutchinson Cancer Research Center has engaged an External Stakeholder Advisory Group (ESAG) in the planning and implementation of the TrACER Study (S1415CD), a five-year pragmatic clinical trial assessing the effectiveness of a guideline-based colony stimulating factor standing order intervention. The trial is being conducted by SWOG through the National Cancer Institute Community Oncology Research Program in 45 clinics. The ESAG includes ten patient partners, two payers, two pharmacists, two guideline experts, four providers and one medical ethicist. This manuscript describes the ESAG's role and impact on the trial. METHODS: During early trial development, the research team assembled the ESAG to inform plans for each phase of the trial. ESAG members provide feedback and engage in problem solving to improve trial implementation. Each year, members participate in one in-person meeting, web conferences and targeted email discussion. Additionally, they complete a survey that assesses their satisfaction with communication and collaboration. The research team collected and reviewed stakeholder input from 2014 to 2018 for impact on the trial. RESULTS: The ESAG has informed trial design, implementation and dissemination planning. The group advised the trial's endpoints, regimen list and development of cohort and usual care arms. Based on ESAG input, the research team enhanced patient surveys and added pharmacy-related questions to the component application to assess order entry systems. ESAG patient partners collaborated with the research team to develop a patient brochure and study summary for clinic staff. In addition to identifying recruitment strategies and patient-oriented platforms for publicly sharing results, ESAG members participated as co-authors on this manuscript and a conference poster presentation highlighting stakeholder influence on the trial. The annual satisfaction survey results suggest that ESAG members were satisfied with the methods, frequency and target areas of their engagement in the trial during project years 1-3. CONCLUSIONS: Diverse stakeholder engagement has been essential in optimizing the design, implementation and planned dissemination of the TrACER Study. The lessons described in the manuscript may assist others to effectively partner with stakeholders on clinical research.
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Ensayos Clínicos como Asunto/métodos , Neoplasias/terapia , Evaluación del Resultado de la Atención al Paciente , Participación de los Interesados , Consultores , Humanos , Participación del PacienteRESUMEN
Loeys-Dietz syndrome (LDS) is a rare autosomal dominant disease related to genetic mutations in receptors for the cytokine transforming growth factor-receptor type 1 (TGFB-R1) or 2 gene (TGFB-R2) on the cell surface. LDS results in abnormal protein synthesis and dysfunctional connective tissue, which can result in unique cardiovascular anesthesia challenges related to perioperative management. Patients with LDS may manifest hypertelorism, bifid uvula or cleft palate, and arterial tortuosity. Virtually all LDS patients show some type of abnormal skin findings and bleeding tendency. These patients may show a rapid progression of aortic dilation, regurgitation, and a propensity towards rupture and/or dissection at a much earlier age and smaller aneurysm size. LDS patients who require surgical intervention require meticulous vigilance from the anesthesiologist. We describe a 26 year old patient with documented LDS type 1 who presented for repair of an ascending/root aneurysm in this case report. Recognition of LDS and intra-operative management of the cardiovascular manifestations of this disease is paramount in ensuring successful surgical outcome and to limit morbidity and mortality.
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Anestesia , Síndrome de Loeys-Dietz/fisiopatología , Atención Perioperativa , Adulto , Femenino , HumanosRESUMEN
Rapid technological advances for the frequent monitoring of health parameters have raised the intriguing possibility that an individual's genotype could be predicted from phenotypic data alone. Here we used a machine learning approach to analyze the phenotypic effects of polymorphic mutations in a mouse model of Huntington's disease that determine disease presentation and age of onset. The resulting model correlated variation across 3,086 behavioral traits with seven different CAG-repeat lengths in the huntingtin gene (Htt). We selected behavioral signatures for age and CAG-repeat length that most robustly distinguished between mouse lines and validated the model by correctly predicting the repeat length of a blinded mouse line. Sufficient discriminatory power to accurately predict genotype required combined analysis of >200 phenotypic features. Our results suggest that autosomal dominant disease-causing mutations could be predicted through the use of subtle behavioral signatures that emerge in large-scale, combinatorial analyses. Our work provides an open data platform that we now share with the research community to aid efforts focused on understanding the pathways that link behavioral consequences to genetic variation in Huntington's disease.
