A 67-year-old Caribbean woman with chronic renal disease needing dialysis was admitted with diarrhoea. Three months before she had had an episode of antibiotic-associated diarrhoea, resulting from Clostridium difficile. She had been treated, the diarrhoea had resolved, and she had no further courses of antibiotics in the interim. She also had psoriasis, had been on prednisolone for many years, and had diverticulosis.
A recent Australian audit of IBD care identified variation in care and poor documentation as major problems. To address these, the Australia and New Zealand Inflammatory Bowel Disease Consortium (ANZIBDC) worked to develop a comprehensive cloud based IBD clinical management system—“Crohn’s Colitis Care” (CCCare). The ANZIBDC is made up of 14 centres across Australia and New Zealand, providing care for ~20000 patients with IBD. The ANZIBDC sent out a request for proposal and worked with the selected software developer. The development team included gastroenterologists, IBD nurses, and IT specialists. Clinical guidelines, standards of care, and usual practice across the 14 sites informed development. CCCare thus captures symptoms, imaging, endoscopy, blood results, medications in standardised fields along with clinic letters, and other correspondence in a single IBD-specific medical record. Safety monitoring, disease management plans, patient reminders, patient portal, and summary reports are all available. De-identified longitudinal data are stored separately in a clinical quality registry. CCCare was tested for feasibility and usability, in two large ANZIBDC sites—the Royal Adelaide and Royal Brisbane Hospitals. Testing assessed use in day-to-day clinical settings including face-to-face, telehealth, and virtual clinic encounters. The patient portal, wherein they enter their history and patient reported outcomes, was also tested. Users’ reactions to CCCare were evaluated with the system usability scale (SUS). SUS broadly classifies usability of a system from poor (<70) to superior (>90). Standardised qualitative feedback was also captured through face to face or telephone interview. System security was assessed by commercial penetration testing. Results from 13 users [clinicians (n = 3), nurses, administrative staff and patients] showed a mean SUS score of 75 (50 – 95). The “Usability” and “Learnability” sub-scores were 77 and 68, respectively. All user groups rated the software as user-friendly and intuitive qualitatively. Patients anticipated better communication with clinical team and improved ability to track their own disease. Clinicians identified structured recording of adherence, the standard management plan to support best practice and centralised data repository as positive features. Penetration test was passed successfully which assured that CCCare is suitable for deployment into the health sector. Preliminary feedback demonstrates that CCCare is usable an secure, and is now ready for use in routine clinical care. We anticipate that using CCCare will create enormous opportunity for improvements in clinical care and uniform data collection.
Abstract A 70-year-old woman was referred for assessment of loss of appetite, nausea, and weight loss of 12kg over the preceding 12 months. She had an iron-deficient, microcytic anaemia.
Remission is the goal of therapy in ulcerative colitis (UC) and a primary endpoint of clinical trials. Disparity between clinical, endoscopic and histological assessments of activity has long been recognised, but since the definition of remission affects clinical and regulatory decisions, the disparity and impact on outcome needs re-evaluation.
Methods
Consecutive patients requesting an early appointment were assessed by 4 gastroenterologists, before videosigmoidoscopy and mucosal biopsy. Each scored clinical and endoscopic activity independently. Histological activity was scored by two pathologists. Clinical activity was defined by the Simple Clinical Colitis Activity Index, endoscopic activity by the Baron score and microscopic activity by the Truelove & Richards9 score (remission scores ≤2, ≤1 and ‘no significant inflammation’ respectively). Outcome measures included treatment escalation, hospitalisation and colectomy. Fleiss9 κ was used to evaluate interobserver variation and two-tailed Fisher9s exact test to compare outcomes.
Results
91 patients were recruited, median age at diagnosis 31 year (11–66); 60 were in remission by at least one definition: 37 (41%) were in clinical, 30/37 (81%) were also in histological remission, 30/37 (81%) were in endoscopic remission and 20/37 (76%) (20/91 = 22%) were in remission by all three measures. Of 56 in endoscopic remission: 26/56 (46%) had clinical activity and 10/26 (38%) had moderate clinical activity (SCCAI 6–8). Of 47 in histological remission only 42 (81%) were in endoscopic remission and 30 (64%) were in clinical remission. Agreement between histological and endoscopic assessment (k=0.58, moderate agreement) was better than between clinical and endoscopic (k=0.27), or clinical and histological (k=0.47), or between all three methods (k=0.44). follow-up data was available in 54/60 (90%), with 29 month (5–35 month) median follow-up; median age at review 48 year (19–74), 57% female, 30% proctitis, 48% distal, 22% extensive. Most (83%) took maintenance therapy: 5ASA (31/54), immunomodulators (13/54), or infliximab (1/54). 43 (80%) maintained steroid-free remission at 12 month and 34 (63%) during follow-up; of those needing steroids, 9 (45%) had >1 course during follow up and 3 (15%) infliximab. 4 (7%) needed hospitalisation and 1 (2%) colectomy. 12 month steroid-free remission did not differ according to the depth of remission (80% all 3 criteria, 75% on 2 criteria, 83% on 1 criterion, p=0.7).
Conclusion
Modest agreement between clinical, endoscopic or histological activity emphasises the differences between the measures, all of which may have prognostic value. Clinical assessment systematically over-estimates disease activity, but the outcome over 2 years was not affected by the definition of remission.
