Emerging concerns following the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) pandemic are the long-term effects of coronavirus disease (COVID)-19. Dysgeusia in COVID-19 is supported by ...the abundant expression of the entry receptor, angiotensin-converting enzyme-2 (ACE2), in the oral mucosa. The invading virus perturbs the commensal biofilm and regulates the host responses that permit or suppress viral infection. We correlated the microbial recognition receptors and soluble ACE2 (sACE2) with the SARS-CoV2 measures in the saliva of COVID-19 patients. Data indicate that the toll-like receptor-4, peptidoglycan recognition protein, and sACE2 are elevated in COVID-19 saliva and correlate moderately with the viral load.
Objectives/IntroductionInflammatory bowel disease (IBD) is a chronic condition that is commonly diagnosed in the paediatric patient cohort. Due to its relapsing-remitting nature, it is important to ...tailor the treatment to each patient and achieveing good control as defined by treating to target which is a combination of symptom scores and objective markers including faecal calprotectin, blood tests, drug and metabolite levels, radiological and endoscopy assessment.The aims of this project are to identify the population of patients in remission in the IBD cohort and to identify the factors which affect this, particularly frequency of contact with IBD services.MethodsA retrospective review was carried out using the data available on electronic hospital records. The data included: patient demographics, type of treatment, most recent biochemical and radiological assessment results and hospital visits from paediatric IBD patients at an NHS hospital. All IBD subtypes were included. A Microsoft Excel spreadsheet was used to collect the data which was then reviewed by a senior consultant and subsequently analysed.ResultsIn total, 150 patients were included. 72.67% of these patients were either found to be in remission or had mild disease activity. Higher remission rates/mild disease activity was observed in patients who had seen a consultant and had biological tests done within 6 months (90.63%) as opposed to patients who had not (38.46%). More patients receiving combination treatment of either 5ASA/a biologic and an immunosuppressant were found to be in remission than patients receiving just one or none of these treatments.Abstract IBD 7 Figure 1ConclusionThere appears to be a link between remission rates and local factors including frequent monitoring through biological and radiological assessments, consultation visits and the type of treatment. Frequent monitoring of IBD patients may lead to higher remission rates. This can be achieved via frequent consultation reviews to include up-to-date symptom scoring indices and biochemical and radiological assessments.
Aim
To compare the diagnostic yield of small intestinal contrast ultrasonography (SICUS) with magnetic resonance enterography (MRE) in routine clinical practice in a cohort of pediatric patients ...investigated for Crohn's disease (CD) attending a UK tertiary center.
Methods and Results
Patients with suspected or established CD who underwent SICUS were identified retrospectively. SICUS was compared to conventional transabdominal ultrasound (TUS), ileocolonoscopy (IC), and MRE. The accuracy and agreement of SICUS in detecting small bowel lesions and CD‐related complications were assessed using kappa (κ) coefficient statistics. A total of 93 patients (median age 15 years, range 2–17, 49 male) underwent SICUS; 58 had suspected and 35 had established CD. In suspected CD, sensitivity and specificity of SICUS in detecting CD small bowel lesions were 81.8 and 100% and for TUS 85.7 and 87.5%, respectively. In established CD, sensitivity and specificity of SICUS were 98.7 and 100% and TUS 80 and 100%, respectively. Agreement between SICUS and IC was substantial for the presence of lesions (κ = 0.73) but fair in TUS (κ = 0.31). Agreement between SICUS and IC was almost perfect for detecting strictures (κ = 0.84), with a sensitivity of 100% and specificity of 97.6%. When comparing SICUS and TUS with MRE, agreement for the presence of lesions was substantial (κ = 0.63) and moderate (κ = 0.53), respectively. Agreement between SICUS and MRE was substantial for detecting strictures (κ = 0.77) and dilatation (κ = 0.68).
Conclusions
SICUS offers a radiation‐free alternative for assessing pediatric small bowel CD, with diagnostic accuracy that is comparable to MRE and IC, supporting its wider use in routine practice.