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Conducta Animal , Genoma/genética , Proteína Huntingtina/genética , Enfermedad de Huntington/genética , Ratones/genética , Fenotipo , Animales , Mapeo Cromosómico/métodos , Estudio de Asociación del Genoma Completo/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Ratones/clasificación , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Thermal death kinetics of Conogethes punctiferalis (Guenée) (Lepidoptera: Pyralidae) at different life stages, heating rate, and temperature is essential for developing postharvest treatments to control pests in chestnuts. Using a heating block system (HBS), the most heat-tolerant life stage of C. punctiferalis and the effects of heating rate (0.1, 0.5, 1, 5, and 10°C/min) on insect mortality were determined. The thermal death kinetic data of fifth-instar C. punctiferalis were obtained at temperatures between 44 and 50°C at a heating rate of 5°C/min. The results showed that the relative heat tolerance of C. punctiferalis was found to be fifth instars>pupae> third instars> eggs. To avoid the enhanced thermal tolerance of C. punctiferalis at low heating rates (0.1 or 0.5°C/min), a high heating rate of 5°C/min was selected to simulate the fast radio frequency heating in chestnuts and further determine the thermal death kinetic data. Thermal death curves of C. punctiferalis followed a 0th-order kinetic reaction model. The minimum exposure time to achieve 100% mortality was 55, 12, 6, and 3 min at 44, 46, 48, and 50°C, respectively. The activation energy for controlling C. punctiferalis was 482.15 kJ/mol with the z value of 4.09°C obtained from the thermal death-time curve. The information provided by thermal death kinetics for C. punctiferalis is useful in developing effective postharvest thermal treatment protocols for disinfesting chestnuts.
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Calor/efectos adversos , Control de Insectos , Mariposas Nocturnas/fisiología , Animales , Calefacción , Larva/crecimiento & desarrollo , Larva/fisiología , Mariposas Nocturnas/crecimiento & desarrollo , Óvulo/crecimiento & desarrollo , Óvulo/fisiología , Pupa/crecimiento & desarrollo , Pupa/fisiologíaRESUMEN
Huntington's disease (HD), a devastating neurodegenerative disorder caused by a CAG repeat expansion on the HTT gene located on chromosome 4, is associated with a characteristic pattern of progressive cognitive dysfunction known to involve early deficits in executive function. A modified Go/No-go successive discrimination task was designed to assess the type of online response control/executive function known to be disrupted in patients with HD. The present studies show that this simple discrimination assay revealed early and robust deficits in two mouse models of HD, the zQ175 KI mouse (deficits from 28 weeks of age) and the R6/2 mouse, carrying ~240 CAG repeats (deficits from 9 weeks of age). These deficits are not due to gross motor dysfunction in the test animals, but instead appear to measure some inability to inhibit responding in the HD mouse models, suggesting this assay may measure deficits in underlying attentional and/or behavioral inhibition processes. Accordingly, this assay may be well suited to evaluation of simple deficits in cognitive function in mouse HD models, providing a potential platform for preclinical screening.
RESUMEN
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of healthcare-associated infections and significant contributor to healthcare cost. Community-associated-MRSA (CA-MRSA) strains have now invaded healthcare settings. A convenience sample of 97 clinical MRSA isolates was obtained from seven hospitals during a one-week period in 2010. We employed a framework integrating Staphylococcus protein A typing and full-genome next-generation sequencing. Single nucleotide polymorphisms were analyzed using phylodynamics. Twenty-six t002, 48 t008, and 23 other strains were identified. Phylodynamic analysis of 30 t008 strains showed ongoing exponential growth of the effective population size the basic reproductive number (R0) ranging from 1.24 to 1.34. No evidence of hospital clusters was identified. The lack of phylogeographic clustering suggests that community introduction is a major contributor to emergence of CA-MRSA strains within hospitals. Phylodynamic analysis provides a powerful framework to investigate MRSA transmission between the community and hospitals, an understanding of which is essential for control.
