MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis

Myelin loss is associated with axonal damage in established multiple sclerosis. This relationship is challenging to study in vivo in early disease. Here, we ask whether myelin loss is associated with axonal damage at diagnosis, by combining non-invasive neuroimaging and blood biomarkers. We performed quantitative microstructural MRI and single molecule ELISA plasma neurofilament measurement in 73 patients with newly diagnosed, immunotherapy naïve relapsing-remitting multiple sclerosis. Myelin integrity was evaluated using aggregate g-ratios, derived from magnetization transfer saturation (MTsat) and neurite orientation dispersion and density imaging (NODDI) diffusion data. We found significantly higher g-ratios within cerebral white matter lesions (suggesting myelin loss) compared with normal-appearing white matter (0.61 vs 0.57, difference 0.036, 95% CI 0.029 to 0.043, p < 0.001). Lesion volume (Spearman’s rho rs= 0.38, p < 0.001) and g-ratio (rs= 0.24 p < 0.05) correlated independently with plasma neurofilament. In patients with substantial lesion load (n = 38), those with higher g-ratio (defined as greater than median) were more likely to have abnormally elevated plasma neurofilament than those with normal g-ratio (defined as less than median) (11/23 [48%] versus 2/15 [13%] p < 0.05). These data suggest that, even at multiple sclerosis diagnosis, reduced myelin integrity is associated with axonal damage. MRI-derived g-ratio may provide useful additional information regarding lesion severity, and help to identify individuals with a high degree of axonal damage at disease onset. York, Martin et al. simultaneously measured g-ratio and plasma neurofilament in 73 relapsing-remitting multiple sclerosis patients at diagnosis using advanced MRI and single molecule ELISA. They demonstrate that g-ratio of cerebral white matter lesions varies at diagnosis, and show that high g-ratio of lesions is associated with elevated plasma neurofilament

Modification of Pseudomonas aeruginosa Interactions with Corneal Epithelial Cells by Human Tear Fluid

Both cytotoxic and invasive strains of Pseudomonas aeruginosa can damage corneal epithelial cells in vitro, but neither can infect healthy corneas in vivo. We tested the hypothesis that whole human tear fluid can protect corneal epithelia against P. aeruginosa virulence mechanisms. Cultured corneal epithelial cells were inoculated with 10(6) CFU of one of 10 strains of P. aeruginosa (five cytotoxic, five invasive)/ml with or without reflex tear fluid collected from the conjunctival sacs of human volunteers. Cytotoxicity was assessed by observation of trypan blue staining and measurement of lactate dehydrogenase release; invasion was quantified by using gentamicin survival assays. Tear fluid retarded growth of only 50% of the P. aeruginosa strains (three of five invasive strains, two of five cytotoxic strains) yet protected corneal cells against invasion by or cytotoxicity of 9 of 10 strains. The only strain resistant to the tear cytoprotective effects was susceptible to tear bacteriostatic activity. Dilution of tear fluid threefold significantly reduced cytoprotection, while bacteriostatic activity prevailed with dilutions beyond 100-fold. Sulfacetamide (1 mg/ml) with bacteriostatic activity matching that of tear fluid was less cytoprotective than tear fluid (80% protection with tear fluid, 48% with sulfacetamide). Video microscopy revealed bacterial chain formation in both tear fluid and sulfacetamide, but tear fluid also blocked bacterial swimming motility. After prolonged tear contact, bacteria regained normal growth rates, swimming motility, and cytotoxic activity, suggesting a breakdown of protective tear factors. Boiled tear fluid lost bacteriostatic activity and effects on bacterial motility but retained cytoprotective function. These results suggest that human tear fluid can protect corneal epithelial cells against P. aeruginosa virulence mechanisms in a manner not dependent upon bacteriostatic activity or effects on bacterial motility. Whether overlapping tear film components are involved in these defense functions is to be determined

Human Tear Fluid Protects against Pseudomonas aeruginosa Keratitis in a Murine Experimental Model

Pseudomonas aeruginosa keratitis is an acute sight-threatening infection. We previously reported that human tear fluid could protect individual human corneal epithelial cells in vitro against invasion by and cytotoxicity due to clinical and laboratory isolates of P. aeruginosa and that the protective mechanism was independent of bacteriostatic activity. In the present study, we examined the effects of human tear fluid in vivo. Tears were collected from healthy human volunteers and were studied in vivo in mice. The effects on the virulence of both invasive and cytotoxic clinical isolates of P. aeruginosa were examined. Tear fluid was found to reduce the severity of disease when corneas were challenged with cytotoxic bacteria immediately after scratch injury, and it completely protected against susceptibility to infection by a cytotoxic strain in a model in which corneas were infected during the healing process 6 h after scratching. Visible protection correlated with the inhibition of bacterial colonization 1, 4, and 48 h postinoculation. Tear fluid also significantly reduced the severity of infections caused by invasive P. aeruginosa in the 6-h-healing model. This result also coincided with significantly reduced bacterial colonization at 48 h. In vitro, human tear fluid significantly reduced the ability of invasive and cytotoxic bacteria to translocate across corneal epithelia and increased transepithelial resistance with or without bacterial inoculation. These data show that human tear fluid can protect against P. aeruginosa corneal infection in vivo and that the mechanism likely involves enhanced epithelial barrier function in addition to protection of individual epithelial cells against bacterial internalization and cytotoxicity

