Artificial intelligence automates and augments baseline impedance measurements from pH-impedance studies in gastroesophageal reflux disease

Background

Artificial intelligence (AI) has potential to streamline interpretation of pH-impedance studies. In this exploratory observational cohort study, we determined feasibility of automated AI extraction of baseline impedance (AIBI) and evaluated clinical value of novel AI metrics.

Methods

pH-impedance data from a convenience sample of symptomatic patients studied off (n = 117, 53.1 ± 1.2 years, 66% F) and on (n = 93, 53.8 ± 1.3 years, 74% F) anti-secretory therapy and from asymptomatic volunteers (n = 115, 29.3 ± 0.8 years, 47% F) were uploaded into dedicated prototypical AI software designed to automatically extract AIBI. Acid exposure time (AET) and manually extracted mean nocturnal baseline impedance (MNBI) were compared to corresponding total, upright, and recumbent AIBI and upright:recumbent AIBI ratio. AI metrics were compared to AET and MNBI in predicting  ≥ 50% symptom improvement in GERD patients.

Results

Recumbent, but not upright AIBI, correlated with MNBI. Upright:recumbent AIBI ratio was higher when AET  > 6% (median 1.18, IQR 1.0–1.5), compared to  < 4% (0.95, IQR 0.84–1.1), 4–6% (0.89, IQR 0.72–0.98), and controls (0.93, IQR 0.80–1.09, p ≤ 0.04). While MNBI, total AIBI, and the AIBI ratio off PPI were significantly different between those with and without symptom improvement (p < 0.05 for each comparison), only AIBI ratio segregated management responders from other cohorts. On ROC analysis, off therapy AIBI ratio outperformed AET in predicting GERD symptom improvement when AET was  > 6% (AUC 0.766 vs. 0.606) and 4–6% (AUC 0.563 vs. 0.516) and outperformed MNBI overall (AUC 0.661 vs. 0.313).

Conclusions

BI calculation can be automated using AI. Novel AI metrics show potential in predicting GERD treatment outcome.

     

Effect of intravenous proton pump inhibitor regimens and timing of endoscopy on clinical outcomes of peptic ulcer bleeding

Background and Aim: The most effective schedule of proton pump inhibitor (PPI) administration and the optimal timing of endoscopy in acute peptic ulcer bleeding remain uncertain. The aim of this study was to determine the most efficient PPI regimen and optimal timing of endoscopy. Methods: Consecutive patients with suspected bleeding peptic ulcers were enrolled and randomized to receive either a standard regimen or a high‐dose intensive intravenous regimen. Only patients with bleeding peptic ulcers diagnosed at initial endoscopy continued the study. High‐risk patients received endoscopic hemostasis. The primary outcome measure of recurrent bleeding was compared between the two dosage regimens and between early and late endoscopy. Secondary outcome measures compared included need for endoscopic treatment, blood transfusion, hospital stay, surgery and mortality. Results: A total of 875 patients completed the study. Recurrent bleeding occurred in 11.0% in the standard regimen group, statistically higher than that in the intensive regimen group (6.4%, P = 0.02). Mean units of blood transfused and duration of hospital stay were also higher in the standard regimen group (P < 0.001 for each compared to intensive regimen group). However, no significant differences were noted between the two groups in the need for endoscopic hemostasis, need for surgery, and mortality. Recurrence of bleeding was similar between the early and late endoscopy groups. Units of blood transfused and length of hospital stay were both significantly reduced with early endoscopy. Conclusion: High‐dose PPI infusion is more efficacious in reducing rebleeding rate, blood transfusion requirements and hospital stay. Early endoscopy is safe and more effective than late endoscopy.     

Quaternary ammonium-linked glucuronidation of 1-substituted imidazoles by liver microsomes: interspecies differences and structure-metabolism relationships.

N-Glucuronidation at an aromatic tertiary amine of 5-membered polyaza ring systems was investigated for a model series of eight 1-substituted imidazoles in liver microsomes from five species. The major objectives were to investigate substrate specificities of the series in human microsomes and interspecies variation for the prototype molecule, 1-phenylimidazole. The formed quaternary ammonium-linked metabolites were characterized by positive ion electrospray mass spectrometry. The incubation conditions for the N-glucuronidation of 1-substituted imidazoles were optimized; where for membrane disrupting agents, alamethicin was more effective than the detergents examined. The need to optimize alamethicin concentration was indicated by 4-fold interspecies variation in optimal concentration and by a change in effect from removal of glucuronidation latency to inhibition on increasing concentration. For the four species with quantifiable N-glucuronidation of 1-phenylimidazole, there were 8- and 18-fold variations in the determined apparent K(m) (range, 0.63 to 4.8 mM) and V(max) (range, 0.08 to 1.4 nmol/min/mg of protein) values, respectively. The apparent clearance values (V(max)/K(m)) were in the following order: human congruent with guinea pig congruent with rabbit > rat congruent with dog (no metabolite detected). Monophasic kinetics were observed for the N-glucuronidation of seven substrates by human liver microsomes, which suggests that one enzyme is involved in each metabolic catalysis. No N-glucuronidation was observed for the substrate containing the para-phenyl substituent with the largest electron withdrawing effect, 1-(4-nitrophenyl)imidazole. Linear correlation analyses between apparent microsomal kinetics and substrate physicochemical parameters revealed significant correlations between K(m) and lipophilicity (pi(para) or log P values) and between V(max)/K(m) and both electronic properties (sigma(para) value) and pKa.     

