Patient-Reported Outcomes and Health-Related Quality of Life in People Living With Ileostomies: A Population-Based, Cross-Sectional Study.

BACKGROUND: The impact of a stoma on long-term health-related quality of life in people living with ileostomies is not clear. OBJECTIVE: This study aimed to describe important patient-reported outcomes and health-related quality of life in people with ileostomies. DESIGN: This is a population-based, cross-sectional study. Patients were invited to answer questionnaires estimating stoma-specific and generic health-related quality of life (EQ-5D-5L and the Major Depression Inventory). Danish norms were retrieved from reference literature. SETTINGS: This study was conducted at the major stoma clinic at Aarhus University Hospital, Denmark. PATIENTS: We invited all patients with ileostomies who were in contact with the clinic between 2012 and 2017. MAIN OUTCOME MEASURES: The primary outcomes measured were patient-reported outcomes specific to people with ileostomies. RESULTS: Of 621 identified patients (50% women), 412 (67%) responded to the survey. Among the responders, 178 (43%) reported that they still had an ileostomy at the time of the survey and were included in the analysis. Fatigue was frequent; 68% (95% CI 60%-75%) reported being tired and 26% (95% CI 20%-33%) answered that they were "always tired," whereas 43% (95% CI 36%-51%) lacked energy, 62% (95% CI 54%-69%) reported poor sleep, and 59% (95% CI 52%-66%) needed to rest during the day. Fifty-six percent (95% CI 48%-63%) needed to know the immediate location of the nearest toilet, and 58% (95% CI 51%-66%) felt sexually unattractive because of their ileostomy. Health-related quality of life measured with generic questions indicated 0.124 points lower health-related quality of life than the Danish norm ( p < 0.001), and 18% (95% CI 13%-25%) scored above the threshold for depression, which is 2.6 times higher than the background population (7%, 95% CI 6%-9%; p < 0.001). LIMITATIONS: This study was limited by potential selection bias, and all participants did not answer all items. CONCLUSIONS: Fatigue and low health-related quality of life is common in people living with ileostomies. Addressing fatigue and stoma-specific challenges in patients with an ileostomy is warranted. See Video Abstract at http://links.lww.com/DCR/B803 . DESENLACES INFORMADOS POR PACIENTES Y CALIDAD DE VIDA RELACIONADA CON LA SALUD EN PERSONAS QUE VIVEN CON ILEOSTOMAS UN ESTUDIO TRANSVERSAL POBLACIONAL: ANTECEDENTES:El impacto de un estoma en la calidad de vida relacionada con la salud a largo plazo en personas que viven con ileostomías no está claro.OBJETIVO:Describir desenlaces importantes informados por pacientes y la calidad de vida relacionada con la salud en personas con ileostomías.DISEÑO:Estudio transversal poblacional. Se invitó a los pacientes a responder cuestionarios que estiman la calidad de vida relacionada con la salud general y específica del estoma (EQ-5D-5L y el Inventario de depresión mayor). Las normas danesas se recopilaron de la literatura de referencia.AJUSTES:El estudio se llevó a cabo en la clínica principal de estomas del Hospital Universitario de Aarhus, Dinamarca.PACIENTES:Invitamos a todos los pacientes con ileostomías que estuvieron en contacto con la clínica entre 2012 y 2017.PRINCIPALES MEDIDAS DE RESULTADO:Resultados informados por el paciente específicos para personas con ileostomías.RESULTADOS:De 621 pacientes identificados (50% mujeres), 412 (66%) respondieron la encuesta. Entre los que respondieron, 178 (43%) informaron que todavía tenían una ileostomía en el momento de la encuesta y fueron incluidos en el análisis. La fatiga era frecuente; el 68% (intervalo de confianza del 95%: 60-75%) informó estar cansado y el 26% (20-33%) respondió "siempre cansado", mientras que el 43% (36-51%) carecía de energía, el 62% (54-69%)) refirieron dormir mal y el 59% (52-6%) necesitaba descansar durante el día. El cincuenta y seis por ciento (48-63%) necesitaba saber la ubicación inmediata del baño más cercano y el 58% (51-66%) se sentía sexualmente poco atractivo debido a su ileostomía. La calidad de vida relacionada con la salud medida con preguntas genéricas indicó una calidad de vida relacionada con la salud 0,124 puntos más baja que la norma danesa ( p < 0,001), y el 18% (13-25%) puntuó con depresión, que es 2.6 veces más alta que la población de base (7%, 6-9%, p < 0,001).LIMITACIONES:Posible sesgo de selección, y no todos los participantes respondieron a todos los ítems.CONCLUSIONES:La fatiga y la baja calidad de vida relacionada con la salud es común en las personas que viven con ileostomías. Se justifica abordar la fatiga y los desafíos específicos del estoma en pacientes con una ileostomía. Consulte Video Resumen en http://links.lww.com/DCR/B803 . (Traducción-Juan Carlos Reyes ).

