Administration of intravenous iron through a home-based infusion strategy is safe and has high patient acceptance.

BACKGROUND AND AIMS: To evaluate the safety and patient experience of a hospital-initiated home-based iron infusion service in patients with iron deficiency with or without anaemia. METHODS: Retrospective cohort study, including adult patients who received intravenous iron through a Hospital in The Home service in a single tertiary centre between August 2020 and 2021. A chart review was conducted for documented adverse events (AEs). A telephone survey assessed patient acceptance with three questions on a 5-point Likert scale: (i) How do you perceive the experience of having your infusion given in the home? (ii) Would you like to have the infusion in the same location if you require one in the future? and (iii) Do you feel safe having your infusion at home? OUTCOME MEASURES: Percentage of patients experiencing AEs and patient acceptance of a home-based iron infusion strategy. RESULTS: One hundred ninety-seven patients were included (181 ferric carboxymaltose and 16 ferric derisomaltose). Six (3%) patients (2 of 181 patients who received ferric carboxymaltose compared with 4 of 16 patients who received ferric derisomaltose, P < 0.001, Fisher's exact) experienced AEs, mostly headache and pruritus. Most patients who participated in the telephone survey had a positive experience (57/58 (98%)), felt safe (57/58 (98%)) and preferred future infusions to occur at home (52/58 (90%)). CONCLUSION: A home-based iron infusion strategy was safe and well accepted by patients. Larger studies evaluating the safety profile of different iron formulations in the home setting are required.

Clinical trial: Combination allopurinol-thiopurine versus standard thiopurine in patients with IBD escalating to immunomodulators (the DECIDER study).

BACKGROUND: Thiopurines are established treatments for inflammatory bowel disease (IBD), yet concerns remain regarding their safety. AIM: To evaluate the use of thiopurine-allopurinol combination therapy compared to standard thiopurine therapy in IBD. METHODS: We performed a multicentre, randomised, placebo-controlled trial to compare the efficacy and safety of thiopurine-allopurinol versus thiopurine with placebo for adults commencing a thiopurine for IBD. Patients had active disease at baseline; dosing of therapy was based on a pre-specified regimen and subsequent metabolites. The primary outcome was the proportion of patients achieving a composite of symptomatic disease activity remission (Harvey Bradshaw Index <5 for Crohn's disease, Simple Clinical Colitis Activity Index <4 for ulcerative colitis) and a faecal calprotectin <150 µg/g after 26 weeks of treatment. RESULTS: The trial was terminated early due to slow recruitment. We randomised 102 participants (54 thiopurine-allopurinol, 48 thiopurine with placebo) with similar age (median 42 vs 48 years) and sex distribution (46% women per group). A higher proportion achieved the primary outcome in the thiopurine-allopurinol group (50% vs 35%, p = 0.14) and fewer participants stopped their allocated therapy due to adverse events (11% vs 29%, p = 0.02). Also, within the thiopurine-allopurinol group, thiopurine dose adjustments were less frequent (69% vs 92%, p = 0.03), a higher proportion achieved an early therapeutic 6-TGN level at week 6 (71% vs 53%, p = 0.19), and adverse events attributed to therapy were less frequent (15% vs 44%, p = 0.002). CONCLUSION: Thiopurine-allopurinol therapy is safe and mitigates thiopurine adverse effects, thus enhancing tolerability without compromising efficacy (ACTRN12613001347752).

Intravenous iron: an update.

Iron deficiency is the most common nutritional deficiency worldwide, with significant adverse health consequences in the presence or absence of anaemia. Total dose intravenous iron replacement is recommended for replacement of iron in patients with severe iron deficiency, especially in the presence of anaemia, intolerance or inefficacy following oral iron, or states of inflammation where upregulation of hepcidin may impair gastrointestinal absorption of iron. Currently, available intravenous iron formulations have been demonstrated to have an excellent overall safety profile, but potential adverse effects, including skin staining, infusion-related reactions and hypophosphataemia, have been described. Knowledge of differences in administration and safety profiles of currently available iron formulations will allow appropriate prescription, counselling, as well as recognition and management of adverse events in patients requiring intravenous iron.