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Infecciones Comunitarias Adquiridas/epidemiología , Genómica , Staphylococcus aureus Resistente a Meticilina/genética , Epidemiología Molecular , Infecciones Estafilocócicas/epidemiología , Técnicas de Tipificación Bacteriana , Infecciones Comunitarias Adquiridas/genética , Infecciones Comunitarias Adquiridas/microbiología , Estudios Transversales , Dermatoglifia del ADN , ADN Bacteriano/análisis , ADN Bacteriano/genética , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Hospitales , Humanos , Staphylococcus aureus Resistente a Meticilina/clasificación , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Filogenia , Infecciones Estafilocócicas/genética , Infecciones Estafilocócicas/microbiologíaRESUMEN
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor, cognitive and psychiatric manifestations. Since the mutation responsible for the disease was identified as an unstable expansion of CAG repeats in the gene encoding the huntingtin protein in 1993, numerous mouse models of HD have been generated to study disease pathogenesis and evaluate potential therapeutic approaches. Of these, knock-in models best mimic the human condition from a genetic perspective since they express the mutation in the appropriate genetic and protein context. Behaviorally, however, while some abnormal phenotypes have been detected in knock-in mouse models, a model with an earlier and more robust phenotype than the existing models is required. We describe here for the first time a new mouse line, the zQ175 knock-in mouse, derived from a spontaneous expansion of the CAG copy number in our CAG 140 knock-in colony [1]. Given the inverse relationship typically observed between age of HD onset and length of CAG repeat, since this new mouse line carries a significantly higher CAG repeat length it was expected to be more significantly impaired than the parent line. Using a battery of behavioral tests we evaluated both heterozygous and homozygous zQ175 mice. Homozygous mice showed motor and grip strength abnormalities with an early onset (8 and 4 weeks of age, respectively), which were followed by deficits in rotarod and climbing activity at 30 weeks of age and by cognitive deficits at around 1 year of age. Of particular interest for translational work, we also found clear behavioral deficits in heterozygous mice from around 4.5 months of age, especially in the dark phase of the diurnal cycle. Decreased body weight was observed in both heterozygotes and homozygotes, along with significantly reduced survival in the homozygotes. In addition, we detected an early and significant decrease of striatal gene markers from 12 weeks of age. These data suggest that the zQ175 knock-in line could be a suitable model for the evaluation of therapeutic approaches and early events in the pathogenesis of HD.
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Conducta Animal , Modelos Animales de Enfermedad , Técnicas de Sustitución del Gen , Enfermedad de Huntington/genética , Animales , Conducta Animal/efectos de la radiación , Peso Corporal/genética , Cognición/fisiología , Oscuridad , Femenino , Marcadores Genéticos/genética , Fuerza de la Mano/fisiología , Heterocigoto , Homocigoto , Enfermedad de Huntington/fisiopatología , Masculino , Ratones , Neostriado/metabolismo , Proteínas del Tejido Nervioso/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Secuencias Repetitivas de Ácidos Nucleicos , Prueba de Desempeño de Rotación con Aceleración Constante , Análisis de Supervivencia , Transcripción Genética/genéticaRESUMEN
Apathy, characterized by generally reduced interest in and likelihood to perform goal-directed actions, is a recognized symptom of Huntington's disease (HD), a devastating neurological disorder caused by a CAG repeat expansion of the Htt gene located on chromosome 4. The present experiments used a modified progressive ratio task that incorporated a fixed-ratio schedule of reinforcement component to assess consummatory behavior, and a progressive-ratio schedule component that required increasing numbers of lever-presses for successive reinforcers (0.01 ml of evaporated milk). The studies revealed an apathetic phenotype in two mouse models of HD, with decreased response rates either overall or only at higher ratio requirements in the progressive-ratio component relative to wild-type controls. Based on the procedure used (within-session fixed- and progressive-ratio components), it is proposed that an observed phenotype can be ascribed either specifically to reduced motivation to work for food reinforcement or more generally to deficits in consummatory behavior. This procedure provides a simple means to assess this type of phenotype in rodents, with issues in consummatory vs. incentive motivation reflected in general alterations in fixed- versus progressive alterations on an escalating-ratio schedules respectively, providing translational measures of the amotivation/apathy construct of the human realm to the homologous construct of incentive motivation in preclinical models of human disease.