Casein glycomacropeptide is well tolerated in healthy adults and changes neither high-sensitive C-reactive protein, gut microbiota nor faecal butyrate: a restricted randomised trial.

Casein glycomacropeptide (CGMP) is a bioactive milk-derived peptide with potential anti-inflammatory effects. Animal studies suggest that CGMP may work by altering gut microbiota composition and enhancing butyrate production. Its effects on intestinal homoeostasis, microbiota and metabolites in humans are unknown. The aim of the present study was to assess both the intestinal and systemic immunomodulatory effects of orally ingested CGMP. We hypothesised that daily oral CGMP intake would reduce high-sensitive C-reactive protein (hsCRP) in healthy adults. In a single-centre limited but randomised, double-blinded, reference-controlled study, we compared the effects of a 4-week intervention of either 25 g of oral powder-based chocolate-flavoured CGMP or a reference drink. We included twenty-four healthy adults who all completed the study. CGMP had no systemic or intestinal immunomodulatory effects compared with a reference drink, with regard to either hsCRP or faecal calprotectin level, faecal microbiota composition or faecal SCFA content. CGMP ingestion did not affect satiety or body weight, and it caused no severe adverse events. The palatability of CGMP was acceptable, and adherence was high. CGMP did not induce or change gastrointestinal symptoms. In conclusion, we found no immunomodulatory effects of CGMP in healthy adults. In a minor group of healthy adults, oral ingestion of 25 g of CGMP during 4 weeks was safe, well tolerated, had acceptable palatability and was without any effects on body weight.

A positive Helicobacter pylori test is associated with low spondylarthritis incidence in a Danish historical cohort study.

Ankylosing spondylitis (AS) and undifferentiated spondylarthritis (uSpA) are related inflammatory diseases affecting the spine and joints with infections among possible etiological factors. Helicobacter pylori (H. pylori) may affect the development of inflammatory diseases. Thus, we hypothesized that H. pylori infection affects AS and uSpA development. This cohort study was performed in Denmark with 56,000 patients from primary health care centers who were enrolled when a UBT was performed. They were followed for a median time of 8 years. From nationwide administrative registries, we extracted personal, diagnostic, and treatment information. Prevalence at time of UBT was studied on enrollment using logistic regression and incidence in the follow-up time of 8 years after UBT was studied using Cox regression, comparing H. pylori positive and H. pylori negative patients and adjusting for confounding variables. The prevalence of AS at the time of the UBT was higher among H. pylori positive individuals (OR = 2.00, CI 1.17-3.41), but likely to be linked to confounding as trends disappeared when stratifying for country of birth. The incidence of AS after UBT was lower for individuals who were previously H. pylori positive (OR = 0.23, CI 0.06-0.93). A similar phenomenon was observed for uSpA. As a novel finding, after UBT, the previously H. pylori infected individuals had lower risk of developing AS and uSpA compared to non-infected. This finding may be caused by etiological effects of previous H. pylori infection or unknown confounders. This suggests that H. pylori may somehow be positively involved in the pathogenesis of AS and uSpA.

Population-based normative data for the inflammatory bowel disease fatigue scale - IBD-F.

