Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Dysbiosis of the intestinal microbiota has been associated with nonalcoholic fatty liver disease (NAFLD). We investigated whether administration of a synbiotic combination of probiotic and prebiotic agents affected liver fat content, biomarkers of liver fibrosis, and the composition of the fecal microbiome in patients with NAFLD. METHODS: We performed a double-blind phase 2 trial of 104 patients with NAFLD in the United Kingdom. Participants (mean age, 50.8 ± 12.6 years; 65% men; 37% with diabetes) were randomly assigned to groups given the synbiotic agents (fructo-oligosaccharides, 4 g twice per day, plus Bifidobacterium animalis subspecies lactis BB-12; n = 55) or placebo (n = 49) for 10-14 months. Liver fat content was measured at the start and end of the study by magnetic resonance spectroscopy, and liver fibrosis was determined from a validated biomarker scoring system and vibration-controlled transient elastography. Fecal samples were collected at the start and end of the study, the fecal microbiome were analyzed by 16S ribosomal DNA sequencing. RESULTS: Mean baseline and end-of-study magnetic resonance spectroscopy liver fat percentage values were 32.3% ± 24.8% and 28.5% ± 20.1% in the synbiotic group and 31.3% ± 22% and 25.2% ± 17.2% in the placebo group. In the unadjusted intention-to-treat analysis, we found no significant difference in liver fat reduction between groups (ß = 2.8; 95% confidence interval, -2.2 to 7.8; P = .30). In a fully adjusted regression model (adjusted for baseline measurement of the outcome plus age, sex, weight difference, and baseline weight), only weight loss was associated with a significant decrease in liver fat (ß = 2; 95% confidence interval, 1.5-2.6; P = .03). Fecal samples from patients who received the synbiotic had higher proportions of Bifidobacterium and Faecalibacterium species, and reductions in Oscillibacter and Alistipes species, compared with baseline; these changes were not observed in the placebo group. Changes in the composition of fecal microbiota were not associated with liver fat or markers of fibrosis. CONCLUSIONS: In a randomized trial of patients with NAFLD, 1 year of administration of a synbiotic combination (probiotic and prebiotic) altered the fecal microbiome but did not reduce liver fat content or markers of liver fibrosis. (ClinicalTrials.gov, Number: NCT01680640).

Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the Welcome* study.

There is no licensed treatment for non-alcoholic fatty liver disease (NAFLD), a condition that increases risk of chronic liver disease, type 2 diabetes and cardiovascular disease. We tested whether 15-18 months treatment with docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA) (Omacor/Lovaza) (4 g/day) decreased liver fat and improved two histologically-validated liver fibrosis biomarker scores (primary outcomes). Patients with NAFLD were randomised in a double blind placebo-controlled trial [DHA+EPA(n=51), placebo(n=52)]. We quantified liver fat percentage (%) by magnetic resonance spectroscopy in three liver zones. We measured liver fibrosis using two validated scores. We tested adherence to the intervention (Omacor group) and contamination (with DHA and EPA) (placebo group) by measuring erythrocyte percentage DHA and EPA enrichment (gas chromatography). We undertook multivariable linear regression to test effects of: a) DHA+EPA treatment (ITT analyses) and b) erythrocyte DHA and EPA enrichment (secondary analysis). Median (IQR) baseline and end of study liver fat% were 21.7 (19.3) and 19.7 (18.0) (placebo), and 23.0 (36.2) and 16.3 (22.0), (DHA+EPA). In the fully adjusted regression model there was a trend towards improvement in liver fat% with DHA+EPA treatment (ß=-3.64 (95%CI -8.0,0.8); p=0.1) but there was evidence of contamination in the placebo group and variable adherence to the intervention in the Omacor group. Further regression analysis showed that DHA enrichment was independently associated with a decrease in liver fat% (for each 1% enrichment, ß=-1.70 (95%CI -2.9,-0.5); p=0.007). No improvement in the fibrosis scores occurred. Conclusion. Erythrocyte DHA enrichment with DHA+EPA treatment is linearly associated with decreased liver fat%. Substantial decreases in liver fat% can be achieved with high percentage erythrocyte DHA enrichment in NAFLD. (Hepatology 2014;).

Clinical impact of syndromic molecular point-of-care testing for gastrointestinal pathogens in adults hospitalised with suspected gastroenteritis (GastroPOC): a pragmatic, open-label, randomised controlled trial.

BACKGROUND: Single-occupancy isolation rooms are a finite resource in UK hospitals but are crucial in preventing transmission of infection. Patients with suspected gastroenteritis are nursed in single-occupancy rooms, but delays in laboratory testing lead to non-infectious patients remaining isolated for prolonged periods unnecessarily. Rapid molecular test panels for gastrointestinal pathogens have a run time of around 1 h but their clinical impact is unknown. We aimed to evaluate the clinical impact of syndromic molecular point-of-care testing (mPOCT) for gastrointestinal pathogens in adult patients presenting to hospital with suspected gastroenteritis on single-occupancy room use and a range of other outcome measures. METHODS: In this pragmatic, open-label, randomised controlled trial, we enrolled adults hospitalised with suspected gastroenteritis in a large UK hospital. Patients were randomly allocated (1:1) to receive syndromic mPOCT of stool or rectal samples, or to routine clinical care (control) with laboratory testing. The primary outcome was the duration of time in single-occupancy rooms assessed on a modified intention-to-treat basis. Secondary outcomes included the time to results, time to de-isolation, antibiotic use, and safety outcomes. The study was registered with ISRCTN, ISRCTN88918395, and is complete. FINDINGS: Between March 20, 2017 and March 17, 2020, from 455 patients assessed for eligibility, we enrolled 278 patients, 138 assigned to mPOCT (one withdrawal) and 140 to the control group. The duration (geometric mean) of single-occupancy room isolation was 1·8 days (95% CI 1·5-2·2) in the mPOCT group compared with 2·6 days (2·2-3·0) in the control group (exponentiated coefficient 0·70 [95% CI 0·56 to 0·87]; p=0·0017). The median (IQR) time to results was 1·7 h (1·5-2·0) for mPOCT and 44·7 h (21·2-66·1) for the control group (p<0·0001). Time to de-isolation was 0·6 days (0·3-1·8) in the mPOCT group compared with 2·2 days (1·2-3·2) in the control group, (p<0·0001). Antibiotics were given in 89 (65%) of 137 in the mPOCT group and 66 (47%) of 140 in the control group (p=0·0028). There were no differences between groups in length of hospital stay, or in safety outcomes including mortality, intensive care unit admission, or readmission to hospital. INTERPRETATION: mPOCT for gastrointestinal pathogens in patients with suspected gastroenteritis returned results more rapidly than conventional testing and was associated with a reduction in single-occupancy room use. However, these benefits need to be balanced against a potential increase in antibiotic use. FUNDING: University Hospital Southampton NHS Foundation Trust.

