bluuebunny/crossref_metadata_2025_split huggingface dataset:
Women's Expectation of Receiving Reproductive Health Care at Catholic and Non‐Catholic Hospitals
Authors: Stulberg Debra B. , Guiahi Maryam , Hebert Luciana E. , Freedman Lori R. 
Published: September 2019

CONTEXTCatholic hospitals operate under directives that prohibit the provision of contraceptives, sterilization and abortion. Little research has examined women's awareness of these institutions’ policies, which affects their ability to make informed decisions about where to seek care.METHODSIn 2016, some 1,430 women aged 18–45 were recruited from a U.S. probability‐based research panel for a survey about hospital care. Respondents were randomized to a hypothetical Catholic or nonreligious hospital group and asked about their expectations for receiving nine specific reproductive services. Multivariable logistic regression analyses were used to evaluate associations between participants’ characteristics and their correctly identifying a hospital as Catholic, as well as between characteristics and expecting that birth control pills, tubal ligation or abortion for serious fetal indications would be provided there.RESULTSWomen randomized to the Catholic hospital group were less likely than those randomized to the nonreligious group to expect provision of birth control pills (77% vs. 86%), tubal ligation (70% vs. 78%) or abortion for serious fetal indications (42% vs. 54%). Income level was associated with correctly identifying the Catholic hospital: Compared with individuals with the lowest income, those in three of the four other income groups were more likely to identify the hospital as Catholic (odds ratios, 1.9–2.2). In comparison with women who misidentified the Catholic hospital, those who identified it as Catholic had lower expectations that the hospital would provide birth control pills (0.3), tubal ligation (0.5) or abortion (0.2).CONCLUSIONSMany women do not realize the breadth of restrictions on reproductive health care at Catholic hospitals. Without institutional transparency, patient autonomy and health outcomes may be compromised.
P: 9 Pharmacotherapies that Specifically Target Ammonia for the Prevention and Treatment of Hepatic Encephalopathy in Adults With Crrhosis
Authors: Zacharias Harry D. , Zacharias Antony P. , Gluud Lise Lotte , Morgan Marsha Y. 
Published: September 2019

BACKGROUND:
Ammonia plays a key role in the genesis of hepatic encephalopathy (HE). Recent interest has focused on drugs which specifically target ammonia, e.g. sodium benzoate (SB), glycerol phenylbutyrate (GPB), ornithine phenylacetate (OP), AST-120, and polyethylene glycol (PEG). This study aims to evaluate the utility of these pharmacotherapies vs. placebo or non-absorbable disaccharides (NAD), for the management of HE in people with cirrhosis. L-ornithine L-aspartate is not included.

METHODS:
Electronic/manual searches of the literature were undertaken for relevant RCTs. The results of the meta-analyses are presented as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CIs). Bias control was assessed using the CHBG domains and the certainty of the evidence using GRADE.

RESULTS:
Eleven RCTs were identified involving SB (n = 1), GPB (n = 1), OA (n = 2), AST-120 (n = 2) and PEG (n = 3). Treatment periods ranged from five days to 16 weeks. All but one trial was at “high risk of bias”; the certainty of the evidence was very low for all outcomes. Nine trials, with 733 participants, reported blood ammonia concentrations. Significant reductions were observed in placebo-controlled trials evaluating SB (MD −32.00, 95% CI −46.85 to −17.15); GPB (MD −12.00, 95% CI −23.37 to −0.63); OP (MD −27.10, 95% CI −48.55 to −5.65) and AST-120 (MD −22.00, 95% CI −26.75 to −17.25). No significant differences in blood ammonia concentrations were observed when compared to NADs. Eleven trials, with 943 participants, reported mortality data, although there were no events in five trials. No beneficial or harmful effects were found in any of the trials. Seven trials, with 521 participants reported data on HE. Beneficial effects were identified for GPB vs. placebo (RR 0.57, 95% CI 0.36 to 0.90; 178 participants; 1 trial; NNTB = 6) and for PEG vs. lactulose (RR 0.19, 95% CI 0.08 to 0.44; 190 participants; 3 trials; NNTB = 4); no beneficial effects were observed in the remaining three trials with extractable data (Figure 1). Ten trials, with 790 participants, reported a total of 130 serious adverse events. There was no evidence of beneficial or harmful effects of the five agents when compared to placebo or NADs.