RESUMEN
Mouse models of Huntington's disease (HD) were trained to acquire one of two simple instrumental responses (a lever press or a nosepoke) to obtain food reinforcement. Animals from several HD strains revealed apparently progressive deficits in this task, being significantly less able than littermate controls to perform the required responses, at ages where motor function is only mildly affected. These data could provide a simple way to measure learning deficits in these mouse models, likely related to the characteristic pattern of neural damage observed in HD mouse models.
RESUMEN
PURPOSE: To detail the presence and severity of ocular and cranial nerve abnormalities found in individuals with CHARGE syndrome in a distinct geographic area. METHODS: Nine individuals with CHARGE syndrome from Maritime Canada identified from a Canadian database were prospectively examined. Structural and sensorial defects associated with functional visual deficits were defined with ophthalmic and neurological evaluation. RESULTS: Consistent with current diagnostic criteria and the literature, colobomas were the major ophthalmic manifestation. These were typically bilateral chorioretinal colobomas involving the optic nerve. All subjects had bilateral severe sensorineural deafness (cranial nerve VIII), and 8 of 9 (89%) had facial nerve (cranial nerve VII) involvement (7 of 9 had unilateral involvement; 1 of 9 had bilateral involvement). Unique to this group of participants were the findings of anisometropia in 8 of the 9 (89%) patients, severe myopic astigmatism in 13 of the 18 eyes (72%), and limited elevation in adduction in 3 of 9 (33%) participants. Associated findings were strabismus, cataracts, microcornea, keratopathy, staphyloma, reduced stereopsis, superior visual field defects, and reduced visual acuity. CONCLUSIONS: The presence of coloboma plus another CHARGE feature warrants further investigation, including genetic screening for the CHD7 gene. Early recognition and management of sensory problems (visual, auditory, and vestibular) are crucial to ensure best psychomotor and cognitive development.
Asunto(s)
Atresia de las Coanas/genética , Coloboma/genética , Enfermedades de los Nervios Craneales/genética , ADN Helicasas/genética , Proteínas de Unión al ADN/genética , Oído/anomalías , Oftalmopatías/genética , Mutación , Adolescente , Adulto , Anisometropía/genética , Astigmatismo/genética , Catarata/genética , Niño , Preescolar , Córnea/anomalías , Femenino , Pérdida Auditiva Sensorineural/genética , Humanos , Masculino , Miopía/genética , Estrabismo/genética , Síndrome , Adulto JovenRESUMEN
Several North American studies have found a connection between domestic violence and animal abuse. This article reports on the first Australian research to examine this connection. A group of 102 women recruited through 24 domestic violence services in the state of Victoria and a nondomestic violence comparison group (102 women) recruited from the community took part in the study. Significantly higher rates of partner pet abuse, partner threats of pet abuse, and pet abuse by other family members were found in the violent families compared with the nondomestic violence group. As hypothesized, children from the violent families were reported by their mothers to have witnessed and committed significantly more animal abuse than children from the nonviolent families. Logistic regression analyses revealed, for the group as a whole, that a woman whose partner had threatened the pets was 5 times more likely to belong to the intimate partner violence group.
