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1.
Seizure ; 70: 90-96, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31323566

RESUMO

PURPOSE: To evaluate whether the onset of pediatric refractory status epilepticus (rSE) is related to time of day. METHOD: We analyzed the time of day for the onset of rSE in this prospective observational study performed from June 2011 to May 2019 in pediatric patients (1 month to 21 years of age). We evaluated the temporal distribution of pediatric rSE utilizing a cosinor analysis. We calculated the midline estimating statistic of rhythm (MESOR) and amplitude. MESOR is the estimated mean number of rSE episodes per hour if they were evenly distributed. Amplitude is the difference between MESOR and maximum rSE episodes/hour, or between MESOR and minimum rSE episodes/hour. We also evaluated the temporal distribution of time to treatment. RESULTS: We analyzed 368 patients (58% males) with a median (p25 - p75) age of 4.2 (1.3-9.7) years. The MESOR was 15.3 (95% CI: 13.9-16.8) and the amplitude was 3.2 (95% CI: 1.1-5.3), p = 0.0024, demonstrating that the distribution is not uniform, but better described as varying throughout the day with a peak in the morning (11am-12 pm) and trough at night (11 pm-12 am). The duration from rSE onset to application of the first non-benzodiazepine antiseizure medication peaked during the early morning (2am-3 am) with a minimum during the afternoon (2 pm-3 pm) (p = 0.0179). CONCLUSIONS: The distribution of rSE onset is not uniform during the day. rSE onset shows a 24-h distribution with a peak in the mid-morning (11am-12 pm) and a trough at night (11 pm-12am).

2.
Pediatr Neurol ; 86: 33-41, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30075875

RESUMO

OBJECTIVE: We aimed to evaluate and compare the status epilepticus treatment pathways used by pediatric status epilepticus research group (pSERG) hospitals in the United States and the American Epilepsy Society (AES) status epilepticus guideline. METHODS: We undertook a descriptive analysis of recommended timing, dosing, and medication choices in 10 pSERG hospitals' status epilepticus treatment pathways. RESULTS: One pathway matched the timeline in the AES guideline; nine pathways described more rapid timings. All pathways matched the guideline's stabilization phase in timing and five suggested that first-line benzodiazepine (BZD) be administered within this period. For second-line therapy timing (initiation of a non-BZD antiepileptic drug within 20 to 40 minutes), one pathway matched the guideline; nine initiated the antiepileptic drug earlier (median 10 [range five to 15] minutes). Third-line therapy timings matched the AES guideline (40 minutes) in two pathways; eight suggested earlier timing (median 20 [range 15 to 30] minutes). The first-line BZD recommended in all hospitals was intravenous lorazepam; alternatives included intramuscular midazolam or rectal diazepam. In second-line therapy, nine pathways recommended fosphenytoin. For third-line therapy, eight pathways recommended additional boluses of second-line medications; most commonly phenobarbital. Two pathways suggested escalation to third-line medication; most commonly midazolam. We found variance in dosing for the following medications: midazolam as first-line therapy, fosphenytoin, and levetiracetam as second-line therapy, and phenobarbital as third-line therapy medications. CONCLUSIONS: The pSERG hospitals status epilepticus pathways are consistent with the AES status epilepticus guideline in regard to the choice of medications, but generally recommend more rapid escalation in therapy than the guideline.


Assuntos
Anticonvulsivantes/administração & dosagem , Tratamento de Emergência , Hospitalização , Estado Epiléptico/terapia , Adolescente , Criança , Pré-Escolar , Esquema de Medicação , Hospitais Pediátricos , Humanos , Lactente , Guias de Prática Clínica como Assunto , Sociedades Médicas , Estados Unidos
3.
Clin Cancer Res ; 23(14): 3510-3519, 2017 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-28193627