Network meta-analysis: efficacy and safety of treatments for fistulising Crohn's disease.

INTRODUCTION: Fistulas are a debilitating complication of Crohn's disease and treatment options remain limited. There is a lack of head-to-head comparisons between treatments. To our knowledge, this is the first network meta-analysis on the efficacy of medical therapies in achieving fistula remission and maintenance of fistula closure in Crohn's disease. METHODS: Biomedical databases and the Cochrane Central Registry were searched between 1978 and 2022 for randomized controlled trials (RCTs) reporting on treatments. A network meta-analysis was performed using the frequentist model with pooled relative risks (RRs) and P -scores used to rank treatments. RESULTS: Twenty-five RCTs were included for analysis with 2239 patients included. At the 16-24 week time point, infliximab produced the only statistically significant result with the 5 mg/kg dose proving the most effective [RR, 2.30; 95% confidence interval (CI), 1.40-3.77]. At 44 weeks, ustekinumab was found to be most superior with it being 2.38 times (RR, 2.38; 95% CI, 1.24-4.56) more superior to placebo, with adalimumab (RR, 2.06; 95% CI, 1.06-3.99) and infliximab 5 mg/kg (RR, 1.68; 95% CI, 1.03-2.75) also producing a statistically significant result. CONCLUSION: Despite infliximab being favoured in international guidelines for the treatment of perianal fistulising Crohn's disease, biologics such as ustekinumab, vedolizumab and adalimumab show promising results.

Development of inflammatory bowel disease patient education and medical information sheets: serving an unmet need.

Inflammatory bowel disease is a chronic gastrointestinal condition that necessitates life-long healthcare engagement and management. Empowering patients with knowledge is fundamental to enhance health literacy, improve health outcomes and facilitate complex decision-making regarding medication and potential surgery. A working group was formed to develop concise, comprehensive patient information sheets to meet this unmet need in the Australian setting.

Extending the Common Sense Model to Explore the Impact of Visceral Sensitivity on Quality of Life in Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease is associated with poor quality of life. The aim of the cross-sectional study was to extend the common sense model to explore the impact of inflammatory bowel disease activity on quality of life and the potential mediating roles of illness perceptions, visceral sensitivity, coping styles, acceptance, and psychological distress. METHODS: A total of 141 inflammatory bowel disease patients (86 with Crohn's disease and 55 with ulcerative colitis; 74 males, 65 females, and 2 gender non-specific, mean age 40.43 years) from 2 metropolitan hospital inflammatory bowel disease outpatient clinics participated. Measures included disease activity (Crohn's Disease Activity Index, Simple Clinical Colitis Activity Index), illness perceptions (Brief Illness Perceptions Questionnaire), visceral sensitivity (Visceral Sensitivity Index), coping styles (Brief Coping Operations Preference Enquiry), acceptance (Acceptance and Action Questionnaire-II), psychological distress (Depression, Anxiety, and Stress Scale), and European Health Interview Survey-Quality of Life (EUROHIS-QoL). RESULTS: A structural equation model of the extended common sense model was found to have a good fit (χ2(10) = 10.07, P = .43, root mean square error of approximation = 0.01, standardized root mean residual = 0.04, comparative index fit = 1.00, Tucker-Lewis index = 1.00, goodness-of-fit = 0.98). After controlling for irritable bowel syndrome diagnosis, the impact of disease activity on quality of life was statistically mediated by illness perceptions, maladaptive coping styles, and psychological distress. In addition, visceral sensitivity bordered on influencing the impact of disease activity and illness perceptions on quality of life through psychological distress. CONCLUSIONS: This study demonstrates that together with illness perceptions and coping styles, visceral sensitivity plays an important role in an individual's adaption to living with inflammatory bowel disease.

