Lemann Index for assessing bowel damage in Crohn's disease: a real world study.

BACKGROUND & AIMS: The Lemann Index (LI), an endpoint to measure cumulative structural bowel damage in Crohn's disease (CD), has been recently updated and validated. We applied this to investigate predictors of bowel damage in a real-world cohort. METHODS: We performed a retrospective study (2008-2022) involving two tertiary referral IBD centers in the US. MR or CT enterographies were reviewed by study radiologists and endoscopy reports by study gastroenterologists, to calculate LI. Baseline and follow-up LI were calculated. We defined high bowel damage as LI ≥2. Factors associated with high LI were identified in patients with ≥2 LI scores using multivariate logistic regression and then assessed for a change in LI (increase vs. no change/decrease) using a multivariate linear mixed-effects model. RESULTS: 447 patients with CD had a median first LI of 7 [IQR, 1.25-14.55]. Median LI scores were significantly different when categorized by disease duration; 2.0 [IQR, 0.6-5.9] for <2 years, 2.6 [IQR, 0.6-9.6] for ≥2 and <10 years, and 12.5 [IQR, 6.4-21.5] for ≥10 years with a p <0.01. Disease duration, presence of perianal disease, elevated C-reactive protein, and Harvey-Bradshaw index, were associated with a high LI at inclusion and increase in LI during follow-up (all p <0.01). CONCLUSIONS: The updated LI quantified cross-sectional and longitudinal cumulative bowel damage in a real-world cohort of patients with CD with predictors identified for a longitudinal increase in LI. Further studies for prospective validation of LI and identification of multi-omic predictors of bowel damage are needed.

Pleasurable and problematic receptive anal intercourse and diseases of the colon, rectum and anus.

The ability to experience pleasurable sexual activity is important for human health. Receptive anal intercourse (RAI) is a common, though frequently stigmatized, pleasurable sexual activity. Little is known about how diseases of the colon, rectum, and anus and their treatments affect RAI. Engaging in RAI with gastrointestinal disease can be difficult due to the unpredictability of symptoms and treatment-related toxic effects. Patients might experience sphincter hypertonicity, gastrointestinal symptom-specific anxiety, altered pelvic blood flow from structural disorders, decreased sensation from cancer-directed therapies or body image issues from stoma creation. These can result in problematic RAI - encompassing anodyspareunia (painful RAI), arousal dysfunction, orgasm dysfunction and decreased sexual desire. Therapeutic strategies for problematic RAI in patients living with gastrointestinal diseases and/or treatment-related dysfunction include pelvic floor muscle strengthening and stretching, psychological interventions, and restorative devices. Providing health-care professionals with a framework to discuss pleasurable RAI and diagnose problematic RAI can help improve patient outcomes. Normalizing RAI, affirming pleasure from RAI and acknowledging that the gastrointestinal system is involved in sexual pleasure, sexual function and sexual health will help transform the scientific paradigm of sexual health to one that is more just and equitable.

Tofacitinib as a Rescue Therapy for Ulcerative Colitis in Pregnancy.

Tofacitinib, a potentially teratogenic nonselective Janus Kinase inhibitor was used as salvage therapy for ulcerative colitis during pregnancy with corticosteroids, maintenance ustekinumab, and rectal 5-ASA therapy. Corticosteroid-free remission ensued, resulting in term delivery without congenital malformations and avoidance of colectomy.

Real-world experience of nintedanib for progressive fibrosing interstitial lung disease in the UK.

Background: Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting. Methods: 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey. Results: 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD. Conclusion: We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting.

In moderate-to-severe Crohn disease, upadacitinib increased clinical remission at 12 and 52 wk.

SOURCE CITATION: Loftus EV Jr, Panés J, Lacerda AP, et al. Upadacitinib induction and maintenance therapy for Crohn's disease. N Engl J Med. 2023;388:1966-1980. 37224198.

The future of telemedicine and wearable technology in IBD.

