Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial From Viral Respiratory Infection.

Importance: Bacterial and viral causes of acute respiratory illness (ARI) are difficult to clinically distinguish, resulting in the inappropriate use of antibacterial therapy. The use of a host gene expression-based test that is able to discriminate bacterial from viral infection in less than 1 hour may improve care and antimicrobial stewardship. Objective: To validate the host response bacterial/viral (HR-B/V) test and assess its ability to accurately differentiate bacterial from viral infection among patients with ARI. Design, Setting, and Participants: This prospective multicenter diagnostic study enrolled 755 children and adults with febrile ARI of 7 or fewer days' duration from 10 US emergency departments. Participants were enrolled from October 3, 2014, to September 1, 2019, followed by additional enrollment of patients with COVID-19 from March 20 to December 3, 2020. Clinical adjudication of enrolled participants identified 616 individuals as having bacterial or viral infection. The primary analysis cohort included 334 participants with high-confidence reference adjudications (based on adjudicator concordance and the presence of an identified pathogen confirmed by microbiological testing). A secondary analysis of the entire cohort of 616 participants included cases with low-confidence reference adjudications (based on adjudicator discordance or the absence of an identified pathogen in microbiological testing). Thirty-three participants with COVID-19 were included post hoc. Interventions: The HR-B/V test quantified the expression of 45 host messenger RNAs in approximately 45 minutes to derive a probability of bacterial infection. Main Outcomes and Measures: Performance characteristics for the HR-B/V test compared with clinical adjudication were reported as either bacterial or viral infection or categorized into 4 likelihood groups (viral very likely [probability score <0.19], viral likely [probability score of 0.19-0.40], bacterial likely [probability score of 0.41-0.73], and bacterial very likely [probability score >0.73]) and compared with procalcitonin measurement. Results: Among 755 enrolled participants, the median age was 26 years (IQR, 16-52 years); 360 participants (47.7%) were female, and 395 (52.3%) were male. A total of 13 participants (1.7%) were American Indian, 13 (1.7%) were Asian, 368 (48.7%) were Black, 131 (17.4%) were Hispanic, 3 (0.4%) were Native Hawaiian or Pacific Islander, 297 (39.3%) were White, and 60 (7.9%) were of unspecified race and/or ethnicity. In the primary analysis involving 334 participants, the HR-B/V test had sensitivity of 89.8% (95% CI, 77.8%-96.2%), specificity of 82.1% (95% CI, 77.4%-86.6%), and a negative predictive value (NPV) of 97.9% (95% CI, 95.3%-99.1%) for bacterial infection. In comparison, the sensitivity of procalcitonin measurement was 28.6% (95% CI, 16.2%-40.9%; P < .001), the specificity was 87.0% (95% CI, 82.7%-90.7%; P = .006), and the NPV was 87.6% (95% CI, 85.5%-89.5%; P < .001). When stratified into likelihood groups, the HR-B/V test had an NPV of 98.9% (95% CI, 96.1%-100%) for bacterial infection in the viral very likely group and a positive predictive value of 63.4% (95% CI, 47.2%-77.9%) for bacterial infection in the bacterial very likely group. The HR-B/V test correctly identified 30 of 33 participants (90.9%) with acute COVID-19 as having a viral infection. Conclusions and Relevance: In this study, the HR-B/V test accurately discriminated bacterial from viral infection among patients with febrile ARI and was superior to procalcitonin measurement. The findings suggest that an accurate point-of-need host response test with high NPV may offer an opportunity to improve antibiotic stewardship and patient outcomes.

A Randomized Controlled Trial of TELEmedicine for Patients with Inflammatory Bowel Disease (TELE-IBD).

