RESUMO
The Centers for Medicare & Medicaid Services (CMS) implemented the Merit-based Incentive Payment System (MIPS) to accelerate the transition of physician payment toward value-based care models and away from traditional fee-for-service payment programs. In recent years, CMS has sought to modify the program by developing a MIPS Value Pathway (MVP) framework intended to use existing and future physician quality and cost measures to reward value-based care delivery. This article describes the multi-step process of the MVP Task Force, convened by the American College of Emergency Physicians (ACEP) to develop an emergency medicine-specific MVP proposal informed by diverse stakeholder perceptions regarding: (1) which existing quality measures reflect high quality emergency care, and (2) the degree to which emergency clinicians can impact clinical outcomes and cost for the care domains captured by existing quality measures. The MVP Task Force synthesized stakeholder feedback and underwent a consensus-building approach to develop the "Adopting Best Practices and Promoting Patient Safety within Emergency Medicine" MVP, recently reviewed and approved by CMS for national implementation starting in 2023. Our process and findings have broad implications for clinicians, administrators, and policymakers navigating the continued transition to value-based care in conjunction with CMS's implementation of the MVP framework.
RESUMO
Attention deficit hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood, and often has effects detectable into adulthood. Advances in genetic linkage and association analysis have begun to elucidate some of the genetic factors underlying this complex disorder. Recently, we identified LPHN3, a novel ADHD susceptibility gene harbored in 4q, and showed that a LPHN3 common haplotype confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Here we present the mutational analysis of the entire coding region of LPHN3 in a cohort of 139 ADHD subjects and 52 controls from across the USA. We identified 21 variants, of which 14 have been reported and 7 are novel. These include 5 missense, 8 synonymous, and 8 intronic changes. Interestingly, neither susceptibility nor protective haplotype alleles are associated with obviously significant coding region changes, or canonical splice site alterations, suggesting that non-coding variations determining the quantity and/or quality of LPHN3 isoforms are the likely contributors to this common behavioral disorder.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Predisposição Genética para Doença , Testes Genéticos , Mutação/genética , Receptores Acoplados a Proteínas G/genética , Receptores de Peptídeos/genética , Sequência de Aminoácidos , Éxons/genética , Humanos , Dados de Sequência Molecular , Fases de Leitura Aberta/genética , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Subunidades Proteicas/química , Subunidades Proteicas/genética , Receptores Acoplados a Proteínas G/química , Receptores de Peptídeos/química , Reprodutibilidade dos Testes , Alinhamento de Sequência , Homologia de Sequência de AminoácidosRESUMO
The autosomal recessive Griscelli syndrome type II (GSII) is caused by mutations in the RAB27A gene. Typical clinical features include immunological impairment, silver-gray scalp hair, eyelashes and eyebrows and hypomelanosis of the skin. Rabs help determine the specificity of membrane trafficking steps within cells. In melanocytes, the GTP-bound form of Rab27A associates with the membranes of mature fully-pigmented melanosomes through its geranylgeranyl group. Once attached, Rab27A recruits the downstream effector Melanophilin (Mlph) and the actin-dependent motor protein Myosin Va (MyoVa). The molecular Rab27A/Mlph/MyoVA tripartite complex, which links melanosomes to the peripheral actin network, is required to achieve melanosome transfer to surrounding keratinocytes in the epidermis. Here we report a novel homozygous missense mutation c.127G>A, p.G43S in exon 2 of the RAB27A gene of an Afghani GSII patient. Laser scanning confocal microscopy showed that the G43S mutation, which is located in the highly conserved switch I region of Rab27A, induces perinuclear localization of melanosomes in normal melanocytes, and fails to restore melanosomes to the actin-rich periphery in GSII melanocytes. Co-immunoprecipitation studies showed that Rab27A(G43S) fails to interact with its effector Melanophilin, indicating that the switch I region functions in the recruitment of Rab effector proteins.
Assuntos
Erros Inatos do Metabolismo/genética , Erros Inatos do Metabolismo/metabolismo , Mutação de Sentido Incorreto , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Afeganistão , Motivos de Aminoácidos , Núcleo Celular/química , Núcleo Celular/genética , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Melanócitos/química , Melanócitos/metabolismo , Melanossomas/química , Melanossomas/metabolismo , Erros Inatos do Metabolismo/diagnóstico , Dados de Sequência Molecular , Ligação Proteica , Alinhamento de Sequência , Síndrome , Proteínas rab de Ligação ao GTP/química , Proteínas rab27 de Ligação ao GTPRESUMO
OBJECTIVES: The objective of this study was to evaluate the effect of a psychiatric observation unit in reducing emergency department (ED) boarding and length of stay (LOS) for patients presenting with primary psychiatric chief complaints. A secondary outcome was to determine the effect of a psychiatric observation unit on inpatient psychiatric bed utilization. METHODS: This study was a before-and-after analysis conducted in a 1,541-bed tertiary care academic medical center including an adult ED with annual census over 90,000 between February 2013 and July 2014. All adult patients (age > 17 years) requiring evaluation by the acute psychiatry service in the crisis intervention unit (CIU) within the ED were included. Patients who left without being seen, left against medical advice, or were dispositioned to the pediatric hospital, hospice, or court/law enforcement were excluded. In December 2013, a 12-bed locked psychiatric observation unit was opened that included dedicated behavioral health staff and was intended for psychiatric patients requiring up to 48 hours of care. The primary outcomes were ED LOS, CIU LOS, and total LOS. Secondary outcomes included the hold rate defined as the proportion of acute psychiatry patients requiring subsequent observation or inpatient admission and the inpatient psychiatric admission rate. For the primary analysis we constructed ARIMA regression models that account for secular changes in the primary outcomes. We conducted two sensitivity analyses, first replicating the primary analysis after excluding patients with concurrent acute intoxication and second by comparing the 3-month period postintervention to the identical 3-month period of the prior year to account for seasonality. RESULTS: A total of 3,501 patients were included before intervention and 3,798 after intervention. The median ED LOS for the preintervention period was 155 minutes (interquartile range [IQR] = 19-346 minutes), lower than the median ED LOS for the postintervention period of 35 minutes (IQR = 9-209 minutes, p < 0.0001). Similar reductions were observed in CIU LOS (865 minutes vs. 379 minutes, p < 0.0001) and total LOS (1,112 minutes vs. 920 minutes, p = 0.003). The psychiatric hold rate was statistically higher after intervention (before = 42%, after = 50%, p < 0.0001), however, coupled with a statistically lower psychiatric admission rate (before = 42%, after = 25%, p < 0.0001). CONCLUSIONS: Creation of an acute psychiatric observation improves ED and acute psychiatric service throughput while supporting the efficient allocation of scare inpatient psychiatric beds. This novel approach demonstrates the promise of extending successful observation care models from medical to psychiatric illness with the potential to improve the value of acute psychiatric care while minimizing the harms of ED crowding.
