RESUMEN
BACKGROUND: Central line-associated bloodstream infections (CLABSI) in ambulatory pediatric populations are difficult to track at an institutional level, especially for complex patients seen by multiple divisions and home health infusion agencies. METHODS: A multidisciplinary team comprised of key stakeholders from divisions with the most patients discharged with a central line utilized Lean Six Sigma methodology of Define-Measure-Analyze-Design-Verify (DMADV) to create a standardized data collection process for all ambulatory CLABSIs and infection event reviews. RESULTS: A surveillance workflow was created to track, identify, and confirm ambulatory CLABSIs in all patients with an indwelling central line. Defined surveillance criteria included scope of patients eligible for ambulatory CLABSI surveillance, numerator definitions, and denominator calculations. Additionally, a novel attribution method was created for ambulatory CLABSIs in complex patient populations shared among multiple divisions and home care infusion services. CONCLUSIONS: This report is a novel institutional approach to accurately surveil, attribute, and calculate ambulatory CLABSI data in a pediatric healthcare system.
Asunto(s)
Bacteriemia , Infecciones Relacionadas con Catéteres , Cateterismo Venoso Central , Catéteres Venosos Centrales , Sepsis , Humanos , Niño , Infecciones Relacionadas con Catéteres/epidemiología , Cateterismo Venoso Central/efectos adversos , Sepsis/epidemiología , Atención a la Salud , Bacteriemia/epidemiologíaRESUMEN
OBJECTIVE: Central-line-associated bloodstream infections (CLABSI) cause morbidity and mortality in critically ill children. We examined novel and/or modifiable risk factors for CLABSI to identify new potential targets for infection prevention strategies. METHODS: This single-center retrospective matched case-control study of pediatric intensive care unit (PICU) patients was conducted in a 60-bed PICU from April 1, 2013, to December 31, 2017. Case patients were in the PICU, had a central venous catheter (CVC), and developed a CLABSI. Control patients were in the PICU for ≥2 days, had a CVC for ≥3 days, and did not develop a CLABSI. Cases and controls were matched 1:4 on age, number of complex chronic conditions, and hospital length of stay. RESULTS: Overall, 72 CLABSIs were matched to 281 controls. Univariate analysis revealed 14 risk factors, and 4 remained significant in multivariable analysis: total number of central line accesses in the 3 days preceding CLABSI (80+ accesses: OR, 4.8; P = .01), acute behavioral health needs (OR, 3.2; P = .02), CVC duration >7 days (8-14 days: OR, 4.2; P = .01; 15-29 days: OR, 9.8; P < .01; 30-59 days: OR, 17.3; P < .01; 60-89 days: OR, 39.8; P < .01; 90+ days: OR, 4.9; P = .01), and hematologic/immunologic disease (OR, 1.5; P = .05). CONCLUSIONS: Novel risk factors for CLABSI in PICU patients include acute behavioral health needs and >80 CVC accesses in the 3 days before CLABSI. Interventions focused on these factors may reduce CLABSIs in this high-risk population.