PURPOSE OF REVIEW: Telemedicine has quickly become an essential part of modern healthcare, particularly in the management of chronic conditions like inflammatory bowel disease. The purpose of this review is to describe the current use of telehealth, mobile applications and wearable devices in inflammatory bowel disease and potential future applications. RECENT FINDINGS: Telemedicine was increasingly used during the Coronavirus Disease 2019 pandemic. Virtual consultations allowed clinical care to continue despite pandemic-related restrictions without compromising the quality of care for patients with inflammatory bowel disease (IBD). It also benefits patients who would not have access to care due to financial or geographical barriers. Mobile applications allow patients with IBD to record disease activity among other metrics, allowing for earlier healthcare provider intervention. Wearable devices are increasingly being explored to monitor physiological indicators of disease activity and flare. SUMMARY: Telehealth and remote patient monitoring has been successfully integrated into the care of IBD patients. The advantages of these modalities include better access to specialist care and remote noninvasive disease monitoring. Careful consideration must be given to patient privacy, data protection and equitable access. These modalities have enormous potential to improve patient care through accurate consistent data collection and even the prediction of disease activity.

An overview of ozanimod as a therapeutic option for adults with moderate-to-severe active ulcerative colitis.

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory condition of the gastrointestinal tract involving a dysregulated immune response. Sphingosine-1-phosphate (S1P) is involved in immune cell regulation. S1P-receptor modulators, such as ozanimod, inhibit lymphocyte migration and have therapeutic potential in UC. AREAS COVERED: Ozanimod is the first S1P-receptor modulator approved for the treatment of UC. It acts as a functional antagonist, causing internalization of S1P receptors on T-cells. Lymphocyte egress from lymph nodes is inhibited, and migration to sites of active inflammation is curtailed. There are several S1P-receptor subtypes, present in various organs, which inform understanding of ozanimod's side-effect profile including bradycardia and macular edema. In this review, the authors discuss the mechanism of action, pharmacokinetics, clinical efficacy, and safety profile of ozanimod in the treatment of patients with moderate-to-severe UC. EXPERT OPINION: The S1P-receptor modulator ozanimod is an oral small molecule with a rapid onset of action and a novel therapeutic mechanism in the treatment of UC. It is an effective treatment both in bio-naïve and bio-exposed patients. Although the safety profile of ozanimod looks favorable, more long-term data are needed. Further studies are required to compare ozanimod to currently available therapies to best define its positioning in UC treatment algorithms.

Visceral adiposity and inflammatory bowel disease.