OBJECTIVE: Fatigue is a common concern among patients with inflammatory bowel disease (IBD). The Inflammatory Bowel Disease Fatigue (IBD-F) scale was developed in 2014 together with patients with IBD. The IBD-F comprises five questions about the frequency and severity of fatigue followed by 30 questions about the experience and impact of fatigue. All questions have generic character. Normative values are needed if the IBD-F scale is to be used extensively. This study aims to generate normative values for the IBD-F scale in a Danish background population. MATERIALS AND METHODS: An age- and gender-stratified random sample of 3460 Danes was drawn from the total population. The IBD-F and a few socio-demographic questions were administered electronically. RESULTS: Of the 3460 drawn individuals, 2952 citizens with electronic access were invited to participate, 1925 (65.2%) citizens accepted the invitation, and 1761 (59.7%) completed the IBD-F questionnaire. Overall, women had more fatigue than men (the frequency and severity, 7.2 vs. 6.6; p < .001) (the experience and impact, 17.0 vs. 13.5; p < .001). Fatigue was most marked for citizens <50 and ≥80 years old. Having no education, working part time, and morbidity were factors associated with more fatigue. Co-habitation was associated with less fatigue. The internal consistency in this population revealed Cronbach's alpha values >0.85. CONCLUSIONS: The IBD-F scale can be used in the background population and this study provides normative data for fatigue. Fatigue was higher for women and specific age groups. Several socio-demographic and morbidity variables were associated with fatigue.

Current, experimental, and future treatments in inflammatory bowel disease: a clinical review.

Inflammatory bowel diseases (IBDs) may result from dysregulated mucosal immune responses directed toward the resident intestinal microbiota. This review describes the hallmark immunobiology of Crohn's disease and ulcerative colitis as well as therapeutic targets and mechanisms of action for current, experimental, and future treatments in IBD. Conventional therapies include 5-aminosalicylic acid, glucocorticosteroids, thiopurines, and methotrexate. Since 1997, monoclonal antibodies have gained widespread use. These consist of antibodies directed against pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-12, and IL-23, or anti-homing antibodies directed against α4ß7 integrin. Emerging oral therapies include modulators of intracellular signal transduction such as Janus kinase inhibitors. Vitamin D may help to regulate innate and adaptive immune responses. Modulation of the intestinal microbiota, using live microorganisms (probiotics), substrates for the colonic microbiota (prebiotics), or fecal microbiota transplantation (FMT), is in development. Dietary supplements are in widespread use, but providing evidence for their benefit is challenging. Stem cell treatment and nervous stimulation are promising future treatments.

Drug-specific hypophosphatemia and hypersensitivity reactions following different intravenous iron infusions.

AIMS: Intravenous (IV) iron infusions have been associated with hypophosphataemia (HP) and hypersensitivity reactions (HSRs). No studies have compared the side effects of ferric carboxymaltose (FCM) with those of isomaltoside 1000 (ISM). This study aimed to describe the occurrence of HP and HSRs following the administration of either FCM or ISM. METHODS: Data on 231 outpatients treated with IV iron infusions, between November 2011 and April 2014, were collected. During that period, the department made a switch from FCM to ISM and then back to FCM. Of the 231 patients, 39 received both FCM and ISM during the period. The prevalences of HP and HSRs were compared between the two drugs. RESULTS: We found more HP events when FCM was given (64 vs. 9; P < 0.01). In contrast, more patients had mild HSRs when ISM was given (2.5% vs. 10.7%; P < 0.01). A comparison of the two drugs in the subpopulation who received both drug types (n = 39) revealed a difference in phosphate decrease (P < 0.01), with the most marked decrease occurring with FCM. Nine patients who had HSRs were exposed to both drugs. No potential HSR crossover between the two drugs was found. CONCLUSION: We found a higher risk of HP with FCM administration when compared to ISM administration. Conversely, we found a higher risk of mild HSRs with ISM administration when compared to FCM administration. The impacts of the two types of side effects should be considered when choosing an IV iron drug.

Casein glycomacropeptide for active distal ulcerative colitis: a randomized pilot study.