RESUMO

Purpose: Invariant NKT cells (iNKT) are innate-like CD1d-restricted T cells with immunoregulatory activity in diseases including cancer. iNKT from advanced cancer patients can have reversible defects including IFNγ production, and iNKT IFNγ production may stratify for survival. Previous clinical trials using iNKT cell activating ligand α-galactosylceramide have shown clinical responses. Therefore, a phase I clinical trial was performed of autologous in vitro expanded iNKT cells in stage IIIB-IV melanoma.Experimental Design: Residual iNKT cells [<0.05% of patient peripheral blood mononuclear cell (PBMC)] were purified from autologous leukapheresis product using an antibody against the iNKT cell receptor linked to magnetic microbeads. iNKT cells were then expanded with CD3 mAb and IL2 in vitro to obtain up to approximately 109 cells.Results: Expanded iNKT cells produced IFNγ, but limited or undetectable IL4 or IL10. Three iNKT infusions each were completed on 9 patients, and produced only grade 1-2 toxicities. The 4th patient onward received systemic GM-CSF with their second and third infusions. Increased numbers of iNKT cells were seen in PBMCs after some infusions, particularly when GM-CSF was also given. IFNγ responses to α-galactosylceramide were increased in PBMCs from some patients after infusions, and delayed-type hypersensitivity responses to Candida increased in 5 of 8 evaluated patients. Three patients have died, three were progression-free at 53, 60, and 65 months, three received further treatment and were alive at 61, 81, and 85 months. There was no clear correlation between outcome and immune parameters.Conclusions: Autologous in vitro expanded iNKT cells are a feasible and safe therapy, producing Th1-like responses with antitumor potential. Clin Cancer Res; 23(14); 3510-9. ©2017 AACR.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Imunoterapia , Melanoma/terapia , Células T Matadoras Naturais/transplante , Subpopulações de Linfócitos T/transplante , Transferência Adotiva/métodos , Adulto , Idoso , Complexo CD3/imunologia , Feminino , Galactosilceramidas/imunologia , Humanos , Interferon gama/imunologia , Interferon gama/uso terapêutico , Interleucina-10/imunologia , Interleucina-2/imunologia , Interleucina-4/imunologia , Estimativa de Kaplan-Meier , Ativação Linfocitária/imunologia , Masculino , Melanoma/imunologia , Melanoma/patologia , Pessoa de Meia-Idade , Células T Matadoras Naturais/imunologia , Subpopulações de Linfócitos T/imunologia
4.
JMIR Med Inform ; 4(1): e6, 2016 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-26872820

RESUMO

BACKGROUND: Electronic consultations (e-consults) offer rapid access to specialist input without the need for a patient visit. E-consult implementation began in 2011 at VA Boston Healthcare System (VABHS). By early 2013, e-consults were available for all clinical services. In this implementation, the requesting clinician selects the desired consultation within the electronic health record (EHR) ordering menu, which creates an electronic form that is pre-populated with patient demographic information and allows free-text entry of the reason for consult. This triggers a message to the requesting clinician and requested specialty, thereby enabling bidirectional clinician-clinician communication. OBJECTIVE: The aim of this study is to examine the utilization of e-consults in a large Veterans Affairs (VA) health care system. METHODS: Data from the electronic health record was used to measure frequency of e-consult use by provider type (physician or nurse practitioner (NP) and/or physician assistant), and by the requesting and responding specialty from January 2012 to December 2013. We conducted chart reviews for a purposive sample of e-consults and semi-structured interviews with a purposive sample of clinicians and hospital leaders to better characterize the process, challenges, and usability of e-consults. RESULTS: A total of 7097 e-consults were identified, 1998 from 2012 and 5099 from 2013. More than one quarter (27.56%, 1956/7097) of the e-consult requests originated from VA facilities in New England other than VABHS and were excluded from subsequent analysis. Within the VABHS e-consults (72.44%, 5141/7097), variability in frequency and use of e-consults across provider types and specialties was found. A total of 64 NPs requested 2407 e-consults (median 12.5, range 1-415). In contrast, 448 physicians (including residents and fellows) requested 2349 e-consults (median 2, range 1-116). More than one third (37.35%, 1920/5141) of e-consults were sent from primary care to specialists. While most e-consults reflected a request for specialist input to a generalist's question in diagnosis or management in the ambulatory setting, we identified creative uses of e-consults, including requests for face-to-face appointments and documentation of pre-operative chart reviews; moreover, 7.00% (360/5141) of the e-consults originated from our sub-acute and chronic care inpatient units. In interviews, requesting providers reported high utility and usability. Specialists recognized the value of e-consults but expressed concerns about additional workload. CONCLUSIONS: The e-consult mechanism is frequently utilized for its initial intended purpose. It has also been adopted for unexpected clinical and administrative uses, developing into a "disruptive innovation" and highlighting existing gaps in mechanisms for provider communication. Further investigation is needed to characterize optimal utilization of e-consults within specialty and the medical center, and what features of the e-consult program, other than volume, represent valid measures of access and quality care.

5.
J Am Med Inform Assoc ; 21(e1): e157-62, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24036155

RESUMO

Few ambulatory medication reconciliation tools exist. Transitions between inpatient and outpatient care can result in medication discrepancies. An interdisciplinary team designed a new 'Secure Messaging for Medication Reconciliation Tool' (SMMRT) within a patient web portal and piloted it among 60 patients at a Veterans Affairs hospital, an integrated system with a shared electronic health record. Recently discharged patients used SMMRT to view their medications in a secure email message and replied using SMMRT's interactive form, verifying their medication regimens and clarifying any inaccuracies. In total, 108 medication discrepancies and 23 potential adverse drug events (ADEs) were seen. Nearly 50% of the potential ADEs were classified as serious. Overall, participants were enthusiastic about SMMRT; 90% said they would use SMMRT again. Enabling patients to conduct medication reconciliation through a web portal is feasible in the transition from inpatient to outpatient care and may improve medication safety.