Practices in the prescription of adrenaline autoinjectors.

BACKGROUND: Anecdotally, the prescription of adrenaline autoinjectors seems to be very variable. We aimed to survey the practice in this area and look at the differences between paediatric allergists and general paediatricians, the factors influencing prescription and implementation of current guidelines. METHODS: We developed an online survey containing 10 paediatric allergy cases and emailed a link to paediatricians. Respondents were asked to identify their prescribing decision in each case, the factors influencing their decisions and which guidelines they had read. RESULTS: Responses were collated from 54 paediatric allergists and 27 general paediatricians. Almost all respondents had read at least one guideline. Prescribing decisions were very inconsistent, and significant influencing factors included peanut or tree nut allergy, trace reactions, remote facilities and parental anxiety. CONCLUSIONS: This study demonstrates that most paediatricians have read at least one anaphylaxis guideline. However, reading the guidelines does not seem to have influenced their daily practice. This suggests that there is a need for improved implementation of anaphylaxis guidelines amongst paediatricians.

Design and rationale of the INSYTE study: A randomised, placebo controlled study to test the efficacy of a synbiotic on liver fat, disease biomarkers and intestinal microbiota in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of fat-related conditions ranging from simple fatty liver, to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. There is growing evidence that NAFLD is a multisystem disease, affecting several extra-hepatic organs and regulatory pathways. Furthermore, since the gut and liver are linked anatomically via the portal vein, disturbances of the gut microbiota (dysbiosis) can affect the liver. OBJECTIVES: In patients with NAFLD, we are testing the effects of a synbiotic which is the combination of a prebiotic (fructooligosaccharides; 4 g/day) and a probiotic (Bifidobacterium animalis subsp. lactis BB-12 at a minimum of 10 billion CFU/day) on a) liver fat percentage, b) NAFLD fibrosis algorithm scores, c) gut microbiota composition. Additionally, there will be several hypothesis-generating secondary outcomes to understand the metaorganismal pathways that influence the development and progression of NAFLD, type 2 diabetes, and cardiovascular risk. DESIGN: In a randomised double-blind placebo-controlled trial, 104 participants were randomised to 10-14 months intervention with either synbiotic (n = 55) or placebo (n = 49). Recruitment was completed in April 2017 and the last study visit will be completed by April 2018. METHODS: Change in gut microbiota composition will be assessed using 16S ribosomal RNA gene sequencing. Change in mean liver fat percentage will be quantified by magnetic resonance spectroscopy (MRS). In addition, change in liver fat severity will be measured using two NAFLD fibrosis algorithm scores. The INSYTE study was approved by the local ethics committee (REC: 12/SC/0614) and is registered at www.clinicaltrials.gov as NCT01680640.

Early parenteral nutrition and growth outcomes in preterm infants: a systematic review and meta-analysis.

BACKGROUND: The achievement of adequate nutritional intakes in preterm infants is challenging and may explain the poor growth often seen in this group. The use of early parenteral nutrition (PN) is one potential strategy to address this problem, although the benefits and harms are unknown. OBJECTIVE: We determined whether earlier administration of PN benefits growth outcomes in preterm infants. DESIGN: We conducted a systematic review of randomized controlled trials (RCTs) and observational studies. RESULTS: Eight RCTs and 13 observational studies met the inclusion criteria (n = 553 and 1796 infants). The meta-analysis was limited by disparate growth-outcome measures. An assessment of bias was difficult because of inadequate reporting. Results are given as mean differences (95% CIs). Early PN reduced the time to regain birth weight by 2.2 d (1.1, 3.2 d) for RCTs and 3.2 d (2.0, 4.4 d) in observational studies. The maximum percentage weight loss with early PN was lower by 3.1 percentage points (1.7, 4.5 percentage points) for RCTs and by 3.5 percentage points (2.6, 4.3 percentage points) for observational studies. Early PN improved weight at discharge or 36 wk postmenstrual age by 14.9 g (5.3, 24.5 g) (observational studies only), but no benefit was shown for length or head circumference. There was no evidence that early PN significantly affects risk of mortality, necrotizing enterocolitis, sepsis, chronic lung disease, intraventricular hemorrhage, or cholestasis. CONCLUSIONS: The results of this review, although subject to some limitations, show that early PN provides a benefit for some short-term growth outcomes. No evidence that early PN increases morbidity or mortality was found. Neonatal research would benefit from the development of a set of core growth outcome measures.