CONCLUSIONS:
These agents generally reduce blood ammonia concentrations, when compared to placebo, but not when compared to NADs. Their overall effects on clinical outcomes of interest and the potential harms associated with their use remain uncertain. Further evidence is needed to fully evaluate their utility in this clinical setting.
P: 16 Traditional Prognostic Tools are Superior to Cognitive Testing and Stool Frequency as Predictors of Poor Outcomes in Cirrhotic Patients Admitted with Hepatic Encephalopathy
Authors: Pringle Bloom Patricia 
Published: September 2019

BACKGROUND:
Model for end-stage liver disease-sodium (MELD-Na) score and extrahepatic organ failures (EHOFs) predict poor outcomes in cirrhotic patients, including those with hepatic encephalopathy (HE); however, there is a need for the development of additional and specific predictors for outcomes in HE. We aimed to determine if cognitive testing, total daily lactulose dose (TDLD), and stool frequency at hospital discharge predicts readmission and other poor outcomes in patients admitted with overt HE.

METHODS:
We performed a prospective study of patients admitted to a single transplant center with overt HE. When the primary team anticipated discharge within 48 hours, consented subjects underwent Psychometric HE Score (PHES), Montreal Cognitive Assessment (MOCA), liver frailty index (LFI), and stool frequency assessment. MELD-Na, EHOFs, and other clinical variables were assessed via chart review. At 30 days post-discharge, subjects were called to evaluate for a composite primary outcome of HE readmission, transition to hospice, liver transplantation, or death. T-test or chi-square test compared predictors between those who did and did not meet the primary endpoint.

RESULTS:
Of 175 potential candidates, 52 patients provided informed consent and enrolled, with the majority (82) of patients excluded for discharge, death, transplant, or transfer to hospice before enrollment could be performed. Within 30 days, 7 patients had a readmission for HE, and 11 died, were transplanted or transferred to hospice. Seventeen patients met the primary composite endpoint. MELD-Na (28.1 ± 8.0 vs. 22.0 ± 6.0, P = .01) and the number of EHOFs (1.3 ± 1.3 vs. 0.5 ± 0.8, P = 0.03) were higher in patients who met the primary composite outcome. Most predictors did not vary between those who met and did not meet the primary endpoint, including MOCA score (P = 0.73), PHES (P = 0.97), stool frequency (P = 0.34), total daily lactulose dose (P = 0.80), LFI (P = 0.57), admission ammonia (P = 0.58), or being discharged on rifaximin (P = 0.70). Stool frequency at discharge did not correlate with PHES (P = 0.71) or MOCA score (P = 0.51).

CONCLUSIONS:
Traditional prognostic tools in cirrhosis, including MELD-Na and EHOF, were superior to cognitive assessments, total daily lactulose dose, and stool frequency in predicting 30-day outcomes for those admitted with overt HE. Future studies should evaluate MELD-Na and the presence of EHOFs as determinants of discharge readiness or discharge destination in patients admitted with cirrhosis and HE.
P: 24 Comparative Morphological Analysis of Astroglia Reactivity in the Hippocampus of Rats With Acute and Chronic Hepatic Encephalopathy
Authors: Omar El Hiba , Abdelaati El Khiat , Mohamed Aitihya , Halima Gamrani 
Published: September 2019

BACKGROUND:
Hepatic encephalopathy (HE) is a serious complication of advanced liver failure which represents the whole neuropsychiatric abnormalities resulting from liver disease ranging from abnormal behavior to coma. Impairment of cognitive function is well described in HE patients, while mechanisms of memory impairment in HE patients is still not fully understood, however, it may involve a possible gliopathy as well as neuropathy in various brain areas, including the hippocampus known as the main brain structure associated to the memorization process. The aim of the present investigation is to assess astroglia reaction of the hippocampus, in a comparative approach between acute and chronic HE in rat.

METHODS:
Sprague-Dawley rats were divided into 3 groups: controls; rats were treated with saline solution (NaCl 0.9 % i.p) during 3 days, chronic HE group: rats were subjected to Bile Duct Ligation and acute HE group; rats were subjected to 3 i.p injections of thioacetamide (TAA) 300 mg/kg BW. Astroglia was assessed through an immunohistochemical analysis using anti-GFAP antibody on frontal sections of the hippocampus following.