Asunto(s)
Bacteriemia/epidemiología , Infecciones Relacionadas con Catéteres/epidemiología , Cateterismo Periférico/estadística & datos numéricos , Catéteres Venosos Centrales/estadística & datos numéricos , Estudios de Casos y Controles , Cateterismo Periférico/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Niño , Trastornos de la Conducta Infantil/epidemiología , Preescolar , Enfermedad Crítica , Femenino , Enfermedades Hematológicas/epidemiología , Humanos , Enfermedades del Sistema Inmune/epidemiología , Lactante , Unidades de Cuidado Intensivo Pediátrico , Masculino , Philadelphia/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
OBJECTIVE: To reduce the healthcare-associated viral infection (HAVI) rate to 0.70 infections or fewer per 1,000 patient days by developing and sustaining a comprehensive prevention bundle. SETTING: A 546-bed quaternary-care children's hospital situated in a large urban area.PatientsInpatients with a confirmed HAVI were included. These HAVIs were identified through routine surveillance by infection preventionists and were confirmed using National Healthcare Safety Network definitions for upper respiratory infections (URIs), pneumonia, and gastroenteritis. METHODS: Quality improvement (QI) methods and statistical process control (SPC) analyses were used in a retrospective observational analysis of HAVI data from July 2012 through June 2016. RESULTS: In total, 436 HAVIs were identified during the QI initiative: 63% were URIs, 34% were gastrointestinal infections, and 2.5% were viral pneumonias. The most frequent pathogens were rhinovirus (n=171) and norovirus (n=83). Our SPC analysis of HAVI rate revealed a statistically significant reduction in March 2014 from a monthly average of 0.81 to 0.60 infections per 1,000 patient days. Among HAVIs with event reviews completed, 15% observed contact with a sick primary caregiver and 15% reported contact with a sick visitor. Patient outcomes identified included care escalation (37%), transfer to ICU (11%), and delayed discharge (19%). CONCLUSIONS: The iterative development, implementation, and refinement of targeted prevention practices was associated with a significant reduction in pediatric HAVI. These practices were ultimately formalized into a comprehensive prevention bundle and provide an important framework for both patient and systems-level interventions that can be applied year-round and across inpatient areas.
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Infección Hospitalaria/prevención & control , Gastroenteritis/epidemiología , Hospitales Pediátricos/normas , Paquetes de Atención al Paciente , Infecciones del Sistema Respiratorio/epidemiología , Preescolar , Infección Hospitalaria/virología , Femenino , Gastroenteritis/virología , Humanos , Lactante , Control de Infecciones/organización & administración , Masculino , Norovirus/aislamiento & purificación , Philadelphia/epidemiología , Neumonía Viral/epidemiología , Prevención Primaria/organización & administración , Mejoramiento de la Calidad/organización & administración , Infecciones del Sistema Respiratorio/virología , Estudios Retrospectivos , Rhinovirus/aislamiento & purificación , Estaciones del AñoRESUMEN
Many young children identified with developmental concerns in pediatric settings do not receive early intervention (EI). We assessed the impact of a video decision aid and text message reminder on knowledge and attitudes regarding developmental delay and EI as well as referral completion. We conducted a pilot randomized controlled trial in an urban setting and enrolled 64 parent-child dyads referred to EI. Compared with controls, participants who received the intervention demonstrated increased knowledge regarding developmental delay and EI as well as more favorable attitudes in certain topics. Although we did not find a significant difference between arms in EI intake and evaluation, we found a pattern suggestive of increased intake and evaluation among participants with low health literacy in the intervention arm. Additional study is needed to identify strategies that improve the EI referral process for families and to understand the potential targeted role for decision aids and text messages.
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Técnicas de Apoyo para la Decisión , Discapacidades del Desarrollo/diagnóstico , Intervención Educativa Precoz , Atención Primaria de Salud/métodos , Derivación y Consulta , Grabación de Cinta de Video , Preescolar , Discapacidades del Desarrollo/terapia , Femenino , Humanos , Lactante , Masculino , Philadelphia , Envío de Mensajes de Texto , Población UrbanaRESUMEN
PURPOSE: Poly(ADP-ribose) polymerases (PARP) and the Mre11, Rad50, and Nbs1 (MRN) complex are key regulators of DNA repair, and have been recently shown to independently regulate telomere length. Sensitivity of cancers to PARPi is largely dependent on the BRCAness of the cells. Unfortunately, the vast majority of cancers are BRCA-proficient. In this study, therefore, we investigated whether a targeted molecular "hit" on the MRN complex, which is upstream of BRCA, can effectively sensitize BRCA-proficient head and neck squamous cell carcinoma (HNSCC) to PARP inhibitor (PARPi). EXPERIMENTAL DESIGN: Human HNSCC cell lines and a mouse model with HNSCC xenografts were used in this study. In vitro and in vivo studies were conducted to evaluate the effects and underlying mechanisms of dual molecular disruption of PARP and the MRN complex, using a pharmacologic inhibitor and a dominant-negative Nbs1 expression vector, respectively. RESULTS: Our findings demonstrate that downregulation of the MRN complex disrupts homologous recombination, and, when combined with PARPi, leads to accumulation of lethal DNA double-strand breaks. Moreover, we show that PARPi and MRN complex disruption induces significantly shortening telomere length. Together, our results demonstrate that dual disruption of these pathways causes significant cell death in BRCA-proficient tumor cells both in vitro and in vivo. CONCLUSION: Our study, for the first time, elucidates a novel mechanism for MRN complex and PARP inhibition beyond DNA repair, demonstrating the feasibility of a dual disruption approach that extends the utility of PARPi to the treatment of BRCA-proficient cancers.
