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The Cochrane Database of Systematic... Jul 2023Hepatic encephalopathy describes the spectrum of neuropsychiatric changes that may complicate the course of cirrhosis and detrimentally affect outcomes. Ammonia plays a... (Review)
Review
BACKGROUND
Hepatic encephalopathy describes the spectrum of neuropsychiatric changes that may complicate the course of cirrhosis and detrimentally affect outcomes. Ammonia plays a key role in its development. Rifaximin is a non-absorbable antibiotic that inhibits urease-producing bacteria and reduces absorption of dietary and bacterial ammonia.
OBJECTIVES
To evaluate the beneficial and harmful effects of rifaximin versus placebo, no intervention, or non-absorbable disaccharides for: (i) the prevention of hepatic encephalopathy, and (ii) the treatment of minimal and overt hepatic encephalopathy, in people with cirrhosis, both when used alone and when combined with a non-absorbable disaccharide.
SEARCH METHODS
We searched the Cochrane Hepato-Biliary Group Clinical Trials Register, CENTRAL, MEDLINE, Embase, three other databases, the reference lists of identified papers, and relevant conference proceedings. We wrote to authors and pharmaceutical companies for information on other published, unpublished, or ongoing trials. Searches were performed to January 2023.
SELECTION CRITERIA
We included randomised clinical trials assessing prevention or treatment of hepatic encephalopathy with rifaximin alone, or with a non-absorbable disaccharide, versus placebo/no intervention, or a non-absorbable disaccharide alone.
DATA COLLECTION AND ANALYSIS
Six authors independently searched for studies, extracted data, and validated findings. We assessed the design, bias risk, and participant/intervention characteristics of the included studies. We assessed mortality, serious adverse events, health-related quality of life, hepatic encephalopathy, non-serious adverse events, blood ammonia, Number Connection Test-A, and length of hospital stay.
MAIN RESULTS
We included 41 trials involving 4545 people with, or at risk for, developing hepatic encephalopathy. We excluded 89 trials and identified 13 ongoing studies. Some trials involved participants with more than one type of hepatic encephalopathy or more than one treatment comparison. Hepatic encephalopathy was classed as acute (13 trials), chronic (7 trials), or minimal (8 trials), or else participants were considered at risk for its development (13 trials). The control groups received placebo (12 trials), no/standard treatment (1 trial), or a non-absorbable disaccharide (14 trials). Eighteen trials assessed rifaximin plus a non-absorbable disaccharide versus a non-absorbable disaccharide alone. We classified 11 trials as at high risk of overall bias for mortality and 28 for non-mortality outcomes, mainly due to lack of blinding, incomplete outcome data, and selective reporting. Compared to placebo/no intervention, rifaximin likely has no overall effect on mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.50 to 1.38; P = 48, I = 0%; 13 trials, 1007 participants; moderate-certainty evidence), and there may be no overall effect when compared to non-absorbable disaccharides (RR 0.99, 95% CI 0.49 to 1.97; P = 0.97, I = 0%; 10 trials, 786 participants; low-certainty evidence). However, there is likely a reduction in the overall risk of mortality when comparing rifaximin plus a non-absorbable disaccharide to a non-absorbable disaccharide alone (RR 0.69, 95% CI 0.55 to 0.86; number needed to treat for an additional beneficial outcome (NNTB) = 22; P = 0.001, I = 0%; 14 trials, 1946 participants; moderate-certainty evidence). There is likely no effect on the overall risk of serious adverse events when comparing rifaximin to placebo/no intervention (RR 1.05, 95% CI 0.83 to 1.32; P = 68, I = 0%; 9 trials, 801 participants; moderate-certainty evidence) and there may be no overall effect when compared to non-absorbable disaccharides (RR 0.97, 95% CI 0.66 to 1.40; P = 85, I = 0%; 8 trials, 681 participants; low-certainty evidence). However, there was very low-certainty evidence that use of rifaximin plus a non-absorbable disaccharide may be associated with a lower risk of serious adverse events than use of a non-absorbable disaccharide alone (RR 0.66, 95% CI 0.45 to 0.98; P = 0.04, I = 60%; 7 trials, 1076 participants). Rifaximin likely results in an overall effect on health-related quality of life