Cytotoxicity of phosphoramidate, bis-amidate and cycloSal prodrug metabolites against tumour and normal cells.

Phosphonate and phosphate prodrugs are integral to enhancing drug permeability, but the potential toxicity of their metabolites requires careful consideration. This study evaluates the impact of widely used phosphoramidate, bis-amidate, and cycloSal phosph(on)ate prodrug metabolites on BxPC3 pancreatic cancer cells, GL261-Luc glioblastoma cells, and primary cultured mouse astrocytes. 1-Naphthol and 2-naphthol demonstrated the greatest toxicity. Notably, 2-naphthol exhibited an ED50 of 21 µM on BxPC3 cells, surpassing 1-naphthol with an ED50 of 82 µM. Real-time xCELLigence experiments revealed notable activity for both metabolites at a low concentration of 16 µM. On primary cultured mouse astrocyte cells, all prodrugs exhibited reduced viability at 128 to 256 µM after only 4 hours of exposure. A cell-type-dependent sensitivity to phosph(on)ate prodrug metabolites was evident, with normal cells showing greater susceptibility than corresponding tumour cells. The results suggest it is essential to consider the potential cytotoxicity of phosph(on)ate prodrugs in the drug design and evaluation process.

An Advanced Practice Practitioner-Based Program to Reduce 30- and 90-Day Readmissions After Liver Transplantation.

Hospital readmissions after liver transplantation (LT) are common and associated with increased morbidity and cost. High readmission rates at our center motivated a change in practice with adoption of a nurse practitioner (NP)-based posttransplant care program. We sought to determine if this program was effective in reducing 30- and 90-day readmissions after LT and to identify variables associated with readmission. We performed a retrospective cohort study of all patients undergoing LT from July 1, 2014, to June 30, 2017, at a tertiary LT referral center. A NP-based posttransplant care program with weekend in-house nurse coordination providers and increased outpatient NP clinic availability was instituted on January 1, 2016. Postdischarge readmission rates at 30 and 90 days were compared in the pre-exposure and postexposure groups, adjusting for associated risk factors. A total of 362 patients were included in the analytic cohort. There were no significant differences in demographics, comorbidities, or index hospitalization characteristics between groups. In the adjusted analyses, the risk of readmission in the postexposure group was significantly reduced relative to baseline at 30 days (hazard ratio [HR] 0.60, 95% confidence interval [CI], 0.39-0.90; P = 0.02) and 90 days (HR, 0.49; 95% CI, 0.34-0.71; P < 0.001). Risk factors positively associated with 30-day readmission included peritransplant dialysis (HR, 1.70; 95% CI, 1.13-2.58; P = 0.01) and retransplant on index hospitalization (HR, 10.21; 95% CI, 3.39-30.75; P < 0.001). Male sex was protective against readmission (HR, 0.66; 95% CI, 0.45-0.97; P = 0.03). In conclusion, implementation of expanded NP-based care after LT was associated with significantly reduced 30- and 90-day readmission rates. LT centers and other service lines using significant postsurgical resources may be able to reduce readmissions through similar programs.

Relationship Between Objective and Behavioral Audiology for Young Children Being Assessed for Cochlear Implantation: Implications for CI Candidacy Assessment.

OBJECTIVE: This study aimed to evaluate the feasibility of making cochlear implant recommendations based on diagnostic ABR and ASSR results. The goal was to challenge the need for behavioral audiometry as part of the standard cochlear implant assessment battery for infants with profound hearing loss and to reduce the age at which cochlear implant recommendation was made. STUDY DESIGN: A retrospective review of 123 patient files for children referred to the pediatric cochlear implant service before 3 years of age over a 3-year period was undertaken. Results for click-ABR, ASSR, and behavioral audiology at 500, 1k, 2k and 4k Hz, and tympanometry were collected and relationships were investigated for 64 children who met the inclusion criteria. Data were excluded for 59 children due to the presence of auditory neuropathy findings, middle ear pathology at the time of testing, if ASSR was not assessed at intensity levels >85 dB, and/or behavioral testing was judged to be unreliable by two experienced clinicians. SETTING: Primary care pediatric cochlear implant program located within a hospital setting. PATIENTS: Pediatric patients referred for cochlear implant evaluation before 3 years of age. INTERVENTIONS(S): Children were assessed using ABR, ASSR, and behavioral audiometry for identification and confirmation of hearing loss. MAIN OUTCOME MEASURES(S): Correlation between diagnostic click-ABR and ASSR thresholds and subsequently obtained behavioral hearing thresholds. RESULTS: Results for objective measures (click-ABR and ASSR) were significantly correlated with behavioral results. The correlations, however, were poorer than expected with limited predictive value. For 6 of the 64 children click-ABR and/or ASSR suggested profound hearing loss and corresponding behavioral hearing threshold was found to be in the severe hearing loss range. CONCLUSIONS: Findings of this study do not support making cochlear implant recommendations based on the findings of diagnostic click-ABR and ASSR alone. Investigating ways to reduce the average age children with severe-to-profound hearing loss receive a cochlear implant is a priority for the study institution. An alternate evaluation pathway for infants which incorporates a multifaceted assessment is warranted and will be the focus of future work at the study institution.

An analysis of social support and insurance on discharge disposition and functional outcomes in patients with acute burns.

