Bariatric surgeons' views on pre-operative factors associated with improved health-related quality of life following surgery.

Bariatric surgery is an effective treatment for severe obesity, affording significant improvements in weight loss and health-related quality of life. However, bariatric surgeons' views on whether certain pre-operative factors predict improvements in post-operative health-related quality of life, and if so, which ones, are largely unknown. This cross-sectional survey study examined the views of 58 bariatric surgeons from Australia and New Zealand. A total of 18 factors were selected for exploration based on their mention in the literature. Participants rated the extent to which they thought these pre-operative factors would improve post-operative health-related quality of life. Responses showed that bariatric surgeons held diverse perspectives and revealed a lack of consensus regarding "predictive" factors. Generally, respondents agreed that better than average health literacy, higher socioeconomic status, good physical and psychological health, and positive social support were predictors of improved health-related quality of life following surgery. However, poor eating behaviours, smoking, and the use of alcohol or other substances were deemed negative predictors. Interestingly, aside from higher socioeconomic status, good psychological health, and positive social support, none of the aforementioned views aligned with existing literature. This study offers an initial insight into bariatric surgeons' views on the influence of different pre-operative factors on post-operative health-related quality of life. The array of views identified suggests that there may be an opportunity for medical education, but the findings warrant caution due to the sample size. Replication with a larger survey may be useful, especially as predicted health-related quality of life outcomes could guide decisions regarding surgical (non)progression.

Weight and BMI Patterns in a Biologicals-Treated IBD Cohort.

BACKGROUND: Biologic therapies are effective at inducing and maintaining remission in people with inflammatory bowel disease (IBD). Previous studies have associated TNF-a inhibitors with weight gain, however, it is unclear if this is a class-specific effect or a manifestation of good disease control. To clarify this issue, a retrospective study was undertaken to examine weight changes over time during therapy with different biologic agents. METHODS: Adult patients with IBD who received any biological therapy for at least 12 months, between 2008 and 2020, were identified at two specialised IBD services. Demographic, disease, and therapy-related data were examined. Weight change and patterns thereof were examined for each specific therapy and relationships amongst weight outcomes and various predictive factors explored. RESULTS: Of 294 patients (156 females), 165 received Infliximab (IFX), 68 Adalimumab (ADA), 36 Vedolizumab (VDZ) and 25 Ustekinumab (UST). There was a statistically significant weight gain over time in the IFX and VDZ groups and more weight gain in the IFX vs ADA and VDZ vs ADA at most time points. Three weight trajectories were identified: around 95% of patients had small weight loss or a modest weight gain but 5% of patients, most of whom were on IFX had marked weight gain (24.3 kg). Having a baseline high BMI, being female, having an initiation CRP ≤ 5 or albumin > 35 reduced the odds of major weight gain. CONCLUSION: Weight gain in biologic treated IBD patients appears to be associated with clinical factors (male gender, high CRP, low albumin) and therapy-specific factors.

Habitual dietary fibre and prebiotic intake is inadequate in patients with inflammatory bowel disease: findings from a multicentre cross-sectional study.

BACKGROUND: Recommendations for dietary fibre intake in patients with inflammatory bowel disease are highly variable. Despite the potential benefits of prebiotic fibres on the gut microbiome, many patients with inflammatory bowel disease follow a low fibre diet. The present study comprehensively evaluated intakes of total and prebiotic fibres in patients with inflammatory bowel disease, aiming to determine the adequacy of fibre intake and factors that may influence intake. METHODS: Outpatients with a formal diagnosis of inflammatory bowel disease were recruited to this multicentre cross-sectional study. Habitual dietary fibre intake including prebiotic fibre types was measured using a validated comprehensive nutrition assessment questionnaire. Adequacy of total fibre intake was compared with Australian Nutrient Reference Values. Multiple linear regressions were performed to determine factors influencing fibre intake. RESULTS: Of 92 participants, 52% had Crohn's disease, 51% were male and the mean age was 40 years. Overall, only 38% of the cohort consumed adequate total fibre (median 24 g day-1 , interquartile range 18.5-32.9 g day-1 ). Adequate fibre consumption was significantly less common in males than females (21.3% versus 55.6%, P = 0.002). Resistant starch intake (median 2.9 g day-1 , interquartile range 2.1-4.8 g day-1 ) was significantly less than the proposed recommendations (20 g day-1 ). Disease-related factors such as phenotype and disease activity were not found to influence fibre intake. CONCLUSIONS: Patients with inflammatory bowel disease habitually consume inadequate fibre, particularly prebiotic fibre resistant starch. The potential deleterious effects of low prebiotic intake on the gut microbiome and disease-related outcomes in inflammatory bowel disease are unknown and warrant further research.