BACKGROUND: Rates of obesity are increasing worldwide, as is the incidence of inflammatory bowel disease (IBD). Obesity is now considered an inflammatory state. Visceral adiposity in particular may be associated with a more severe inflammatory phenotype in IBD. AIM: The aim of this review article is to summarise the current literature on the association between visceral adiposity and outcomes in inflammatory bowel disease METHODS: To collect relevant articles, PubMed/MEDLINE and Embase searches were performed using Boolean search phrases. Grey literature and manual searches were also performed. Abstracts were selected by two independent reviewers based on pre-determined criteria. Full text articles were reviewed, and data extracted and assessed. RESULTS: One hundred twenty-seven abstracts were obtained through the initial search, with 85 abstracts reviewed and 22 full text articles included. Characteristics are included in Table 1. Most of these were retrospective studies and of moderate or weak quality. Studies suggested visceral fat content is higher in Crohn's disease than in healthy controls. Visceral adiposity was associated with an increased risk of complex Crohn's disease phenotype (OR 26.1 95% CI 2-75.4; p = 0.02). Post-operative recurrence was higher in patients with higher visceral fat indices (RR 2.1; CI 1.5-3; p = 0.012). There were conflicting data regarding the effect of visceral adiposity on post-operative complications and the efficacy of medical therapy. Table 1 Study characteristics Author Year Country Study type Study numbers Control group Disease type Methodology e.g. CT Body composition measurements Results Argeny [24] 2018 Austria Retrospective cohort N = 95 N/A Crohn's disease CT; L3 level Visceral fat area (cm2) Visceral fat index (VFA/m2) No association between VFA or VFI and short-term post-operative outcomes Bryant [30] 2018 Australia Prospective cohort N = 110 N/A Crohn's disease and UC DXA Visceral adipose tissue (VAT) (cm3) Visceral adipose tissue (grams) VAT/height index (cm3/m2) VAT:subcutaneous adipose tissue ratio Fat mass index (kg/m2) VAT and VHI increased significantly over 24 months Bryant [13] 2018 Australia Prospective cohort N = 72 N/A Crohn's disease; female DXA Visceral adipose tissue (VAT) (cm3) Visceral adipose tissue (grams) VAT/height index (cm3/m2) VAT:subcutaneous adipose tissue ratio VAT:SAT positively associated with stricturing disease Adiposity not associated with fistulising disease phenotype VAT:SAT significantly associated with faecal calprotectin in L3 phenotype VAT:SAT significantly negatively associated with VHI and QoL over 24 months Buning [25] 2015 Germany Case control N = 50 N = 19 healthy controls Crohn's disease MRI US VAT Thickness of abdominal fat Distance to posterior wall of aorta Area of inferior part of perirenal fat VAT accumulation was higher in CD patients vs healthy controls VAT and VAT/fat mass ratio higher in patients in short-term remission vs long-term remission VAT/FM higher in stricturing/fistulising disease vs inflammatory subtype No association between VAT/FM and CDAI, HBI or anti-TNF treatment Connolly [26] 2014 US Retrospective cohort N = 143 N/A Crohn's disease CT (L1-L5 level) Visceral/intra-abdominal adiposity (VA) Subcutaneous adiposity (SA) VA not associated with post-operative morbidity Decreased SA and increased visceral/subcutaneous ratio were predictive of post-op complications. (p = 0.02; p < 0.001) Cravo [27] 2017 Portugal Retrospective cohort N = 71 N/A Crohn's disease CT (L3 level) Smooth muscle area (cm2) Visceral fat area (cm2) Subcutaneous fat area (cm2) Visceral fat index Muscle radiation attenuation L2 phenotype associated with lower muscle attenuation and higher visceral fat index (non-significant) B2/B3/surgery - significantly lower muscle attenuation. VFI associated with increased risk of complicated phenotype. (OR 26.1; 95% CI 1-75; p = 0.02) Ding [17] 2016 US Retrospective cohort N = 164 N/A Crohn's disease CT (L3 level) Visceral fat area (cm2) Subcutaneous fat area Total fat area Visceral obesity associated with longer duration of surgery, increased intra-operative blood loss and longer length of bowel resected Higher complication rates in patients with visceral obesity (p < 0.001) VFA independent risk factor of adverse post-op outcomes Ding [14] 2017 Retrospective cohort N = 106 N/A Crohn's disease CT (L3 level) Visceral fat area Subcutaneous fat area Skeletal muscle area Skeletal muscle index Visceral obesity and myopenic obesity not significantly associated with risk of primary non-response Body composition factors not associated with secondary loss of response Erhayiem [18] 2011 UK Retrospective cohort N = 50 N/A Crohn's disease CT (L4 level) Mesenteric fat index (visceral:subcutaneous area ratio)N = 50 Mesenteric fat index was significantly higher in complicated Crohn's disease. ROC analysis for MFI in identifying complicated Crohn's disease: AUC = 0.95 (95% CI 0.89-1.0) Feng [28] 2018 China Retrospective cohort N = 80 Non-IBD GI patients