RESUMEN
Importance: Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders. Objective: To determine whether assessing maternal blood pressure (BP) and associated symptoms at time of well-child visits is associated with increased detection of postpartum preeclampsia and need for hospitalization for medical management. Design, Setting, and Participants: This is a pre-post quality improvement (QI) study. Individuals who attended the well-child visits between preimplementation (December 2017 to December 2018) were compared with individuals who enrolled after the implementation of the QI program (March 2019 to December 2019). Individuals were enrolled at an academic pediatric clinic. Eligible participants included birth mothers who delivered at the hospital and brought their newborn for well-child check at 2 days, 2 weeks, and 2 months. A total of 620 individuals were screened in the preintervention cohort and 680 individuals were screened in the QI program. Data was analyzed from March to July 2022. Exposures: BP evaluation and preeclampsia symptoms screening were performed at the time of the well-child visit. A management algorithm-with criteria for routine or early postpartum visits, or prompt referral to the obstetric emergency department-was followed. Main Outcome and Measures: Readmission due to postpartum preeclampsia. Comparisons across groups were performed using a Fisher exact test for categorical variables, and t tests or Mann-Whitney tests for continuous variables. Results: A total of 595 individuals (mean [SD] age, 27.2 [6.1] years) were eligible for analysis in the preintervention cohort and 565 individuals (mean [SD] age, 27.0 [5.8] years) were eligible in the postintervention cohort. Baseline demographic information including age, race and ethnicity, body mass index, nulliparity, and factors associated with increased risk for preeclampsia were not significantly different in the preintervention cohort and postintervention QI program. The rate of readmission for postpartum preeclampsia differed significantly in the preintervention cohort (13 individuals [2.1%]) and the postintervention cohort (29 individuals [5.6%]) (P = .007). In the postintervention QI cohort, there was a significantly earlier time frame of readmission (median [IQR] 10.0 [10.0-11.0] days post partum for preintervention vs 7.0 [6.0-10.5] days post partum for postintervention; P = .001). In both time periods, a total of 42 patients were readmitted due to postpartum preeclampsia, of which 21 (50%) had de novo postpartum preeclampsia. Conclusions and Relevance: This QI program allowed for increased and earlier readmission due to postpartum preeclampsia. Further studies confirming generalizability and mitigating associated adverse outcomes are needed.
Asunto(s)
Preeclampsia , Humanos , Femenino , Adulto , Embarazo , Preeclampsia/diagnóstico , Preeclampsia/terapia , Diagnóstico Precoz , Mejoramiento de la Calidad , Readmisión del Paciente/estadística & datos numéricos , Periodo Posparto , Hipertensión/diagnóstico , Hipertensión/terapia , Recién Nacido , Trastornos Puerperales/terapia , Trastornos Puerperales/diagnósticoRESUMEN
The Saccharomyces cerevisiae FLO1 gene encodes a cell wall protein that imparts cell-cell adhesion. FLO1 transcription is regulated via the antagonistic activities of the Tup1-Cyc8 co-repressor and Swi-Snf co-activator complexes. Tup1-Cyc8 represses transcription through the organization of strongly positioned, hypoacetylated nucleosomes across gene promoters. Swi-Snf catalyzes remodeling of these nucleosomes in a mechanism involving histone acetylation that is poorly understood. Here, we show that FLO1 de-repression is accompanied by Swi-Snf recruitment, promoter histone eviction and Sas3 and Ada2(Gcn5)-dependent histone H3K14 acetylation. In the absence of H3K14 acetylation, Swi-Snf recruitment and histone eviction proceed, but transcription is reduced, suggesting these processes, while essential, are not sufficient for de-repression. Further analysis in the absence of H3K14 acetylation reveals RNAP II recruitment at the FLO1 promoter still occurs, but RNAP II is absent from the gene-coding region, demonstrating Sas3 and Ada2-dependent histone H3 acetylation is required for transcription elongation. Analysis of the transcription kinetics at other genes reveals shared mechanisms coupled to a distinct role for histone H3 acetylation, essential at FLO1, downstream of initiation. We propose histone H3 acetylation in the coding region provides rate-limiting control during the transition from initiation to elongation which dictates whether the gene is permissive for transcription.