Our findings provide preliminary evidence to suggest that small intestinal contrast ultrasonography (SICUS) offers a comparable diagnostic yield to that of magnetic resonance enterography (MRE) and ileocolonoscopy (IC) and performed better than transabdominal ultrasound (TUS) in a paediatric cohort with suspected or established Crohn's disease (CD). Our work comparing SICUS and MRE in routine clinical practice adds to the existing, albeit very limited, evidence that SICUS offers a radiation‐free alternative to MRE for the evaluation of CD in children and adolescents.
Abstract
The present study was carried out at the Thycattussery area in Vembanad lake and assessed the ichthyo-diversity, variability in climatic variables, the exploited status of predominant ...small-scale sector fisheries (SSFs) and impact of climatic variables upon an existing SSF. Fish, as well as clam specimens collected from the study area, were identified. Diversity indices and dominance curves helped to identify monsoon (June–September) as the diverse season in the wetland. SIMPER (similarity percentage) analysis indicated that Villorita cyprinoides (clam) was the predominant species in the wetland with a mean relative abundance of 16.1%. Canonical correspondence analysis (CCA) of variables with clam production identified calcium hardness and rainfall with axis loadings of –0.56 and 0.50 respectively as the variables predominantly contributing to clam production. Stepwise regression indicated that temperature and rainfall were the determinants of clam production. A decrease in rainfall and an increase in temperature at an annual rate of 0.02 and 0.8%, respectively, decreased the clam production by 5.37%/year in the study area. Further, the generalized linear model (GLM) indicated stagnancy in clam production until 2035 below 400,000 kg per year. The study introduced diversification of livelihood systems using clam culture in climate resilient pen structures (CRPS) as an adaptation strategy.
Decreased salivary secretion is not only a risk factor for carious lesions in Sjögren's disease (SD) but also an indicator of deterioration of teeth with every restorative replacement. This study ...determined the longevity of direct dental restorations placed in patients with SD using matched electronic dental record (EDR) and electronic health record (EHR) data.
We conducted a retrospective cohort study using EDR and EHR data of Indiana University School of Dentistry patients who have a SD diagnosis in their EHR. Treatment history of patients during 15 years with SD (cases) and their matched controls with at least one direct dental restoration were retrieved from the EDR. Descriptive statistics summarized the study population characteristics. Cox regression models with random effects analyzed differences between cases and controls for time to direct restoration failure. Further the model explored the effect of covariates such as age, sex, race, dental insurance, medical insurance, medical diagnosis, medication use, preventive dental visits per year, and the number of tooth surfaces on time to restoration failure.
At least one completed direct restoration was present for 102 cases and 42 controls resulting in a cohort of 144 patients' EDR and EHR data. The cases were distributed as 21 positives, 57 negatives, and 24 uncertain cases based on clinical findings. The average age was 56, about 93% were females, 54% were White, 74% had no dental insurance, 61% had public medical insurance, < 1 preventive dental visit per year, 94% used medications and 93% had a medical diagnosis that potentially causes dry mouth within the overall study cohort. About 529 direct dental restorations were present in cases with SD and 140 restorations in corresponding controls. Hazard ratios of 2.99 (1.48-6.03; p = 0.002) and 3.30 (1.49-7.31, p-value: 0.003) showed significantly decreased time to restoration failure among cases and positive for SD cases compared to controls, respectively. Except for the number of tooth surfaces, no other covariates had a significant influence on the survival time.
Considering the rapid failure of dental restorations, appropriate post-treatment assessment, management, and evaluation should be implemented while planning restorative dental procedures among cases with SD. Since survival time is decreased with an increase in the number of surfaces, guidelines for restorative procedures should be formulated specifically for patients with SD.
Anti–tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug ...antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.
We performed a genome-wide association study to identify variants associated with time to development of anti-drug antibodies in a discovery cohort of 1240 biologic-naïve patients with Crohn’s disease starting infliximab or adalimumab therapy. Immunogenicity was defined as an anti-drug antibody titer ≥10 AU/mL using a drug-tolerant enzyme-linked immunosorbent assay. Significant association signals were confirmed in a replication cohort of 178 patients with inflammatory bowel disease.
