Introduction

Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies are ineffective, the UK National Institute for Health and Care Excellence guidance suggests considering low dose tricyclic antidepressants (TCAs) as second-line treatment, but their effectiveness in primary care is unknown and they are infrequently prescribed in this setting.

Aims & Methods

ATLANTIS was a randomised, double-blind, placebo-controlled trial at 55 UK primary care centres. Eligible patients were ≥18 years with Rome IV IBS of any subtype, with ongoing symptoms (IBS Severity Scoring System (IBS-SSS) score ≥75 points) despite first-line therapies, a normal full blood count and C-reactive protein, negative coeliac serology, and no evidence of suicidal ideation. Participants were randomised (1:1) to low-dose oral amitriptyline (10-30mg once daily) or placebo for 6 months with dose titration over 3 weeks, according to symptoms and tolerability. Participants, primary care physicians and other health-care providers, and investigators were all masked to allocation throughout. Primary and key secondary endpoints were IBS-SSS score and subjective global assessment (SGA) of relief of IBS symptoms at 6 months. Effectiveness analyses were according to intention to treat, safety analyses were according to treatment receipt.

Results

463 patients (mean age 48.5 years (SD 16.1 years), 315 (68.0%) female) were randomised to amitriptyline (232) or placebo (231). Primary outcome analysis showed a significant difference in IBS-SSS score between arms at 6 months (-27.0; 95% CI -46.9 to -7.10, p=0.008) in favour of amitriptyline. For the key secondary endpoint of SGA of relief of IBS symptoms, amitriptyline was superior to placebo at 6 months (125/204 (61.3%) vs. 88/195 (45.1%), odds ratio 1.78; 95% CI 1.19 to 2.66, p=0.005). Amitriptyline was superior to placebo across other secondary endpoints but had no impact on psychological symptom scores (Table). 46 (19.8%) patients discontinued amitriptyline (30 (12.9%) adverse events) and 59 discontinued placebo (25.5%) (20 (8.7%) adverse events). There were 5 serious adverse reactions (2 amitriptyline, 3 placebo).

	Amitriptyline (n = 232)	Placebo (n = 231)	Effect* (95% CI), p value
IBS-SSS Mean IBS-SSS (SD)† ≥50-point decrease in IBS-SSS (%)	170.4 (107.7) 131/204 (64.2)	200.1 (114.5) 106/197 (53.8)	-27.0 (-46.9, -7.10), p = 0.008 1.48 (0.97, 2.27), p = 0.068
SGA of relief of IBS symptoms (%)‡	125/204 (61.3)	88/195 (45.1)	1.78 (1.19, 2.66), p = 0.005
Adequate weekly relief of IBS symptoms over 25 weeks⁑ (%)	123/222 (55.4)	93/221 (42.1)	1.56 (1.20, 2.03), p<0.001
Mean HADS-A (SD)	6.7 (4.4)	6.9 (4.0)	0.08 (-0.49, 0.65), p = 0.78
Mean HADS-D (SD)	3.9 (3.6)	4.0 (3.5)	-0.20 (-0.75, 0.34), p = 0.46
Mean WSAS (SD)	8.1 (7.6)	9.4 (7.8)	-1.04 (-2.30, 0.23), p = 0.11
Mean PHQ-12 (SD)	5.7 (3.4)	5.9 (3.2)	-0.04 (-0.58, 0.49), p = 0.88
Acceptability of treatment (%)	122/211 (57.8)	100/213 (46.9)	1.60 (1.08, 2.35), p = 0.018
Adherence to treatment (%)§	172/232 (74.1)	155/228 (68.0)	..

*Mean difference for continuous, odds ratio for categorical.
†Primary endpoint.
‡Key secondary endpoint.
⁑n/N (%) indicates number with adequate relief for ≥50% of weeks, whereas effect indicates the odds of relief across all 25 weeks estimated from a generalised linear marginal mixed model of weekly data.
§“On medication every day or nearly every day” or “Half the days or more than half the days”. Proportional odds assumption not satisfied, descriptive analysis only.

Conclusion

This is the largest trial of a TCA in IBS ever conducted. Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple endpoints and was safe. Primary care physicians should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies.
Funding: National Institute for Health Research Health Technology Assessment Programme (grant reference: 16/162/01).

Introduction

A wide range of relationships between the microbial community and various environmental or individual factors have been proposed. Monozygotic and dizygotic twins provide a unique model for assessing host-microbial interactions. The mycobiome has been increasingly implicated in the development of several diseases, but knowledge of the dynamics of the fungal community, particularly in twins, has not been addressed.

Aims & Methods

In this work, we investigated the fungal community in a twin cohort and explored its relationship with associated genetic and environmental factors through in-depth analysis.
The twin cohort consisted of 106 well-characterised and systematically studied monozygotic and dizygotic pairs (212 stool samples). DNA was extracted and PCR reactions were performed to sequence the lower gastrointestinal microbiome and the mycobiome community. The bacterial community was characterised using the V1-V2 region of the 16 rRNA gene and the fungal community was analysed using the ITS1-ITS2 region.

