Using clinical cases to guide healthcare.

Evidence-based practice (EBP) has been the gold standard in healthcare for nearly three centuries and aims to assist physicians in providing the safest and most effective healthcare for their patients. The well-established hierarchy of evidence lists systematic reviews and meta-analyses at the top however these methodologies are not always appropriate or possible and in these instances case-control studies, case series and case reports are utilised to support EBP. Case-control studies allow simultaneous study of multiple risk factors and can be performed rapidly and relatively cheaply. A recent example was during the Coronavirus pandemic where case-control studies were used to assess the efficacy of personal protective equipment for healthcare workers. Case series and case reports also play a role in EBP and are particularly useful to study rare diseases such as inflammatory bowel disease in transgender and gender non-conforming individuals. They are also vital in generating and disseminating early signals and encouraging further research. Whilst these methodologies have weaknesses, particularly with regards to bias and loss of patient confidentiality for rare pathologies, they have an important part to play in EBP and when appropriately utilised can significantly impact upon clinical practice.

Chronic abdominal pain in inflammatory bowel disease: a practical guide.

Pain is common in inflammatory bowel disease (IBD), yet many patients feel their pain is not addressed by healthcare professionals. Listening to a patient's concerns about pain, assessing symptoms and acknowledging the impact these have on daily life remain crucial steps in addressing pain in IBD. While acute pain may be effectively controlled by pain medication, chronic pain is more complex and often pharmacological therapies, particularly opioids, are ineffective. Low-dose tricyclic antidepressants and psychological approaches, including cognitive-behavioural therapy, have shown some promise in offering effective pain management while lifestyle changes such as a trial of low-fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet in those with overlapping irritable bowel syndrome may also reduce pain. Patients benefit from a long-term, trusting relationship with their healthcare professional to allow a holistic approach combining pharmacological, psychological, lifestyle and dietary approaches to chronic pain. We present a practical review to facilitate management of chronic abdominal pain in IBD.

Opioid use and associated factors in 1676 patients with inflammatory bowel disease: a multicentre quality improvement project.

Objective: Despite its association with poorer outcomes, opioid use in inflammatory bowel disease (IBD) is not well characterised in the UK. We aimed to examine the extent of opioid use, the associated factors and the use of mitigation techniques such as pain-service review and opioid weaning plans among individuals with IBD. Methods: Data were collected from consecutive patients attending IBD outpatient appointments at 12 UK hospitals. A predefined questionnaire was used to collect data including patient demographics, IBD history, opioid use in the past year (>2 weeks) and opioid-use mitigation techniques. Additionally, consecutive IBD-related hospital stays leading up to July 2019 were reviewed with data collected regarding opioid use at admission, discharge and follow-up as well as details of the admission indication. Results: In 1352 outpatients, 12% had used opioids within the past 12 months. Over half of these individuals were taking opioids for non-IBD pain and less than half had undergone an attempted opioid wean.In 324 hospitalised patients, 27% were prescribed opioids at discharge from hospital. At 12 months postdischarge, 11% were using opioids. Factors associated with opioid use in both cohorts included female sex, Crohn's disease and previous surgery. Conclusions: 1 in 10 patients with IBD attending outpatient appointments were opioid exposed in the past year while a quarter of inpatients were discharged with opioids, and 11% continued to use opioids 12 months after discharge. IBD services should aim to identify patients exposed to opioids, reduce exposure where possible and facilitate access to alternative pain management approaches.

Systematic review with meta-analysis: Time to diagnosis and the impact of delayed diagnosis on clinical outcomes in inflammatory bowel disease.

BACKGROUND: The impact of diagnostic delay on the clinical course of inflammatory bowel disease (IBD) remains uncertain. AIM: To perform a systematic review of time to diagnosis and the impact of delayed diagnosis on clinical outcomes in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We searched EMBASE and Medline from inception to 30th November 2022 for studies reporting diagnostic interval, from symptom onset to IBD diagnosis. We calculated the median, interquartile range (IQR) and pooled weighted median, of median diagnostic intervals of eligible studies. We defined delayed diagnosis as individuals above the 75th centile of longest time to diagnosis in each study. Using random effects meta-analysis, we pooled odds ratios (ORs) with 95% confidence intervals (CI) for studies reporting clinical outcomes, according to delayed diagnosis. RESULTS: One hundred and one studies representing 112,194 patients with IBD (CD = 59,359; UC = 52,835) met inclusion criteria. The median of median times to diagnosis was 8.0 (IQR: 5.0-15.2) and 3.7 months (IQR: 2.0-6.7) in CD and UC, respectively. In high-income countries, this was 6.2 (IQR: 5.0-12.3) and 3.2 months (IQR: 2.2-5.3), compared with 11.7 (IQR: 8.3-18.0) and 7.8 months (IQR: 5.2-21.8) in low-middle-income, countries, for CD and UC respectively. The pooled weighted median was 7.0 (95% CI: 3.0-26.4) and 4.6 (95% CI: 1.0-96.0) months, for CD and UC respectively. Eleven studies, representing 6164 patients (CD = 4858; UC = 1306), were included in the meta-analysis that examined the impact of diagnostic delay on clinical outcomes. In CD, delayed diagnosis was associated with higher odds of stricturing (OR = 1.88; CI: 1.35-2.62), penetrating disease (OR = 1.64; CI: 1.21-2.20) and intestinal surgery (OR = 2.24; CI: 1.57-3.19). In UC, delayed diagnosis was associated with higher odds of colectomy (OR = 4.13; CI: 1.04-16.40). CONCLUSION: Delayed diagnosis is associated with disease progression in CD, and intestinal surgery in both CD and UC. Strategies are needed to achieve earlier diagnosis of IBD.

