Within the range of concentrations examined in this study, the effect of hypertonic saline appears to be dose dependent. Inhalation of hypertonic saline remains a potentially useful treatment for patients with cystic fibrosis.
Throughout the world, infants and children with HIV-1 infection are increasingly surviving into adolescence and adulthood. As HIV Nef is an important determinant of the pathogenic potential of the virus, we examined nef alleles in a cohort of extreme long-term survivors of HIV infection (average age of 16.6 years) to determine if Nef defects might have contributed to patient survival. HIV nef gene sequences were amplified for phylogenetic analysis from 15 adolescents and adults infected by mother-to-child transmission (n = 10) or by blood transfusion (n = 5). Functional analysis was performed by inserting patient-derived nef sequences into an HIV-derived vector that permits simultaneous evaluation of the impact of the Nef protein on MHC-I and CD4 cell surface expression. We found evidence of extensive nef gene diversity, including changes in known functional domains involved in the downregulation of cell surface MHC-I and CD4. Only 3 of 15 individuals (20%) had nef alleles with a loss of the ability to downregulate either CD4 or MHC-I. Survival into adulthood with HIV infection acquired in infancy is not uniformly linked to loss of function in nef. The Nef protein remains a potential target for immunization or pharmacologic intervention.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a prevalent pathogen in patients with cystic fibrosis (CF) associated with increased morbidity. Ceftaroline fosamil is an intravenous (IV) cephalosporin with activity against MRSA. There are minimal data regarding dosing in the CF population. The objective of this study was to determine the pharmacokinetic and pharmacodynamic profile of IV ceftaroline in patients with CF. Methods: We conducted a single-center prospective study of children and young adults with CF receiving ceftaroline (15 mg/kg IV up to 600 mg every 8 h) as part of treatment for a CF pulmonary exacerbation between June 2016 and April 2017. Seven patients were enrolled for a total of 10 treatment courses. For each treatment course, up to 8 plasma samples were assayed for ceftaroline using ultra-high performance liquid chromatography with mass spectrometry. Maximum plasma concentration, systemic clearance, and elimination half-life were calculated. The area under the curve (AUC) above the minimum inhibitory concentration (MIC) and the percent time above the MIC (%fT N MIC) were determined for each subject using MICs of 0.5, 1, and 2 μg/mL and the measured MIC if available. Results: The mean (SD) age for the 7 patients was 20.3 (8.0) years. Mean (SD) maximum plasma concentration of ceftaroline was 22.7 (9.6) μg/mL, systemic clearance 7.9 (3.3) L/h, and half-life 1.1 (0.4) hours. Using a MIC of 1 μg/mL, accepted as the MIC 90 of MRSA isolates, AUC above MIC mean (SD) was 53.6 (19.5) μg•h/mL, mean (SD) %fT N MIC was 75.7 (10.4), and all subjects had N 60%fT N MIC. Conclusions: In this cohort of CF patients, mean ceftaroline half-life was 1.1 h, which is notably lower than the general population. The dosing regimen studied, which exceeds the recommended dosing in the non-CF population, was adequate to achieve N 60% time above the MIC in all patients.
ObjectivesPopulation density can limit the level of care that can be provided in local facilities in Ontario, and as such, patients with severe illnesses often require interfacility transfers to access specialized care. This study aimed to identify causes of delay in interfacility transport by air ambulance in Ontario.MethodsCauses of delay were identified by manual review of electronic patient care records (ePCRs). All emergent interfacility transfers conducted by Ornge, the sole provider of air-based medical transport in Ontario, between January 1, 2016 and December 31, 2016 were included. The ePCRs were reviewed if they met one or more of the following: (1) contained a standardized delay code; (2) contained free text including “delay”, “wait”, or “duty-out”; (3) were above the 75th percentile in total transport time; or (4) were above the 90th percentile in time to bedside, time at the sending hospital, or time to receiving facility.ResultsOur search strategy identified 1,220 ePCRs for manual review, which identified a total of 872 delays. Common delays cited included aircraft refueling (234 delays), waiting for land emergency medical service (EMS) escort (146), and staffing- or dispatch-related issues (124). Other delays included weather/environmental hazards (43); mechanical issues (36); and procedures, imaging, or stabilization (80).ConclusionsSome common causes of interfacility delay are potentially modifiable: better trip planning around refueling and improved coordination with local EMS, could reduce delays experienced during interfacility trips. To better understand causes of delay, we would benefit from improved documentation and record availability which limited the results in this study.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.