Crohn's disease CT-energy spectral Visceral fat area (cm2) Subcutaneous fat area (cm2) Mesenteric fat index No significant difference in VFA between Crohn's disease cohort and control group. (p = 0.669). ROC analysis: detection of disease based on VFA and MFI: AUC 0.776 Sensitivity 77.5% Specificity 67.5% Hafraoui [16] 1998 France/Belgium Prospective N = 43 Healthy volunteers n = 13 Intestinal resection n = 9 Crohn's disease MRI (umbilicus) Total abdominal fat (cm2) Intra-abdominal fat (cm2) Subcutaneous fat (cm2) Ratio of intra-abdominal:total fat area was significantly higher in patients with Crohn's vs controls. (p = 0.012) No correlation between abdominal fat tissue and disease activity, duration or steroid therapy Holt [29] 2017 Australia/New Zealand RCT N = 44 N = 11 placebo group Crohn's disease CT/MRI (L3, L4-5 levels) Visceral adipose tissue area Subcutaneous adipose tissue area Skeletal muscle area Visceral adipose tissue/height index VHI > 1.5 times gender mean was specific for endoscopic recurrence (100%) with sensitivity of 29%. PPV = 1 (0.59-1.00) There was no significant difference in disease activity at 18 months post-resection based on VHI > 1.5 gender mean Li [31] 2015 China Retrospective cohort N = 72 N/A Crohn's disease CT (umbilicus) Visceral fat area (cm2) Subcutaneous fat area (cm2) Mesenteric fat index Post-op recurrence was more frequent with high VFA values. (p = 0.019) VFA and MFI were independent risk factors for post-operative recurrence. (p = 0.013 and p = 0.028, respectively) High VFA and high MFI were significantly higher in patients with endoscopic activity (p = 0.023) Liu [32] 2016 Retrospective case-control N = 59 N = 30 (< 15% increase VFA) IBD with IPAA CT (L3) Visceral fat area Subcutaneous fat area No difference in pouchitis, pouch sinus formation and composite adverse pouch outcomes between the 2 groups with and without VFA increase > 15%. Excessive VAT gain was an independent risk factor for the composite adverse pouch outcomes. (OR 12.6 (95% CI 1.19-133.5) Magro [33] 2018 Brazil Cross-sectional study N = 78 N = 28 Health control Crohn's disease DEXA Fat and lean masses Visceral fat (kg) Visceral fat/BMI Visceral fat per %body fat VF was higher in Crohn's disease group (p = 0.004) compared to controls Parmentier-Decrucq [34] 2009 Prospective study N = 132 N/A Crohn's disease MRI Subcutaneous fat Visceral fat Total abdominal fat increased 18% in Crohn's disease patients treated with infliximab induction therapy Shen [35] 2018 China Retrospective N = 97 N/A Crohn's disease CT (umbilicus) Subcutaneous fat area Visceral fat area Mesenteric fat index VFA and MFI were significantly lower in patients with mucosal healing (post-infliximab). (p < 0.0001) SFA was not significantly different VFA correlated with CDAI (p < 0.001) and was an independent predictive factor for mucosal healing Stidham [15] 2015 Retrospective N = 269 N/A Crohn's disease CT(T10-L5) Subcutaneous fat volume Visceral fat volume No significant difference in visceral fat volume between patients with surgical complications Thiberge [36] 2018 France Retrospective N = 149 N/A Crohn's disease CT (L3 level) Skeletal muscle index Visceral adiposity index Subcutaneous adiposity index SAI and VAI were significantly lower in patients who underwent surgery or who died in 6 months post-CT(p = 0.009 and p < 0.001) VanDerSloot [37] 2017 Cohort study N/A Crohn's disease CT (T11-S5) Visceral adipose tissue volume Non-significant trend toward increased risk of surgery and penetrating disease with increasing VAT Wei [38] 2018 China Retrospective N = 86 N/A IBD post-resection CT (L3 level) Visceral adipose volume Subcutaneous adipose volume Increased visceral:subcutaneous fat ratio was associated with increased procalcitonin levels on post-op days 1, 3 and 5 Yadav [39] 2017 India Prospective N = 97 N/A IBD CT (L4 level) Visceral fat area Subcutaneous fat area No statistically significant correlation between visceral fat and disease behaviour in Crohn's disease N/A not applicable, VFA visceral fat area, VFI visceral fat index, VAT visceral adipose tissue, VHI visceral adipose tissue to height index, SAT subcutaneous adipose tissue, DXA dual-energy X-ray absorptiometry, CT computer tomography, MRI magnetic resonance imaging, US ultrasound, CDAI Crohn's disease activity index, HBI Harvey-Bradshaw Index, anti-TNF anti-tumour necrosis factor, SA subcutaneous adiposity, ROC receiver operating curve, AUC area under the curve, MFI mesenteric fat index, SAI subcutaneous adiposity index, PPV positive predictive value CONCLUSION: Visceral adiposity appears to be increased in Crohn's disease with some evidence that it is also associated with more complex disease phenotypes. There is also a signal that post-operative recurrence rates are affected by increasing mesenteric adiposity. There is a relative lack of data in UC patients and furtherhigh-quality studies are necessary to elucidate the relationship between visceral adiposity and IBD and the implications for patient outcomes.