The HLA-DQA1*05 allele, carried by approximately 40% of Europeans, significantly increased the rate of immunogenicity (hazard ratio HR, 1.90; 95% confidence interval CI, 1.60–2.25; P = 5.88 × 10–13). The highest rates of immunogenicity, 92% at 1 year, were observed in patients treated with infliximab monotherapy who carried HLA-DQA1*05; conversely the lowest rates of immunogenicity, 10% at 1 year, were observed in patients treated with adalimumab combination therapy who did not carry HLA-DQA1*05. We confirmed this finding in the replication cohort (HR, 2.00; 95% CI, 1.35–2.98; P = 6.60 × 10–4). This association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32–2.70) or infliximab (HR, 1.92; 95% CI, 1.57–2.33), and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37–2.22) or in combination with an immunomodulator (HR, 2.01; 95% CI, 1.57–2.58).
In an observational study, we found a genome-wide significant association between HLA-DQA1*05 and the development of antibodies against anti-TNF agents. A randomized controlled biomarker trial is required to determine whether pretreatment testing for HLA-DQA1*05 improves patient outcomes by helping physicians select anti-TNF and combination therapies. ClinicalTrials.gov ID: NCT03088449.
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Anti-TNF drugs are effective treatments for the management of Crohn's disease but treatment failure is common. We aimed to identify clinical and pharmacokinetic factors that predict primary ...non-response at week 14 after starting treatment, non-remission at week 54, and adverse events leading to drug withdrawal.
The personalised anti-TNF therapy in Crohn's disease study (PANTS) is a prospective observational UK-wide study. We enrolled anti-TNF-naive patients (aged ≥6 years) with active luminal Crohn's disease at the time of first exposure to infliximab or adalimumab between March 7, 2013, and July 15, 2016. Patients were evaluated for 12 months or until drug withdrawal. Demographic data, smoking status, age at diagnosis, disease duration, location, and behaviour, previous medical and drug history, and previous Crohn's disease-related surgeries were recorded at baseline. At every visit, disease activity score, weight, therapy, and adverse events were recorded; drug and total anti-drug antibody concentrations were also measured. Treatment failure endpoints were primary non-response at week 14, non-remission at week 54, and adverse events leading to drug withdrawal. We used regression analyses to identify which factors were associated with treatment failure.
We enrolled 955 patients treated with infliximab (753 with originator; 202 with biosimilar) and 655 treated with adalimumab. Primary non-response occurred in 295 (23·8%, 95% CI 21·4-26·2) of 1241 patients who were assessable at week 14. Non-remission at week 54 occurred in 764 (63·1%, 60·3-65·8) of 1211 patients who were assessable, and adverse events curtailed treatment in 126 (7·8%, 6·6-9·2) of 1610 patients. In multivariable analysis, the only factor independently associated with primary non-response was low drug concentration at week 14 (infliximab: odds ratio 0·35 95% CI 0·20-0·62, p=0·00038; adalimumab: 0·13 0·06-0·28, p<0·0001); the optimal week 14 drug concentrations associated with remission at both week 14 and week 54 were 7 mg/L for infliximab and 12 mg/L for adalimumab. Continuing standard dosing regimens after primary non-response was rarely helpful; only 14 (12·4% 95% CI 6·9-19·9) of 113 patients entered remission by week 54. Similarly, week 14 drug concentration was also independently associated with non-remission at week 54 (0·29 0·16-0·52 for infliximab; 0·03 0·01-0·12 for adalimumab; p<0·0001 for both). The proportion of patients who developed anti-drug antibodies (immunogenicity) was 62·8% (95% CI 59·0-66·3) for infliximab and 28·5% (24·0-32·7) for adalimumab. For both drugs, suboptimal week 14 drug concentrations predicted immunogenicity, and the development of anti-drug antibodies predicted subsequent low drug concentrations. Combination immunomodulator (thiopurine or methotrexate) therapy mitigated the risk of developing anti-drug antibodies (hazard ratio 0·39 95% CI 0·32-0·46 for infliximab; 0·44 0·31-0·64 for adalimumab; p<0·0001 for both). For infliximab, multivariable analysis of immunododulator use, and week 14 drug and anti-drug antibody concentrations showed an independent effect of immunomodulator use on week 54 non-remission (odds ratio 0·56 95% CI 0·38-0·83, p=0·004).