Project RED Impacts Patient Experience

Background: Hospitalized patients are frequently unprepared to care for themselves after discharge often leading to unplanned hospital readmission. One strategy to reduce readmission rates is improving the quality of patient education and preparation before hospital discharge. The ReEngineered Discharge (RED) is a standardized hospital-based program designed to provide patients and caregivers the information they need to continue care at home. Objectives: We sought to study the impact of the RED intervention on posthospitalization adult patient experience scores in an urban academic safety-net hospital. Methods: We conducted a descriptive study of a pilot program that compared posthospitalization survey responses to the Press Ganey survey item “Instructions were given about how to care for yourself at home.” We compared the survey results for 3 groups of adult patients: those receiving the RED program, those receiving a standard discharge on the same hospital unit, and those receiving a standard discharge on other hospital units. Results: A greater percentage of adult patients who received the RED discharge program rated the quality of their discharge as “very good” as compared to those receiving a standard discharge on the same hospital unit and those receiving a standard discharge on other hospital units (61%, 35%, and 41%, respectively, P = .0001). Conclusion: Delivery of a standardized hospital discharge program resulted in a larger proportion of top-box “very good” responses on a Press Ganey posthospitalization survey. Future research should examine whether hospital-based transition programs can sustain improvement in patient experience measures and whether these improvements can be observed in other patient populations

Factors Determining the Uptake of Influenza Vaccination among Children with Chronic Conditions

Background: Studies report that the influenza vaccination uptake rate among children with chronic conditions is alarmingly low. In Hong Kong, there has been no study examining parental decision making about influenza vaccination for children with chronic conditions, thereby limiting the knowledge base to inform the development of specific strategies to improve influenza vaccination rates. The aim of this study was to identify factors determining the uptake of influenza vaccination among children with chronic conditions. Methods: We conducted a cross-sectional survey of 623 parents with children having a chronic condition recruited from pediatric wards and specialty outpatient departments of 2 acute hospitals. A questionnaire developed by Daley et al based on the Health Belief Model was used to examine parents' beliefs and attitudes toward influenza and vaccination. Results: The parents' and their children's mean age were 40.1 ± 8.1 and 8.0 ± 4.5 years, respectively. Among the children, the most prevalent chronic conditions were asthma, chronic respiratory disease and cardiomyopathy. One-third (33%) of the children had influenza vaccination in the past 12 months. More than one-third (39%) of parents intended to vaccinate their children against influenza in the coming influenza season. A multivariable logistic regression analysis revealed that all subscale scores except perceived severity and knowledge about influenza were independently significantly associated with uptake. Conclusions: The findings indicate that parents of children with chronic conditions lack awareness of the risks of influenza and have insufficient understanding about the benefits of vaccination. These findings could inform the development of interventions to promote vaccination uptake among children with chronic conditions

A population-based matched cohort study examining the mortality and costs of patients with community-onset <i>Clostridium difficile</i> infection identified using emergency department visits and hospital admissions

<div><p>Few studies have evaluated the mortality or quantified the economic burden of community-onset <i>Clostridium difficile</i> infection (CDI). We estimated the attributable mortality and costs of community-onset CDI. We conducted a population-based matched cohort study. We identified incident subjects with community-onset CDI using health administrative data (emergency department visits and hospital admissions) in Ontario, Canada between January 1, 2003 and December 31, 2010. We propensity-score matched each infected subject to one uninfected subject and followed subjects in the cohort until December 31, 2011. We evaluated all-cause mortality and costs (unadjusted and adjusted for survival) from the healthcare payer perspective (2014 Canadian dollars). During our study period, we identified 7,950 infected subjects. The mean age was 63.5 years (standard deviation = 22.0), 62.7% were female, and 45.0% were very high users of the healthcare system. The relative risk for 30-day, 180-day, and 1-year mortality were 7.32 (95% confidence interval [CI], 5.94–9.02), 3.55 (95%CI, 3.17–3.97), and 2.59 (95%CI, 2.37–2.83), respectively. Mean attributable cumulative 30-day, 180-day, and 1-year costs (unadjusted for survival) were $7,434 (95$7,122-$7,762),$12,517 (95%CI, $11,687-$13,366), and $13,217 (95$12,062-$14,388). Mean attributable cumulative 1-, 2-, and 3-year costs (adjusted for survival) were$10,700 (95%CI, $9,811-$11,645), $13,312 (95$12,024-$14,682), and$15,812 (95%CI, $14,159-$17,571). Infected subjects had considerably higher risk of all-cause mortality and costs compared with uninfected subjects. This study provides insight on an understudied patient group. Our study findings will facilitate assessment of interventions to prevent community-onset CDI.</p></div