when compared to placebo/no intervention (mean difference (MD) -1.43, 95% CI -2.87 to 0.02; P = 0.05, I = 81%; 4 trials, 214 participants; moderate-certainty evidence), and may benefit health-related quality of life in people with minimal hepatic encephalopathy (MD -2.07, 95% CI -2.79 to -1.35; P < 0.001, I = 0%; 3 trials, 176 participants). The overall effect on health-related quality of life when comparing rifaximin to non-absorbable disaccharides is very uncertain (MD -0.33, 95% CI -1.65 to 0.98; P = 0.62, I = 0%; 2 trials, 249 participants; very low-certainty evidence). None of the combined rifaximin/non-absorbable disaccharide trials reported on this outcome. There is likely an overall beneficial effect on hepatic encephalopathy when comparing rifaximin to placebo/no intervention (RR 0.56, 95% CI 0.42 to 0.77; NNTB = 5; P < 0.001, I = 68%; 13 trials, 1009 participants; moderate-certainty evidence). This effect may be more marked in people with minimal hepatic encephalopathy (RR 0.40, 95% CI 0.31 to 0.52; NNTB = 3; P < 0.001, I = 10%; 6 trials, 364 participants) and in prevention trials (RR 0.71, 95% CI 0.56 to 0.91; NNTB = 10; P = 0.007, I = 36%; 4 trials, 474 participants). There may be little overall effect on hepatic encephalopathy when comparing rifaximin to non-absorbable disaccharides (RR 0.85, 95% CI 0.69 to 1.05; P = 0.13, I = 0%; 13 trials, 921 participants; low-certainty evidence). However, there may be an overall beneficial effect on hepatic encephalopathy when comparing rifaximin plus a non-absorbable disaccharide to a non-absorbable disaccharide alone (RR 0.58, 95% CI 0.48 to 0.71; NNTB = 5; P < 0.001, I = 62%; 17 trials, 2332 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
Compared to placebo/no intervention, rifaximin likely improves health-related quality of life in people with minimal hepatic encephalopathy, and may improve hepatic encephalopathy, particularly in populations with minimal hepatic encephalopathy and when it is used for prevention. Rifaximin likely has no overall effect on mortality, serious adverse events, health-related quality of life, or hepatic encephalopathy compared to non-absorbable disaccharides. However, when used in combination with a non-absorbable disaccharide, it likely reduces overall mortality risk, the risk of serious adverse events, improves hepatic encephalopathy, reduces the length of hospital stay, and prevents the occurrence/recurrence of hepatic encephalopathy. The certainty of evidence for these outcomes is very low to moderate; further high-quality trials are needed.
Topics: Humans; Hepatic Encephalopathy; Rifaximin; Quality of Life; Ammonia; Liver Cirrhosis; Disaccharides
PubMed: 37467180
DOI: 10.1002/14651858.CD011585.pub2 -
Journal of Clinical PsychopharmacologyHyperammonemia is an adverse effect that poses clinical uncertainty around valproic acid (VPA) use. The prevalence of symptomatic and asymptomatic hyperammonemia and its...
BACKGROUND
Hyperammonemia is an adverse effect that poses clinical uncertainty around valproic acid (VPA) use. The prevalence of symptomatic and asymptomatic hyperammonemia and its relationship to VPA concentration is not well established. There is also no clear guidance regarding its management. This results in variability in the monitoring and treatment of VPA-induced hyperammonemia. To inform clinical practice, this systematic review aims to summarize evidence available around VPA-associated hyperammonemia and its prevalence, clinical outcomes, and management.
METHODS
An electronic search was performed through Ovid MEDLINE, Ovid Embase, Web of Science, and PsycINFO using search terms that identified hyperammonemia in patients receiving VPA. Two reviewers independently performed primary title and abstract screening with a third reviewer resolving conflicting screening results. This process was repeated during the full-text review process.
RESULTS
A total of 240 articles were included. Prevalence of asymptomatic hyperammonemia (5%-73%) was higher than symptomatic hyperammonemia (0.7%-22.2%) and occurred within the therapeutic range of VPA serum concentration. Various risk factors were identified, including concomitant medications, liver injury, and defects in carnitine metabolism. With VPA discontinued, most symptomatic patients returned to baseline mental status with normalized ammonia level. There was insufficient data to support routine monitoring of ammonia level for VPA-associated hyperammonemia.
