Reliability of Intestinal Ultrasound for Evaluating Crohn's Disease Activity Using Point-of-care and Central Reading.

BACKGROUND & AIMS: Intestinal ultrasound (IUS) is increasingly used to assess Crohn's disease (CD) activity in clinical practice. However, application in clinical trials has been limited by heterogeneous scoring methods and concerns about reliability. We aimed to determine the inter- and intra-rater reliability of locally and centrally read IUS parameters for evaluating CD using prospectively performed scans. METHODS: Twenty-four participants with CD and 6 gastroenterologists participated in a 2-day workshop where each participant underwent 6 IUS scans in total. Eight IUS parameters (bowel wall thickness [BWT], bowel wall stratification [BWS], color Doppler signal [CDS], inflammatory mesenteric fat [i-fat], submucosal prominence, submucosal layer thickness, haustra coli/peristalsis, and affected segment length) and an overall measure of sonographic disease activity were blindly assessed by the 6 local readers and 4 central gastroenterologist-sonographers. Reliability was quantified using intraclass correlation coefficients (ICCs). Institutional review board approval was granted for this study (12938). RESULTS: Five IUS parameters demonstrated at least moderate (ICC ≥0.41) inter- and intra-rater reliability when local and central reading was performed (BWT, CDS, i-fat, submucosal prominence, and affected segment length). Reliability was generally better with central, in distinction to local, reading. ICCs for BWS and i-fat were highest when evaluated as binary outcomes. Sensitivity analyses demonstrated that IUS parameters are most reliable when evaluated in the worst affected segment. Fair reliability was observed when local readers identified the worst affected segment. CONCLUSIONS: Local and central reading of IUS demonstrated at least moderate inter- and intra-rater reliability for several parameters. This study supports refining existing activity indices and incorporating IUS central reading into clinical trials.

Intestinal ultrasound as first-line investigation in low-risk gastrointestinal symptoms: a new model of care.

BACKGROUND: Functional gut disorders (FGD) are common. Diagnosis is symptom based, although symptoms may be indistinguishable from inflammatory bowel disease. As a result of this, investigations are common, diagnostic yield is low. A streamlined novel model of care may reduce costly investigations. AIM: To compare a new model of care for patients with low-risk gastrointestinal symptoms to a matched historical cohort. METHODS: Data were prospectively collected over 12 months. General practitioner referrals for low-risk abdominal symptoms were triaged to a new multidisciplinary clinic structure utilising intestinal ultrasound. Outcomes were compared to the historical model in the preceding 12 months. Duration of care (time from referral to discharge), number of contact episodes and investigations ordered were reviewed. RESULTS: Thirty-seven patients meeting strict inclusion criteria completed their care. Compared with the historical cohort, colonoscopies reduced from 0.7 to 0.05 per patient (P < 0.0001). Gastroenterology consults reduced from 1.5 to 1.2 (P = 0.303) and dietitian review increased from 0.8 to 1.5 (P < 0.0001). Total contact episodes reduced from 3.2 to 1.8 (P < 0.0001). Duration of care reduced from a median of 252 days to 130 days (interquartile ranges (IQR) 287 and 69, respectively; P < 0.0001). Time from first consultation to discharge reduced from 125 to 42 days (IQR 188 and 63; P < 0.0001). CONCLUSION: This multidisciplinary approach to care of low-risk abdominal symptoms significantly reduced contact episodes, time in care and invasive investigations. It decreased costly gastroenterology consultation and increased allied health exposure. It demonstrates improved health service outcomes.

The gut microbiota: cause and cure of gut diseases.

The gastrointestinal microbiota is emerging as a central factor in the pathogenesis of a range of gastrointestinal and hepatic disorders. Epidemiological studies, and experimental studies in animals and humans, have highlighted a likely causative role of this microbial community in the modern global epidemics of inflammatory bowel disease, non-alcoholic fatty liver disease, non-alcoholic steato-hepatitis, obesity and metabolic syndrome. New techniques for microbial culture and gene sequencing are enabling the identification of specific pathogens and protective organisms in these conditions. Factors that change the microbiota are being defined: dietary pattern, specific foods, food additives in processed food and drinks, such as emulsifiers and non-sugar sweeteners, and antibiotics. Microbiota changes in early life appear critical to the later development of a range of inflammatory disorders. For many of these conditions, the treatment paradigm will change, at least in part, from immune suppression and drug therapy to treatments that reshape the microbiota or restore its integrity. These treatments include dietary changes, specific microbial manipulation and faecal microbiota transplantation. A dialogue is needed regarding population strategies that target disease prevention. This will include how food is produced, what additives it contains, and how it is processed. Widespread use of antibiotics, from agricultural and veterinary to medicinal settings, needs more attention. At the individual level, microbial profiles may be able to predict who is at risk of disease when subjected to particular environmental influences, and what microbial restoration is needed to minimise risk.