Asunto(s)
Regulación Fúngica de la Expresión Génica , Histona Acetiltransferasas/genética , Histonas/genética , Lectinas de Unión a Manosa/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Factores de Transcripción/genética , Acetilación , Pared Celular/genética , Pared Celular/metabolismo , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Histona Acetiltransferasas/metabolismo , Histonas/metabolismo , Lectinas de Unión a Manosa/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Nucleosomas/química , Nucleosomas/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , ARN Polimerasa II/genética , ARN Polimerasa II/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Elongación de la Transcripción Genética , Factores de Transcripción/metabolismoAsunto(s)
Antituberculosos/uso terapéutico , Isoniazida/uso terapéutico , Tuberculosis Latente/tratamiento farmacológico , Tamizaje Masivo , Rifampin/uso terapéutico , Niño , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/enfermería , Enfermería Pediátrica , Guías de Práctica Clínica como AsuntoRESUMEN
A fifteen-year-old girl was treated with isoniazid (INH) for latent tuberculosis infection (LTBI), and subsequently developed epigastric pain, vomiting, and jaundice after three months of treatment. Acute fulminant hepatic failure was diagnosed. INH was stopped, and she received N-acetyl cysteine and Vitamin K. Liver biopsy showed moderate to severe lymphocytic and plasmacytic portal and lobular inflammation, prominent ductal proliferation, moderate cholestasis (predominantly hepatocellular and canalicular), hepatocellular damage, and stage 3 bridging fibrosis. She was treated with steroids and azathioprine for probable autoimmune hepatitis (AIH). She received six months of rifampicin treatment for LTBI. Liver biopsy two years later showed mild portal inflammation, predominantly lymphocytitic, mild portal fibrosis without bridging, irregular bile ducts without cholestasis, and no significant hepatocellular damage; overall the later biopsy demonstrated significant improvement. This case illustrates overlapping morphologic presentation in INH hepatotoxicity with hepatocellular injury and plasma cell infiltrate (due to probable AIH), as well as cholestatic features. Although her follow-up liver biopsy indicated lymphocytic inflammation, she is now asymptomatic with normal hepatic transaminases.
Asunto(s)
Isoniazida/efectos adversos , Hígado/efectos de los fármacos , Hígado/patología , Adolescente , Biopsia , Femenino , Fibrosis , Humanos , Inflamación/patología , Linfocitos/efectos de los fármacos , Linfocitos/patologíaRESUMEN
BACKGROUND: Interferon-γ-release assays (IGRAs) have been developed for the diagnosis of tuberculosis infection, but few data are available for children. There currently is no reference standard for the diagnosis of tuberculosis infection. OBJECTIVE: To compare the performance of 1 IGRA, the T-SPOT.TB assay with the tuberculin skin test (TST) in children with different epidemiologic risk factors for tuberculosis. METHODS: We conducted a prospective study of 210 patients referred to 3 pediatric tuberculosis clinics, including those with no risk factors for tuberculosis (low risk, n = 27), risk factors but no identifiable source case (intermediate risk, n = 78), contact with a known source case (high risk, n = 74), and active disease (n = 31). Children were tested with TST and T-SPOT.TB. Concordance analyses were performed, and assay outcomes were modeled by multivariate logistic regression. RESULTS: For 13 children with culture-confirmed tuberculosis disease, sensitivity of TST and T-SPOT.TB was 77% and 92%, respectively, and concordance was 69%. For high-risk children, concordance was 94% for BCG-unimmunized children and 88% for BCG-immunized children. For intermediate-risk children, concordance was 74% for BCG-unimmunized children and 33% for BCG-immunized children. For low-risk children, concordance was 74% for BCG-unimmunized children and 20% for BCG-immunized children. Multivariate analysis revealed that contact with a source case was associated with T-SPOT.TB result, but age and BCG immunization were not. CONCLUSIONS: T-SPOT.TB is comparable to the TST in the diagnosis of tuberculosis disease and identification of high-risk children with tuberculosis infection and is more specific than the TST in children who have received the BCG vaccine.