Anti-TNF treatment failure is common and is predicted by low drug concentrations, mediated in part by immunogenicity. Clinical trials are required to investigate whether personalised induction regimens and treatment-to-target dose intensification improve outcomes.
Guts UK, Crohn's and Colitis UK, Cure Crohn's Colitis, AbbVie, Merck Sharp and Dohme, Napp Pharmaceuticals, Pfizer, and Celltrion.
BackgroundCOVID-19 has impacted on healthcare provision. Anecdotally, investigations for children with inflammatory bowel disease (IBD) have been restricted, resulting in diagnosis with no ...histological confirmation and potential secondary morbidity. In this study, we detail practice across the UK to assess impact on services and document the impact of the pandemic.MethodsFor the month of April 2020, 20 tertiary paediatric IBD centres were invited to contribute data detailing: (1) diagnosis/management of suspected new patients with IBD; (2) facilities available; (3) ongoing management of IBD; and (4) direct impact of COVID-19 on patients with IBD.ResultsAll centres contributed. Two centres retained routine endoscopy, with three unable to perform even urgent IBD endoscopy. 122 patients were diagnosed with IBD, and 53.3% (n=65) were presumed diagnoses and had not undergone endoscopy with histological confirmation. The most common induction was exclusive enteral nutrition (44.6%). No patients with a presumed rather than confirmed diagnosis were started on anti-tumour necrosis factor (TNF) therapy.Most IBD follow-up appointments were able to occur using phone/webcam or face to face. No biologics/immunomodulators were stopped. All centres were able to continue IBD surgery if required, with 14 procedures occurring across seven centres.ConclusionsDiagnostic IBD practice has been hugely impacted by COVID-19, with >50% of new diagnoses not having endoscopy. To date, therapy and review of known paediatric patients with IBD has continued. Planning and resourcing for recovery is crucial to minimise continued secondary morbidity.
BackgroundTherapeutic options for paediatric inflammatory bowel disease (IBD) are limited, especially for younger children. Unlike in adults, vedolizumab and ustekinumab are not licensed for ...paediatric use in the UK. We aimed to understand the real-world access to, and use of, these therapies in the paediatric population.MethodsWe surveyed UK IBD centres to assess the incident use of vedolizumab and ustekinumab from 1 January 2021 to 31 December 2021. We collected information on funding, dose escalations and therapeutic drug monitoring.Results18 of 21 centres responded, covering an estimated 5260 patients. One hundred and thirteen were started on vedolizumab, prescription incidence 2.2%, median prescriptions per centre was 4 (range 1–20). Considering ustekinumab, 73 patients were commenced, prescription incidence 1.4%. Median prescription per centre was 3.5 (range 1–13). Prescription rates at each centre were not predicted by patient number cared for at that centre (p=0.2). Dose escalation was common in vedolizumab (66.7% centres) and ustekinumab (55.5%).Funding strategies varied substantially, and multiple funding sources were used; 12 of 18 centres (66.7%) reported funding through routine National Health Service (NHS) England/Scottish arrangements. There was local NHS trust funding in 8 of 18 centres (44.4%). Individual funding requests (IFRs) were used in 5 of 18 (27.8%), although IFRs are reserved for patients with unique additional characteristics. Four centres were unable to achieve funding in pre-pubescent children.ConclusionsThere is widespread use of vedolizumab and ustekinumab across the UK, although practice is highly variable. Access to therapy appeared to differ substantially. There is a growing disparity between international guidelines and real-world practice. Establishing early and effective therapy in all patients remains a priority.
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