Impairment and burn injury outcomes are often influenced by an intermingling of physical and psychosocial factors. We hypothesized that patients without insurance would be more likely to return home. We also believed that patients with inadequate social support would be less likely to return home. The data for this report comes from a prospective study of 252 patients aged 16 and older who were discharged from an acute burn unit between February 2004 and December 2006. As a group, only 4 of 71 uninsured patients were discharged to post-acute inpatient care, compared to 48 of 181 insured patients. Of the 200 patients discharged to home, 92% had adequate social support. Of the 52 patients not discharged directly to home, only 38.5% had adequate support. By using a chi-square analysis, patients with social support were 44.642 times more likely to be discharged to home when compared to patients without social support. Patients without insurance were almost seven times more likely to be discharged to home. Average Functional Independence Measure (FIM) scores were assessed. The group with the lowest FIM scores are patients lacking adequate social support; subjects in this group are also generally older in age. In contrast, our uninsured group has significantly higher FIM scores, and also tends to be younger in age. Physical predictors of disposition include TBSA of injury, age, sex, and presence of inhalation injury. Our study illustrates that social support and access to insurance are important variables that predict outcome and disposition.

The relationship of body mass index and functional outcomes in patients with acute burns.

Obesity may contribute to the functional decline in elderly adults. It can also increase the risk of mortality in burn patients. However, little data exist regarding the relationship between obesity and functional outcomes in patients with burns. Data were collected regarding admission body mass index (BMI), length of stay, TBSA burn, inhalation injury, age, sex, discharge disposition, and discharge functional independence measure (FIM) scores for 221 patients. We used the classification and regression trees (CART) method to determine the strongest predictors of discharge disposition and FIM scores. Patients older than 59, with 0 to 30.75% TBSA burn, and a BMI of less than 27 were more likely to return home when compared with matched patients with a greater BMI. Regardless of age and BMI, patients with greater than 30.75% TBSA burn were less likely to return home (27.6%) posthospitalization when compared with patients with less than 30.75% TBSA burn (82.8%). Patients aged 54 to 72 years with less than 22.50% TBSA burn and a higher BMI (>25.15) demonstrated lower FIM locomotion scores than corresponding patients with a lower BMI (<25.15). Older patients (>72.5 years) with burns less than 22.50% TBSA and a larger BMI (>31.25) had lower transfer FIM scores when compared with matched patients with a smaller BMI (< or =31.25). Among patients with greater than 22.50 TBSA burn, women demonstrated lower FIM transfer and locomotion scores when compared with men. BMI may contribute to lower functional scores and the likelihood of discharge to an inpatient setting in elderly patients with less severe burns.

Analysis of functional outcomes in patients discharged from an acute burn center.

Burn patients require careful consideration of their post-discharge needs to maximize their recovery. Patient-specific variables or a combination of variables that might allow clinicians to develop pathways and objective endpoints for appropriate discharge would assist in expediting the patient's post-discharge care. While there have been numerous studies examining a single variable and its ability to predict outcomes, these studies may not be directly applicable to burn patients. A burn clinician must incorporate a number of variables into their prediction of discharge disposition and outcomes. Our study included 202 burn patients aged 16 and older discharged from the acute burn unit from February 2004 to June 2005. Descriptive data collection included age, total body surface area, location of burn, presence/absence of inhalation injury, gender, length of stay, discharge disposition, insurance status, and presence/absence of social support. The analysis that also incorporated data containing functional status consisted of FIM scores for locomotion, transfers, dressing, and feeding. The classification tree analysis was utilized to demonstrate what variables could predict discharge disposition. The only variable that could strongly predict those patients that went home versus another setting was the FIM locomotion score. Of the patients who went home, 87.2% were at or above a supervision level for locomotion, whereas 85.2% of the patients not discharged to home were at or below a maximal assist level. The level of functional independence at the time of a patient's discharge as assessed by the patient's ability to walk was the most powerful identifier of their ongoing needs.

Sheep blowfly strike reduction using a synthetic lure system.

The effectiveness of a synthetic lure system to reduce the incidence of blowfly strike in sheep flocks was assessed, using randomised field trials. Four field trials used eight total groups of sheep randomised to treatment (flytrap) or control on two properties in southern Queensland between 1999 and 2001. Treatment consisted of the operation of flytraps in paddocks as per manufacturer's recommendations. All sheep were inspected physically each month for flystrikes. Flytraps were associated with a reduction in flystrike incidence of 38-55%, compared to control sheep. Results confirm that traps are a useful component of a flystrike-control program. The use of fly traps by a substantial proportion of woolgrowers could assist the Australian wool industry to meet targets of reduced pesticides on shorn wool.

A practical method of predicting the loudness of complex electrical stimuli.

The output of speech processors for multiple-electrode cochlear implants consists of current waveforms with complex temporal and spatial patterns. The majority of existing processors output sequential biphasic current pulses. This paper describes a practical method of calculating loudness estimates for such stimuli, in addition to the relative loudness contributions from different cochlear regions. The method can be used either to manipulate the loudness or levels in existing processing strategies, or to control intensity cues in novel sound processing strategies. The method is based on a loudness model described by McKay et al [J. Acoust. Soc. Am. 110, 1514-1524 (2001)] with the addition of the simplifying approximation that current pulses falling within a temporal integration window of several milliseconds' duration contribute independently to the overall loudness of the stimulus. Three experiments were carried out with six implantees who use the CI24M device manufactured by Cochlear Ltd. The first experiment validated the simplifying assumption, and allowed loudness growth functions to be calculated for use in the loudness prediction method. The following experiments confirmed the accuracy of the method using multiple-electrode stimuli with various patterns of electrode locations and current levels.