ABSTRACT
Background: Delays in diagnosis can be patient and health-system related. Such delays have been reported to increase overall complications in Inflammatory Bowel Diseases (IBD). The aim of our study was to report on the impact of delays on IBD-related adverse outcomes (AOs), as hospitals currently face challenges with long waiting lists in the post-COVID-19 era. Method(s): New patients referred for suspected IBD to a single tertiary care centre between Jan 2013 to Dec 2017 were identified using EMR. A cut-off time was set for each delay-type based on best average hospital waiting times. Reasons for delays until start of treatment and data on pre-defined AOs (steroid & other rescue therapies, hospitalisations, surgery) were recorded for each patient until end of June 2021. Data was analysed using multiple Pearson correlations and Cox proportional Hazard model to determine if there was a difference in survival without AOs between patients with and without delay. Result(s): 105 patients were identified using strict criteria (M=58;median age=32y) with a median follow-up of 55 months. The most frequent presenting complaints were abdominal pain (44, 41.9%), loose stools (40, 38.1%), bloody diarrhoea (37, 35.2%) and bleeding perrectum (33, 31.4%). 65, 27 and 13 patients had a final diagnosis of Ulcerative colitis, Crohn's disease and Unclassified colitis respectively, and were analysed jointly. The longest delay-types noted: Patients seeking medical attention (median= 4 months;range 1 to 84 months);arranging gastroenterology clinic review after GP referral (median=5 weeks;1 to 30 weeks);and waiting for index endoscopy (median=3 weeks;1 to 36 weeks). Patient stratification based on delay-type, using specific cut-off times for each showed a statistically significant difference in survival without AOs for all (when comparing delay vs no delay). - delay in seeking medical attention (cut-off=1m;p=0.004) (Fig 1A) - delay in GP referral to specialty review (cut-off=1w;p=0.048) - delay in index endoscopy (cut-off=4w;p=0.01) (Fig 1B) - delay in starting treatment (cut-off=4w;p=0.03) Conclusion(s): Several bottlenecks of delays increase AOs in IBD over the follow-up period. A delay as short as a week, between GP referral to specialty review, is significant in determining AOs, relevant for specialist IBD centres particularly in the post-Covid period. Endoscopy units should prioritise suspected IBD patients to reduce AOs, which is likely to have implications on service delivery and planning. Long delays observed in patients seeking medical attention highlights the need for better patient education in the community.
ABSTRACT
Background Delays in diagnosis could be patient-related and health-system related. It has been reported that such delays increase overall complications in Inflammatory Bowel Diseases (IBD). The aim of our study was to report on the impact of delays on IBD-related adverse outcomes (AOs), as most hospitals currently face challenges with long waiting lists in the post-Covid-19 era. Methods New patients referred for suspected IBD to a single tertiary care centre between Jan 2013 to Dec 2017 were identified using EMR. For purposes of the study, a cut-off time was set by investigators for each delay-type based on best average hospital waiting times. The reasons for delays in patient journey until start of treatment and data on predefined AOs (steroid & other rescue therapies, hospitalisations, surgery) were recorded for each patient until end of June 2021. The data were analysed using multiple Pearson correlations and Cox proportional Hazard model to determine whether there is a difference in survival without AOs between patients with and without a delay. Results Total of 105 patients were identified using stringent criteria (M=58 ;median age=32y) with a long median followup of 55 months. The most frequent presenting complaints were abdominal pain (44, 41,9%), loose stools (40, 38,1%), bloody diarrhoea (37, 35,2%) and bleeding per-rectum (33, 31,4%) and only 16% declared a family history. 65, 27 and 13 patients had final diagnosis of Ulcerative colitis, Crohn's disease and Unclassified colitis respectively, and analysed collectively. In our cohort, the longest delay-types noted were - patients seeking medical attention (median= 4 months;range 1 to 84 months), arranging gastroenterology clinic review after referral from primary care (median=5 weeks;range 1 to 30 weeks), and waiting for index endoscopy (median=3 weeks;1 to 36 weeks). Patient stratification based on delay-type, using specific cutoff times for each showed a statistically significant difference in survival without AOs for all (when comparing delay v/s no delay). 1. delay in seeking medical attention (cut-off=1m;p=0.004) (figure 1A) . delay in GP referral specialty review (cut-off=1w;p=0.048) . delay in index endoscopy (cut-off= 4w;p=0.01) (Fig 1B) . delay in starting treatment (cut-off= 4w;p=0.03) Conclusion . Several bottlenecks of delays increase AOs in IBD over the follow-up period. . A delay as short as a week, between GP referral specialty review, is significant in determining AOs;this has implications on specialist IBD centres particularly in the post-Covid period. . Endoscopy units should prioritise suspected IBD patients to reduce AOs, which is likely to have implications on service delivery and planning. . Long delays observed in patients seeking medical attention highlights the need for both primary and secondary care to undertake patient education in the community.
ABSTRACT
Background: Gastrointestinal (GI) symptoms are the most common extrapulmonary manifestation of coronavirus disease 2019 (COVID-19). Therefore, we sought to determine the impact of GI symptoms on disease outcomes and the systemic inflammatory response in COVID-19. Methods: In two large, independent cohorts of hospitalized COVID-19 patients in the United States (n=634) and Italy (n=287) we examined GI symptoms on admission and related them to mortality and circulating proteomic biomarkers. Disease severity defined by oxygenation and end organ damage was also examined as an outcome in the US cohort. In both cohorts, a multivariate logistic regression was performed to determine the association of GI symptoms (nausea, vomiting, and diarrhea) present on admission and outcomes adjusting for age, gender and examined comorbid diseases. A prediction model was built based on the initial US cohort and validated with a distinct US cohort (n=242). In a subset of patients (n=238), circulating cytokines and chemokines were examined using a multiplexed proteomic assay (Olink) that simultaneously quantified 92 protein analytes. Results: A significant reduction in disease-associated mortality in COVID-19 patients presenting with GI symptoms was observed both in the US cohort (OR 0.54, 95% CI 0.34-0.86) and the Italian cohort (OR 0.33, 95% CI 0.13-0.67) which was independent of age, gender and comorbidities. A prediction model consisting of age and BMI with the addition of GI symptoms had a significantly improved ability to predict disease severity and mortality compared with age and BMI alone (median area under the curve (AUC) of 0.64 (age + BMI+ GI symptoms) vs 0.59 (age + BMI) for disease severity and 0.73 (age + BMI + GI symptoms) vs 0.70 (age + BMI) for mortality). The proteomic analysis revealed 6 clusters based on their co-segregation across all COVID-19 patients. Among these 6 clusters, clusters 4 and 5, which were enriched in the "Hallmark Inflammatory Response" and “KEGG JAK/STAT Signaling Pathway” respectively, and were reduced in patients with diarrhea. The observed mortality reduction in COVID-19 patients with GI symptoms was associated with lower circulating levels of key inflammatory proteins including IL-6, IL-8, IL-17A and CCL28 that are known to be associated with poor outcomes in COVID-19;while there was an increase in IL-7 and TRAIL, which both have important immunoregulatory functions. Conclusions: COVID-19 patients with GI symptoms have reduced inflammatory biomarkers and improved survival after adjusting for comorbidities, age and gender. These data highlight GI involvement as an important parameter for severity stratification in COVID-19 and point towards an immunomodulatory role of the GI tract in response to SARS-CoV-2 infection. (Figure presented)