Performance of an algorithm-based approach to the diagnosis and management of functional gastrointestinal disorders: A pilot trial.

BACKGROUND: Recent advances in the development of diagnostic criteria and effective management options for functional gastrointestinal disorders (FGIDs) have not yet been integrated into clinical practice. There is a clear need for the development and validation of a simple clinical pathway for the diagnosis and management of FGIDs which can be used in primary care. METHODS: In this controlled pilot study, we designed and evaluated a non-specialist-dependent, algorithm-based approach for the diagnosis and management of FGIDs (ADAM-FGID). Patients referred to 1 tertiary referral center with clinically suspected functional gastrointestinal disorders were allocated to waitlist control or algorithm group. The algorithm group was screened for organic disease, and those without clinical alarms received a written FGID diagnosis and management options. All participants were followed up for 1 year. KEY RESULTS: The ADAM-FGID was found to be feasible and acceptable to both patients and primary healthcare providers. The diagnostic component identified that 39% of referrals required more urgent gastroenterological review than original triage category, with organic disease subsequently diagnosed in 31% of these. The majority of patients (82%) diagnosed with a FGID did not receive a relevant alternative diagnosis during follow-up. Patient buy-in to the model was good, with all reading the diagnostic/management letter, 80% entering management, and 61% reporting symptom improvement at 6 weeks. Moreover, 68% of patients and all referring doctors found the approach to be at least moderately acceptable. Patients reported being reassured by the approach and found the management options useful. Primary healthcare providers acknowledged the potential of this approach to reduce waiting times for endoscopic procedures and to provide reassurance to both patients and themselves. CONCLUSIONS & INFERENCES: This pilot study provides preliminary evidence to support a clinical pathway for the diagnosis and management of FGIDs which does not depend upon specialist review. Further rigorous testing within primary care is needed to conclusively establish safety and efficacy. However, this approach is safer than current management and has potential to build capacity by reducing specialist burden and expediting effective care.

Review article: consensus statements on therapeutic drug monitoring of anti-tumour necrosis factor therapy in inflammatory bowel diseases.

BACKGROUND: Therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients receiving anti-tumour necrosis factor (TNF) agents can help optimise outcomes. Consensus statements based on current evidence will help the development of treatment guidelines. AIM: To develop evidence-based consensus statements for TDM-guided anti-TNF therapy in IBD. METHODS: A committee of 25 Australian and international experts was assembled. The initial draft statements were produced following a systematic literature search. A modified Delphi technique was used with 3 iterations. Statements were modified according to anonymous voting and feedback at each iteration. Statements with 80% agreement without or with minor reservation were accepted. RESULTS: 22/24 statements met criteria for consensus. For anti-TNF agents, TDM should be performed upon treatment failure, following successful induction, when contemplating a drug holiday and periodically in clinical remission only when results would change management. To achieve clinical remission in luminal IBD, infliximab and adalimumab trough concentrations in the range of 3-8 and 5-12 µg/mL, respectively, were deemed appropriate. The range may differ for different disease phenotypes or treatment endpoints-such as fistulising disease or to achieve mucosal healing. In treatment failure, TDM may identify mechanisms to guide subsequent decision-making. In stable clinical response, TDM-guided dosing may avoid future relapse. Data indicate drug-tolerant anti-drug antibody assays do not offer an advantage over drug-sensitive assays. Further data are required prior to recommending TDM for non-anti-TNF biological agents. CONCLUSION: Consensus statements support the role of TDM in optimising anti-TNF agents to treat IBD, especially in situations of treatment failure.

Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis.

BACKGROUND: Faecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods. AIM: To determine whether FMT is effective and safe for the induction of remission in active UC. METHODS: Medline (Ovid), Embase and the Cochrane Library were searched from inception through February 2017. Original studies reporting remission rates following FMT for active UC were included. All study designs were included in the systematic review and a meta-analysis performed including only randomised controlled trials (RCTs). RESULTS: There were 14 cohort studies and four RCTs that used markedly different protocols. In the meta-analysis of RCTs, clinical remission was achieved in 39 of 140 (28%) patients in the donor FMT groups compared with 13 of 137 (9%) patients in the placebo groups; odds ratio 3.67 (95% CI: 1.82-7.39, P<.01). Clinical response was achieved in 69 of 140 (49%) donor FMT patients compared to 38 of 137 (28%) placebo patients; odds ratio 2.48 (95% CI: 1.18-5.21, P=.02). In cohort studies, 39 of 168 (24%; 95% CI: 11%-40%) achieved clinical remission. CONCLUSIONS: Despite variation in processes, FMT appears to be effective for induction of remission in UC, with no major short-term safety signals. Further studies are needed to better define dose frequency and preparation methods, and to explore its feasibility, efficacy and safety as a maintenance agent.