RESULTS:
Our data showed in the TAA rats (3 days following 3 TAA injections) compared to controls, a significant increase of GFAP immunoreactivity within the whole hippocampal areas, while astrocytic processes length and ramification were reduced, the GFAP-immunoreactive area was increased. In contrast to BDL rats, at the cirrhotic stage (4 weeks after surgery), showing the opposite tendency with a drop of the astrocytic GFAP-immunoreactive area as well as the astrocytic length and ramification levels.

CONCLUSIONS:
The present finding sustains a differential astroglial reactivity within the hippocampus of acute and chronic HE rats. Astrocytic morphology changes depends to the severity of liver failure and seems to HE type-dependent, while those astroglial changes lead to a severe gliopathy which may be behind the disturbed cognitive function, especially memory seen in patients with chronic as well as acute HE.
P: 28 Decreased Mean Kurtosis in the Putamen Is a Diagnostic Feature of Minimal Hepatic Encephalopathy in Patients With Cirrhosis
Authors: Sato Takuro 
Published: September 2019

BACKGROUND:
To prevent development of overt hepatic encephalopathy, early intervention for minimal hepatic encephalopathy (MHE) based on accurate diagnosis is essential. This study evaluated to investigate whether magnetic resonance diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) could detect brain microstructure abnormalities in MHE. The aim was to confirm whether brain microstructure abnormalities detected by magnetic resonance imaging were used as diagnosis of MHE.

METHODS:
Thirty-two subjects were prospectively examined with a 3-T MR scanner. Tract-based spatial statistics and region of interest analyses of diffusion imaging were performed to compare mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) values between patients with/without minimal hepatic encephalopathy. Diagnostic performance for detection of MHE was assessed with the receiver operating characteristic analysis.

RESULTS:
Ten subjects were diagnosed as MHE by neuropsychological testing. After exclusion of unsuitable subjects, we analyzed 9 subjects with MHE and 14 subjects without MHE. There were no significant differences in the sex, age, and etiology of liver cirrhosis (alcohol/HCV/NAFLD; 4/3/2 vs 7/3/4, P = 0.87) in the MHE group and non-MHE group. In TBSS, compared with FA and MD, MK detected the broadest area with significant changes in the white matter of patients with MHE (MK, 54.8%; FA, 34.3%; MD, 4.0%, respectively). Regarding ROI analysis in the basal ganglia, FA values of the caudate nucleus (CN), putamen (Put), and globus pallidus (GP) were significantly lower in the MHE group (0.15, 0.19, and 0.29, respectively) when compared with the non-MHE group (0.16, 0.21, and 0.32, respectively) (P = 0.012, 0.002, and 0.0001, respectively). In contrast, MD values in the basal ganglia showed no apparent differences between the groups. Subsequently, we performed ROC analysis on the sites where significant differences were found in the ROI analysis. Among the metrics, MK values of the Put achieved AUROC of 0.90, and sensitivity, specificity, positive predictive value, and negative predictive value of more than 80% (0.89, 0.86, 0.80, and 0.92, respectively) between the MHE and non-MHE groups. In conclusion, mean kurtosis on the putamen was a useful finding to distinguish patients with MHE among subjects with liver cirrhosis.

CONCLUSIONS:
DKI detects changes in the cerebral white matter and basal ganglia regions of the patients with MHE more sensitively than DTI. MK values in the putamen can be a useful marker for diagnosing MHE from cirrhotic patients without MHE.
P: 36 Antibiotic Rifaximin for Treatment of Chronic Liver Disease-Induced HE: A Longitudinal In Vivo 1H-MRS Study of Brain Metabolism on BDL Rats
Authors: Flatt Emmanuelle , Braissant Olivier , Mitrea Stefanita , Sessa Dario , Gruetter Rolf , McLin Valérie A. , Cudalbu Cristina 
Published: September 2019

BACKGROUND:
Rifaximin is a commonly-used antibiotic to treat hepatic encephalopathy (HE), a complex neuropsychiatric syndrome caused by hepatic dysfunction. Rifaximin aims at reducing the production of gut ammonia, an important toxin in HE pathogenesis. In a previous study using bile duct ligated (BDL) rats, we showed that rifaximin at the recommended human dose may help reduce brain Gln levels in early stages of HE.1 These findings raised the question of the efficacy of the dose used at later stages. Therefore we hypothesized that the effect of rifaximin on neurometabolic profile may be dose-related. In this study, the effects of a dose 6.2x that recommended in humans 2 were assessed in vivo and longitudinally in BDL rats. They were compared with non-treated rats (n = 17) and human-dose treated rats (15.7 mg/kg/day, n = 12).1