Review article: investigation and management of internal fistulae in Crohn's disease.

BACKGROUND: Crohn's disease is an inflammatory, penetrating intestinal disease associated with fistula formation. Fistulae in Crohn's disease can be classified into external and internal fistulae. Internal fistulae form between the gastrointestinal tract and another internal organ and include enteroenteric, enterocolic, enterovesical and rectovaginal fistulae. They are associated with significant morbidity and a decreased quality of life. AIM: To review the classification, diagnosis, medical and surgical management of internal fistulae in Crohn's disease, and propose a treatment algorithm. METHODS: A literature review on internal fistulae in Crohn's disease in the adult population was undertaken, synthesised and summarised. RESULTS: Internal fistulae occur in up to 15% of patients with Crohn's disease. Multi-modal assessment including a combination of endoscopy and cross-sectional imaging, usually magnetic resonance, is required to diagnose fistulae and determine extent of disease. Determining optimal treatment strategies for these complex fistulae remains a challenge due to limited and generally low-quality data. Most studies to date have focussed on luminal disease, with (usually post hoc) outcomes more often reported for external fistulae, particularly perianal fistulae, than internal fistulae. Anti-tumour necrosis factor therapies have emerged as the mainstay of medical therapy, with particularly promising data for enterovesical fistulae, but many patients will still require surgical intervention. The indications and optimal timing of surgery vs medical therapy remains uncertain; thus multi-disciplinary input when making such decisions is important. CONCLUSIONS: Internal fistulae result in significantly increased morbidity in Crohn's disease, and further studies to determine optimal multi-modality management strategies incorporating medical and surgical therapy are required.

Hypophosphataemia after ferric carboxymaltose is unrelated to symptoms, intestinal inflammation or vitamin D status.

BACKGROUND: Intravenous iron replacement is recommended for iron-deficient patients with inflammatory bowel disease (IBD), but may be associated with hypophosphataemia, predisposing to osteomalacia and fractures. This study aimed to evaluate the incidence and risk factors for hypophosphataemia following intravenous ferric carboxymaltose (FCM) in patients with IBD. METHODS: This prospective observational study of patients with and without IBD evaluated serum phosphate for 28 days following intravenous FCM, and assessed associations with symptoms, markers of inflammation and vitamin D status. RESULTS: Twenty-four patients with IBD (11 with Crohn's disease [CD], 13 with ulcerative colitis [UC], mean age 45 years [range 19-90], 7 female), and 20 patients without IBD (mean age 56 [22-88] y, 11 female), were included. Overall, serum phosphate declined by a mean of 36% at Day 7, with a mean fall of 42% (SD 19%) at some time point over 28 days (p <  0.001). Twenty-four of 44 (55%) patients developed moderate to severe hypophosphataemia (serum phosphate < 0.6 mmol/L). No differences between patients with and without IBD were seen, but patients with CD had greater decline in phosphate than those with UC. There was no association between hypophosphataemia and symptomatic adverse events, faecal calprotectin, C-reactive protein, albumin, platelet count, 25(OH) vitamin D, or 1,25(di-OH) vitamin D. Serum phosphate < 1.05 mmol/L on Day 2 predicted susceptibility to moderate-severe hypophosphataemia (OR 7.0). CONCLUSIONS: Hypophosphataemia following FCM is common, unrelated to symptomatic adverse events, baseline intestinal or systemic inflammation, or vitamin D status.

Imbalance of the renin-angiotensin system may contribute to inflammation and fibrosis in IBD: a novel therapeutic target?

