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Defining predictors of responsiveness to advanced therapies in Crohns disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine

Por: Wyatt · N. J. · Watson · H. · Anderson · C. A. · Kennedy · N. A. · Raine · T. · Ahmad · T. · Allerton · D. · Bardgett · M. · Clark · E. · Clewes · D. · Cotobal Martin · C. · Doona · M. · Doyle · J. A. · Frith · K. · Hancock · H. C. · Hart · A. L. · Hildreth · V. · Irving · P. M. · Iqbal · S
Introduction

Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient’s quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.

Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.

IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments.

Methods and analysis

This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures.

Ethics and dissemination

Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk.

Trial registration number

ISRCTN96296121.

Comparing the effectiveness of mother-focused interventions to that of mother-child focused interventions in improving maternal postpartum depression outcomes: A systematic review

by Divya Kumar, Waqas Hameed, Bilal Iqbal Avan

Background

Most empirically researched interventions for postpartum depression (PPD) tend to target mothers’ depression alone. Harmful effects of PPD on physical and mental health of both mother and child has led researchers to investigate the impact of interventions on PPD and child outcomes together. So far, the evidence is limited regarding how these interventions compare with those focusing only on mothers’ depression. This review compares the effectiveness of PPD-improving interventions focusing only on mothers with those focusing on mother and child together.

Methods

Nine electronic databases were searched. Thirty-seven studies evaluating mother-focused (n = 30) and mother-child focused interventions (n = 7) were included. Under each category, three theoretical approaches—psychological, psychosocial and mixed—were compared using standardized qualitative procedures. The review’s primary outcome was maternal PPD.

Results

A higher proportion of mother-focussed interventions [20/30 (66.7%)] brought significant reduction in PPD outcomes as compared to a lower proportion of mother-child focused interventions [4/7 (57.14%)]. Mother-focused mixed approaches [3/3 (100%)] performed better in improving PPD than psychological [16/24 (67%)] or psychosocial approaches [1/3 (33.3%)] alone. Amongst mother-child focused interventions, psychosocial approaches performed well with two-thirds demonstrating positive effects on PPD.

Conclusion

The evidence strongly favors mother-focused interventions for improving PPD with mixed interventions being more effective. Psychosocial approaches performed better with PPD once child-related elements were added, and also seemed best for child outcomes. Psychological approaches were most practiced and effective for PPD, irrespective of the intervention’s focus. Further trials are needed to unpack intervention components that improve PPD and increase uptake, especially in lower-and middle-income countries.

Dietary replacement of soybean meal with black soldier fly larvae meal in juvenile <i>Labeo rohita</i> and <i>Catla catla</i>: Effects on growth, nutritional quality, oxidative stress biomarkers and disease resistance

by Shafaq Fatima, Ayesha Afzal, Hamna Rashid, Saba Iqbal, Rosheen Zafar, Komal Khalid, Ayman Rauf, Maryam Majeed, Aqsa Malik, Chris G. Carter

This experiment aimed to investigate the effects of partial substitution of crude protein from soybean meal (SBM) with black soldier fly (Hermetia illucens) larvae meal (BSFLM) in juvenile rohu (Labeo rohita) and catla (Catla catla). Four isonitrogenous diets (23% crude protein) were formulated to replace 0% (T0), 40% (T40), 80% (T80) and 100% (T100) crude protein from SBM with BSFLM. Triplicate groups of each species (10 fish per replicate) were fed in an eight week growth experiment. After final sampling (n = 20 fish per dietary group), the remaining fish were exposed to bacterial (Staphylococcus aureus) challenge (0.80 CFU/ml) for 15 days. Rohu fed with BSFLM substituted diets showed significantly higher growth and feed conversion ratio as compared to those in T0. Catla fed with BSFLM substituted diets showed slightly higher growth indices. The growth response of rohu to BSFLM substitution was better than that noted in catla in all groups. The chemical composition, amino acids and fatty acids profile, haematological and biochemical parameters, levels of liver function enzymes measured in T0, T40, T80 and T100 were similar between four dietary groups in both species. However, the maximum value of cholesterol and triglycerides were noted in T100 both in catla and rohu. The values of lauric acid, α-linolenic acid, decosahexanoic acid, n3:n6 fatty acids ratio progressively increased with dietary increase of BSFLM in both species. At end of the growth experiment, the levels of catalase, superoxide dismutase and lysozyme increased linearly with the inclusion of BSFLM in both species while malondialdehyde showed similar values between different groups. However, catalase, and superoxide dismutase increased (T0
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