METHODS:
Plasma measurements of NH4+, bilirubin and 1H-MRS scans were performed on adult Wistar rats (n = 8) before BDL ('week 0') and at weeks 2, 4, 6, 8 post-BDL. Rifaximin was administered twice daily (6x-human-dose = 97.3 mg/kg/day) starting two weeks after BDL-surgery ('week 2'). In vivo 1H-MRS was performed on a 9.4 Tesla MRI system. Changes in metabolites were studied in the hippocampus (2 × 2.8 × 2 mm3) using SPECIAL3 sequence (TE = 2.8 ms). Metabolite concentrations were estimated by LCModel using water as internal reference. Open field test was performed at week 4, 6 and 8 to evaluate motor activity.4

RESULTS:
Plasma measurements of bilirubin confirmed the presence of CLD in all groups of rats. They displayed similar ammonium concentration across groups (Figure 1a). 1H-MRS revealed some significant differences between the 'high-dose rifaximin' rats and non-treated rats: glutamine increase was lower in the 'high-dose rifaximin' group at week 6 and at week 8, both in absolute value and relative to week 2 (+42% vs +118% at week 8, Figure 1b). Moreover, a decrease of glutamine was observed between week 4 and week 6 in the 'high-dose rifaximin' group (−10%), contrary to the non-treated group (Figure 1b). Also, in the 'high-dose rifaximin' group, decreases in the following metabolites were less pronounced during the time course of the study: myo-inositol, taurine, glutamate, ascorbate, creatine, total creatine (Figure 1c).

CONCLUSIONS:
While rifaximin at human dose appeared to have an effect only at the early stages of the disease, a higher dose gave stronger positive effects on the neurometabolic profile. Importantly, no differences between the groups were observed in behavioural tests, but the 'high-dose rifaximin' rats had the tendency to move less. It is therefore possible that such a high dose of antibiotics also leads to some undesirable side-effects such as electrolyte abnormalities or inherent drug toxicity.5,6
P: 42 To Assess Frequency of Hepatic Encephalopathy in Spontaneous Bacterial Peritonitis Patients
Authors: Hassan Adil , Ali Mashooque , Bughio Ubedullah , Bhatti Rehmatullah , Ali Mohsin , Iqbal Javed , Hafeez Abdul 
Published: September 2019

BACKGROUND:
Hepatic encephalopathy (HE) is a commonly encountered complication in cirrhotics. The incidence of HE ranges from 2% to 20% per year in patients with liver cirrhosis. HE is associated with increased morbidity and mortality as well as significant utilization of health care resources. Most cases of significant HE are precipitated by gastrointestinal bleeding, infection, constipation, electrolyte imbalance and medications. Spontaneous bacterial peritonitis (SBP) is an independent predictor of HE. We evaluated frequency of HE in SBP patients.

METHODS:
This cross-sectional study was conducted at the Gastro-hepatology section of Asian Institute of Medical Sciences in Hyderabad, Pakistan from April 2017 to March 2019. 120 Patients with paracentesis-proven SBP [Absolute Neutrophils counts (ANC) >250/mm3], aged from 18 to 80 years were included. Frequency of HE evaluated.

RESULTS:
A total of 120 patients of SBP with mean age 47.80 years, with 88 (73.3%) males and 32 (26.7%) females were examined. Most common serology was HCV (61.7%). 21 were CTP B (17.5%) and 99 were Child C (82.5%). HE was present in 75 (62.5%) with most common grades were II (29.33%) and III (29.33%) and IV (21.33%). Mean ANC 5086, 96 (80%) were PPI users and 64.58% have HE.