Long-term Nucleos(t)ides Analogues for Chronic Hepatitis B Improve Liver and Spleen Size: A Noninvasive Sonographic Study

Background

Histological improvement and regression of liver fibrosis after long-term use of nucleos(t)ides analogues (NUCs) have been documented. The aim of the present investigation was to evaluate the usefulness of traditional sonography to detect hepatic and splenic changes during NUC therapy in chronic hepatitis B (CHB) patients.

Predictors of Minimum Acceptable Diet among Children Aged 6–23 Months in Nepal: A Multilevel Analysis of Nepal Multiple Indicator Cluster Survey 2019

Background: Minimum Acceptable Diet (MAD), developed by the WHO and UNICEF, is a binary indicator of infant and young child feeding practice that assesses the quality and sufficiency of a child’s diet between the ages of 6 and 23 months. Identifying factors associated with MAD among children can inform policymakers to improve children’s nutritional status. Methods: We extracted data of 1930 children aged 6–23 months from the Nepal Multiple Indicator Cluster Survey 2019. Multilevel analysis was performed to identify factors associated with MAD. Results: Only 30.1% of the children received MAD. Children aged 13–18 months [aOR (Adjusted odds ratio): 2.37, 95% CI (95% Confidence Interval): 1.77, 3.17] and 19–23 months (aOR: 2.6, 95% CI: 1.95, 3.47) were more likely to receive MAD than children aged 6–12 months. Early breastfed children (aOR: 1.34, 95% CI: 1.05, 1.72), those currently breastfeeding (aOR: 4.13, 95% CI: 2.21, 7.69) and children without siblings aged under five (aOR: 1.33, 95% CI: 1.03, 1.73) were more likely to receive MAD. Younger maternal age (aOR: 0.97, 95% CI: 0.95–1.0), higher level of mother’s education (aOR: 1.04, 95% CI: 1.0–1.08) and more media exposure among mothers (aOR: 1.66, 95% CI: 1.24, 2.21) were positive predictors of MAD. Relatively disadvantaged ethnicity/caste (aOR: 0.71, 95% CI: 0.53, 0.94), rural residence (aOR: 1.45, 95% CI: 1.06, 2.00) and residing in Madhesh province (aOR: 0.61, 95% CI: 0.37, 1.0) were also significant predictors of MAD. Conclusions: Children aged 6–12 months, without appropriate breastfeeding, having under-five years siblings, with older mother or mother without media exposure or low education, from relatively disadvantaged ethnicity/caste, from urban areas and residing in Madhesh Province were less likely to receive MAD. Our findings can inform infant and young child feeding policies and practices in Nepal.     

Quantitative structure activity relationship analysis of angiotensin II AT1 receptor antagonists

The quantitative structure activity relationship (QSAR) models were developed using multiple linear regression (MLR) and partial least square (PLS) for a set of 85 AT₁ receptor antagonists of hydantoin series. The MLR and PLS generated comparable models with good predictive ability and all the other statistical values, such as r, r², \textr_(\textcv)² , {\text{r}}_{{({\text{cv}})}}^{2} , and F and s values, were satisfactory. The results obtained from this study indicate the importance of steric (K-alpha3), hydrophobic (log P, and total lipole), and total energy (Cosmic total energy) in determining the activity of AT₁ receptor antagonists. The results clearly explained that optimum hydrophobicity of substituent at R₂ position is favorable for the activity and presence of a substituent of particular size and shape on phenyl ring at R₃ position is essential for the activity. This information is pertinent to the further design of new AT₁ receptor antagonist containing the hydantoin nucleus.     

Safety and efficacy of clobazam versus phenytoin-sodium in the antiepileptic drug treatment of solitary cysticercus granulomas

BACKGROUND: It is now agreed that the prognosis of seizure disorder due to solitary cysticercus granuloma (SCG) is generally good. However, the choice antiepileptic drugs (AEDs) remain empirical, with no comparative trials of different AEDs being available. AIMS: To determine the safety and efficacy (measured by the incidence of 'treatment failure') of clobazam in comparison to standard treatment with phenytoin-sodium for prevention of seizures in persons with solitary cysticercus granulomas (SCGs). SETTINGS AND DESIGN: This pilot study was conducted in a neurology department of a medical college hospital in the form of a prospective, randomized, open-labeled trial. MATERIALS AND METHODS: Forty-eight patients with seizures due to SCG were randomized in an open-labeled trial to either, clobazam (1 mg/kg oral loading followed by 0.5 mg/kg/d) (n=21) or phenytoin (15 mg/kg, oral loading in 3 divided doses over 24 h, followed by 5 mg/kg/d) (n=27). They were followed over 6 months with the primary outcome measure being treatment failure (either discontinuation or modification of AEDs) due to either adverse effects or breakthrough seizures. RESULTS: Treatment failures were noted to be significantly less common (P =0.03) in the clobazam-treated group (n=1; 4.7%) than in phenytoin-treated group (n=9; 33.3%). These included one patient (4.7%) in the clobazam-group who had breakthrough seizures and 3 (11.1%) who had breakthrough seizures and 6 (22.2%) in the phenytoin-treated group who had adverse effects requiring treatment discontinuation. CONCLUSIONS: Clobazam was well tolerated, safe and more effective than phenytoin in the AED treatment of patients with SCG.