1.
Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.
Laharie, D, Bourreille, A, Branche, J, Allez, M, Bouhnik, Y, Filippi, J, Zerbib, F, Savoye, G, Vuitton, L, Moreau, J, et al
Gut. 2018;67(2):237-243
-
-
-
Free full text
-
Plain language summary
Intravenous steroids are the first-line therapy for ulcerative colitis (UC) patients who are hospitalised during a severe UC flare-up. In the 40% of patients who don’t respond to steroids, the drugs ciclosporin and infliximab have been found to be efficient in preventing surgery to remove part or all of the colon, but there is a lack of data on the long-term outcomes of using these medications in UC patients. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. Between 2007 and 2010, 115 patients with UC that did not respond to steroids were randomised to receive ciclosporin or infliximab in association with azathioprine. Patients were followed to January 2015 or death. After a median follow-up of 5.4 years, colectomy-free survival rates at 1 and 5 years were, respectively, 70.9% and 61.5% in patients who received ciclosporin and 69.1% and 65.1% in those who received infliximab. Long-term colectomy-free survival was independent from initial treatment. However, a higher proportion of patients initially treated with ciclosporin needed a new treatment compared with those who received infliximab first. The researchers concluded that these results further confirm a similar efficacy and good safety profiles of both drugs.
Abstract
OBJECTIVE Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.
2.
Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome.
Zuo, T, Wong, SH, Lam, K, Lui, R, Cheung, K, Tang, W, Ching, JYL, Chan, PKS, Chan, MCW, Wu, JCY, et al
Gut. 2018;67(4):634-643
-
-
-
Free full text
-
Plain language summary
The microbiome and its effects on health have received plenty of attention and research. A lot less is known about the virome, the collection of viruses in and on our bodies. This pilot observational study looked at the connection between the viruses and bacteria in the guts of patients with Clostridium difficile infection (CDI), compared to healthy controls, and changes and treatment outcomes observed after faecal microbiota transplantation (FMT) compared to vancomycin treatment. The study showed that, compared to healthy household controls, people with CDI had significant viral dysbiosis, in particular higher abundance but lower diversity, richness and evenness of the bacteriophage (a virus that infects bacteria) Caudovirales, the most abundant intestinal bacteriophage in humans. FMT changed both, the composition of the microbiome as well as the virome, whilst antibiotic treatment did not affect the bacteriophage composition. Treatment outcome with FMT depended on changes in Caudivirales. Although a small pilot study, according to the authors, this is the biggest study into the importance of intestinal viruses, and their correlation with the microbiome, in disease and for treatment outcomes. The authors point out that, as this was an observational study, it is not possible to ascertain whether the altered virome is a cause or a consequence of the disease.
Abstract
OBJECTIVE Faecal microbiota transplantation (FMT) is effective for the treatment of recurrent Clostridium difficile infection (CDI). Studies have shown bacterial colonisation after FMT, but data on viral alterations in CDI are scarce. We investigated enteric virome alterations in CDI and the association between viral transfer and clinical outcome in patients with CDI. DESIGN Ultra-deep metagenomic sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on stool samples from 24 subjects with CDI and 20 healthy controls. We longitudinally assessed the virome and bacterial microbiome changes in nine CDI subjects treated with FMT and five treated with vancomycin. Enteric virome alterations were assessed in association with treatment response. RESULTS Subjects with CDI demonstrated a significantly higher abundance of bacteriophage Caudovirales and a lower Caudovirales diversity, richness and evenness compared with healthy household controls. Significant correlations were observed between bacterial families Proteobacteria, Actinobacteria and Caudovirales taxa in CDI. FMT treatment resulted in a significant decrease in the abundance of Caudovirales in CDI. Cure after FMT was observed when donor-derived Caudovirales contigs occupied a larger fraction of the enteric virome in the recipients (p=0.024). In treatment responders, FMT was associated with alterations in the virome and the bacterial microbiome, while vancomycin treatment led to alterations in the bacterial community alone. CONCLUSIONS In a preliminary study, CDI is characterised by enteric virome dysbiosis. Treatment response in FMT was associated with a high colonisation level of donor-derived Caudovirales taxa in the recipient. Caudovirales bacteriophages may play a role in the efficacy of FMT in CDI. TRIAL REGISTRATION NUMBER NCT02570477.
3.
Elevated methane levels in small intestinal bacterial overgrowth suggests delayed small bowel and colonic transit.
Suri, J, Kataria, R, Malik, Z, Parkman, HP, Schey, R
Medicine. 2018;97(21):e10554
-
-
-
Free full text
-
Plain language summary
Whilst the most conclusive way to diagnose SIBO is to use an invasive procedure (endoscopy) to take samples from the middle section of the small intestine (jejunum), lactulose breath testing of methane and hydrogen gasses has become the most commonly used test to rule SIBO in or out. This cohort study used historic data (retrospective) of 78 individuals to compare intestinal transit time in patients with a positive lactulose breath test to those with a negative result, as well as compare patients with hydrogen-positive results with those with methane-positive results. All patients experienced gastrointestinal (GI) symptoms of nausea, bloating, constipation, diarrhea and gas to varying degrees. No significant difference in GI symptom severity was found between those with a positive lactulose breath test and those with a negative result. However, those with a hydrogen-gas positive result had a significantly higher level of reported nausea compared to the methane-gas positive patients. A positive SIBO result on the breath test also did not affect GI transit time in comparison to a negative result. However, those with a methane-gas peak on their positive lactulose breath test had a statistically significant slower GI transit time when compared to those with a hydrogen-positive result.