CONCLUSIONS:
Hepatic encephalopathy has strong association with SBP and PPI use. Screening for asymptomatic SBP in all patients with HE should be considered and over-the-counter PPI use should be restrained.
P: 65 Drug-induced Hyperammonaemia: Data From VigiBase, the WHO Database
Authors: Weiss Nicolas , Salem Joe-Elie , LeBrun-Vignes Benedicte , Bihan Kevin , Rudler Marika , Bouzbib Charlotte , Sultanik Philippe , Thabut Dominique 
Published: September 2019

BACKGROUND:
Altered consciousness secondary to metabolic encephalopathies represents a major cause of ICU admission with favorable outcome when diagnosed and treated rapidly. Ammonia dosage is thus recommended in most textbooks in the absence of any diagnosis after etiological work-up encompassing biological sampling, cerebral imaging and EEG. Despite hyperammonaemia is most commonly secondary to liver diseases, portosystemic shunts, inborn errors of metabolism, mostly urea cycle defects, microbial pullulation or drug-induced hyperammonaemia (DIH) are other possible causes. DIH is poorly described but is mainly recognized as the consequence of valproic acid. Some antineoplastic agents, fluorouracile or asparaginase, have been implicated but this class is evolving rapidly. To describe the drugs associated with DIH.

METHODS:
We used VigiBase, the WHO global Individual Case Safety Report (ICSR) database, which contains reports of suspected adverse drug reactions (ADRs) collected by national drug authorities in over 130 countries between 1967 and 8 May 2019. This observational retrospective study included all ADRs reported as "hyperammonaemia" according to the Medical Dictionary for Drug Regulatory Activities (MedDRAv21.1) term (Prefered term [PT] level). The drugs considered in the analysis were those notified as suspected treatments. Drugs used to treat hyperammonaemia or hepatic encephalopathy were excluded as were drugs reported less than 3 times. Drugs with a positive lower end of the 95% credibility interval for the information component (IC025) ≥0, an indicator value for disproportionate Bayesian reporting, was considered as causative of hyperammonaemia.

RESULTS:
Among 19 438 165 ICSRs, 576 drugs were identified for the term "hyperammonaemia [PT]". Six were excluded because they were used to treat hyperammonaemia or hepatic encephalopathy. Thus, 73 drugs had a an IC025 ≥0 and represented 2759 cases (0.014%). Twelve drugs were reported more than thirty times (Table 1).

CONCLUSION:
Besides commonly involved drugs, some other commonly used drugs seem associated in DIH. These data could help in the etiological work-up of hyperammonemia.
P: 81 Previously Identified Candidate Gene Associations in Hepatic Encephalopathy Do Not Replicate in the STOPAH Cohort
Authors: Atkinson Stephen R. , Forrest Ewan , Goh Ee Teng , Thursz Mark R. , McQuillin Andrew , Morgan Marsha Y. 
Published: September 2019

BACKGROUND:
Hepatic encephalopathy (HE) is a common complication of cirrhosis and negatively affects quality of life and prognosis. However, the development of HE is not inevitable, even in patients severe hepatic decompensation. Recently, there has been interesting the possibility that the susceptibility to develop HE is, at least in part, genetically determined. In 2017, Gil-Gómez et al (J Hepatol 2017;66(Suppl 1):S144) reported significant associations between variants in nine candidate genes and the presence of overt HE in 400 patients included in the CLIF consortium cross-sectional study. In this study overt HE was diagnosed using the West Haven criteria, while acute on chronic liver failure (ACLF) was diagnosed using the CLIF-OF score. The aim of the present study was to replicate these findings in participants in the STOPAH alcoholic hepatitis treatment trial.

METHODS:
Genomic DNA was available in 731 participants in the STOPAH trial. Overt HE was diagnosed using the West Haven criteria; ACLF was diagnosed using the CLIF-OF score. Data on six of the nine SNP associated with overt HE and/or ACLF in the Spanish study were identified in the STOPAH GWAS database. Genotypic association analyses were undertaken for each of the genetic variants in the entire population and in subgroups defined by the presence of overt HE and/or ACLF.

RESULTS:
A total of 199 (27.2%) of the 731 STOPAH participants had overt HE on admission, while 193 (26.4%) had ACLF; patients were classified as follows: HE and ACLF (n = 61), HE but no ACLF (138); ACLF but no HE (n = 132); no ACLF and no HE (n = 400). Only one significant association was identified viz. rs752949 in SLC1A2 in participants with overt HE but without ACLF (Table 1); however, the significance of this association was lost when the data were corrected for multiple testing.

CONCLUSIONS:
The previously reported genetic associations with overt HE were not replicated in the present study. The number of participants was almost double that in the Spanish study but the proportions of patients with HE and ACLF were similar. Not all of the reported SNPs were available but at least two SNPs were tested for association in each patient subgroup. Further large case-control studies and meta-analyses of existing data are needed.