INTRODUCTION: Telemedicine has shown promise in inflammatory bowel disease (IBD). The objective of this study was to compare disease activity and quality of life (QoL) in a 1-year randomized trial of IBD patients receiving telemedicine vs. standard care. METHODS: Patients with worsening symptoms in the prior 2 years were eligible for randomization to telemedicine (monitoring via texts EOW or weekly) or standard care. The primary outcomes were the differences in change in disease activity and QoL between the groups; change in healthcare utilization among groups was a secondary aim. RESULTS: 348 participants were enrolled (117 control group, 115 TELE-IBD EOW, and 116 TELE-IBD weekly). 259 (74.4%) completed the study. Age was 38.9 ± 12.3 years, 56.6% were women, 91.9% were Caucasian, 67.9% had Crohn's disease (CD) and 42.5% had active disease at baseline. In CD, all groups experienced a decrease in disease activity (control -5.2 ± 5.0 to 3.7 ± 3.6, TELE-IBD EOW 4.7 ± 4.1 to 4.2 ± 3.9, and TELE-IBD weekly 4.2 ± 4.2 to 3.2 ± 3.4, p < 0.0001 for each of the groups) In UC, only controls had a significant decrease in disease activity (control 2.9 ± 3.1 to 1.4 ± 1.4, p = 0.01, TELE-IBD EOW 2.7 ± 3.1 to 1.7 ± 1.9, p = 0.35, and TELE-IBD Weekly 2.5 ± 2.5 to 2.0 ± 1.8, p = 0.31). QoL increased in all groups; the increase was significant only in TELE-IBD EOW (control 168.1 ± 34.0 to 179.3 ± 28.2, p = 0.06, TELE-IBD EOW 172.3 ± 33.1 to 181.5 ± 28.2, p = 0.03, and TELE-IBD Weekly 172.3 ± 34.5 to 179.2 ± 32.8, p = 0.10). Unadjusted and adjusted changes in disease activity and QoL were not significantly different among groups. Healthcare utilization increased in all groups. TELE-IBD weekly were less likely to have IBD-related hospitalizations and more likely to have non-invasive diagnostic tests and electronic encounters compared to controls; both TELE-IBD groups had decreased non-IBD related hospitalizations and increased telephone calls compared to controls. DISCUSSION: Disease activity and QoL, although improved in all participants, were not improved further through use of the TELE-IBD system. TELE-IBD participants experienced a decrease in hospitalizations with an associated increase in non-invasive diagnostic tests, telephone calls and electronic encounters. Research is needed to determine if TELE-IBD can be improved through patient engagement and whether it can decrease healthcare utilization by replacing standard care.

The Use of Temporary Fecal Diversion in Colonic and Perianal Crohn's Disease Does Not Improve Outcomes.

AIMS: To determine whether temporary fecal diversion for refractory colonic and/or perianal Crohn's disease can lead to clinical remission and restoration of intestinal continuity after optimization of medical therapy. METHODS: We retrospectively reviewed our prospectively maintained database of patients treated at the University of Maryland for Crohn's disease between May 2004 and July 2014. Patients with colonic, perianal, or colonic and perianal Crohn's disease, who had fecal diversion for control of medically refractory and/or severe disease, were included. Outcomes, including disease activity and rate of ileostomy reversal, were evaluated up to 24 months from stoma formation. RESULTS: Thirty patients were identified. Fecal diversion was performed for perianal disease in 37%, colonic disease in 33%, and both in 30% of patients. Twelve (40%) patients underwent ileostomy reversal. Twenty-five percent of patients with perianal disease had their ostomies reversed compared to 70% of patients with colonic disease alone. More patients with complex compared to simple perianal disease remained diverted (p = 0.02). Six (20%) patients required colectomy. Of these, 50% had complex perianal disease, all had received two or more biologics, and two-thirds were on combination therapy pre-diversion. CONCLUSIONS: Our study found that nearly two-thirds of patients with medically refractory colonic and/or severe perianal Crohn's disease treated with fecal diversion and optimization of postoperative medical therapy remain diverted or require colectomy within two years after ileostomy formation. In patients with severe, refractory perianal disease and those treated with combination therapy and >1 biologic exposure pre-diversion, colectomy rather than temporary fecal diversion should be considered.

Risk Factors for Vitamin D Deficiency and Impact of Repletion in a Tertiary Care Inflammatory Bowel Disease Population.

INTRODUCTION: Many patients with inflammatory bowel disease (IBD) are vitamin D deficient. The purpose of our study was to identify risk factors for vitamin D deficiency in IBD and to assess the impact of vitamin D repletion on disease activity and quality of life (QOL). METHODS: Patients with at least one 25-OH vitamin D level measured between 2004 and 2011 were included. Patients with a level <30 ng/ml at baseline were followed until the time of repletion. QOL and disease activity scores were measured at baseline and repletion. RESULTS: A total of 255 patients were identified. 33, 29, and 39% had a vitamin D level of ≥30, 20-29, and <20 ng/ml, respectively. When adjusting for disease type and duration, gender, smoking, and race, non-Caucasians had 5.3 (2.3-12.3) and UC patients had a 0.59 (0.33-1.03) odds of having a vitamin D <30 ng/ml. Women were 1.7 times more likely to have a 25-OH vitamin D level <20 ng/ml than men. 55 patients underwent repletion. In CD patients, the HBI and SIBDQ prior to repletion was 5.5 ± 4.9 and 44.3 ± 16.4, respectively; these improved to 3.6 ± 3.4 and 48.6 ± 14.2 after repletion (p = 0.0154 and p = 0.0684). CONCLUSIONS: In this tertiary care IBD cohort, the majority of patients have low vitamin D levels. Non-Caucasian race and female gender are associated with low vitamin D. UC was associated with lower risk of vitamin D insufficiency. In CD, vitamin D repletion is associated with decreased disease activity and increased QOL.

