Recruitment of endogenous neural progenitor cells by malignant neoplasms of the central nervous system

It is proposed here that malignancies of the central nervous system (CNS) are capable of recruiting non-malignant CNS precursor cells and that doing so worsens the course of the disease. In particular, the argument is put forward that such tumors can activate resident neural stem cells, attract them or their progeny to the tumor site, and induce them to proliferate. What begins as a normal wound repair response by the recruited cells can eventually result in augmentation of the tumor. In support of this hypothesis, evidence consistent with the ideas proposed is presented. Since these recruited cells are non-malignant, it should be possible to interfere with this process. This would not necessarily remove the threat posed by the cancer, but could beneficially impact patients by slowing progression. Interfering with recruitment could simultaneously serve to block autocrine stimulation by tumor cells. In contrast, introducing exogenous stem cells could exacerbate the recruitment process unless measures are taken to preclude this possibility. Finally, it is worth noting that the situation described in the current hypothesis might apply to a variety of other stem and precursor cell-containing systems throughout the body.     

Closing the gap in postfracture care at the population level: a randomized controlled trial

Background:

Postfracture care is suboptimal, and strategies to address this major gap in care are necessary. We investigated whether notifications sent by mail to physicians and patients would lead to improved postfracture care.

Methods:

We conducted a randomized controlled trial (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT00594789","term_id":"NCT00594789"}}NCT00594789) in the province of Manitoba, Canada, from June 2008 to May 2010. Using medical claims data, we identified 4264 men and women age 50 years or older who recently reported major fractures, and who had not undergone recent bone mineral density testing or treatment for osteoporosis. Participants were randomized to three groups: group 1 received usual care (n = 1480), patients in group 2 had mailed notification of the fracture sent to their primary care physicians (n = 1363), and group 3 had notifications sent to both physicians and patients (n = 1421). Bone mineral density testing and the start of pharmacologic treatment for osteoporosis within the following 12 months were documented.

Results:

Among participants in group 1 (usual care), 15.8% of women and 7.6% of men underwent testing for bone mineral density or started pharmacologic treatment for osteoporosis. Outcome measures improved among participants in group 2 (30.3% of women and 19.0% of men, both p < 0.001) and group 3 (34.0% of women and 19.8% of men, both p < 0.001). No additional benefit was seen with patient notification in addition to physician notification. Combining groups 2 and 3, the absolute increase for the combined end point of bone mineral density testing or pharmacologic treatment was 14.9% (16.4% among women, 11.8% among men). The number needed to notify to change patient care was 7 (6 for women, 6 for men). The adjusted odds ratio (OR) to change patient care in group 2 was 2.45 (95% confidence interval [CI] 2.01–2.98); for group 3 the OR was 2.82 (95% CI 2.33–3.43).

Interpretation:

This notification system provides a relatively simple way to enhance post-fracture care.The recently published 2010 clinical practice guidelines for osteoporosis care in Canada identified a large “care gap” for people who have sustained fragility fractures.¹ Most of the people who have had a major osteoporotic fracture (more than 80% in a recent Manitoba study) do not undergo testing for bone mineral density or pharmacologic treatment to assist in preventing further fractures.^2,3 This gap in care is a missed opportunity for secondary prevention, because people who have already sustained a fragility fracture are at much higher risk for recurrent fractures.⁴Educational initiatives are necessary but are insufficient for effecting a system-wide improvement in care.^5,6 Although such initiatives can have short-term benefits, they do not produce long-term changes in postfracture care.^7,8 Approaches that target the health care system and process of care have the potential to effect broad and long-term changes in patient care.^9,10Administrative health care data provide a convenient source of population-based information. In theory, these data might permit identification of incident fractures with targeted notification aimed at improving care.We investigated whether notifying the primary care physicians associated with patients’ long-term care and providing them with simple information on appropriate management would help to close the gap in care, and whether the addition of patient notification would further enhance this initiative.     

Differentially Expressed RNA from Public Microarray Data Identifies Serum Protein Biomarkers for Cross-Organ Transplant Rejection and Other Conditions

Serum proteins are routinely used to diagnose diseases, but are hard to find due to low sensitivity in screening the serum proteome. Public repositories of microarray data, such as the Gene Expression Omnibus (GEO), contain RNA expression profiles for more than 16,000 biological conditions, covering more than 30% of United States mortality. We hypothesized that genes coding for serum- and urine-detectable proteins, and showing differential expression of RNA in disease-damaged tissues would make ideal diagnostic protein biomarkers for those diseases. We showed that predicted protein biomarkers are significantly enriched for known diagnostic protein biomarkers in 22 diseases, with enrichment significantly higher in diseases for which at least three datasets are available. We then used this strategy to search for new biomarkers indicating acute rejection (AR) across different types of transplanted solid organs. We integrated three biopsy-based microarray studies of AR from pediatric renal, adult renal and adult cardiac transplantation and identified 45 genes upregulated in all three. From this set, we chose 10 proteins for serum ELISA assays in 39 renal transplant patients, and discovered three that were significantly higher in AR. Interestingly, all three proteins were also significantly higher during AR in the 63 cardiac transplant recipients studied. Our best marker, serum PECAM1, identified renal AR with 89% sensitivity and 75% specificity, and also showed increased expression in AR by immunohistochemistry in renal, hepatic and cardiac transplant biopsies. Our results demonstrate that integrating gene expression microarray measurements from disease samples and even publicly-available data sets can be a powerful, fast, and cost-effective strategy for the discovery of new diagnostic serum protein biomarkers.     