CONCLUSIONS
Valproic acid-associated hyperammonemia is a common adverse effect that may occur within therapeutic range of VPA. Further studies are required to determine the benefit of routine ammonia level monitoring and to guide the management of VPA-associated hyperammonemia.
Topics: Humans; Valproic Acid; Anticonvulsants; Epilepsy; Hyperammonemia; Ammonia; Clinical Decision-Making; Uncertainty; Drug-Related Side Effects and Adverse Reactions
PubMed: 37126830
DOI: 10.1097/JCP.0000000000001689 -
Transplant International : Official... 2022Hyperammonemia after lung transplantation (HALT) is a rare but serious complication with high mortality. This systematic review delineates possible etiologies of HALT... (Review)
Review
Hyperammonemia after lung transplantation (HALT) is a rare but serious complication with high mortality. This systematic review delineates possible etiologies of HALT and highlights successful strategies used to manage this fatal complication. Seven biomedical databases and grey literature sources were searched using keywords relevant to hyperammonemia and lung transplantation for publications between 1995 and 2020. Additionally, we retrospectively analyzed HALT cases managed at our institution between January 2016 and August 2018. The systematic review resulted in 18 studies with 40 individual cases. The mean peak ammonia level was 769 μmol/L at a mean of 14.1 days post-transplant. The mortality due to HALT was 57.5%. In our cohort of 120 lung transplants performed, four cases of HALT were identified. The mean peak ammonia level was 180.5 μmol/L at a mean of 11 days after transplantation. HALT in all four patients was successfully treated using a multimodal approach with an overall mortality of 25%. The incidence of HALT (3.3%) in our institution is comparable to prior reports. Nonetheless, ammonia levels in our cohort were not as high as previously reported and peaked earlier. We attributed these significant differences to early recognition and prompt institution of multimodal treatment approach.
Topics: Ammonia; Cohort Studies; Humans; Hyperammonemia; Lung Transplantation; Retrospective Studies
PubMed: 35620675
DOI: 10.3389/ti.2022.10433 -
Journal of the International Society of... Dec 2023Citrulline is a popular dietary supplement, primarily thought to exert ergogenic effects on exercise performance through the enhancement of nitric oxide (NO) synthesis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Citrulline is a popular dietary supplement, primarily thought to exert ergogenic effects on exercise performance through the enhancement of nitric oxide (NO) synthesis and ammonia buffering. However, recent findings surrounding citrulline's effect on endurance performance have been inconsistent. A systematic review and meta-analysis of the relevant literature have yet to be undertaken.
AIM
To determine if acute ingestion of citrulline has an ergogenic effect on endurance performance in young healthy adults.
METHODS
A systematic search of three databases was undertaken to find peer-reviewed randomized controlled trials (RCTs) published in English investigating the effects of citrulline supplementation on endurance performance in young healthy adults. Two independent investigators completed a three-phased screening procedure against pre-determined eligibility criteria. Included studies evaluated loading or bolus dosage regimes of citrulline in participants aged 18 or over that were at least recreationally active. Outcome measures focused on time-to-completion (TTC) or time-to-exhaustion (TTE) in continuous submaximal intensity exercise. Cochrane's Risk of Bias 2 (RoB 2) tool was used to assess the risk of bias in individual studies. Meta-analysis was conducted using a fixed-effects model to pool the weighted estimate of standardized mean differences (SMD) across studies. A chi-squared test assessed heterogeneity between studies. This review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Nine studies ( = 158 participants) met the eligibility criteria; five reported TTE outcomes (I = 0%, χ = 0.37, df = 4, = 0.99) and four reported TTC outcomes (I = 0%, χ = 0.46, df = 3, = 0.93), both with a low between-study heterogeneity. The results of the meta-analyses showed no significant difference in the endurance performance measures, TTE (pooled SMD = 0.03 [-0.27, 0.33]) and TTC (pooled SMD = -0.07 [-0.50, 0.15]), after acute ingestion of citrulline supplementation or a control in young healthy adults.
DISCUSSION
The current evidence suggests no significant benefit of citrulline supplementation for endurance performance. However, the small evidence base requires further research to fully evaluate this topic. Recommendations include a focus on female populations; higher continuous doses of citrulline over seven days; and TTC outcome measures over longer distances to simulate competition.