Abstract Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn’s disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases.
BACKGROUND Wearable digital health technologies and mobile apps (personal digital health technologies [DHTs]) hold great promise for transforming health research and care. However, engagement in personal DHT research is poor. OBJECTIVE The objective of this paper is to describe how participant engagement techniques and different study designs affect participant adherence, retention, and overall engagement in research involving personal DHTs. METHODS Quantitative and qualitative analysis of engagement factors are reported across 6 unique personal DHT research studies that adopted aspects of a participant-centric design. Study populations included (1) frontline health care workers; (2) a conception, pregnant, and postpartum population; (3) individuals with Crohn disease; (4) individuals with pancreatic cancer; (5) individuals with central nervous system tumors; and (6) families with a Li-Fraumeni syndrome affected member. All included studies involved the use of a study smartphone app that collected both daily and intermittent passive and active tasks, as well as using multiple wearable devices including smartwatches, smart rings, and smart scales. All studies included a variety of participant-centric engagement strategies centered on working with participants as co-designers and regular check-in phone calls to provide support over study participation. Overall retention, probability of staying in the study, and median adherence to study activities are reported. RESULTS The median proportion of participants retained in the study across the 6 studies was 77.2% (IQR 72.6%-88%). The probability of staying in the study stayed above 80% for all studies during the first month of study participation and stayed above 50% for the entire active study period across all studies. Median adherence to study activities varied by study population. Severely ill cancer populations and postpartum mothers showed the lowest adherence to personal DHT research tasks, largely the result of physical, mental, and situational barriers. Except for the cancer and postpartum populations, median adherences for the Oura smart ring, Garmin, and Apple smartwatches were over 80% and 90%, respectively. Median adherence to the scheduled check-in calls was high across all but one cohort (50%, IQR 20%-75%: low-engagement cohort). Median adherence to study-related activities in this low-engagement cohort was lower than in all other included studies. CONCLUSIONS Participant-centric engagement strategies aid in participant retention and maintain good adherence in some populations. Primary barriers to engagement were participant burden (task fatigue and inconvenience), physical, mental, and situational barriers (unable to complete tasks), and low perceived benefit (lack of understanding of the value of personal DHTs). More population-specific tailoring of personal DHT designs is needed so that these new tools can be perceived as personally valuable to the end user.
Abstract Background The SCCAI was designed to facilitate assessment of disease activity in ulcerative colitis (UC). We aimed to interrogate the metric properties of individual items of the SCCAI using item response theory (IRT) analysis, to simplify and improve its performance. Methods The original 9-item SCCAI was collected through TrueColours, a real-time software platform which allows remote entry and monitoring of patients with UC. Data were securely uploaded onto Dementias Platform UK Data Portal, where they were analysed in Stata 16.1 SE. A 2-parameter (2-PL) logistic IRT model was estimated to evaluate each item of the SCCAI for its informativeness (discrimination). A revised scale was generated and re-assessed following systematic removal of items. Results SCCAI data for 516 UC patients (41 years, SD = 15) treated in Oxford were examined. After initial item deletion (Erythema nodosum, Pyoderma gangrenosum), a 7-item scale was estimated. Discrimination values (information) ranged from 0.41 to 2.52 indicating selected item inefficiency with three items < 1.70 which is a suggested discriminatory value for optimal efficiency. Systematic item deletions found that a 4-item scale (bowel frequency day; bowel frequency nocturnal; urgency to defaecation; rectal bleeding) was more informative and discriminatory of trait severity (discrimination values of 1.50 to 2.78). The 4-item scale possesses higher scalability and unidimensionality, suggesting that the responses to items are either direct endorsement (patient selection by symptom ) or non-endorsement of the trait (disease activity). Conclusion Reduction of the SCCAI from the original 9-item scale to a 4-item scale provides optimum trait information that will minimise response burden. This new 4-item scale needs validation against other measures of disease activity such as faecal calprotectin, endoscopy and histopathology.
Abstract Currently, the main targets of drug therapy for ulcerative colitis [UC] are endoscopic and clinical remission. However, there is active discussion about the additional advantages of including histological remission as a target. Accumulating evidence indicates that microscopic activity persists in endoscopically quiescent UC, that histological changes may lag behind clinical remission after treatment, and that absence of histological activity predicts lower rates of relapse, hospitalization, surgery and subsequent neoplasia. Obtaining useful information from mucosal biopsies in this setting depends on accurate and consistent evaluation of histological features. However, there is no standardization of biopsy procedures, histological sample processing technique or histological scoring systems, and there is no agreement on the definitions of histological remission, response or activity. Accordingly, a consensus expert panel convened by the European Crohn’s and Colitis Organisation [ECCO] reviewed the literature and agreed a number of position statements regarding harmonization of UC histopathology. The objective was to provide evidence-based guidance for the standardization and harmonization of procedures, definitions and scoring systems for histology in UC, and to reach expert consensus where possible. We propose the absence of intraepithelial neutrophils, erosion and ulceration as a minimum requirement for the definition of histological remission. For randomized control trials we recommend the use of the Robarts histopathology index [RHI] or the Nancy index [NI]. For observational studies or in clinical practice we recommend the use of the NI. To predict the risk of future neoplasia in UC, cumulative histological scores over time are more useful than single scores.
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