Mucosal inflammation downregulates PHD1 expression promoting a barrier-protective HIF-1α response in ulcerative colitis patients.

The HIF hydroxylase enzymes (PHD1-3 and FIH) are cellular oxygen-sensors which confer hypoxic-sensitivity upon the hypoxia-inducible factors HIF-1α and HIF-2α. Microenvironmental hypoxia has a strong influence on the epithelial and immune cell function through HIF-dependent gene expression and consequently impacts upon the course of disease progression in ulcerative colitis (UC), with HIF-1α being protective while HIF-2α promotes disease. However, little is known about how inflammation regulates hypoxia-responsive pathways in UC patients. Here we demonstrate that hypoxia is a prominent microenvironmental feature of the mucosa in UC patients with active inflammatory disease. Furthermore, we found that inflammation drives transcriptional programming of the HIF pathway including downregulation of PHD1 thereby increasing the tissue responsiveness to hypoxia and skewing this response toward protective HIF-1 over detrimental HIF-2 activation. We identified CEBPα as a transcriptional regulator of PHD1 mRNA expression which is downregulated in both inflamed tissue derived from patients and in cultured intestinal epithelial cells treated with inflammatory cytokines. In summary, we propose that PHD1 downregulation skews the hypoxic response toward enhanced protective HIF-1α stabilization in the inflamed mucosa of UC patients.

Hypoxia-inducible factor hydroxylase inhibition enhances the protective effects of cyclosporine in colitis.

Inflammatory bowel disease (IBD) is characterized by epithelial barrier dysfunction with resultant inflammation as the mucosal immune system becomes exposed to luminal antigens. The hydroxylase inhibitor dimethyloxalylglycine (DMOG) reduces symptoms in experimental colitis through the upregulation of genes promoting barrier function and inhibition of epithelial cell apoptosis. The immunosuppressive drug cyclosporine reduces inflammation associated with IBD via suppression of immune cell activation. Given the distinct barrier protective effect of DMOG and the anti-inflammatory properties of cyclosporine, we hypothesized that combining these drugs may provide an enhanced protective effect by targeting both barrier dysfunction and inflammation simultaneously. We used the dextran sulfate sodium model of colitis in C57BL/6 mice to determine the combinatorial efficacy of cyclosporine and DMOG. While cyclosporine and DMOG ameliorated disease progression, in combination they had an additive protective effect that surpassed the level of protection afforded by either drug alone. The ability of DMOG to augment the anti-inflammatory effects of cyclosporine was largely due to preservation of barrier function and at least in part due to zonula occludens-1 regulation. We propose that combining the barrier protective effects of a hydroxylase inhibitor with the anti-inflammatory effects of cyclosporine provides added therapeutic benefit in colitis.NEW & NOTEWORTHY Inflammatory bowel disease is the result of decreased intestinal epithelial barrier function leading to exposure of the mucosal immune system to luminal antigens causing inflammation, which in turn further decreases epithelial barrier function. We demonstrate for the first time that strengthening the epithelial barrier with a hydroxylase inhibitor in combination with the administration of the immunosuppressive cyclosporine provides additive therapeutic advantage in a murine model of colitis.