Standardisation of intestinal ultrasound scoring in clinical trials for luminal Crohn's disease.

BACKGROUND: Intestinal ultrasound (IUS) is a valuable tool for assessment of Crohn's disease (CD). However, there is no widely accepted luminal disease activity index. AIMS: To identify appropriate IUS protocols, indices, items, and scoring methods for measurement of luminal CD activity and integration of IUS in CD clinical trials. METHODS: An expert international panel of adult and paediatric gastroenterologists (n = 15) and radiologists (n = 3) rated the appropriateness of 120 statements derived from literature review and expert opinion (scale of 1-9) using modified RAND/UCLA methodology. Median panel scores of 1 to ≤3.5, >3.5 to <6.5 and ≥6.5 to 9 were considered inappropriate, uncertain and appropriate ratings respectively. The statement list and survey results were discussed prior to voting. RESULTS: A total of 91 statements were rated appropriate with agreement after two rounds of voting. Items considered appropriate measures of disease activity were bowel wall thickness (BWT), vascularity, stratification and mesenteric inflammatory fat. There was uncertainty if any of the existing IUS disease activity indices were appropriate for use in CD clinical trials. Appropriate trial applications for IUS included patient recruitment qualification when diseased segments cannot be adequately assessed by ileocolonoscopy and screening for exclusionary complications. At outcome assessment, remission endpoints including BWT and vascularity, with or without mesenteric inflammatory fat, were considered appropriate. Components of an ideal IUS disease activity index were identified based upon panel discussions. CONCLUSIONS: The panel identified appropriate component items and applications of IUS for CD clinical trials. Empiric evidence, and development and validation of an IUS disease activity index are needed.

Meta-Analysis of Heterogeneity in the Effects of Wildfire Smoke Exposure on Respiratory Health in North America.

Epidemiological studies consistently show an association between wildfire-related smoke exposure and adverse respiratory health. We conducted a systematic review of evidence in published literature pertaining to heterogeneity of respiratory effects from this exposure in North America. We calculated the within-study ratio of relative risks (RRR) and 95% confidence intervals (CI) to examine heterogeneity of effect by population subgroup, and then summarized the RRRs using meta-analysis. We found evidence of a greater effect of wildfire smoke on respiratory health among females relative to males for asthma (RRR: 1.035, 95% CI: 1.013, 1.057) and chronic obstructive pulmonary disease (RRR: 1.018, 95% CI: 1.003, 1.032). There was evidence of a lower relative risk for all respiratory outcomes among youth compared to adults (RRR: 0.976, 95% CI: 0.963, 0.989). We also found wildfire smoke effects stratified by income, race, education, health behaviors, access to care, housing occupancy, geographic region, and urban/rural status. However, data were insufficient to quantitatively evaluate effect modification by these characteristics. While we found evidence that certain demographic subgroups of the population are more susceptible to respiratory health outcomes from wildfire smoke, it is unclear whether this information can be used to inform policy aimed to reduce health impact of wildfires.

Highly sensitive detection of blood by surface enhanced Raman scattering.

Raman spectroscopy for forensic body fluid analysis has received some attention due to the nondestructive nature and potential application for identification at the crime scene; however, its usage has been limited by low detection sensitivity. Surface enhanced Raman scattering (SERS) was evaluated for blood identification for forensic applications. Specifically, a SERS-active substrate was fabricated, composed of nickel nanotips coated with Ag nanoparticles. Compared with a conventional substrate, the SERS substrate enhanced Raman scattering by more than two orders of magnitude and allowed blood to be identified to a dilution of 1:100,000. Blood was also successfully detected by swabbing the SERS substrate directly on mock evidence. Most importantly, Raman spectra obtained by swabbing the SERS substrate on blood stains were free of luminescence even when blood was deposited on luminescent fabrics. The nondestructive character, simplicity of sample preparation, and high sensitivity make SERS a prime candidate for field and laboratory-based blood identification.