While therapeutic drug monitoring should be performed at trough, a drug level ≥4.9 μg/mL obtained during the first 9 days predicts a therapeutic trough drug level with reasonable confidence.
Background: Accurate definition of the gastroduodenal and ileocaecal junctions (GDJ, ICJ) is essential for the measurement of regional transit times.
Aims:To compare the assessment of these landmarks using the novel gas-sensing capsule and validated wireless motility capsule (WMC), and to evaluate intra-subject variance in transit times Methods: Healthy subjects ingested the gas-sensing capsule and WMC tandemly in random order. Inter-observer agreement was evaluated by intra-class correlation coefficient (ICC). Agreement between the paired devices' transit times was assessed using Bland-Altman analysis; coefficient of variation was performed to express intraindividual variance in transit times. Similar analyses were completed with tandemly ingested gas-sensing capsules.
Results:The inter-observer agreement for landmarks for both capsules was excellent (mean ICC ≥0.97) in 50 studies. The GDJ was identifiable in 92% of the gas-sensing capsule studies versus 82% of the WMC studies (p = 0.27); the ICJ in 96% versus 84%, respectively (p = 0.11). In the primary cohort (n = 26), median regional transit times differed by less than 6 min between paired capsules. Bland-Altman revealed a bias of −0.12 (95% limits of agreement, −0.94 to 0.70) hours for GDJ and − 0.446 (−2.86 to 2.0) hours for ICJ. Similar results were found in a demographically distinct validation cohort (n = 24). For tandemly ingested gas-sensing capsules, coefficients of variation of transit times were 11%-35%, which were similar to variance between the paired gas-sensing capsule and WMC, as were the biases. The capsules were well tolerated.Conclusions: Key anatomical landmarks are accurately identified with the gas-sensing capsule in healthy individuals. Intra-individual differences in transit times between capsules are probably due to physiological factors. Studies in populations with gastrointestinal diseases are now required.
SVR12 rates with sofosbuvir/daclatasvir in advanced liver disease are lower than in compensated disease. Although treatment improves MELD and Child-Pugh in most patients, a significant proportion will die or require transplantation. In those with MELD ≥20, it may be better to delay treatment until post-transplant.
He has received research grants for investigator-driven studies from Atmo Biosciences. He holds shares in Atmo Biosciences. His Department financially benefits from the sales of a digital application, booklets and online courses on the FODMAP diet. REB: Consultant or advisory board member for Allergan, Atmo Biosciences, Antara. She has received speaking honoraria from Bayer.
A 60-year-old woman was admitted with sepsis, relative bradycardia, CT evidence of numerous small liver abscesses and 'skin bronzing' consistent with hereditary haemochromatosis (HH). Yersinia enterocolitica O:9 infection was confirmed by serology specimens taken 10 days apart. Iron overload was detected, and homozygous C282Y gene mutation confirmed HH. Liver biopsy revealed grade IV siderosis with micronodular cirrhosis. Haemochromatosis is a common, inherited disorder leading to iron overload that can produce end-organ damage from excess iron deposition. Haemochromatosis diagnosis allowed aggressive medical management with phlebotomy achieving normalisation of iron stores. Screening for complications of cirrhosis was started that included hepatoma surveillance. Iron overload states are known to increase patient susceptibility to infections caused by lower virulence bacteria lacking sophisticated iron metabolism pathways, for example, Yersinia enterocolitica Although these serious disseminated infections are rare, they may serve as markers for occult iron overload and should prompt haemochromatosis screening.
Summary
Background
Carbohydrate fermentation plays a pivotal role in maintaining colonic health with excessive proximal and deficient distal fermentation being detrimental.
Aims
To utilise telemetric gas‐ and pH‐sensing capsule technologies for defining patterns of regional fermentation following dietary manipulations, alongside conventional techniques of measuring fermentation.
Methods
In a double‐blind crossover trial, 20 patients with irritable bowel syndrome were fed low FODMAP diets that included no extra fibre (total fibre content 24 g/day), or additional poorly fermented fibre, alone (33 g/day) or with fermentable fibre (45 g/day) for 2 weeks. Plasma and faecal biochemistry, luminal profiles defined by tandem gas‐ and pH‐sensing capsules, and faecal microbiota were assessed.
Results
Plasma short‐chain fatty acid (SCFA) concentrations (μmol/L) were median (IQR) 121 (100–222) with fibre combination compared with 66 (44–120) with poorly fermented fibre alone (p = 0.028) and 74 (55–125) control (p = 0.069), but no differences in faecal content were observed. Luminal hydrogen concentrations (%), but not pH, were higher in distal colon (mean 4.9 [95% CI: 2.2–7.5]) with fibre combination compared with 1.8 (0.8–2.8) with poorly fermented fibre alone (p = 0.003) and 1.9 (0.7–3.1) control (p = 0.003). Relative abundances of saccharolytic fermentative bacteria were generally higher in association with supplementation with the fibre combination.
Conclusions
A modest increase in fermentable plus poorly fermented fibres had minor effects on faecal measures of fermentation, despite increases in plasma SCFA and abundance of fermentative bacteria, but the gas‐sensing capsule, not pH‐sensing capsule, detected the anticipated propagation of fermentation distally in the colon. The gas‐sensing capsule technology provides unique insights into localisation of colonic fermentation.
Trial registration: ACTRN12619000691145.
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