BACKGROUND: In ulcerative colitis (UC), dietary supplements may have anti-inflammatory properties and improve disease course. We investigated the effects of casein glycomacropeptide (CGMP), a fraction of bovine whey protein, in active UC. MATERIALS AND METHODS: In a randomized open-label intervention study, 24 patients with active UC involving 10-40 cm of the distal colon were randomized in a 2 : 1 ratio into two groups. The first group was administered their usual treatment plus a daily supplement of CGMP 30 g, and the second group was administered a dose escalation to 4800 mg oral mesalamine daily (standard treatment) for 4 weeks. Clinical, endoscopic, mucosal and circulating disease activity markers were monitored. Acceptance of and adherence to CGMP up to 8 weeks were documented. RESULTS: After 4 weeks of treatment, 10 of 16 (63%) patients who received CGMP had an unchanged or decreased Simple Clinical Colitis Activity Index (SCCAI), which was similar to the four of eight (50%) (P = 0·67) patients on the standard treatment. The number of patients in which SCCAI decreased by three or more did not differ between the two groups: nine of 16 (56%) in the CGMP group vs. four of eight (50%) in the standard treatment group (P = 0·77). Changes in disease extent and severity were similar between the two groups. CGMP was well tolerated and accepted by the patients. CONCLUSIONS: The addition of CGMP as a nutritional therapy to standard treatment was safe and accepted by patients with active distal UC. The disease-modifying effect of CGMP was similar to that of the mesalamine dose escalation.

Patient-reported outcomes after acute nonvariceal upper gastrointestinal hemorrhage.

OBJECTIVE: Nonvariceal acute upper gastrointestinal bleeding (AUGIB) is often associated with significant blood loss and anemia. Both the bleeding episode itself and the subsequent anemia are likely to significantly impact a patient's health-related quality of life (HRQoL). Treating the anemia is essential to increase the hemoglobin levels. The HRQoL impact has not been investigated. This longitudinal study aimed to determine the relationship between anemia, HRQoL, and fatigue in patients after nonvariceal AUGIB. MATERIALS AND METHODS: A total of 97 patients (51 males and 46 females; mean age 70 years) were followed in a longitudinal study with a 6-month follow-up. All patients had AUGIB and were anemic at inclusion. Anemia, HRQoL (EQ-5D-3L), and fatigue (using the Multidimensional Fatigue Inventory) were assessed at baseline, and at 1, 3, and 6 months. The patients were initially included in an iron supplementation study. RESULTS: The patients' HRQoL increased and their fatigue levels decreased from baseline to month 3 and month 6. Approximately half of the patients had full health at month 3; similar results were observed in the general population. Three and six months after the bleeding episodes, neither the HRQoL nor fatigue was affected by the anemia. CONCLUSION: This study did not uncover relationships between anemia and HRQoL or anemia and fatigue after nonvariceal AUGIB.

Changes in the levels of mannan-binding lectin and ficolins during head-down tilted bed rest.

BACKGROUND: Spaceflight studies and ground-based analogues of microgravity indicate a weakening of human immunity. Mannan-binding lectin (MBL) and H-, L-, and M-ficolin together constitute the lectin pathway and mediate the clearance of pathogens through complement activation. We hypothesized that simulated microgravity may weaken human innate immune functions and studied the impact of 6° head-down tilted bed rest (HDT) for 21 d on MBL and ficolin levels. METHODS: Within a 6-mo period, seven men underwent two periods of HDT. Blood samples were analyzed for MBL, H-, L-, and M-ficolin, mannose-binding lectin-associated protein of 44 kDa (MAp44), and collectin liver 1 (CL-L1) by time-resolved immunofluorometric assays (TRIFMA). RESULTS: We observed well-defined individual preintervention levels of MBL and ficolins. Remarkably similar intraindividual changes occurred for MBL and MBL levels decreased (mean 282 ng · ml⁻¹) in the recovery phase. Conversely, CL-L1, a protein with MBL-like properties, increased (mean 102 ng · ml⁻¹) during the recovery phase. M-ficolin increased (mean 79 ng · ml⁻¹) within the first 2 d of HDT, followed by a decrease (mean 112 ng · ml⁻¹) during the recovery phase. L-ficolin increased (mean 304 ng · ml⁻¹) during HDT, while H-ficolin was essentially unaffected. MAp44, a down-regulator of the lectin pathway, decreased initially (mean 78 ng · ml⁻¹) in the recovery phase followed by an increase (mean 131 ng · ml⁻¹). DISCUSSION: Alterations in MBL and ficolin levels were modest and with our current knowledge do not lead to overt immunodeficiency. Pronounced changes occurred when the subjects resumed the upright position. In selected individuals, these changes appear to be a conserved response to HDT.

Oral vitamin D3 supplementation reduces monocyte-derived dendritic cell maturation and cytokine production in Crohn's disease patients.

