Stool DNA Analysis is Cost-Effective for Colorectal Cancer Surveillance in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Patients with chronic ulcerative colitis are at increased risk for colorectal neoplasia (CRN). Surveillance by white-light endoscopy (WLE) or chromoendoscopy may reduce risk of CRN, but these strategies are underused. Analysis of DNA from stool samples (sDNA) can detect CRN with high levels of sensitivity, but it is not clear if this approach is cost-effective. We simulated these strategies for CRN detection to determine which approach is most cost-effective. METHODS: We adapted a previously published Markov model to simulate the clinical course of chronic ulcerative colitis, the incidence of cancer or dysplasia, and costs and benefits of care with 4 surveillance strategies: (1) analysis of sDNA and diagnostic chromoendoscopy for patients with positive results, (2) analysis of sDNA with diagnostic WLE for patients with positive results, (3) chromoendoscopy with targeted collection of biopsies, or (4) WLE with random collection of biopsies. Costs were based on 2014 Medicare reimbursement. The primary outcome was the incremental cost-effectiveness ratio (incremental cost/incremental difference in quality-adjusted life-years) compared with no surveillance and a willingness-to-pay threshold of $50,000. RESULTS: All strategies fell below the willingness-to-pay threshold at 2-year intervals. Incremental cost-effectiveness ratios were $16,362 per quality-adjusted life-year for sDNA analysis with diagnostic chromoendoscopy; $18,643 per quality-adjusted life-year for sDNA analysis with diagnostic WLE; $23,830 per quality-adjusted life-year for chromoendoscopy alone; and $27,907 per quality-adjusted life-year for WLE alone. In sensitivity analyses, sDNA analysis with diagnostic chromoendoscopy was more cost-effective than chromoendoscopy alone, up to a cost of $1135 per sDNA test. sDNA analysis remained cost-effective at all rates of compliance; when combined with diagnostic chromoendoscopy, this approach was preferred over chromoendoscopy alone, when the specificity of the sDNA test for CRN was >65%. CONCLUSIONS: Based on a Markov model, surveillance for CRN is cost-effective for patients with chronic ulcerative colitis. Analysis of sDNA with chromoendoscopies for patients with positive results was more cost-effective than chromoendoscopy or WLE alone.

Multisystem Inflammatory Syndrome in Children (MIS-C) Related to SARS-CoV-2 and 1-Year Follow-up.

OBJECTIVE: To study the demographics, clinical profile, management, outcome and 1-y follow-up of children with multisystem inflammatory syndrome in children (MIS-C). METHODS: This was a retrospective observational study of 54 Children satisfying the WHO MIS-C criteria admitted during the study period. RESULTS: Fifty-four children were included in the study, median age was 5.5 (IQR 8.75), 68.5% were males. PICU admissions were 77%. Most involved organ was gastrointestinal (92%), followed by cardiovascular 85%, central nervous system (CNS) 74%, respiratory 72%, mucocutaneous 59%, and renal 31%, and hypotension was the presenting symptom in 43%. Coronary artery dilatation was seen in 1 (1.8%) child. All patients presented with more than three organs involvement. Raised procalcitonin was seen in 100%, raised BNP in 31.5%, low ejection fraction in 83.3%, and abnormal radiograph in 59%. All children were positive for anti-SARS-CoV-2 antibodies and negative for cultures. Methylprednisolone or intravenous immunoglobulin (IVIg) was used in 77%, mechanical ventilation in 18.5%, and inotropic support in 77%. Aspirin was used in 48% and low molecular weight heparin (LMWH) in 54%. The median stay in hospital was 7 d (IQR 2). There was 1 mortality (1.8%). On 7-d follow-up, 98% children had a normal echocardiography; on 6 mo and 1-y follow-up, all children had normal echocardiography. CONCLUSION: MIS-C is an important complication of COVID-19 infection. Cardiac involvement resolves completely. Coronary artery involvement is not common.

Differential impact of test performance characteristics on burden-to-benefit tradeoffs for blood-based colorectal cancer screening: A microsimulation analysis.

OBJECTIVES: To inform the development and evaluation of new blood-based colorectal cancer (CRC) screening tests satisfying minimum United States (US) coverage criteria, we estimated the impact of the different test performance characteristics on long-term testing benefits and burdens. METHODS: A novel CRC-Microsimulation of Adenoma Progression and Screening (CRC-MAPS) model was developed, validated, then used to assess different screening tests for CRC. We compared multiple, hypothetical blood-based CRC screening tests satisfying minimum coverage criteria of 74% CRC sensitivity and 90% specificity, to measure how changes in a test's CRC sensitivity, specificity, and adenoma sensitivity (sizes 1-5 mm, 6-9 mm, ≥10 mm) affect total number of colonoscopies (COL), CRC incidence reduction (IR), CRC mortality reduction (MR), and burden-to-benefit ratios (incremental COLs per percentage-point increase in IR or MR). RESULTS: A blood test meeting minimum US coverage criteria for performance characteristics resulted in 1576 lifetime COLs per 1000 individuals, 46.7% IR and 59.2% MR compared to no screening. Tests with increased CRC sensitivity of 99% ( + 25%) vs. increased ≥10 mm adenoma sensitivity of 13.6% ( + 3.6%) both yielded the same MR, 62.7%. Test benefits improved the most with increases in all-size adenoma sensitivity, then size-specific adenoma sensitivities, then specificity and CRC sensitivity, while increases in specificity or ≥10 mm adenoma sensitivity resulted in the most favorable burden-to-benefit tradeoffs (ratios <11.5). CONCLUSIONS: Burden-to-benefit ratios for blood-based CRC screening tests differ by performance characteristic, with the most favorable tradeoffs resulting from improvements in specificity and ≥10 mm adenoma sensitivity.