DUBLIN [Degree of Ulcerative colitis Burden of Luminal Inflammation] Score, a Simple Method to Quantify Inflammatory Burden in Ulcerative Colitis.

BACKGROUND AND AIMS: Endoscopic scores of local severity do not reflect disease extent, or disease burden. The DUBLIN score is a simple bedside clinical score that estimates inflammatory burden using both disease severity and extent. As the need to personalize therapy for ulcerative colitis [UC] patients increases, a score accurately assessing disease burden will be of great relevance. The aim of this study was to assess the clinical utility of the DUBLIN score by comparing its performance with objective biomarkers. METHODS: The DUBLIN score was calculated as a product of the Mayo Endoscopic Score [0-3] and disease extent [E1-E3]. Correlation with objective biomarkers was performed in a retrospective 'discovery cohort'. A 'validation cohort was recruited from a single centre, where clinical outcomes, colectomy rate, and biochemical data were collected prospectively. RESULTS: The discovery cohort included 70 patients with UC. The DUBLIN score correlated significantly with faecal calprotectin [FCP] levels [r = 0.394; p < 0.01]. Receiver operating characteristic [ROC] analysis using FCP>50µg/g showed a higher area under the ROC curve [AUC] with the DUBLIN score [AUC = 0.76] than with the Mayo Score [AUC = 0.73]. The validation cohort included 41 patients. Patients with a high inflammatory burden [DUBLIN >3] had higher C-reactive protein and FCP, and lower albumin than patients with a low inflammatory burden. A high DUBLIN score was associated with an increased risk of treatment failure. [hazard ratio 2.98 95%, confidence interval 1.002-8.87; p = 0.049]. CONCLUSION: The DUBLIN score is a simple measure of inflammatory burden, which correlates with objective inflammatory markers and is associated with clinical outcomes, such as treatment failure. The DUBLIN score has the potential to assist in personalizing therapy for patients with UC.

Acceptance and Commitment Therapy Reduces Psychological Stress in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Patients with Crohn's disease or ulcerative colitis have relatively high levels of stress and psychological dysfunction. Acceptance and commitment therapy (ACT) is a psychological intervention that comprises acceptance and mindfulness procedures, along with commitment and behavior change strategies, to increase psychological flexibility and reduce stress. We performed a randomized controlled trial to investigate the effect of ACT on stress in patients with inflammatory bowel diseases (IBD). METHODS: A total of 122 patients with quiescent or stable, mildly active IBD were randomly assigned to an 8-week ACT program or treatment as usual (control group). Clinical, demographic, disease activity, and psychological data and blood and feces were collected at baseline and at 8 weeks and 3 months after the intervention (week 20). Scalp hair was collected at baseline and week 20 for measurement of steroid concentrations. The primary endpoint was change in stress symptoms, assessed with the Depression Anxiety Stress Scale. Secondary endpoints included changes in perceived stress, anxiety, depression, quality-of-life domains, disease activity, and cortisol concentration in hair. RESULTS: Overall, 79 participants were included in the complete case intention-to-treat analysis. There were 39% and 45% reductions in stress in the treatment group from baseline to 8 and 20 weeks, respectively, compared with 8% and 11% in the control group (group × time interaction, P = .001). ACT was associated with reduced perceived stress (P = .036) and depression (P = .010), but not anxiety (P = .388), compared with control individuals. In the intention-to-treat analysis, changes in all 4 quality-of-life domains over time were similar in the ACT and control groups. In the per-protocol analysis, the overall well-being quality-of-life domain improved in the ACT group compared with the control group (P = .009). Subjective and objective disease activity measurements were similar between groups over the study period (all P values >.05). Hair cortisol concentrations correlated with stress (rs = 0.205, P = .050) and anxiety (rs = 0.208, P = .046) at baseline but did not change significantly in the ACT group over the study period compared with the control group (P = .831). CONCLUSION: In a randomized controlled trial of patients with IBD, an 8-week ACT therapy course improved stress and other indices of psychological health.ClinicalTrials.gov Identifier: NCT02350920.