OBJECTIVE: We evaluated the influence of the renin-angiotensin system (RAS) on intestinal inflammation and fibrosis. DESIGN: Cultured human colonic myofibroblast proliferation and collagen secretion were assessed following treatment with angiotensin (Ang) II and Ang (1-7), their receptor antagonists candesartan and A779, and the ACE inhibitor captopril. Circulating and intestinal RAS components were evaluated in patients with and without IBD. Disease outcomes in patients with IBD treated with ACE inhibitors and angiotensin receptor blockers (ARBs) were assessed in retrospective studies. RESULTS: Human colonic myofibroblast proliferation was reduced by Ang (1-7) in a dose-dependent manner (p<0.05). Ang II marginally but not significantly increased proliferation, an effect reversed by candesartan (p<0.001). Colonic myofibroblast collagen secretion was reduced by Ang (1-7) (p<0.05) and captopril (p<0.001), and was increased by Ang II (p<0.001). Patients with IBD had higher circulating renin (mean 25.4 vs 18.6 mIU/L, p=0.026) and ACE2:ACE ratio (mean 0.92 vs 0.69, p=0.015) than controls without IBD. RAS gene transcripts and peptides were identified in healthy and diseased bowels. Colonic mucosal Masson's trichrome staining correlated with Ang II (r=0.346, p=0.010) and inversely with ACE2 activity (r=-0.373, p=0.006). Patients with IBD who required surgery (1/37 vs 12/75, p=0.034) and hospitalisation (0/34 vs 8/68, p=0.049) over 2 years were less often treated with ACE inhibitors and ARBs than patients not requiring surgery or hospitalisation. CONCLUSIONS: The RAS mediates fibrosis in human cell cultures, is expressed in the intestine and perturbed in intestinal inflammation, and agents targeting this system are associated with improved disease outcomes.

Symptomatic severe hypophosphatemia after intravenous ferric carboxymaltose.

Intravenous iron is commonly prescribed for treatment of iron deficiency, with modern formulations demonstrating an acceptable safety profile in the majority of patients. We report the case of a patient who was hospitalised with muscle pain, deteriorating mobility and multiple fractures following repeated ferric carboxymaltose infusions. Investigations revealed severe hypophosphatemia with serum phosphate of 0.27 mmol/L, 25-hydroxyvitamin D (25OHD) level of 32 nmol/L and insufficiency fractures of the sacrum and L5 transverse process. The patient's hypophosphatemia was corrected with several infusions of intravenous phosphate, as well as oral phosphate and calcitriol, with subsequent resolution of her muscle aches, back pain and immobility. The risk of persistent hypophosphatemia and osteomalacia may be higher with iron carboxymaltose than other iron formulations and a transient increase in intact fibroblast growth factor-23 with reduced renal tubular phosphate absorption has been postulated as the key mechanism. This risk appears increased by repeated iron infusions, underlying malnutrition, hypophosphatemia at baseline, vitamin D deficiency, hyperparathyroidism or anti-resorptive medication use. The true risk and incidence of hypophosphatemia need to be clarified so that appropriate monitoring, prevention and treatment strategies can be developed.

Endocuff Vision is safe to use for dysplasia surveillance in patients with ulcerative colitis: a feasibility study.

Background and study aims Endocuff Vision improves adenoma detection rates in patients without inflammatory bowel disease. This study aimed to investigate the safety and feasibility of Endocuff Vision-assisted high-definition white light endoscopy (HDWLE) with dye-spray chromoendoscopy for detection of dysplasia in patients with ulcerative colitis. Patients and methods Patients with clinically inactive ulcerative colitis due for dysplasia surveillance were recruited. Procedural endpoints included safety, cecal intubation rate (CIR), terminal ileum intubation rate (TIR), withdrawal time, polyp detection rate, dysplasia detection rate (DDR), and sessile serrated lesion detection rate. Results Twenty-five patients (9 female, median age 57 [range 28 - 82] years) were studied. Endocuff Vision-assisted HDWLE was completed in all participants, with a CIR of 100 %, in a median 4 minutes (range 2 - 16), and a TIR of 88% in a median of 6.5 minutes (range 3 - 19). Median withdrawal time was 18 minutes (range 10 - 55), including application of dye-spray, biopsies and polypectomy. The Mayo Endoscopic subscore was 0 in 11, 1 in 9, and 2 in 5 patients. The DDR was 24 % (6 patients had a total of 12 dysplastic lesions) and sessile serrated lesion detection rate was 12 % (3 patients had a total of 4 sessile serrated polyps). No serious adverse events occurred, with one patient developing clinically insignificant minor mucosal bleeding. Conclusion Endocuff Vision-assisted HDWLE is feasible and safe in patients with ulcerative colitis undergoing dysplasia surveillance. Further studies are required to assess superiority of this technique compared with standard high-definition white light endoscopy with chromoendoscopy.