BACKGROUND: Low serum vitamin D levels may provoke or aggravate Crohn's disease (CrD). Vitamin D3 is a well-known immune modulator that affects immune functions in vitro and may prevent CrD flares. Dendritic cells (DC) are key mediators of vitamin D3 effects. In this study, we describe changes in monocyte-derived DC (mo-DC) maturation marker expression and cytokine production following 26 weeks of oral vitamin D3 supplementation in CrD patients. METHODS: Ten CrD patients who had increased serum 25-hydroxy vitamin D levels after oral vitamin D3 and calcium treatment and ten seasonally matched placebo-treated patients were selected for this study. Mo-DC were generated before and after the 26 weeks and induced to mature upon lipopolysaccharide (LPS) stimulation. Maturation marker expression and cytokine production were analysed. Mo-DC function was analysed in a mixed leucocyte reaction (MLR). RESULTS: Compared with baseline values, LPS-matured mo-DC exhibited reduced expression of CD80 and reduced production of the cytokines IL-10, IL-1ß, and IL-6 following 26 weeks of oral vitamin D3 supplementation. Mo-DC performance in an allogeneic MLR was unchanged after vitamin D3 supplementation. Treatment with the placebo did not affect maturation markers, cytokine production, or the MLR. CONCLUSIONS: Vitamin D3 treatment in CrD patients led to hypo-responsive LPS-stimulated mo-DC. This finding indicates that vitamin D3 levels have an impact on the monocytic precursors of mo-DC in vivo and may explain the positive effects of vitamin D3 supplementation on CrD patients. Alternatively, CrD patients with high serum vitamin D3 levels may represent a subgroup with low disease activity.

High burden of iron deficiency and different types of anemia in inflammatory bowel disease outpatients in Scandinavia: a longitudinal 2-year follow-up study.

OBJECTIVE: The prevalence of anemia in inflammatory bowel disease (IBD) has been broadly described. The recurrence, type and burden of anemia remain unenlightened. The primary objective was to describe this. The secondary objective was to evaluate the implementation of European guidelines. MATERIALS AND METHODS: This longitudinal follow-up study included 300 IBD outpatients from six centers in Scandinavia. Patients were enrolled in a research cohort, in which each center included 5% of their IBD cohort. The study was prospectively planned, while data were retrospectively collected. The burden of anemia was calculated as number of months with anemia. A Markov model was used to calculate the probabilities of transitioning between stages. The European guidelines were used as the standard for anemia management. RESULTS: Anemia affected > 50% of IBD outpatients during the 2-year observation period. Totally, 20% of the total observation time was spent in anemia. Over the 7200 months of observation, anemia was found in 1410 months. The most frequent type was combined anemia (63%). Combined anemia covers both anemia of chronic disease (ACD) and iron-deficiency anemia (IDA). Pure ACD was present in 21% of burden time, while pure IDA was present in 16% of burden time. The European guidelines have mainly been implemented. CONCLUSION: Anemia affected a majority of the IBD outpatients. One in five months, the patients were anemic. Anemia related to inflammation dominated the different types of anemia. Pure IDA was found in for 16%. These findings, despite a fair implementation of guidelines.

25-Hydroxy vitamin D3 modulates dendritic cell phenotype and function in Crohn's disease.

BACKGROUND: In Crohn's disease (CrD), vitamin D may help to balance an exaggerated immune response and thereby improve the disease course. The immunomodulating effects depend on the activation of 25-hydroxy vitamin D3 (25-D3), into 1,25-dihydroxy vitamin D3 (1,25-D3). This activation has previously been shown to take place in dendritic cells (DC) from healthy individuals. We hypothesised that DC from CrD patients are able to regulate and control inflammatory responses through 25-D3 activation. METHODS: During differentiation, monocyte-derived DC from 20 CrD patients were cultured with either 25-D3 or 1,25-D3 and matured with lipopolysaccharide (LPS). We examined DC surface marker expression, cytokine production, and the ability to induce cell proliferation in an allogeneic mixed leukocyte reaction. RESULTS: Following stimulation with LPS, DC exposed to either 25-D3 or 1,25-D3 exhibited lower expression levels of CD80, CD83, CD86, and HLA-DR and diminished TNF-α production compared with DC cultured with LPS alone. In contrast, CD14 expression and IL-6 production were higher following 25-D3 or 1,25-D3 treatment. Compared with LPS alone, both forms of vitamin D3 reduced the ability of DC to activate lymphocytes. CONCLUSIONS: Following stimulation with 25-D3, DC from CrD patients displayed a reduced response to LPS with a diminished capability to activate T cells compared with DC stimulated with LPS alone. These data indicate that intrinsic activation of 25-D3 occurs in DC from CrD patients and show that 25-D3 can modulate DC function in CrD. Our data suggest that vitamin D deficiency may contribute to the uncontrolled inflammatory process seen in CrD.

