A better way: training for direct observations in healthcare.

Direct observation is valuable for identifying latent threats and elucidating system complexity in clinical environments. This approach facilitates prospective risk assessment and reveals workarounds, near-misses and recurrent safety problems difficult to diagnose retrospectively or via outcome data alone. As observers are an instrument of data collection, developing effective and comprehensive observer training is critical to ensuring the reliability of the data collection and reproducibility of the research. However, methodological rigour for ensuring these data collection properties remains a key challenge in direct observation research in healthcare. Although prior literature has offered key considerations for observational research in healthcare, operationalising these recommendations may pose a challenge and unless guidance is also provided on observer training. In this article, we offer guidelines for training non-clinical observers to conduct direct observations including conducting a training needs analysis, incorporating practice observations and evaluating observers and inter-rater reliability. The operationalisation of these guidelines is described in the context of a 5-year multisite observational study investigating technology integration in the operating room. We also discuss novel tools developed during the course our project to support data collection and examine inter-rater reliability among observers in direct observation studies.

Preventing or controlling periodontitis reduces the occurrence of osteonecrosis of the jaw (ONJ) in rice rats (Oryzomys palustris).

INTRODUCTION: Osteonecrosis of the jaw (ONJ) is an adverse event that requires association of both systemic risk factors, such as powerful anti-resorptives (pARs; e.g. zoledronic acid [ZOL]), and local oral risk factors (e.g. tooth extraction, periodontitis). Whereas optimal oral health prior to initiate pARs is recognized as critically important for minimizing ONJ risk, the efficacy of preventive/maintenance measures in patients who are taking pARs is understudied. Rice rats fed a standard diet (STD), rich in insoluble fiber, develop localized periodontitis. STD-rats with localized periodontitis treated with ZOL for 18-24 wk develop ONJ. Hence, we hypothesized that controlling/preventing localized periodontitis in the ZOL-treated rats, reduces ONJ occurrence. METHODS: We used two approaches to attempt reducing periodontitis prevalence: 1) periodontal cleaning (PC); and 2) replacing the STD-diet with a nutritionally-equivalent diet high in soluble fiber (SF). 75 four-week-old male rats were weight-randomized into five groups (n = 15) in a 24-week experiment. Three groups ate the STD-diet and two the high SF-diet. STD-diet groups received intravenous (IV) vehicle (VEH) q4wks (STD + VEH), 80 µg/kg ZOL q4wks IV (STD + ZOL), or ZOL plus PC q2wks (STD + ZOL + PC). The SF-diet groups received VEH (SF + VEH) or ZOL (SF + ZOL). Jaws were processed for histopathology and evaluated for ONJ prevalence and tissue-level periodontitis. RESULTS: 1) 40% of STD + VEH rats developed maxillary localized periodontitis with no ONJ; 2) 50% of STD + ZOL rats developed ONJ; 3) 7% of STD + ZOL + PC rats developed ONJ (p < 0.01 vs. STD + ZOL); and 4) one SF + ZOL rat developed localized periodontitis, and no SF + VEH or SF + ZOL rats developed ONJ (p < 0.001 vs. STD + ZOL). CONCLUSIONS: 1) Periodontal cleaning in ZOL-treated rats decreases localized periodontitis severity and reduces ONJ prevalence; and 2) feeding a SF-diet to ZOL-treated rats reduces both incidence of localized periodontitis and ONJ. Our data indicates strong oral microbial community shifts according to oral health condition and trends in the shifts associated with diet.

Tristetraprolin Is Required for Alveolar Bone Homeostasis.

Tristetraprolin (TTP) is an RNA-binding protein that targets numerous immunomodulatory mRNA transcripts for degradation. Many TTP targets are key players in the pathogenesis of periodontal bone loss, including tumor necrosis factor-α. To better understand the extent that host immune factors play during periodontal bone loss, we assessed alveolar bone levels, inflammation and osteoclast activity in periodontal tissues, and immune response in draining cervical lymph nodes in TTP-deficient and wild-type (WT) mice in an aging study. WT and TTP-deficient (knockout [KO]) mice were used for all studies under specific pathogen-free conditions. Data were collected on mice aged 3, 6, and 9 mo. Microcomputed tomography (µCT) was performed on maxillae where 3-dimensional images were generated and bone loss was assessed. Decalcified sections of specimens were scored for inflammation and stained with tartrate-resistant acid phosphate (TRAP) to visualize osteoclasts. Immunophenotyping was performed on single-cell suspensions isolated from primary and peripheral lymphoid tissues using flow cytometry. Results presented indicate that TTP KO mice had significantly more alveolar bone loss over time compared with WT controls. Bone loss was associated with significant increases in inflammatory cell infiltration and an increased percentage of alveolar bone surfaces apposed with TRAP+ cells. Furthermore, it was found that the draining cervical lymph nodes were significantly enlarged in TTP-deficient animals and contained a distinct pathological immune profile compared with WT controls. Finally, the oral microbiome in the TTP KO mice was significantly different with age from WT cohoused mice. The severe bone loss, inflammation, and increased osteoclast activity observed in these mice support the concept that TTP plays a critical role in the maintenance of alveolar bone homeostasis in the presence of oral commensal flora. This study suggests that TTP is required to inhibit excessive inflammatory host responses that contribute to periodontal bone loss, even in the absence of specific periodontal pathogens.

