Translating knowledge on best practice into improving quality of RRT care: a systematic review of implementation strategies

Recent studies showed wide variation in the extent to which guidelines and other types of best practice have been implemented as part of routine health care. This is also true for the delivery of renal replacement therapy (RRT) for ESRD patients. Increasing uptake of best practice within such complex care systems requires an understanding of implementation strategies and specific quality improvement (QI) techniques. Therefore, we systematically reviewed over 5000 titles published since 1990 and included papers describing planned attempts to accelerate uptake of best RRT practice into daily care. This resulted in a list of 93 QI initiatives, categorized in order to expedite shared learning. The majority of the initiatives were executed within the domains of vascular access, nutrition, and anemia management. Strategies oriented at patients were most common and many initiatives pre-defined an improvement target before starting implementation. Of the 93 initiatives, 22 were sufficiently robust methodologically to be analyzed in more detail. Our results tend to support previous findings that multifaceted strategies are more effective than single strategies. Improving our understanding of how to successfully implement best practice can inform system-level change and is the only way to close the gap between knowledge on what works and the actual care delivered to ESRD patients. Research into implementation, using specific QI techniques, should therefore be given priority in future.     

Descending projections from the rostral ventromedial medulla (RVM) to trigeminal and spinal dorsal horns are morphologically and neurochemically distinct

Neurons in the rostral ventromedial medulla (RVM) are thought to modulate nociceptive transmission via projections to spinal and trigeminal dorsal horns. The cellular substrate for this descending modulation has been studied with regard to projections to spinal dorsal horn, but studies of the projections to trigeminal dorsal horn have been less complete. In this study, we combined anterograde tracing from RVM with immunocytochemical detection of the GABAergic synthetic enzyme, GAD67, to determine if the RVM sends inhibitory projections to trigeminal dorsal horn. We also examined the neuronal targets of this projection using immunocytochemical detection of NeuN. Finally, we used electron microscopy to verify cellular targets. We compared projections to both trigeminal and spinal dorsal horns. We found that RVM projections to both trigeminal and spinal dorsal horn were directed to postsynaptic profiles in the dorsal horn, including somata and dendrites, and not to primary afferent terminals. We found that RVM projections to spinal dorsal horn were more likely to contact neuronal somata and were more likely to contain GAD67 than projections from RVM to trigeminal dorsal horn. These findings suggest that RVM neurons send predominantly GABAergic projections to spinal dorsal horn and provide direct input to postsynaptic neurons such as interneurons or ascending projection neurons. The RVM projection to trigeminal dorsal horn is more heavily targeted to dendrites and is only modestly GABAergic in nature. These anatomical features may underlie differences between trigeminal and spinal dorsal horns with regard to the degree of inhibition or facilitation evoked by RVM stimulation.     

Association between preoperative magnetic resonance imaging, pain intensity and quantitative sensory testing in patients awaiting lumbar diskectomy

Introduction: Magnetic resonance imaging (MRI) offers important information regarding the morphology, location and size of a herniated disc, which influences the decision to offer lumbar diskectomy (LD). This study aims to examine the association between clinical neurophysiologic indices including pain intensity and quantitative sensory testing (QST), and the degree of lumbar nerve root compromise depicted on magnetic resonance (MR) in patients awaiting LD. Methods: With institutional ethical approval, 16 patients (American Society of Anaesthesiologists Grades I‐II, 18–65 years) with radicular pain for greater than 3 months undergoing elective LD were studied. Preoperative pain was assessed using (i) a visual analogue scale measuring pain intensity at rest and with movement and (ii) by quantifying pain sensory thresholds (St), pain perception thresholds (PPt), and pain tolerance threshold (PTt) using QST. MR images were independently graded by two radiologists blinded to the clinical data using the Pfirrmann grading system. Statistical analyses using Student's t‐tests and Pearson's correlation were preformed where appropriate. Results: This study showed that: (i) findings on MR imaging corresponded with the symptomatic side and distribution of the pain; (ii) the degree of nerve root compromise, detected on MRI correlated with increased pain intensity at rest; and (iii) QST identified a trend towards higher St, PPt and PTt in patients with higher Pfirrmann grades. Conclusions: The Pfirrmann grading system of nerve root compromise may be clinically useful preoperatively as a method of identifying individuals who would benefit most from LD. However, additional studies with greater patient numbers and longer follow‐up are required to definitively confirm the findings of this study.     