Infliximab vs. adalimumab in Crohn's disease: results from 327 patients in an Australian and New Zealand observational cohort study.

BACKGROUND: Maintenance anti-tumour necrosis factor-α (anti-TNFα) treatment for Crohn's disease is the standard of care for patients with an inadequate response to corticosteroids and immunomodulators. AIM: To compare the efficacy and safety of infliximab and adalimumab in clinical practice and assess the value of concomitant immunomodulator therapy. METHODS: We performed an observational cohort study in consecutive patients with Crohn's disease qualifying for anti-TNFα treatment in Australia and New Zealand between 2007 and 2011. Demographic and clinical data were prospectively recorded to identify independent factors associated with induction and maintenance of response to infliximab or adalimumab, or to either anti-TNFα therapy. RESULTS: Three hundred and twenty-seven patients (183 infliximab, 144 adalimumab) successfully applied for treatment. Eighty-nine percent responded in all groups and median maintenance of response was similar for the two agents. Concomitant immunomodulator with infliximab, but not adalimumab, demonstrated a significantly longer response overall (P = 0.002), and significantly fewer disease and treatment-related complications (P = 0.017). Corticosteroids at baseline, and/or in the preceding 12 months, were associated with a 9-13 times greater risk of disease flare during maintenance treatment as compared to no corticosteroids (P < 0.0001). Maintenance of response was similar in the anti-TNF naïve and anti-TNF experienced subgroups. CONCLUSIONS: In this large, real-life study, we demonstrate infliximab and adalimumab to have similar response characteristics. However, infliximab requires concomitant immunomodulator to achieve optimal maintenance of response comparable to adalimumab monotherapy. The results of this study will assist clinicians in further optimising patient care in their day-to-day clinical practice.

Inpatient healthcare utilisation in patients with alcoholic liver disease: what are the costs and outcomes?

BACKGROUND: Alcoholic liver disease (ALD) carries a significant cost burden and often leads to inpatient care. It is unclear whether inpatient care for ALD is any more costly than admission for other reasons. AIMS: To compare the costs and outcomes of inpatient care for ALD to two groups: a control group of matched cases admitted in the same time frame and people admitted for other chronic liver diseases (CLD). METHODS: All admissions for ALD and other CLD in a 3-month period were retrospectively identified. Five randomly identified gender- and age-matched contemporaneously admitted controls were allocated. Length of stay (LoS), mortality, inpatient costs, blood product utilisation and discharge destination were compared. RESULTS: Of the 71 admissions due to CLD, ALD was the most frequent cause (53/71, 75%). ALD admissions cost more (median $10 100 vs $5294; P = 0.0012) and had greater LoS (median LoS 7.2 days (interquartile range (IQR) 0.2-40.7)) than controls (2.6 days (IQR 1.1-6.8); P = 0.0001). A larger proportion of the ALD cohort required blood transfusion and had a higher mortality than controls (24.5 vs 6.4%, P = 0.002 and 13.2 vs 0.2%; P < 0.0001 respectively). Self-discharge was more common in the ALD group (13.2 vs 1.1%, P < 0.0001). CONCLUSIONS: ALD inpatient hospital admissions have greater median total cost, longer LoS, greater blood product utilisation, higher mortality and greater rate of discharge against medical advice than age- and gender-matched controls. These data emphasise the large inpatient care burden, high mortality and suboptimal engagement in those with ALD, which justifies the more active provision of services for ALD.

Review article: acute severe ulcerative colitis - evidence-based consensus statements.