A cluster randomized controlled trial comparing three methods of disseminating practice guidelines for children with croup [ISRCTN73394937]

Background

The optimal management of croup – a common respiratory illness in young children – is well established. In particular, treatment with corticosteroids has been shown to significantly reduce the rate and duration of intubation, hospitalization, and return to care for on-going croup symptoms. Furthermore treatment with a single dose of corticosteroids does not appear to result in any significant adverse outcomes, and yields overall cost-savings for both families and the health care system. However, as has been shown with many other diseases, there is a significant gap between what we know and what we do. The overall aim of this study is to identify, from a societal perspective, the costs and associated benefits of three strategies for implementing a practice guideline that addresses the management of croup.

Methods/designs

We propose to use a matched pair cluster trial in 24 Alberta hospitals randomized into three intervention groups. We will use mixed methods to assess outcomes including linkage and analysis of administrative databases obtained from Alberta Health and Wellness, retrospective medical chart audit, and prospective telephone surveys of the parents of children diagnosed to have croup. The intervention strategies to be compared will be mailing of printed educational materials (low intensity intervention), mailing plus a combination of interactive educational meetings, educational outreach visits, and reminders (intermediate intensity intervention), and a combination of mailing, interactive sessions, outreach visits, reminders plus identification of local opinion leaders and establishment of local consensus processes (high intensity intervention). The primary objective is to determine which of the three intervention strategies are most effective at lowering the rate of hospital days per 1,000 disease episodes. Secondary objectives are to determine which of the three dissemination strategies are most effective at increasing the use of therapies of known benefit. An economic analysis will be conducted to determine which of the three intervention strategies will most effectively reduce total societal costs including all health care costs, costs borne by the family, and costs stemming from the strategies for disseminating guidelines.     

A Randomized Controlled Trial of Storytelling as a Communication Tool

Introduction

Stories may be an effective tool to communicate with patients because of their ability to engage the reader. Our objective was to evaluate the effectiveness of story booklets compared to standard information sheets for parents of children attending the emergency department (ED) with a child with croup.

Methods

Parents were randomized to receive story booklets (n=208) or standard information sheets (n=205) during their ED visit. The primary outcome was change in anxiety between triage to ED discharge as measured by the State-Trait Anxiety Inventory. Follow-up telephone interviews were conducted at 1 and 3 days after discharge, then every other day until 9 days (or until resolution of symptoms), and at 1 year. Secondary outcomes included: expected future anxiety, event impact, parental knowledge, satisfaction, decision regret, healthcare utilization, time to symptom resolution.

Results

There was no significant difference in the primary outcome of change in parental anxiety between recruitment and ED discharge (change of 5 points for the story group vs. 6 points for the comparison group, p=0.78). The story group showed significantly greater decision regret regarding their decision to go to the ED (p<0.001): 6.7% of the story group vs. 1.5% of the comparison group strongly disagreed with the statement “I would go for the same choice if I had to do it over again”. The story group reported shorter time to resolution of symptoms (mean 3.7 days story group vs. 4.0 days comparison group, median 3 days both groups; log rank test, p=0.04). No other outcomes were different between study groups.

Conclusions

Stories about parent experiences managing a child with croup did not reduce parental anxiety. The story group showed significantly greater decision regret and quicker time to resolution of symptoms. Further research is needed to better understand whether stories can be effective in improving patient-important outcomes.

Trial Registration

Current Controlled Trials, ISRCTN39642997 (http://www.controlled-trials.com/ISRCTN39642997)     

Empirical tests of the role of disruptive coloration in reducing detectability

Disruptive patterning is a potentially universal camouflage technique that is thought to enhance concealment by rendering the detection of body shapes more difficult. In a recent series of field experiments, artificial moths with markings that extended to the edges of their 'wings' survived at higher rates than moths with the same edge patterns inwardly displaced. While this result seemingly indicates a benefit to obscuring edges, it is possible that the higher density markings of the inwardly displaced patterns concomitantly reduced their extent of background matching. Likewise, it has been suggested that the mealworm baits placed on the artificial moths could have created differential contrasts with different moth patterns. To address these concerns, we conducted controlled trials in which human subjects searched for computer-generated moth images presented against images of oak trees. Moths with edge-extended disruptive markings survived at higher rates, and took longer to find, than all other moth types, whether presented sequentially or simultaneously. However, moths with no edge markings and reduced interior pattern density survived better than their high-density counterparts, indicating that background matching may have played a so-far unrecognized role in the earlier experiments. Our disruptively patterned non-background-matching moths also had the lowest overall survivorship, indicating that disruptive coloration alone may not provide significant protection from predators. Collectively, our results provide independent support for the survival value of disruptive markings and demonstrate that there are common features in human and avian perception of camouflage.     

Coronary artery compliance in the dog

Measurement of left anterior descending coronary arterial pressure, phasic coronary flow, and intramyocardial pressure in an open-chest dog provided data, which when entered into the computer model of the coronary circulation, permitted calculation of coronary artery compliance and resistance during systole and diastole. Resting in vivo compliance averaged 0.21 x 10(-3) mL/mmHg (1 mmHg = 133.322 Pa) while systolic resistance averaged 4.05 mmHg X min-1 X mL-1 and during diastole 2.06 mmHg X min-1 X mL-1. Left stellate ganglion stimulation or vasodilation caused minimal changes in compliance but glutaraldehyde applied to arterial wall caused a decrease in compliance. Sympathetic stimulation and vasodilation decreased both diastolic and systolic resistance. Transmural distribution of coronary flow was not significantly altered by the experimental changes in compliance and resistance.