Severe Symptomatic Primary CMV Infection in Inflammatory Bowel Disease Patients with Low Population Seroprevalence.

BACKGROUND: Cytomegalovirus disease in patients with inflammatory bowel disease is frequently the result of viral reactivation. Conversely, primary CMV infection is believed to be uncommon in immunocompetent adults due to high population seroprevalence. OBJECTIVES: The aim of this study was to examine the frequency and severity of primary cytomegalovirus infection in an adult cohort of IBD patients. STUDY DESIGN: A retrospective review of a prospectively maintained database of 3200 IBD patients attending a single academic centre was performed. Patients with primary CMV infection 2010-13 were identified; clinical, serologic, and virologic parameters were studied in detail. The seroprevalence of CMV in the patient population was also evaluated. RESULTS: Eight patients with IBD (UC = 3, IBD-U = 1, CD = 4) presented with primary CMV infection. Patients presented with both gastrointestinal and extraintestinal symptoms. Mean age was 33 years, and median duration of disease was 72 months. All eight patients were receiving a thiopurine immunomodulator. Median duration of IM use was 144 weeks (range 7-720 weeks). All 8 patients required hospitalisation, with 1 ICU admission; the median length of hospital stay was 11 days (range 6-27). Infection resolved in all cases with withdrawal of immunomodulator and/or antiviral therapy. Seroprevalence of IgG to CMV, indicating prior exposure, in a subgroup of IBD patients (n = 80) was 30.5% and increased with age. CONCLUSION: Primary cytomegalovirus infection can cause a severe illness in IBD patients, particularly those receiving immunosuppression. In areas where adult CMV seroprevalence is low, evidence of CMV should be sought in IBD patients presenting with any febrile systemic illness.

Ustekinumab Drug Levels in Maternal and Cord Blood in a Woman With Crohn's Disease Treated Until 33 Weeks of Gestation.

A 35-year old woman with ileocolonic, perianal, and vulval Crohn's disease was treated with subcutaneous ustekinuamb [USK] throughout pregnancy. Dose intervals were shortened from 6-weekly to 4-weekly to maintain clinical remission. The last dose of USK was administered at 33 weeks of gestation, and a healthy baby boy was delivered by caesarean section at 37 weeks. Maternal trough USK levels remained stable during pregnancy. Cord blood USK levels were nearly 2-fold higher than contemporaneous maternal serum levels. To our knowledge, this is the first report of maternal and cord USK levels in a patient with Crohn's disease.

Multifocal Motor Neuropathy Associated with Infliximab.

BACKGROUND: The anti-tumour necrosis factor [TNF] monoclonal antibody, infliximab, is commonly prescribed in both ulcerative colitis and Crohn's disease. Neurological side effects such as optic neuritis are well recognised, although not as frequently seen as hypersensitivity and serious infections. CASE: We present a case of peripheral neuropathy in a young man on infliximab therapy for ulcerative colitis. This presented as an asymmetrical and slowly progressive weakness in his right upper limb, severely impacting on function. Investigations confirmed a diagnosis of multifocal motor neuropathy [MMN]. This has been previously described in patients receiving infliximab for rheumatological conditions. The exact mechanism is unclear, but the neuropathy responds well to intravenous immunoglobulin. In our case, infliximab was discontinued. The patient was treated with immunoglobin for 5 days and recovered rapidly. Mercaptopurine was instituted as maintanence therapy, with good effect. CONCLUSION: Gastroenterologists prescribing infliximab should be cognisant of both peripheral and central neurological complications, ensuring prompt withdrawal of the offending agent and appropriate alternative treatment.