Abstract
Limited research exists regarding the relationship between small intestinal bacterial overgrowth (SIBO), small bowel transit (SBT), and colonic transit (CT). Furthermore, symptom analysis is limited between the subtypes of SIBO hydrogen producing (H-SIBO) and methane producing (M-SIBO). The primary aims of this study are to: compare the SBT and CT in patients with a positive lactulose breath test (LBT) to those with a normal study; compare the SBT and CT among patients with H-SIBO or M-SIBO; compare the severity of symptoms in patients with a positive LBT to those with a normal study; compare the severity of symptoms among patients with H-SIBO or M-SIBO.A retrospective review was performed for 89 patients who underwent a LBT and whole gut transit scintigraphy (WGTS) between 2014 and 2016. Seventy-eight patients were included. WGTS evaluated gastric emptying, SBT (normal ≥40% radiotracer bolus accumulated at the ileocecal valve at 6 hours), and CT (normal geometric center of colonic activity = 1.6-7.0 at 24 hours, 4.0-7.0 at 48 hours, 6.2-7.0 at 72 hours; elevated geometric center indicates increased transit). We also had patients complete a pretest symptom survey to evaluate nausea, bloating, constipation, diarrhea, belching, and flatulence.A total of 78 patients (69 females, 9 males, mean age of 48 years, mean BMI of 25.9) were evaluated. Forty-seven patients had a positive LBT (H-SIBO 66%, M-SIBO 34%). Comparison of SBT among patients with a positive LBT to normal LBT revealed no significant difference (62.1% vs 58.6%, P = .63). The mean accumulated radiotracer was higher for H-SIBO compared to M-SIBO (71.5% vs 44.1%; P < .05). For CT, all SIBO patients had no significant difference in geometric centers of colonic activity at 24, 48, and 72 hours when compared to the normal group. When subtyping, H-SIBO had significantly higher geometric centers compared to the M-SIBO group at 24 hours (4.4 vs 3.1, P < .001), 48 hours (5.2 vs 3.8, P = .002), and at 72 hours (5.6 vs 4.3, P = .006). The symptom severity scores did not differ between the positive and normal LBT groups. A higher level of nausea was present in the H-SIBO group when compared to the M-SIBO group.Overall, the presence of SIBO does not affect SBT or CT at 24, 48, and 72 hours. However, when analyzing the subtypes, M-SIBO has significantly more delayed SBT and CT when compared to H-SIBO. These results suggest the presence of delayed motility in patients with high methane levels on LBT.
4.
Comparison of the construct validity and reproducibility of four different types of patient-reported outcome measures (PROMs) in patients with rheumatoid arthritis.
Renskers, L, van Uden, RJJC, Huis, AMP, Rongen, SAA, Teerenstra, S, van Riel, PLCM
Clinical rheumatology. 2018;37(12):3191-3199
-
-
-
Plain language summary
Rheumatoid arthritis is an inflammatory autoimmune disease characterised by chronic joint inflammation, which leads to pain, stiffness, function loss, and fatigue. During outpatient visits, patient-reported outcome measures (PROMs) are taking a more central place because they directly apply to the patients’ personal perception and can identify key concerns that need to be addressed. The objective of this study was to measure and compare construct validity of four scale types of PROMs within four different domains. The study is a prospective longitudinal study which recruited adult patients with rheumatoid arthritis. Two-hundred eleven patients were included for the construct validity assessment and one hundred fifty-three patients for the reproducibility assessment. Results showed that within the construct validity assessment, the differences between the four scale types were small and appeared not different. On the other hand, the assessment on reproducibility of the scales was moderate to high. The exception was for the domain of general well-being, as correlations both for construct validity as well as for reproducibility were lower compared to the other domains. Authors conclude that the numerical rating scale is the preferred PROM scale for patients with rheumatoid arthritis.
Abstract
Patient-reported outcome measures (PROMs) are increasingly used in the assessment of patients with rheumatoid arthritis (RA). The aim of this study was to assess the construct validity and reproducibility of four types of PROMs (numerical rating scale (NRS), visual analogue scale (VAS), verbal rating scale (VRS), and Likert scale). In addition, patients' preference for one of these PROMs was measured. Patients with stable RA and no change in pain medication or steroid medication (n = 211) were asked to complete a questionnaire directly following, and 5 days after their outpatient visit. The questionnaire measured the validity of the PROMs in four domains (pain, fatigue, experienced disease activity, and general well-being). To assess construct validity, Pearson correlation coefficients were calculated using the Disease Activity Score-3. To assess reproducibility, intraclass correlation coefficients (ICCs) were calculated. Correlation coefficients between the different PROMs within each domain were compared. There were no differences regarding construct validity between the different PROM scale types. Regarding reproducibility, VAS and NRS scored better in the domains pain and experienced disease activity. Patients chose NRS as preferred measurement method, with the VAS in second place. The four scale types of PROMs appeared to be equally valid to assess pain, fatigue, experienced disease activity, and general well-being. VAS and NRS appeared to be more reliable for measuring pain and experienced disease activity. The patients favoured NRS. In combination with other practical advantages of NRS over VAS, we do advise the NRS as the preferred scale type for PROMs.