Cathepsin S from both tumor and tumor‐associated cells promote cancer growth and neovascularization

Recent murine studies have demonstrated that tumor‐associated macrophages in the tumor microenvironment are a key source of the pro‐tumorigenic cysteine protease, cathepsin S. We now show in a syngeneic colorectal carcinoma murine model that both tumor and tumor‐associated cells contribute cathepsin S to promote neovascularization and tumor growth. Cathepsin S depleted and control colorectal MC38 tumor cell lines were propagated in both wild type C57Bl/6 and cathepsin S null mice to provide stratified depletion of the protease from either the tumor, tumor‐associated host cells, or both. Parallel analysis of these conditions showed that deletion of cathepsin S inhibited tumor growth and development, and revealed a clear contribution of both tumor and tumor‐associated cell derived cathepsin S. The most significant impact on tumor development was obtained when the protease was depleted from both sources. Further characterization revealed that the loss of cathepsin S led to impaired tumor vascularization, which was complemented by a reduction in proliferation and increased apoptosis, consistent with reduced tumor growth. Analysis of cell types showed that in addition to the tumor cells, tumor‐associated macrophages and endothelial cells can produce cathepsin S within the microenvironment. Taken together, these findings clearly highlight a manner by which tumor‐associated cells can positively contribute to developing tumors and highlight cathepsin S as a therapeutic target in cancer.     

X-ray image enhancement via determinant based feature selection

Previous work has investigated the feasibility of using Eigenimage-based enhancement tools to highlight abnormalities on chest X-rays (Butler et al in J Med Imaging Radiat Oncol 52:244–253, 2008). While promising, this approach has been limited by computational restrictions of standard clinical workstations, and uncertainty regarding what constitutes an adequate sample size. This paper suggests an alternative mathematical model to the above referenced singular value decomposition method, which can significantly reduce both the required sample size and the time needed to perform analysis. Using this approach images can be efficiently separated into normal and abnormal parts, with the potential for rapid highlighting of pathology.     

Common laboratory tests predict imminent death in ward patients

Objective

To estimate the ability of commonly measured laboratory variables to predict an imminent (within the same or next calendar day) death in ward patients.

Design

Retrospective observational study.

Setting

Two university affiliated hospitals.

Patients

Cohort of 42,701 patients admitted for more than 24 hours and external validation cohort of 13,137 patients admitted for more than 24 hours.

Intervention

We linked commonly measured laboratory tests with event databases and assessed the ability of each laboratory variable or combination of variables together with patient age to predict imminent death.

Measurements and main results

In the inception teaching hospital, we studied 418,897 batches of tests in 42,701 patients (males 55%; average age 65.8 ± 17.6 years), for a total of >2.5 million individual measurements. Among these patients, there were 1596 deaths. Multivariable logistic modelling achieved an AUC–ROC of 0.87 (95% CI: 0.85–0.89) for the prediction of imminent death. Using an additional 105,074 batches from a cohort of 13,137 patients from a second teaching hospital, the multivariate model achieved an AUC–ROC of 0.88 (95% CI: 0.85–0.90).

Conclusions

Commonly performed laboratory tests can help predict imminent death in ward patients. Prospective investigations of the clinical utility of such predictions appear justified.     

Combining extant datasets with differing outcome measures across studies of older adults after cancer surgery

Combining extant datasets with differing outcome measures, an economical method to generate evidence guiding older adults' cancer care, may introduce heterogeneity leading to invalid study results. We recently conducted a study combining extant datasets from five oncology nurse-directed clinical trials (parent studies) using norm-based scoring to standardize the differing outcome measures. The purpose of this article is to describe and analyze our methods in the recently completed study. Despite addressing and controlling for heterogeneity, our analysis found statistically significant heterogeneity (p < 0.0001) in temporal trends among the five parent studies. We concluded that assessing heterogeneity in combined extant datasets with differing outcome measures is important to ensure similar magnitude and direction of findings across parent studies. Future research should include investigating reasons for heterogeneity to generate hypotheses about subgroup differences or differing measurement domains that may have an impact on outcomes.