The intestinal vitamin D receptor in inflammatory bowel disease: inverse correlation with inflammation but no relationship with circulating vitamin D status.

BACKGROUND: The intestinal vitamin D receptor (VDR) remains poorly characterized in patients with inflammatory bowel disease (IBD). METHODS: Colonoscopic biopsies and intestinal resection specimens from the terminal ileum, ascending and sigmoid colon, from patients with and without IBD, were analyzed for VDR mRNA quantification by polymerase chain reaction, and protein localization and semi-quantification by immunohistochemistry. The relationship between VDR and intestinal inflammation, serum 25(OH)D and oral vitamin D intake was elicited. RESULTS: A total of 725 biopsies from 20 patients with Crohn's disease (CD), 15 with ulcerative colitis (UC) and 14 non-IBD controls who underwent colonoscopy were studied. VDR gene expression and protein staining intensity was similar across all three groups, and across the intestinal segments. Sigmoid colon VDR mRNA expression inversely correlated with faecal calprotectin (r = -0.64, p = 0.026) and histological score (r = -0.67, p = 0.006) in UC, and histological score (r = -0.58, p = 0.019) in patients with CD. VDR staining intensity was higher in quiescent than diseased segments. No relationship with serum 25(OH)D or oral vitamin D intake was noted. Immunohistochemical staining of 28 intestinal resection specimens from 15 patients (5 each with CD, UC and non-IBD controls) showed diffuse VDR staining in the mucosa, submucosa and circular muscle. CONCLUSIONS: VDR transcript expression and protein staining intensity are inversely related to inflammation in IBD, but unrelated to serum 25(OH)D, and similar to non-IBD controls. Strategies to upregulate intestinal VDR, potentially translating to modulation of disease activity, require investigation.

Dysphagia: Thinking outside the box.

Dysphagia is a common symptom that is important to recognise and appropriately manage, given that causes include life threatening oesophageal neoplasia, oropharyngeal dysfunction, the risk of aspiration, as well as chronic disabling gastroesophageal reflux (GORD). The predominant causes of dysphagia varies between cohorts depending on the interplay between genetic predisposition and environmental risk factors, and is changing with time. Currently in white Caucasian societies adopting a western lifestyle, obesity is common and thus associated gastroesophageal reflux disease is increasingly diagnosed. Similarly, food allergies are increasing in the west, and eosinophilic oesophagitis is increasingly found as a cause. Other regions where cigarette smoking is still prevalent, or where access to medical care and antisecretory agents such as proton pump inhibitors are less available, benign oesophageal peptic strictures, Barrett's oesophagus, adeno- as well as squamous cell carcinoma are endemic. The evaluation should consider the severity of symptoms, as well as the pre-test probability of a given condition. In young white Caucasian males who are atopic or describe heartburn, eosinophilic esophagitis and gastroesophageal reflux disease will predominate and a proton pump inhibitor could be commenced prior to further investigation. Upper gastrointestinal endoscopy remains a valid first line investigation for patients with suspected oesophageal dysphagia. Barium swallow is particularly useful for oropharyngeal dysphagia, and oesophageal manometry mandatory to diagnose motility disorders.