Identifying causes of delay in interfacility transfer of patients by air ambulance.

OBJECTIVES: Population 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. METHODS: Causes 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. RESULTS: Our 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). CONCLUSIONS: Some 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.

Comparison of Vancomycin Pharmacokinetics in Cystic Fibrosis Patients Pre and Post-lung Transplant.

BACKGROUND: Vancomycin is commonly used to treat acute cystic fibrosis (CF) exacerbations associated with methicillin-resistant Staphylococcus aureus (MRSA). Multiple studies have demonstrated pharmacokinetic differences of antimicrobials in the CF population. Very little data exist regarding pharmacokinetics postlung transplant, but 2 studies have noted changes in tobramycin pharmacokinetics. No such studies exist evaluating vancomycin in CF patients postlung transplant. METHODS: A retrospective cohort review of CF patients who underwent lung transplantation and received vancomycin pre- and posttransplant was conducted. CF patients who underwent transplant between 2007 and 2016 at 4 medical centers throughout the United States were included. The primary endpoint was the change in elimination rate constant. The secondary endpoints were subgroup analyses of patients grouped by age, time posttransplant, and number of nephrotoxic medications. RESULTS: A total of 25 patients were included, of which just under half were pediatric. Patients were significantly older and heavier posttransplant and had higher serum creatinine and number of nephrotoxic medications. The change in elimination rate constant from pre- to posttransplant was -0.50 hr-1 which was statistically significant (P < .001). This significant decrease was consistent among all subgroups of patients evaluated with the exception of pediatric patients. CONCLUSION: Vancomycin pharmacokinetics are significantly altered in CF patients in the posttransplant setting as evidenced by a decrease in elimination rate constant. This decrease may be related to a decrease in renal clearance and higher numbers of nephrotoxic medications posttransplant. Regardless, pretransplant vancomycin regimens may not predict appropriate posttransplant regimens.

Ceftaroline pharmacokinetics and pharmacodynamics in patients with cystic fibrosis.

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 (15mg/kg IV up to 600mg every 8h) 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>MIC) were determined for each subject using MICs of 0.5, 1, and 2µg/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>MIC was 75.7 (10.4), and all subjects had >60%fT>MIC. CONCLUSIONS: In this cohort of CF patients, mean ceftaroline half-life was 1.1h, 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 >60% time above the MIC in all patients.

High-sucrose diets in male rats disrupt aspects of decision making tasks, motivation and spatial memory, but not impulsivity measured by operant delay-discounting.

Excessive consumption of sugar sweetened drinks is proposed to produce functional changes in the hippocampus and prefrontal cortex, leading to perturbations in behavioural control. Impairments in behavioural control have been observed in obese people on tasks that involve making choices, including delay-discounting, indicative of increased impulsivity. In this study we examined the impact of 2h daily access to 10% sucrose (or no sucrose in controls) in young male rats on behavioural tasks reliant on hippocampal function including delay-discounting, T-maze forced choice alternation and place recognition memory, as well as progressive ratio to measure motivation. We observed deficits in place recognition memory and T-maze forced choice alternation, indicative of hippocampal deficits in rats with a history of sucrose consumption. Moreover, rats with a history of sucrose consumption were less motivated to lever press for rewards on a progressive ratio schedule. However, rats with a history of sucrose consumption performed equally to control animals during the delay-discounting task, suggesting that they discounted for reward size over a delay in a manner comparable to control animals. These findings indicate that high-sucrose diets impact on spatial and working memory processes, but do not induce impulsive-like choice behaviours in rats, suggesting that unhealthy diet choices may not influence this aspect of decision-making behaviour.

Functional analysis of HIV type 1 Nef gene variants from adolescent and adult survivors of perinatal infection.

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.