RESUMO
BACKGROUND: Adolescent patients with moderate to severe idiopathic scoliosis who have completed their skeletal growth face a significant choice in their treatment path: watchful waiting or spinal fusion. Shared decision making (SDM) assists patients and clinicians to find treatments that make intellectual, practical and emotional sense. Our objective was to develop a tool that supports SDM for patients with scoliosis and their families. METHODS: We used a user-centered design approach that included collaboration between patients, surgeons and SDM experts, observation of clinician encounters, and literature review. We focused on adolescent idiopathic scoliosis patients 13 or more years of age with less than 1 year of growth remaining (Risser stage 3 or greater) and curves between 40 and 65 degrees. RESULTS: We included 22 patients, and collected 22 video recordings. From these videos, we identified salient patient priorities for decision making including treatment benefits, surgical complications, pain, scheduling and recovery, and cost. For each theme, we conducted a focused review to obtain the best estimate of effect. Then, an expert SDM designer developed an electronic prototype called Scoliosis Choice. CONCLUSIONS: The initial prototype of the scoliosis SDM was finalized and is currently being field tested in clinic. Scoliosis Choice may help patients and surgeons better understand the potential risks and benefits of spinal fusion vs. observation for scoliosis treatment and improve validated measures of quality in patient-parent-surgeon communication.
Assuntos
Tomada de Decisão Compartilhada , Complicações Pós-Operatórias , Psicometria/métodos , Escoliose , Fusão Vertebral , Conduta Expectante/métodos , Adolescente , Desenvolvimento do Adolescente , Adulto , Feminino , Humanos , Masculino , Preferência do Paciente , Relações Médico-Paciente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/psicologia , Relações Profissional-Família , Reprodutibilidade dos Testes , Medição de Risco , Escoliose/psicologia , Escoliose/cirurgia , Escoliose/terapia , Índice de Gravidade de Doença , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Fusão Vertebral/psicologiaRESUMO
Efforts to develop STAT3 inhibitors have focused on its SH2 domain starting with short phosphotyrosylated peptides based on STAT3 binding motifs, e.g. pY905LPQTV within gp130. Despite binding to STAT3 with high affinity, issues regarding stability, bioavailability, and membrane permeability of these peptides, as well as peptidomimetics such as CJ-887, have limited their further clinical development and led to interest in small-molecule inhibitors. Some small molecule STAT3 inhibitors, identified using structure-based virtual ligand screening (SB-VLS); while having favorable drug-like properties, suffer from weak binding affinities, possibly due to the high flexibility of the target domain. We conducted molecular dynamic (MD) simulations of the SH2 domain in complex with CJ-887, and used an averaged structure from this MD trajectory as an "induced-active site" receptor model for SB-VLS of 110,000 compounds within the SPEC database. Screening was followed by re-docking and re-scoring of the top 30% of hits, selection for hit compounds that directly interact with pY + 0 binding pocket residues R609 and S613, and testing for STAT3 targeting in vitro, which identified two lead hits with good activity and favorable drug-like properties. Unlike most small-molecule STAT3 inhibitors previously identified, which contain negatively-charged moieties that mediate binding to the pY + 0 binding pocket, these compounds are uncharged and likely will serve as better candidates for anti-STAT3 drug development. IMPLICATIONS: SB-VLS, using an averaged structure from molecular dynamics (MD) simulations of STAT3 SH2 domain in a complex with CJ-887, a known peptidomimetic binder, identify two highly potent, neutral, low-molecular weight STAT3-inhibitors with favorable drug-like properties.
Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Fator de Transcrição STAT3/antagonistas & inibidores , Domínios de Homologia de src , Alquilação , Sítios de Ligação/efeitos dos fármacos , Western Blotting , Linhagem Celular Tumoral/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Ligantes , Simulação de Acoplamento Molecular , Estrutura Terciária de Proteína , Fator de Transcrição STAT3/química , Fator de Transcrição STAT3/genética , Relação Estrutura-Atividade , Ressonância de Plasmônio de Superfície , Domínios de Homologia de src/efeitos dos fármacosRESUMO
BACKGROUND: Given that abdominal aorta is a retroperitoneal structure, increased body mass index (BMI) may have an adverse effect upon the quality of aortic ultrasonographic imaging. PURPOSE: To assess the hypothesis that increased BMI is associated with worsening point-of-care abdominal aortic ultrasonographic image quality. METHODS: This is a retrospective single-center study of point-of-care abdominal aortic ultrasound examinations performed in an academic emergency department (ED) with fellowship-trained emergency ultrasonography faculty performing quality assurance review. RESULTS: Mean ± SD BMI was 27.4 ± 6.2, among the 221 included records. The overall quality rating decreased as BMI increased (correlation coefficient - 0.24; P < .001) and this persisted after adjustment for age and sex (P < .001). Although BMI was higher on average in the records that were of insufficient quality for clinical decisions when compared with those of sufficient quality (mean BMI 28.7 vs 27.0), this did not reach statistical significance in a univariable setting (P = .11) or after adjusting for age and sex (P = .14). CONCLUSION: This study data shows a decrease in point-of-care abdominal aorta ultrasound imaging quality as BMI increases, though this difference did not result in a statistically significant impairment in achieving the minimum quality for clinical decisions. This finding may help ameliorate some clinician concerns about ultrasonography for patients with high BMI.
Assuntos
Aorta Abdominal/diagnóstico por imagem , Índice de Massa Corporal , Ultrassonografia/normas , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Físico , Testes Imediatos/normas , Estudos Retrospectivos , Ultrassonografia/métodosRESUMO
BACKGROUND: Many clinicians believe that a patient's body mass index (BMI) affects the likelihood of obtaining high quality ultrasound images. OBJECTIVES: To assess the hypothesis that increased BMI is associated with worsening focused assessment with sonography in trauma (FAST) image quality. METHODS: We conducted a retrospective single-center study of FAST examinations performed in a large academic emergency department (ED) with fellowship-trained emergency ultrasonography faculty performing quality assurance review. RESULTS: Mean (SD) BMI was 28.0 (6.6) among the 302 included studies. The overall quality rating tended to decrease as BMI increased but did not achieve statistical significance in a univariable setting (P = .06) or after adjustment for age and sex (P = .06). Operators perception of image adequacy was largely unaffected by BMI, with the exception of the pericardial view. CONCLUSION: This study did not identify a statistically significant difference in FAST quality with increased BMI. This result may help assuage clinician concerns about ultrasonography for patients in the ED.