Task Force on Design and Analysis in Oral Health Research: Host-Microbiome Interactions in Dysbiosis.

Knowledge Transfer Statement: This article discusses the proceedings of the conference organized by the Task Force on Design and Analysis in Oral Health Research on the new advances in host-microbiome interactions, analytical methods, and their implication in inflammatory periodontal disease management.

Plasma levels of interleukin-1 receptor antagonist (IL1Ra) predict radiographic progression of symptomatic knee osteoarthritis.

OBJECTIVE: Pro- and anti-inflammatory mediators, such as IL-1ß and IL1Ra, are produced by joint tissues in osteoarthritis (OA), where they may contribute to pathogenesis. We examined whether inflammatory events occurring within joints are reflected in plasma of patients with symptomatic knee osteoarthritis (SKOA). DESIGN: 111 SKOA subjects with medial disease completed a 24-month prospective study of clinical and radiographic progression, with clinical assessment and specimen collection at 6-month intervals. The plasma biochemical marker IL1Ra was assessed at baseline and 18 months; other plasma biochemical markers were assessed only at 18 months, including IL-1ß, TNFα, VEGF, IL-6, IL-6Rα, IL-17A, IL-17A/F, IL-17F, CRP, sTNF-RII, and MMP-2. RESULTS: In cross-sectional studies, WOMAC (total, pain, function) and plasma IL1Ra were modestly associated with radiographic severity after adjustment for age, gender and body mass index (BMI). In addition, elevation of plasma IL1Ra predicted joint space narrowing (JSN) at 24 months. BMI did associate with progression in some but not all analyses. Causal graph analysis indicated a positive association of IL1Ra with JSN; an interaction between IL1Ra and BMI suggested either that BMI influences IL1Ra or that a hidden confounder influences both BMI and IL1Ra. Other protein biomarkers examined in this study did not associate with radiographic progression or severity. CONCLUSIONS: Plasma levels of IL1Ra were modestly associated with the severity and progression of SKOA in a causal fashion, independent of other risk factors. The findings may be useful in the search for prognostic biomarkers and development of disease-modifying OA drugs.

Trends and developments in bioinformatics in 2010: prospects and perspectives.

OBJECTIVES: To survey major developments and trends in the field of Bioinformatics in 2010 and their relationships to those of previous years, with emphasis on long-term trends, on best practices, on quality of the science of informatics, and on quality of science as a function of informatics. METHODS: A critical review of articles in the literature of Bioinformatics over the past year. RESULTS: Our main results suggest that Bioinformatics continues to be a major catalyst for progress in Biology and Translational Medicine, as a consequence of new assaying technologies, most pre-dominantly Next Generation Sequencing, which are changing the landscape of modern biological and medical research. These assays critically depend on bioinformatics and have led to quick growth of corresponding informatics methods development. Clinical-grade molecular signatures are proliferating at a rapid rate. However, a highly publicized incident at a prominent university showed that deficiencies in informatics methods can lead to catastrophic consequences for important scientific projects. Developing evidence-driven protocols and best practices is greatly needed given how serious are the implications for the quality of translational and basic science. CONCLUSIONS: Several exciting new methods have appeared over the past 18 months, that open new roads for progress in bioinformatics methods and their impact in biomedicine. At the same time, the range of open problems of great significance is extensive, ensuring the vitality of the field for many years to come.

PhyloChip microarray analysis reveals altered gastrointestinal microbial communities in a rat model of colonic hypersensitivity.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic, episodic gastrointestinal disorder that is prevalent in a significant fraction of western human populations; and changes in the microbiota of the large bowel have been implicated in the pathology of the disease. METHODS: Using a novel comprehensive, high-density DNA microarray (PhyloChip) we performed a phylogenetic analysis of the microbial community of the large bowel in a rat model in which intracolonic acetic acid in neonates was used to induce long lasting colonic hypersensitivity and decreased stool water content and frequency, representing the equivalent of human constipation-predominant IBS. KEY RESULTS: Our results revealed a significantly increased compositional difference in the microbial communities in rats with neonatal irritation as compared with controls. Even more striking was the dramatic change in the ratio of Firmicutes relative to Bacteroidetes, where neonatally irritated rats were enriched more with Bacteroidetes and also contained a different composition of species within this phylum. Our study also revealed differences at the level of bacterial families and species. CONCLUSIONS & INFERENCES: The PhyloChip is a useful and convenient method to study enteric microflora. Further, this rat model system may be a useful experimental platform to study the causes and consequences of changes in microbial community composition associated with IBS.