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Bienestar del Animal , Animales Domésticos , Mujeres Maltratadas/psicología , Vínculo Humano-Animal , Maltrato Conyugal/psicología , Adulto , Animales , Femenino , Humanos , Control Interno-Externo , Masculino , Persona de Mediana Edad , Parejas Sexuales , Encuestas y Cuestionarios , VictoriaRESUMEN
BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is an emerging pathogen. The causal role of antibiotic selective pressure versus patient-to-patient transmission has not been assessed. The objective of this study was to quantify the amount of patient-to-patient transmission among patients who acquire an ESBL-producing E coli infection using perianal surveillance cultures in an intensive care unit (ICU) population. METHODS: A prospective cohort of patients admitted between September 1, 2001, and September 1, 2004, to the medical and surgical ICUs at a tertiary care hospital was studied. Patients had perianal cultures on admission, weekly, and upon discharge. Strain typing by pulsed-field gel electrophoresis (PFGE) and epidemiologic criteria were used to quantify the amount of patient-to-patient transmission. RESULTS: There were 1806 patients admitted to the ICUs. There were 74 patients who had ESBL-producing E coli on admission to the ICU and 23 patients who acquired ESBL-producing E coli. Among these 23 patients, there were 14 PFGE types, and 3 (13%) patient acquisitions were defined as patient-to-patient transmission by similar PFGE type and overlapping time in the hospital. CONCLUSION: Our data suggest that patient-to-patient transmission is not an important cause of the acquisition of ESBL-producing E coli colonization in the ICU setting.
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Infección Hospitalaria/microbiología , Infección Hospitalaria/transmisión , Infecciones por Escherichia coli/transmisión , Escherichia coli/enzimología , Unidades de Cuidados Intensivos , beta-Lactamasas/biosíntesis , Centros Médicos Académicos , Adulto , Canal Anal/microbiología , Baltimore , Medios de Cultivo , Electroforesis en Gel de Campo Pulsado , Escherichia coli/clasificación , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/microbiología , Humanos , Vigilancia de la PoblaciónRESUMEN
BACKGROUND: Preoperative low-molecular-weight heparin (LMWH) is often used when warfarin therapy is interrupted for surgery. OBJECTIVE: To determine the preoperative anticoagulant activity of LMWH following a standardized "bridging" regimen. DESIGN: Prospective cohort study. SETTING: Single university hospital. PATIENTS: Consecutive patients who had warfarin therapy interrupted before an invasive procedure. INTERVENTION: Enoxaparin, 1 mg/kg of body weight, twice daily. The last dose was administered the evening before surgery. MEASUREMENTS: Blood anti-factor Xa heparin levels measured shortly before surgery. RESULTS: Preoperative anti-Xa heparin levels were obtained in 80 patients at an average of 14 hours after the last dose of enoxaparin was administered. The average anti-Xa heparin level was 0.6 U/mL. The anti-Xa heparin level, measured shortly before surgery, was 0.5 U/mL or greater in 54 (68%) patients and 1.0 U/mL or greater in 13 (16%) patients. A shorter interval since the last dose (P < 0.001) and a higher body mass index (P = 0.001) were associated with higher preoperative anti-Xa heparin levels. LIMITATIONS: The small sample size limits accurate estimates of the frequency of the clinical outcomes. A single regimen of LMWH was evaluated. CONCLUSIONS: Anti-Xa heparin levels often remain high at the time of surgery if a last dose of a twice-daily regimen of LMWH is given the evening before surgery.