Donor, patient age and exposure to antibiotics are associated with the outcome of faecal microbiota transplantation for recurrent Clostridioides difficile infection: A prospective cohort study.

BACKGROUND: Faecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (rCDI), but its effect varies inexplicably. AIMS: To optimise the effectiveness of FMT for rCDI and validate determinants for effect METHODS: We conducted a cohort study, including all patients treated with FMT for rCDI between October 2018 and June 2020. Statistical process control was used to evaluate the impact of prospective quality improvement on the effect of single FMT treatments per 10-11 patients. Targeting an 80% effect, optimisations included changes to processing procedures, preparation and clinical application of FMT. The primary outcome was the resolution of Clostridioides difficile-associated diarrhoea at week 8. If CDI recurred, FMT was repeated. All patients were followed for 8 weeks after their latest FMT. RESULTS: 183 patients with rCDI received 290 FMT treatments. A single FMT achieved resolution at week 8 in 127 (69%, 95% CI: 62%-76%), while repeated FMT cumulatively achieved resolution in 167/183 (91%, 95% CI: 86%-95%). The single FMT effect varied between 36% and 100% over time. In a mixed-effect model, patient age above 65 years, non-rCDI antibiotics at week 1 post-FMT, and donor were associated with effect. Neither increasing the dosages of faecal microbes nor standardising the processing improved outcomes. CONCLUSION: FMT has a high cumulative effectiveness in patients with rCDI following multiple administrations, but the single FMT effect is variable and may be optimised using statistical process control. Optimising FMT by considering patient age, post-FMT antibiotics, donor and multiple administrations may improve the treatment outcomes. CLINICALTRIALS: gov (Study identifier: NCT03712722).

The mucosal addressin cell adhesion molecule antibody PF-00547,659 in ulcerative colitis: a randomised study.

BACKGROUND AND AIMS: Leucocyte migration to gut mucosa, mediated by integrin binding to mucosal addressin cell adhesion molecule (MAdCAM), is a promising target for therapeutic intervention in inflammatory bowel disease. This first-in-human study of a monoclonal antibody to MAdCAM, PF-00547,659, aimed to explore the safety and preliminary efficacy of this gut-specific mechanism in ulcerative colitis. METHODS: In this randomised, double-blind placebo-controlled study, 80 patients with active ulcerative colitis received single or multiple (three doses, 4-week intervals) doses of PF-00547,659 0.03-10 mg/kg IV/SC, or placebo. Safety was assessed by adverse events, laboratory tests, and immunogenicity. Exploratory efficacy analyses were based on Mayo score and endoscopic responder rates at weeks 4 and 12. Faecal calprotectin was quantified as a measure of disease activity, and the number of α4ß7⁺ lymphocytes was measured to demonstrate drug activity. RESULTS: No obvious drug-related side effects were observed in the PF-00547,659 group, while patient numbers, especially those fully exposed, were small. Overall responder/remission rates at 4 and 12 weeks were 52%/13% and 42%/22%, respectively with combined PF-00547,659 doses compared with 32%/11% and 21%/0%, respectively with placebo. Equivalent endoscopic responder rates were 50% and 42% versus 26% and 29%, respectively. Faecal calprotectin levels decreased to a greater extent with PF-00547,659 than placebo (week 4: 63% vs 18%). Despite variability, there was a trend for an increase in α4ß7⁺ lymphocytes in patients receiving PF-00547,659. CONCLUSIONS: The favourable short-term safety profile and preliminary efficacy findings for PF-00547,659 in this first-in-human study pave the way for further investigation in larger trials, to establish the role of PF-00547,659 in ulcerative colitis treatment. Trial Register No: NCT00928681.