Asunto(s)
Reparación del ADN , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Telómero/genética , Telómero/metabolismo , Ácido Anhídrido Hidrolasas , Animales , Proteína BRCA1/genética , Carcinoma de Células Escamosas/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Roturas del ADN de Cadena Simple/efectos de los fármacos , Enzimas Reparadoras del ADN/metabolismo , Proteínas de Unión al ADN/metabolismo , Modelos Animales de Enfermedad , Femenino , Inestabilidad Genómica , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Humanos , Proteína Homóloga de MRE11 , Ratones , Modelos Biológicos , Complejos Multiproteicos/metabolismo , Proteínas Nucleares/metabolismo , Compuestos Orgánicos/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Poli(ADP-Ribosa) Polimerasas/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello , Acortamiento del Telómero , Carga Tumoral/efectos de los fármacos , Carga Tumoral/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: We have recently developed a novel inner ear drug delivery system using chitosan glycerophosphate (CGP) hydrogel loaded with drugs commonly used for treatment of inner ear diseases, significantly improving the drugs' sustained delivery. The goal of this study is to evaluate the effectiveness of chitosanase as a "switch off" mechanism for this drug delivery system when side effects and potential ototoxicities appear during treatment. To evaluate this effect, we tested gentamicin (GENT) in the inner ear following CGP delivery with/without regulation. METHODS: Purified chitosanase was obtained and used for regulating the CGP delivery system. In vitro studies were performed to evaluate the effect of the interaction between chitosanase and CGP-hydrogel loaded with GENT or Texas Red-labeled GENT (GTTR). In vivo studies were performed using our mouse model to investigate the regulatory effect of chitosanase application on the delivery of GENT to the inner ear. To assess the potential drug rerouting regulatory effect of chitosanase the GTTR fluorescence intensity was evaluated at the round window niche (RWN) and the Eustachian tube (ET). To further characterize this regulatory effect, GENT concentration in the perilymph of the inner ear was analyzed by chromatographic tandem mass spectrometry (LC-MS/MS), and the uptake in the inner ear cells was measured using fluorescence microscopy following CGP delivery with/without chitosanase application. RESULTS: The chitosanase effectively digested the CGP-hydrogel, quickly releasing GENT and GTTR from the system in vitro. When reacted with GENT alone chitosanase did not produce any reducing sugars and did not affect GENT's antimicrobial activity. In vivo GTTR was effectively rerouted from the RWN to the ET, limiting its uptake in inner ear hair cells. Concurrent with these findings, GENT concentration in the inner ear perilymph was significantly decreased after chitosanase application. CONCLUSION: Our study findings suggest that, for the first time, sustained and controlled inner ear drug delivery can be successfully regulated enhancing its translation potential for clinical application. The use of chitosanase to digest the CGP-hydrogel results in the rerouting of the loaded drug away from the RWN, effectively downregulating its delivery to the inner ear. This important modification to our drug delivery system has the ability to deliver therapy to the inner ear until desired effect is achieved and to stop this process when side effects or treatment-related ototoxicities start to occur, providing a novel and salient approach for safe and effective delivery to the inner ear.