Detecting salivary host and microbiome RNA signature for aiding diagnosis of oral and throat cancer.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) can go undetected resulting in late detection and poor outcomes. We describe the development and validation of CancerDetect for Oral & Throat cancer™ (CDOT), to detect markers of OSCC and/or OPSCC within a high-risk population. MATERIAL AND METHODS: We collected saliva samples from 1,175 individuals who were 50 years or older, or adults with a tobacco use history. 945 of those were used to train a classifier using machine learning methods, resulting in a salivary microbial and human metatranscriptomic signature. The classifier was then independently validated on the 230 remaining samples prospectively collected and unseen by the classifier, consisting of 20 OSCC (all stages), 76 OPSCC (all stages), and 134 negatives (including 14 pre-malignant). RESULTS: On the validation cohort, the specificity of the CDOT test was 94 %, sensitivity was 90 % for participants with OSCC, and 84.2 % for participants with OPSCC. Similar classification results were observed among people in early stage (stages I & II) vs late stage (stages III & IV). CONCLUSIONS: CDOT is a non-invasive test that can be easily administered in dentist offices, primary care centres and specialised cancer clinics for early detection of OPSCC and OSCC. This test, having received FDA's breakthrough designation for accelerated review, has the potential to enable early diagnosis, saving lives and significantly reducing healthcare expenditure.

Evaluation of the Economic Benefit of Earlier Systemic Lupus Erythematosus (SLE) Diagnosis Using a Multivariate Assay Panel (MAP).

OBJECTIVE: Diagnosis of systemic lupus erythematosus (SLE) made by standard diagnostic laboratory tests (SDLTs) has sensitivity and specificity of 83% and 76%, respectively. A multivariate assay panel (MAP) combining complement C4d activation products on erythrocytes and B cells with SDLTs yields a sensitivity and specificity of 80% and 86%, respectively, presumably enabling earlier SLE diagnosis at lower severity, with associated lower health care costs compared with SDLT diagnoses. We compared the payer budget impact of diagnosing SLE using MAP (incremental cost of $108) versus SDLTs. METHODS: We modeled a health plan of 1 million enrollees. SLE diagnosis among suspected patients was 9.2%. The MAP arm assumed 80%/20% of patients were tested with MAP/SDLTs, versus 100% tested with SDLTs in the SDLT arm. Prediagnosis direct costs were estimated from claims data, and postdiagnosis costs were obtained from the literature. Based on improved MAP performance, the assumed hazard ratio for diagnosis rate compared with SDLTs was 1.74 (71%, 87%, 90%, and 91% of patients who develop SLE are diagnosed in years 1 to 4 compared with 53%, 75%, 84%, and 88% of patients diagnosed with SDLTs). RESULTS: Total 4-year pre- and postdiagnosis direct costs for patients with suspected SLE tested with MAP were $59 183 666 compared with $61 174 818 tested by SDLTs, with lower costs in the MAP arm due primarily to prediagnosis savings related to reduced hospital admissions. CONCLUSION: Incorporating MAP into SLE diagnosis results in estimated 4-year direct cost savings of $1 991 152 ($0.04 per member per month). By facilitating earlier diagnosis of SLE, MAP may enhance patient outcomes.

Flexible Bronchoscopic Removal of Foreign Bodies from Airway of Children: Single Center Experience Over 12 Years.

OBJECTIVE: To report our experience of tracheobronchial foreign body removal in children using flexible bronchoscopy as the primary mode. METHODS: Hospital records of tracheobronchial foreign body extractions between January, 2006 and January, 2018 were reviewed. Clinical presentations, radiological findings, location and types of tracheobronchial foreign bodies, types of bronchoscopes, complications and outcome of the procedures were analyzed. RESULTS: 283 extractions in children with median (range) age of 18 (5-168) months were reviewed. Extraction by flexible bronchoscope, using wire baskets or grasping forceps, was successful in 260 cases. No major complications were encountered. Mean (SD) time for the procedure was 31 (6.3) minutes. CONCLUSION: Airway foreign bodies can safely be removed by flexible bronchoscopy with minimal complications. This procedure can be considered the primary mode for removal of airway foreign bodies by a trained and experienced person.