Midwives' reflections on their educational programme: a traditional or problem-based learning approach?

OBJECTIVE: to explore the longer-term effect of a problem-based learning (PBL) programme on midwives in practice. DESIGN: qualitative study. Graduates involved in an earlier study of the implementation of a PBL programme were interviewed between 5 and 6 years after graduating to explore the possible longer-term effect of a PBL programme on their practice as midwives. SETTING: Thames Valley University with graduates who had completed an 18-month programme on one of two campuses on a variety of clinical sites. PARTICIPANTS: interviews were held with four graduates who had completed their programme before the implementation of PBL and five who had completed a PBL programme. Key themes were identified and compared cross-sectionally. FINDINGS: midwives who had graduated from a PBL programme found that the approach was valuable in enabling them to access information and to develop a critical questioning approach. Some felt anxious at the beginning of their programme and said that they would have benefited from more direction and feedback from the facilitator early on in the programme. The focus on individual presentations sometimes inhibited the students learning from others in the group. The success of the PBL approach was felt to be dependent on the way in which the group worked together. The quality of the clinical placement, and the support of mentors and link teachers in the clinical setting, was a key factor in learning for students from both programmes. CONCLUSIONS: PBL has been incorporated into some programmes because it is thought to benefit practice disciplines, especially in a world of uncertain and changing evidence. However, no clear picture has emerged about the benefits of a PBL programme for midwifery education. IMPLICATIONS FOR PRACTICE: our findings have implications for curriculum development to ensure the potential benefits of PBL are realised in practice. This may include providing further guidance and feedback to students, particularly at the start of their programme. Further research using innovative methodologies is needed to critically assess the longer-term effect of this approach to education.

Problem based learning in midwifery--the students' perspective.

Problem based learning (PBL) has been adopted in many settings for the education of health professionals. It has generally been evaluated well by students although much of the literature comes from medical education. The aim of this study was to ascertain the views of student midwives at the beginning and at the end of their programme and three months after graduation about the use of a PBL based programme in midwifery. Eight focus groups were conducted with students whilst undertaking a PBL programme from both a shortened and three year programme across two sites. A questionnaire was sent 3 months after graduation to midwives who had completed the programme. Key themes which emerged from this study were that although students gained skills in information retrieval and critique some did not always feel well prepared for practice. The focus on individual presentations in the tutorial tended to be interpreted as performance rather than discussion in a spirit of enquiry. Students reported being particularly anxious at the beginning of their programme about their learning. They felt that their experience was dependent upon the participation and motivation of the group members.

Problem based learning in midwifery - the teachers perspective.

BACKGROUND: Problem- or evidence-based learning (PBL or EBL) has become more widely used in the education of health professionals. Although there has been research exploring its effectiveness and the student's perspective, there has been little research exploring the perceptions of the teacher. The objective of this study was to investigate the experiences of teachers facilitating a problem based learning curriculum in midwifery. The study took place at Thames Valley University, which has implemented this approach across the entire curriculum. METHODS: Semi-structured interviews were undertaken following random selection from two groups of teachers; those more experienced as teachers and those who had entered teaching more recently. FINDINGS AND DISCUSSION: Aspects of the teacher's role identified included questioning students to draw out their knowledge and understanding and to help students challenge each other, discuss and evaluate their learning. Strategies used varied depending on the stage of the programme. Difficulties encountered were mostly in relation to facilitating groups of differing backgrounds and ability and seeking to enable the students to work well together. Key challenges for teachers were in relation to developing facilitation skills, balancing input or guidance with facilitating independent learning. CONCLUSIONS: Problem based learning was perceived to be beneficial in helping students relate theory to practice and in encouraging an active and enquiring approach to evidence, but teachers raised important questions about its practice. Tensions were identified between the constructivist theories on which the model of PBL rests and the formal requirements of an externally regulated professional curriculum.