Towards standardized measurement of adverse events in spine surgery: conceptual model and pilot evaluation

BACKGROUND: Independent of efficacy, information on safety of surgical procedures is essential for informed choices. We seek to develop standardized methodology for describing the safety of spinal operations and apply these methods to study lumbar surgery. We present a conceptual model for evaluating the safety of spine surgery and describe development of tools to measure principal components of this model: (1) specifying outcome by explicit criteria for adverse event definition, mode of ascertainment, cause, severity, or preventability, and (2) quantitatively measuring predictors such as patient factors, comorbidity, severity of degenerative spine disease, and invasiveness of spine surgery. METHODS: We created operational definitions for 176 adverse occurrences and established multiple mechanisms for reporting them. We developed new methods to quantify the severity of adverse occurrences, degeneration of lumbar spine, and invasiveness of spinal procedures. Using kappa statistics and intra-class correlation coefficients, we assessed agreement for the following: four reviewers independently coding etiology, preventability, and severity for 141 adverse occurrences, two observers coding lumbar spine degenerative changes in 10 selected cases, and two researchers coding invasiveness of surgery for 50 initial cases. RESULTS: During the first six months of prospective surveillance, rigorous daily medical record reviews identified 92.6% of the adverse occurrences we recorded, and voluntary reports by providers identified 38.5% (surgeons reported 18.3%, inpatient rounding team reported 23.1%, and conferences discussed 6.1%). Trained observers had fair agreement in classifying etiology of 141 adverse occurrences into 18 categories (kappa = 0.35), but agreement was substantial (kappa ≥ 0.61) for 4 specific categories: technical error, failure in communication, systems failure, and no error. Preventability assessment had moderate agreement (mean weighted kappa = 0.44). Adverse occurrence severity rating had fair agreement (mean weighted kappa = 0.33) when using a scale based on the JCAHO Sentinel Event Policy, but agreement was substantial for severity ratings on a new 11-point numerical severity scale (ICC = 0.74). There was excellent inter-rater agreement for a lumbar degenerative disease severity score (ICC = 0.98) and an index of surgery invasiveness (ICC = 0.99). CONCLUSION: Composite measures of disease severity and surgery invasiveness may allow development of risk-adjusted predictive models for adverse events in spine surgery. Standard measures of adverse events and risk adjustment may also facilitate post-marketing surveillance of spinal devices, effectiveness research, and quality improvement

Integrative Genomic Analyses Identify BRF2 as a Novel Lineage-Specific Oncogene in Lung Squamous Cell Carcinoma

William Lockwood and colleagues show that the focal amplification of a gene, BRF2, on Chromosome 8p12 plays a key role in squamous cell carcinoma of the lung

The human cytomegalovirus ul11 protein interacts with the receptor tyrosine phosphatase cd45, resulting in functional paralysis of t cells

Human cytomegalovirus (CMV) exerts diverse and complex effects on the immune system, not all of which have been attributed to viral genes. Acute CMV infection results in transient restrictions in T cell proliferative ability, which can impair the control of the virus and increase the risk of secondary infections in patients with weakened or immature immune systems. In a search for new immunomodulatory proteins, we investigated the UL11 protein, a member of the CMV RL11 family. This protein family is defined by the RL11 domain, which has homology to immunoglobulin domains and adenoviral immunomodulatory proteins. We show that pUL11 is expressed on the cell surface and induces intercellular interactions with leukocytes. This was demonstrated to be due to the interaction of pUL11 with the receptor tyrosine phosphatase CD45, identified by mass spectrometry analysis of pUL11-associated proteins. CD45 expression is sufficient to mediate the interaction with pUL11 and is required for pUL11 binding to T cells, indicating that pUL11 is a specific CD45 ligand. CD45 has a pivotal function regulating T cell signaling thresholds; in its absence, the Src family kinase Lck is inactive and signaling through the T cell receptor (TCR) is therefore shut off. In the presence of pUL11, several CD45-mediated functions were inhibited. The induction of tyrosine phosphorylation of multiple signaling proteins upon TCR stimulation was reduced and T cell proliferation was impaired. We therefore conclude that pUL11 has immunosuppressive properties, and that disruption of T cell function via inhibition of CD45 is a previously unknown immunomodulatory strategy of CMV

Ab initio studies of strained wurtzite GaN surfaces

In GaN and other group III nitrides the considerable lattice mismatch with the substrates normally employed during growth, such as sapphire, 6H-SiC and ZnO, can lead to the presence of strain which may affect the surface properties. Here we have studied the effect of biaxial strain on the structure, electronic configuration and formation energy of various GaN(0001) and (000¯1) 1 × 1 surfaces. In particular, we consider the Ga and N tetrahedral (T4), hexagonal (H3) and asymmetric top (atop) configurations. The ab initio total energy calculation studies presented here employ the density functional formalism using a pseudopotential plane-wave basis set approach in order to obtain the minimum energy configurations of the unstrained and biaxially strained structures. We show in bulk GaN a good linearity between the biaxial strain imposed and the calculated structural cell parameters. The calculated formation energies of the GaN surfaces show that the most stable configuration for the different reconstructions is not influenced by the biaxial strain

Dietary Intake Assessment: From Traditional Paper-Pencil Questionnaires to Technology-Based Tools

Self-reported methods of recall and real-time recording are the most commonly used approaches to assess dietary intake, both in research as well as the health-care setting. The traditional versions of these methods are limited by various methodological factors and burdensome for interviewees and researchers. Technology-based dietary assessment tools have the potential to improve the accuracy of the data and reduce interviewee and researcher burden. Consequently, various research groups around the globe started to explore the use of technology-based tools. This paper provides an overview of the: (1) most-commonly used and generally accepted methods to assess dietary intake; (2) errors encountered using these methods; and (3) web-based and app-based tools (i.e., Compl-eatTM, Traqq, Dutch FFQ-TOOLTM, and “Eetscore”) that have been developed by researchers of the Division of Human Nutrition and Health of Wageningen University during the past years