Ustekinumab for the treatment of moderate to severe ulcerative colitis: a multicentre UK cohort study.

Objective: Ustekinumab is an interleukin-12/interleukin-23 receptor antagonist licensed for the treatment of ulcerative colitis (UC). Clinical trial data were promising; however, real-world data are limited. We assessed the safety and effectiveness of ustekinumab in UC in a real-world setting. Design/method: This was a multicentre, retrospective, observational cohort study between February 2020 and January 2022. Disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI). Clinical remission was defined as a SCCAI≤2. The primary endpoints were rates of corticosteroid-free remission (CSFR) at week 16 and at week 26. Objective outcomes, including faecal calprotectin (FCAL), were also collected. Results: 110 patients with UC (65% male; median age 40 (IQR range 29-59); 96% with prior biologic and/or tofacitinib exposure) had a median follow-up of 28 weeks (IQR 17-47). CSFR was 36% (18/50) at week 16% and 33% (13/39) at week 26, corresponding with a significant fall in SCCAI from 6 (IQR 4-8) at baseline to 3 (IQR 0-5) at week 26, p<0.001. By week 16, there was improvement of median FCAL measurements, which fell from a baseline of 610 µg/g (IQR 333-1100) to 102 µg/g (IQR 54-674) at week 16. At the end of follow-up, 15% (17/110) had discontinued treatment; 13 patients due to primary non-response or loss of response, and 1 patient for family planning. Treatment was discontinued in three patients due to adverse events. Conclusion: In the largest real-world study to date, ustekinumab was effective with a reassuring safety profile in a refractory cohort of patients.

Systematic review with meta-analysis: effectiveness of anti-inflammatory therapy in immune checkpoint inhibitor-induced enterocolitis.

BACKGROUND: Immune checkpoint inhibitors have revolutionised cancer treatment, but at the cost of off-target immune-mediated organ damage. This includes checkpoint inhibitor-induced enterocolitis which frequently requires hospitalisation and may be life-threatening. Empiric treatment typically includes corticosteroids and infliximab, although no large-scale studies have confirmed their effectiveness. AIM: To investigate the effectiveness of anti-inflammatory therapy in checkpoint inhibitor-induced enterocolitis METHODS: We performed a systematic review and meta-analysis of studies reporting clinical outcomes of checkpoint inhibitor-induced enterocolitis in adult cancer patients treated with anti-inflammatory agents. We searched Medline, EMBASE, and the Cochrane library through April and extracted the proportion of patients responding to anti-inflammatory therapy. Variation in effect size was studied using a random-effects meta-regression analysis, with checkpoint inhibitor agent and tumour type as the variables. RESULTS: Data were pooled from 1210 treated patients across 39 studies. Corticosteroids were effective in 59% (95% CI 54- 65) of patients, with response significantly more favourable in patients treated with anti-PD-1/L1 monotherapy, compared with anti-CTLA-4 containing regimens (78%, 95% CI 69-85 vs 56 %, 95% CI 49-63, P = 0.003), and more favourable in lung cancer patients compared with melanoma patients (88%, 95% CI 62-97 vs 55%, 95% CI 47-63, P = 0.04). Infliximab was effective in 81% (95% CI 73-87) of patients, and vedolizumab in 85% (95% CI 60-96). CONCLUSION: Corticosteroids, infliximab and vedolizumab, are effective in the treatment of checkpoint inhibitor-induced enterocolitis. Checkpoint inhibitor regimen and cancer type were significant moderators in response to corticosteroid therapy.

UK Patients of Bangladeshi Descent with Crohn's Disease Respond Less Well to TNF Antagonists Than Caucasian Patients.

BACKGROUND: Patients with inflammatory bowel disease are currently managed with the assumption that trial data are applicable to all ethnic groups. Previous studies demonstrate differences in disease severity and phenotype of Asian patients with Crohn's disease (CD), including Bangladeshi Asians within the UK. No study has evaluated the impact of ethnicity on response to anti-TNFs. AIM: Our primary endpoint was a comparison of failure-free survival on first prescribed anti-TNF (anti-tumor necrosis factor) therapy in UK Bangladeshi and Caucasian patients with CD. Our secondary aims were to evaluate disease phenotype, indication for anti-TNF prescription, and duration from diagnosis until first anti-TNF prescribed between groups. METHODS: The records of consecutive outpatient appointments over a 12-month period were used to identify Caucasian and Bangladeshi patients prescribed an anti-TNF for CD. Information on patient demographics, ethnicity, disease phenotype, immunomodulator use, outcome from first biologic, duration of therapy, and reason for cessation was recorded. RESULTS: In total, 224 Caucasian and Bangladeshi patients were prescribed an anti-TNF for CD. Bangladeshi patients started an anti-TNF 4.3 years earlier after diagnosis than Caucasian patients (3.9 years vs. 8.2 years: p < 0.01). Bangladeshi patients experienced shorter failure-free survival than Caucasian patients (1.8 vs. 4.8 years p < 0.01). By 2 years, significantly more Bangladeshi patients had stopped anti-TNF due to loss of response (OR 6.35, p < 0.01). CONCLUSIONS: This is the first study to suggest that Bangladeshi patients resident in the UK with CD respond less well to treatment with TNF antagonists than Caucasian patients.