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Anticoagulantes/administración & dosificación , Anticoagulantes/farmacocinética , Enoxaparina/administración & dosificación , Enoxaparina/farmacocinética , Cuidados Preoperatorios/métodos , Anciano , Anticoagulantes/efectos adversos , Esquema de Medicación , Enoxaparina/efectos adversos , Factor Xa/metabolismo , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tamaño de la Muestra , Tromboembolia/inducido químicamente , Warfarina/uso terapéutico , Privación de TratamientoRESUMEN
Branching of ureteric bud-derived epithelial tubes is a key morphogenetic process that shapes development of the kidney. Glial cell line-derived neurotrophic factor (GDNF) initiates ureteric bud formation and promotes subsequent branching morphogenesis. Exactly how GDNF coordinates branching morphogenesis is unclear. Here we show that the absence of the receptor tyrosine kinase antagonist Sprouty1 (Spry1) results in irregular branching morphogenesis characterized by both increased number and size of ureteric bud tips. Deletion of Spry1 specifically in the epithelium is associated with increased epithelial Wnt11 expression as well as increased mesenchymal Gdnf expression. We propose that Spry1 regulates a Gdnf/Ret/Wnt11-positive feedback loop that coordinates mesenchymal-epithelial dialogue during branching morphogenesis. Genetic experiments indicate that the positive (GDNF) and inhibitory (Sprouty1) signals have to be finely balanced throughout renal development to prevent hypoplasia or cystic hyperplasia. Epithelial cysts develop in Spry1-deficient kidneys that share several molecular characteristics with those observed in human disease, suggesting that Spry1 null mice may be useful animal models for cystic hyperplasia.
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Factor Neurotrófico Derivado de la Línea Celular Glial/fisiología , Riñón/embriología , Proteínas de la Membrana/fisiología , Fosfoproteínas/fisiología , Uréter/embriología , Proteínas Adaptadoras Transductoras de Señales , Animales , Modelos Animales de Enfermedad , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Hiperplasia , Riñón/patología , Enfermedades Renales Quísticas/genética , Enfermedades Renales Quísticas/patología , Proteínas de la Membrana/genética , Ratones , Ratones Noqueados , Fosfoproteínas/genética , Uréter/patología , Urotelio/embriología , Urotelio/patologíaRESUMEN
OBJECTIVE: To compare alternative class-sparing antiretroviral regimens in treatment-naive subjects. DESIGN: Open-label, multicenter, randomized trial of up to 3 consecutive treatment regimens over 96 weeks. METHODS: Two hundred ninety-one subjects received abacavir (ABC) and lamivudine and efavirenz (nonnucleoside reverse transcriptase inhibitors [NNRTIs]), ritonavir-boosted amprenavir (protease inhibitor [PI]), or stavudine (nucleoside reverse transcriptase inhibitor [NRTI]) by random assignment. The primary end points were the percentages of subjects with plasma HIV-1 RNA levels <400 copies/mL and time to treatment failure over 96 weeks. RESULTS: Ninety percent of subjects completed 96 weeks of follow-up, and 79% remained on study treatment. At week 96, there were no differences between arms in the percentages of subjects with plasma HIV-1 RNA levels <400 and <50 copies/mL, mean changes in plasma HIV-1 RNA levels, time to treatment failure, time to first or second virologic failure, or CD4 cell counts. The NNRTI arm had a greater percentages of subjects with RNA levels Asunto(s)
Fármacos Anti-VIH/uso terapéutico
, Infecciones por VIH/tratamiento farmacológico
, Inhibidores de la Proteasa del VIH/administración & dosificación
, Inhibidores de la Proteasa del VIH/farmacocinética
, Adulto
, Alquinos
, Fármacos Anti-VIH/efectos adversos
, Benzoxazinas
, Ciclopropanos
, Resistencia a Medicamentos
, Quimioterapia Combinada
, Femenino
, Inhibidores de la Proteasa del VIH/efectos adversos
, Humanos
, Lamivudine/administración & dosificación
, Lamivudine/efectos adversos
, Masculino
, Oxazinas/administración & dosificación
, Oxazinas/efectos adversos
, Ritonavir/administración & dosificación
, Ritonavir/efectos adversos
, Estavudina/administración & dosificación
, Estavudina/efectos adversos
, Resultado del Tratamiento