Health-related quality of life in patients with recurrent Clostridioides difficile infections.

Background: The health-related quality of life (HrQoL) can be substantially affected in patients with recurrent Clostridioides difficile infection (rCDI) but the impact of effective treatment of the infection remains unclear. This study aimed to evaluate the HrQoL in patients with rCDI and estimate the gain in HrQoL associated with effective treatment of rCDI. Methods: Patients' HrQoL was estimated based on EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaires obtained from a Danish randomised controlled trial (RCT). In the RCT, 64 patients with rCDI were randomised to receive either vancomycin (n = 16), fidaxomicin (n = 24) or faecal microbiota transplantation (FMT) preceded by vancomycin (n = 24). The primary outcome in the RCT was rCDI resolution. Patients were closely monitored during the RCT, and rescue FMT was offered to those who failed their primary treatment. Patients' HrQoL was measured at baseline and at 8- and 26-weeks follow-up. Linear regression analyses conditional on the differences between baseline and follow-up measurements were used to assess statistical significance (p < 0.05). Results: Within 26 weeks of follow-up, 13 (81%) patients treated with vancomycin, 12 (50%) patients treated with fidaxomicin, and 3 (13%) patients treated with FMT had a subsequent recurrence and received a rescue FMT. The average HrQoL for untreated patients with rCDI was 0.675. After receiving effective treatment, this value increased by 0.139 to 0.813 (p < 0.001) at week 8 and by 0.098 to 0.773 (p = 0.003) at week 26 of follow-up compared with baseline. Conclusion: The HrQoL was adversely affected in patients with an active episode of rCDI but increased substantially after receiving an effective treatment algorithm in which rescue FMT was provided in case of a primary treatment failure. Trial registration: The RCT was preregistered at EudraCT (j.no. 2015-003004-24, https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-003004-24/results) and at ClinicalTrials.gov (study identifier NCT02743234, https://clinicaltrials.gov/ct2/show/NCT02743234).

Lower Incidence of Hepatobiliary Cancer in Helicobacter pylori-Infected Persons: A Cohort Study of 53.633 Persons.

Background and aims: Helicobacter pylori (HP) is known to be involved in intestinal carcinogenesis. As regards hepatobiliary cancers, there are few and inconsistent reports. We investigated HP infection and its association with the incidence of hepatobiliary cancers in a large cohort study. The cohort's appropriateness for the purpose was gauged by its ability to identify the established risk relation to gastric cancer. Methods: This historical study was performed in the Central Denmark Region. Patients were included from primary healthcare after being tested for HP infection with a urea breath test. Patients' diagnoses, age, gender, and country of birth were obtained from Danish national administrative registries. Cox regression was used to compare incidences of hepatobiliary and gastric cancer between HP-positive and HP-negative persons, adjusting for confounding variables. Results: A total of 53,633 persons were included and 10,553 were tested HP-positive. They were followed for a median of 4.6 years (total 250,515 person-years). We found 64 hepatobiliary cancers, with a markedly lower incidence in HP-positive persons; HR = 0.27 (95% CI 0.11-0.68). A higher incidence of gastric cancer in HP-positive persons was confirmed (HR = 1.99 (95% CI 1.35-2.94)). Conclusion: The incidence of hepatobiliary cancers was remarkably lower in HP-infected persons after adjusting for age, gender, cirrhosis, alcohol-related diagnoses, chronic viral hepatitis, and country of origin. We found no methodological cause for this unexpected finding, and the pathogenic links between the infection and cancer remain to be identified. Our results must be confirmed in a similar cohort.

Impact of fibre and red/processed meat intake on treatment outcomes among patients with chronic inflammatory diseases initiating biological therapy: A prospective cohort study.