Assuntos
Internet , Sistemas Computadorizados de Registros Médicos , Reconciliação de Medicamentos/métodos , Participação do Paciente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Hospitais de Veteranos , Humanos , Alta do Paciente , Projetos Piloto , Estados Unidos
6.
J Med Internet Res ; 15(12): e264, 2013 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-24297865

RESUMO

BACKGROUND: Virtual (non-face-to-face) medication reconciliation strategies may reduce adverse drug events (ADEs) among vulnerable ambulatory patients. Understanding provider perspectives on the use of technology for medication reconciliation can inform the design of patient-centered solutions to improve ambulatory medication safety. OBJECTIVE: The aim of the study was to describe primary care providers' experiences of ambulatory medication reconciliation and secure messaging (secure email between patients and providers), and to elicit perceptions of a virtual medication reconciliation system using secure messaging (SM). METHODS: This was a qualitative study using semi-structured interviews. From January 2012 to May 2012, we conducted structured observations of primary care clinical activities and interviewed 15 primary care providers within a Veterans Affairs Healthcare System in Boston, Massachusetts (USA). We carried out content analysis informed by the grounded theory. RESULTS: Of the 15 participating providers, 12 were female and 11 saw 10 or fewer patients in a typical workday. Experiences and perceptions elicited from providers during in-depth interviews were organized into 12 overarching themes: 4 themes for experiences with medication reconciliation, 3 themes for perceptions on how to improve ambulatory medication reconciliation, and 5 themes for experiences with SM. Providers generally recognized medication reconciliation as a valuable component of primary care delivery and all agreed that medication reconciliation following hospital discharge is a key priority. Most providers favored delegating the responsibility for medication reconciliation to another member of the staff, such as a nurse or a pharmacist. The 4 themes related to ambulatory medication reconciliation were (1) the approach to complex patients, (2) the effectiveness of medication reconciliation in preventing ADEs, (3) challenges to completing medication reconciliation, and (4) medication reconciliation during transitions of care. Specifically, providers emphasized the importance of medication reconciliation at the post-hospital visit. Providers indicated that assistance from a caregiver (eg, a family member) for medication reconciliation was helpful for complex or elderly patients and that patients' social or cognitive factors often made medication reconciliation challenging. Regarding providers' use of SM, about half reported using SM frequently, but all felt that it improved their clinical workflow and nearly all providers were enthusiastic about a virtual medication reconciliation system, such as one using SM. All providers thought that such a system could reduce ADEs. CONCLUSIONS: Although providers recognize the importance and value of ambulatory medication reconciliation, various factors make it difficult to execute this task effectively, particularly among complex or elderly patients and patients with complicated social circumstances. Many providers favor enlisting the support of pharmacists or nurses to perform medication reconciliation in the outpatient setting. In general, providers are enthusiastic about the prospect of using secure messaging for medication reconciliation, particularly during transitions of care, and believe a system of virtual medication reconciliation could reduce ADEs.


Assuntos
Reconciliação de Medicamentos/métodos , Atenção Primária à Saúde , Telemedicina/métodos , Interface Usuário-Computador , Assistência Ambulatorial , Boston , Segurança Computacional , Feminino , Humanos , Masculino , Médicos de Atenção Primária , Enfermagem de Atenção Primária , Mensagem de Texto , Estados Unidos , United States Department of Veterans Affairs
7.
Immunity ; 37(3): 574-87, 2012 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-22981538

RESUMO

Invariant natural killer T (iNKT) cells are evolutionarily conserved innate T cells that influence inflammatory responses. We have shown that iNKT cells, previously thought to be rare in humans, were highly enriched in human and murine adipose tissue, and that as adipose tissue expanded in obesity, iNKT cells were depleted, correlating with proinflammatory macrophage infiltration. iNKT cell numbers were restored in mice and humans after weight loss. Mice lacking iNKT cells had enhanced weight gain, larger adipocytes, fatty livers, and insulin resistance on a high-fat diet. Adoptive transfer of iNKT cells into obese mice or in vivo activation of iNKT cells via their lipid ligand, alpha-galactocylceramide, decreased body fat, triglyceride levels, leptin, and fatty liver and improved insulin sensitivity through anti-inflammatory cytokine production by adipose-derived iNKT cells. This finding highlights the potential of iNKT cell-targeted therapies, previously proven to be safe in humans, in the management of obesity and its consequences.


Assuntos
Tecido Adiposo/imunologia , Citocinas/imunologia , Doenças Metabólicas/imunologia , Células T Matadoras Naturais/imunologia , Obesidade/imunologia , Tecido Adiposo/metabolismo , Transferência Adotiva , Adulto , Animais , Antígenos CD1d/genética , Antígenos CD1d/imunologia , Antígenos CD1d/metabolismo , Antígeno CD11c/imunologia , Antígeno CD11c/metabolismo , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Citometria de Fluxo , Humanos , Fígado/imunologia , Fígado/metabolismo , Contagem de Linfócitos , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Pessoa de Meia-Idade , Células T Matadoras Naturais/metabolismo , Células T Matadoras Naturais/transplante , Obesidade/etiologia , Obesidade/metabolismo , Baço/imunologia , Baço/metabolismo , Adulto Jovem
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