BACKGROUND: Acute severe ulcerative colitis (ASUC) is a potentially life-threatening complication of ulcerative colitis. AIM: To develop consensus statements based on a systematic review of the literature of the management of ASUC to improve patient outcome. METHODS: Following a literature review, the Delphi method was used to develop the consensus statements. A steering committee, based in Australia, generated the statements of interest. Three rounds of anonymous voting were carried out to achieve the final results. Acceptance of statements was pre-determined by ≥80% votes in 'complete agreement' or 'agreement with minor reservation'. RESULTS: Key recommendations include that patients with ASUC should be: hospitalised, undergo unprepared flexible sigmoidoscopy to assess severity and to exclude cytomegalovirus colitis, and be provided with venous thromboembolism prophylaxis and intravenous hydrocortisone 100 mg three or four times daily with close monitoring by a multidisciplinary team. Rescue therapy such as infliximab or ciclosporin should be started if insufficient response by day 3, and colectomy considered if no response to 7 days of rescue therapy or earlier if deterioration. With such an approach, it is expected that colectomy rate during admission will be below 30% and mortality less than 1% in specialist centres. CONCLUSION: These evidenced-based consensus statements on acute severe ulcerative colitis, developed by a multidisciplinary group, provide up-to-date best practice recommendations that improve and harmonise management as well as provide auditable quality assessments.

Faecal microbiota transplant for recurrent Clostridium difficile infection using long-term frozen stool is effective: clinical efficacy and bacterial viability data.

BACKGROUND: Faecal microbial transplant (FMT) for recurrent Clostridium difficile infection (rCDI) is greatly facilitated by frozen stool banks. However, the effect of frozen storage of stool for greater than 2 months on the viability of stool bacteria is unknown and the efficacy of FMT is not clear. AIM: To evaluate the viability of bacteria in stool frozen for up to 6 months, and the clinical efficacy of FMT with stool frozen for 2-10 months, for the treatment of rCDI. METHODS: Viability of six representative groups of faecal bacteria after 2 and 6 months of storage at -80 °C, in normal saline (NS) or 10% glycerol were assessed by culture on plate media. The clinical outcomes of 16 consecutive patients with rCDI treated with aliquots of stool frozen in 10% glycerol and stored for 2-10 months were also examined. RESULTS: Viability at both 2 and 6 months was similar to baseline, in specimens stored in 10% glycerol and at 2 months in stool stored in NS, but was reduced by >1 log at 6 months for Aerobes (P < 0.01), total Coliforms (P < 0.01) and Lactobacilli (P < 0.01) in NS. Using stool frozen for 2-10 months in 10% glycerol, the cure rate for rCDI was 88% with one FMT and 100% after repeat FMT in those who relapsed. CONCLUSION: Stool for faecal microbial transplant to treat rCDI can be safely stored frozen in 10% glycerol for at least 6 months without loss of clinical efficacy or viability in the six bacterial groups tested.

Efficacy of thiopurines and adalimumab in preventing Crohn's disease recurrence in high-risk patients - a POCER study analysis.

BACKGROUND: Crohn's disease recurs in the majority of patients after intestinal resection. AIM: To compare the relative efficacy of thiopurines and anti-TNF therapy in patients at high risk of disease recurrence. METHODS: As part of a larger study comparing post-operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine-intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment. RESULTS: A total of 101 patients [50% male; median (IQR) age 36 (25-46) years] were included. There were no differences in disease history between thiopurine- and adalimumab-treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2-i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab-treated patients [intention-to-treat (ITT); P = 0.028] or 24 of 62 (39%) vs. 3 of 24 (13%) respectively [per-protocol analysis (PPA); P = 0.020]. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab). CONCLUSIONS: In Crohn's disease patients at high risk of post-operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.

Ulcerative colitis outpatient management: development and evaluation of tools to support primary care practitioners.

BACKGROUND: Current models of care for ulcerative colitis (UC) across healthcare systems are inconsistent with a paucity of existing guidelines or supportive tools for outpatient management. AIMS: This study aimed to produce and evaluate evidence-based outpatient management tools for UC to guide primary care practitioners and patients in clinical decision-making. METHODS: Three tools were developed after identifying current gaps in the provision of healthcare services for patients with UC at a Clinical Insights Meeting in 2013. Draft designs were further refined through consultation and consolidation of feedback by the steering committee. Final drafts were developed following feasibility testing in three key stakeholder groups (gastroenterologists, general practitioners and patients) by questionnaire. The tools were officially launched into mainstream use in Australia in 2014. RESULTS: Three quarters of all respondents liked the layout and content of each tool. Minimal safety concerns were aired and those, along with pieces of information that were felt to be omitted, that were reviewed by the steering committee and incorporated into the final documents. The majority (over 80%) of respondents felt that the tools would be useful and would improve outpatient management of UC. CONCLUSION: Evidence-based outpatient clinical management tools for UC can be developed. The concept and end-product have been well received by all stakeholder groups. These tools should support non-specialist clinicians to optimise UC management and empower patients by facilitating them to safely self-manage and identify when medical support is needed.