Background: Biologic disease-modifying drugs have revolutionised the treatment of a number of chronic inflammatory diseases (CID). However, up to 60% of the patients do not have a sufficient response to treatment and there is a need for optimization of treatment strategies. Objective: To investigate if the treatment outcome of biological therapy is associated with the habitual dietary intake of fibre and red/processed meat in patients with a CID. Methods: In this multicentre prospective cohort study, we consecutively enrolled 233 adult patients with a diagnosis of Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis (RA), Axial Spondyloarthritis, Psoriatic Arthritis and Psoriasis, for whom biologic therapy was planned, over a 3 year period. Patients with completed baseline food frequency questionnaires were stratified into a high fibre/low red and processed meat exposed group (HFLM) and an unexposed group (low fibre/high red and processed meat intake = LFHM). The primary outcome was the proportion of patients with a clinical response to biologic therapy after 14-16 weeks of treatment. Results: Of the 193 patients included in our primary analysis, 114 (59%) had a clinical response to biologic therapy. In the HFLM group (N = 64), 41 (64%) patients responded to treatment compared to 73 (56%) in the LFHM group (N = 129), but the difference was not statistically significant (OR: 1.48, 0.72-3.05). For RA patients however, HFLM diet was associated with a more likely clinical response (82% vs. 35%; OR: 9.84, 1.35-71.56). Conclusion: Habitual HFLM intake did not affect the clinical response to biological treatment across CIDs. HFLM diet in RA patients might be associated with better odds for responding to biological treatment, but this would need confirmation in a randomised trial. Trial registration: (clinicaltrials.gov), identifier [NCT03173144].

The prevalence of anemia and iron deficiency in IBD outpatients in Scandinavia.

OBJECTIVE: To evaluate the prevalence of anemia and iron deficiency (ID) among patients with inflammatory bowel disease (IBD) in the Scandinavian countries. MATERIAL AND METHODS: A cross-sectional study including 429 IBD patients from six centers in Denmark, Norway and Sweden. Patients were screened for anemia and ID. Each center included ~5% of their IBD cohort. Patients were consecutively seen in the outpatient clinic, regardless of disease activity and whether the visits were scheduled or not. RESULTS: The overall prevalence of anemia was 19% (95% CI: 16-23%). The prevalence was higher among patients with Crohn's disease than among patients with ulcerative colitis (p = 0.01). The etiology of anemia was as follows: iron deficiency anemia (20%), anemia of chronic disease (12%), and both conditions (68%). Less than 5% had folate acid or vitamin B12 deficiency. ID was found in 35% (CI: 31-40%) of the patients. CONCLUSIONS: Anemia was present in every fifth IBD patient and ID in every third IBD patient.

Gastric transit and small intestinal transit time and motility assessed by a magnet tracking system.

BACKGROUND: Tracking an ingested magnet by the Magnet Tracking System MTS-1 (Motilis, Lausanne, Switzerland) is an easy and minimally-invasive method to assess gastrointestinal transit. The aim was to test the validity of MTS-1 for assessment of gastric transit time and small intestinal transit time, and to illustrate transit patterns detected by the system. METHODS: A small magnet was ingested and tracked by an external matrix of 16 magnetic field sensors (4 × 4) giving a position defined by 5 coordinates (position: x, y, z, and angle: θ, φ). Eight healthy subjects were each investigated three times: (1) with a small magnet mounted on a capsule endoscope (PillCam); (2) with the magnet alone and the small intestine in the fasting state; and (3) with the magnet alone and the small intestine in the postprandial state. RESULTS: Experiment (1) showed good agreement and no systematic differences between MTS-1 and capsule endoscopy when assessing gastric transit (median difference 1 min; range: 0-6 min) and small intestinal transit time (median difference 0.5 min; range: 0-52 min). Comparing experiments (1) and (2) there were no systematic differences in gastric transit or small intestinal transit when using the magnet-PillCam unit and the much smaller magnetic pill. In experiments (2) and (3), short bursts of very fast movements lasting less than 5% of the time accounted for more than half the distance covered during the first two hours in the small intestine, irrespective of whether the small intestine was in the fasting or postprandial state. The mean contraction frequency in the small intestine was significantly lower in the fasting state than in the postprandial state (9.90 min-1 vs. 10.53 min-1) (p = 0.03). CONCLUSION: MTS-1 is reliable for determination of gastric transit and small intestinal transit time. It is possible to distinguish between the mean contraction frequency of small intestine in the fasting state and in the postprandial state.

The use of 5-aminosalicylate for patients with Crohn's disease in a prospective European inception cohort with 5 years follow-up - an Epi-IBD study.

BACKGROUND: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice. AIMS: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease. METHODS: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists. RESULTS: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)). CONCLUSION: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.