Results

The fungal community, represented by the sum of all fungal sequences, showed a significantly higher heterogeneity than the bacterial community. Several individual and genetic factors, such as the zygotic status of the twins (monozygotic vs. dizygotic), as well as sex, mode of birth, breast-feeding as newborns or living in the same household, were independent of the total number of fungal sequences. The bacterial community was significantly more abundant than the fungal community, the most common representatives of which were Candida and Geotrichum with sometimes very high abundances. Saccharomyces was also common in the cohort, but only in low abundance, other fungi with a wider distribution were Cladosporium or Penicillium. The environmental and individual factors mentioned above were also correlated with the individual fungal genera, but there were no significant correlations found here either. The next step was to correlate the bacterial and fungal communities with each other, and strong negative correlations were found with certain bacteria such as Prevotella.

Conclusion

Genetic factors in twins are not associated with dynamics in the faecal fungal community and were the subject of high inter-individual variability. However, there is a strong association between bacterial and mycobial interaction, which requires further in-depth understanding of microbial interactions.

Disclosure

No conflict of interest to declare

Introduction

Chronic liver disease remains one of the most common causes for admission in the Gastroenterology department, with high morbidity and mortality rates. As quality-of-care gains traction in our clinical practice, chronic liver disease, particularly when regarding decompensated cirrhotic patients in the emergency department, remains without a standardized approach. Additionally, timely and adequate management within the first 24 hours of admission reduces morbidity and mortality in decompensated cirrhosis. In the United Kingdom, a standardized cirrhosis care bundle as been effectively applied.

Aims & Methods

We conducted a retrospective review to determine baseline management of patients with decompensated cirrhosis attending two Portuguese hospital centers, in 2021 and 2022.

Results

We included a total of 148 patients from 2 hospital centers, 141 were male (95.3%) and had a median age of 62 years at admission (IQR 15). Median Child-Pugh and Model for End-stage Liver Disease (MELD) -Na scores at admission were 9 (IQR 3) and 18 (IQR 10) points, respectively.
The most common decompensations were gastrointestinal bleeding in 33.1% of patients, ascites in 30.8% and hepatic encephalopathy in 25.6%. Sixty-five patients had more than 1 decompensation (43.9%). It was their first liver disease decompensation in 55 patients (37.2%). Regarding etiology, alcoholic liver disease was the most common, in 134 patients (90.5%). Median duration of admission was 8 days (IQR 6). The in-hospital mortality rate was 4.7% (7 patients) and mortality rate at 6 weeks after admission was 8.8% (13 patients). Forty-six patients were readmitted up to 3 months (31.1%).
In patients with ascites, 29 did not undergo paracentesis (33.3%). In patients with recent history of alcohol abuse, 5 did not receive thiamine (7.5%) and 6 did not undergo alcohol abstinence syndrome prevention therapy (9%). In suspected infection, 4 out of 38 patients did not receive empirical antibiotics in the first 24 hours of admission (10.5%). In acute renal lesion, 2 patients did not stop diuretics and/or nephrotoxic drugs (5.6%) and 4 did not receive fluids and/or albumin (12.1%). In 3 patients there was no diuresis monitoring (7.5%). At admission for gastrointestinal bleeding, 3 patients received a nonrestrictive approach regarding transfusions (5.5%), 18 did not undergo vasopressor therapy (32.1%) and in 5 prophylactic antibiotics were not administered (8.9%). Prophylactic lactulose was used in 25 patients (45.5%). Only 1 patient did not undergo upper endoscopy before 12 hours of admission (1.8%). In hepatic encephalopathy, the precipitating factor was recognized in 29 patients (69%), with infection as the most commonly identified (55.2%). Venous Thromboembolism prophylaxis was not administered (45.3%) in 67 patients and 88 patients did not undergo a nutritional evaluation during admission (59.5%).

Conclusion

We were able to identify several areas in need of improvement: one-third of patients with ascites did not undergo diagnostic ascitic taps, nearly on-third of patients did not start vasopressor therapy at admission and more than half had no nutritional evaluation.
Training and best practice policies are a priority in Gastroenterology nowadays, and the identification of poor performance areas is relevant for the betterment of our clinical practice. An adapted bundle for prospective application is underway in our centers as we hope to reduce overall hospital stay and mortality in decompensated cirrhosis.

References

Dyson JK, et al. Implementation of a ‘care bundle’ improves the management of patients admitted to hospital with decompensated cirrhosis. Aliment Pharmacol Ther 2016; 44: 1030–1038, doi:10.1111/apt.13806
McPherson S, et al. Decompensated Cirrhosis Care Bundle - First 24 Hours. Disponível em: https://www.bsg.org.uk/wp-content/uploads/2019/12/BSG-BASL-Decompensated-Cirrhosis-Care-Bundle-First-24-Hours.pdf