Assuntos
Unidades de Observação Clínica/organização & administração , Aglomeração , Serviço Hospitalar de Emergência/organização & administração , Transtornos Mentais/diagnóstico , Centros Médicos Acadêmicos , Adulto , Feminino , Hospitalização , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Admissão do PacienteRESUMO
BACKGROUND/AIMS: In renal epithelial cells, mechanical forces produced from urinary obstruction serve as potential mediators of apoptosis by activating specific intracellular signaling pathways. In this study, we sought to further define the role of JNK and p38 SAPK-2 pathway and caspase activation in stretch-induced apoptosis. METHODS: Immortalized cell lines derived from the various components of the nephron were subjected to cyclical stretch and their differential apoptotic response was assessed. Pharmacologic inhibitors and Western blot analysis were used to assess the involvement of the MAPK pathways. Caspases' activity was assessed with ELISA and by Western blot analysis. RESULTS: Stretch-induced apoptosis was dependent upon the cell phenotype and the degree of stretch. In NRK-52E cells, it was mediated through both JNK and p38 SAPK-2 pathways, and inhibition of either pathway reduced the degree of stretch-induced apoptosis. Stretched cells showed increased activity of caspase-3 and -9 but not -2 or -8. Stretch-induced apoptosis was modulated by inhibition of caspase-3 and to a lesser extent by caspase-9. CONCLUSION: These findings suggest that stretch induces apoptosis in renal epithelial cells through the specific activation of JNK/SAPK and p38 SAPK-2 pathways and is dependent on the activation of caspase-3 and -9.
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Apoptose/fisiologia , Caspases/fisiologia , Proteínas Quinases JNK Ativadas por Mitógeno/fisiologia , Rim/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3 , Caspase 9 , Inibidores de Caspase , Caspases/metabolismo , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Células Epiteliais/fisiologia , Humanos , Isoenzimas/fisiologia , Rim/citologia , Camundongos , Ratos , Transdução de Sinais/fisiologia , Estresse MecânicoRESUMO
Shoulder injuries are among the most common musculoskeletal complaints seen in US emergency departments (EDs). ED evaluation of the shoulder must account for the broad range of potential fracture patterns seen in the clavicle, scapula, and humerus. Acromioclavicular dislocation is often encountered in the ED and treatment varies by severity. Dislocation of the shoulder is frequently seen, and the ED physician must be skilled in several reduction techniques to optimize a successful reduction. An understanding of when orthopedic consultation is appropriate and when patients can be dispositioned with timely follow-up are integral to complete patient recovery.
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Serviço Hospitalar de Emergência , Fraturas Ósseas , Úmero/lesões , Luxações Articulares , Lesões do Ombro , Articulação Acromioclavicular/lesões , Clavícula/lesões , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/terapia , Humanos , Luxações Articulares/diagnóstico , Luxações Articulares/terapia , Escápula/lesões , Luxação do Ombro/diagnóstico , Luxação do Ombro/terapiaRESUMO
BACKGROUND: There are numerous studies in the adult literature correlating comorbidities and pre- and intraoperative parameters with postoperative outcomes. However, there is a paucity of similar data in the pediatric population. Our goal was to elucidate which pre- and intraoperative patient characteristics in children undergoing surgery are associated with an increased risk of major complication within 30 days. STUDY DESIGN: We identified 108 children who underwent surgery at our institution between June 2005 and May 2007 and had major complication or death within 30 days of surgery. Forty-two preoperative patient characteristics and 22 intraoperative variables were evaluated. The severity of the complications was graded based on the Clavien classification system, with major complications grade III or greater. We randomly selected 723 controls who had undergone surgery within a 3-month date range of the original cohort, but did not develop complications. Statistical significance was assessed by univariate and multivariate analyses. RESULTS: Most complications were cardiovascular, occurred 1 to 3 days after surgery, and were classified as grade IIIB. We identified 5 independent risk factors on multivariate analysis: ≤36 weeks of gestation, American Society of Anesthesiologists score >3, undergoing a cardiovascular or neurosurgical procedure, and receiving an intraoperative albumin transfusion. Three scoring systems (overall, preoperative, and intraoperative complication score) were developed to provide objective risk stratification. CONCLUSIONS: We found 5 patient-specific parameters that were independent risk factors for major complications or death after pediatric surgery. Future prospective studies will help to fully stratify risk and guide interventions to improve postoperative outcomes.