Psoriasiform Skin Lesions Are Caused by Anti-TNF Agents Used for the Treatment of Inflammatory Bowel Disease.

BACKGROUND: Tumor necrosis factor (TNF) antagonists used for the treatment of inflammatory bowel disease (IBD) have been associated with the development of psoriasiform skin lesions. We assessed the demographic and clinical characteristics associated with and outcomes of patients with anti-TNF-induced psoriasiform lesions. METHODS: Patients with Crohn's disease (CD) and ulcerative colitis (UC) receiving treatment with anti-TNF therapy (infliximab, adalimumab, or certolizumab pegol) at a tertiary referral center were identified using an IRB-approved clinical data repository. Patients that developed psoriasiform skin lesions after initiation of anti-TNF therapy were included as cases. A group of anti-TNF-treated patients without drug-related psoriasiform lesions were identified as controls. The association between demographic and clinical variables and psoriasiform lesions was assessed using Chi-square analyses and multivariable logistic regression. RESULTS: Five hundred twenty-one patients with IBD undergoing treatment with anti-TNF therapy were identified; of these, 18 (3.5%) had psoriasiform lesions (16 CD and 2 UC). Seventy-two patients were identified as controls. Lesions developed a mean of 58 weeks (range 4-240 weeks) after starting anti-TNF therapy. The majority of patients were female and Caucasian (63 and 78%, respectively). Thirty-nine percent of patients had upper tract disease location. Forty-five patients (50%) were current or former smokers. Location of psoriasiform lesions included palmo-plantar (53%), trunk (47%), and scalp (53%), with 88% reporting involvement of ≥2 locations. Treatment of psoriasiform lesions was instituted with topical therapy in eight patients and systemic therapy (± phototherapy) in five patients. Discontinuation of anti-TNF therapy was recommended in nine patients (50%); of those, three were retreated with a second anti-TNF agent and all had recurrence of psoriasiform lesions. When adjusted for multiple variables, upper GI tract disease was significantly associated with psoriasiform lesions. CONCLUSIONS: Anti-TNF-induced psoriasiform lesions developed in 3.5% of patients with IBD at a tertiary referral center. Similar to prior published studies, most patients were female, had involvement of the palmo-plantar and scalp regions, and did not have severe IBD activity. The presence of upper tract disease was associated with the development of psoriasiform lesions. Skin lesions led to discontinuation of anti-TNF therapy in 50% of patients. Based upon these results, IBD providers should educate patients about this adverse effect, refer to dermatology for treatment, and discuss alternative IBD therapeutic options early if a severe psoriasiform rash develops.

Neighborhood socioeconomic status and use of colonoscopy in an insured population--a retrospective cohort study.

BACKGROUND: Low-socioeconomic status (SES) is associated with a higher colorectal cancer (CRC) incidence and mortality. Screening with colonoscopy, the most commonly used test in the US, has been shown to reduce the risk of death from CRC. This study examined if, among insured persons receiving care in integrated healthcare delivery systems, differences exist in colonoscopy use according to neighborhood SES. METHODS: We assembled a retrospective cohort of 100,566 men and women, 50-74 years old, who had been enrolled in one of three US health plans for ≥1 year on January 1, 2000. Subjects were followed until the date of first colonoscopy, date of disenrollment from the health plan, or December 31, 2007, whichever occurred first. We obtained data on colonoscopy use from administrative records. We defined screening colonoscopy as an examination that was not preceded by gastrointestinal conditions in the prior 6-month period. Neighborhood SES was measured using the percentage of households in each subject's census-tract with an income below 1999 federal poverty levels based on 2000 US census data. Analyses, adjusted for demographics and comorbidity index, were performed using Weibull regression models. RESULTS: The average age of the cohort was 60 years and 52.7% were female. During 449,738 person-years of follow-up, fewer subjects in the lowest SES quartile (Q1) compared to the highest quartile (Q4) had any colonoscopy (26.7% vs. 37.1%) or a screening colonoscopy (7.6% vs. 13.3%). In regression analyses, compared to Q4, subjects in Q1 were 16% (adjusted HR = 0.84, 95% CI: 0.80-0.88) less likely to undergo any colonoscopy and 30%(adjusted HR = 0.70, CI: 0.65-0.75) less likely to undergo a screening colonoscopy. CONCLUSION: People in lower-SES neighborhoods are less likely to undergo a colonoscopy, even among insured subjects receiving care in integrated healthcare systems. Removing health insurance barriers alone is unlikely to eliminate disparities in colonoscopy use.