Topics: Female; Humans; Adult; Citrulline; Exercise; Dietary Supplements; Nutritional Status
PubMed: 37155582
DOI: 10.1080/15502783.2023.2209056 -
Indoor Air Nov 2021Indoor ammonia (NH ) pollution has been paid more and more attention in view of its health risk. However, few studies have investigated the exposure level in the... (Review)
Review
Indoor ammonia (NH ) pollution has been paid more and more attention in view of its health risk. However, few studies have investigated the exposure level in the non-occupational environment in China. This study systematically reviewed the indoor ammonia exposure level in different regions, the equivalent exposure concentration of different populations, and the factors that influence indoor air ammonia in residences, offices, and schools in China. The literature published in 1980-2019 from main databases was searched and detailed screened, and finally, 56 related studies were selected. The results illustrated that the median concentration of indoor air ammonia in residences, offices, and school buildings was 0.21 mg/m , 0.26 mg/m , and 0.15 mg/m . There were 46.4%, 71.4%, and 40% of these samples exceeding the NH standard, respectively. The national concentrations and the equivalent exposure levels of adults and children were calculated and found to be higher than 0.20 mg/m . The concentration of ammonia varied greatly in different climate zones and economic development regions. Higher concentrations were found in the severe cold zone and the regions with higher economic level. This review reveals a high exposure risk of indoor air ammonia and the crucial impact of human emission, indoor air temperature, new concrete, and economic level, suggesting further investigation on indoor air ammonia evaluation and health effects.
Topics: Adult; Air Pollutants; Air Pollution, Indoor; Ammonia; Child; China; Environmental Monitoring; Humans; Schools
PubMed: 34181775
DOI: 10.1111/ina.12864 -
Orphanet Journal of Rare Diseases Oct 2020N-Acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder affecting the urea cycle, leading to episodes of hyperammonemia... (Review)
Review
BACKGROUND
N-Acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder affecting the urea cycle, leading to episodes of hyperammonemia which can cause significant morbidity and mortality. Since its recognition in 1981, NAGS deficiency has been treated with carbamylglutamate with or without other measures (nutritional, ammonia scavengers, dialytic, etc.). We conducted a systematic literature review of NAGS deficiency to summarize current knowledge around presentation and management.
METHODS
Case reports and case series were identified using the Medline database, as well as references from other articles and a general internet search. Clinical data related to presentation and management were abstracted by two reviewers.
RESULTS
In total, 98 cases of NAGS deficiency from 79 families, in 48 articles or abstracts were identified. Of these, 1 was diagnosed prenatally, 57 were neonatal cases, 34 were post-neonatal, and 6 did not specify age at presentation or were asymptomatic at diagnosis. Twenty-one cases had relevant family history. We summarize triggers of hyperammonemic episodes, diagnosis, clinical signs and symptoms, and management strategies. DNA testing is the preferred method of diagnosis, although therapeutic trials to assess response of ammonia levels to carbamylglutamate may also be helpful. Management usually consists of treatment with carbamylglutamate, although the reported maintenance dose varied across case reports. Protein restriction was sometimes used in conjunction with carbamylglutamate. Supplementation with citrulline, arginine, and sodium benzoate also were reported.
CONCLUSIONS
Presentation of NAGS deficiency varies by age and symptoms. In addition, both diagnosis and management have evolved over time and vary across clinics. Prompt recognition and appropriate treatment of NAGS deficiency with carbamylglutamate may improve outcomes of affected individuals. Further research is needed to assess the roles of protein restriction and supplements in the treatment of NAGS deficiency, especially during times of illness or lack of access to carbamylglutamate.
Topics: Amino-Acid N-Acetyltransferase; Ammonia; Humans; Hyperammonemia; Infant, Newborn; Urea Cycle Disorders, Inborn
PubMed: 33036647
DOI: 10.1186/s13023-020-01560-z -
Clinical and Experimental Hepatology Jun 2023Patients with minimal hepatic encephalopathy (MHE) have no recognizable clinical symptoms of hepatic encephalopathy (HE), but the mild cognitive and psychomotor deficits...
AIM OF THE STUDY
Patients with minimal hepatic encephalopathy (MHE) have no recognizable clinical symptoms of hepatic encephalopathy (HE), but the mild cognitive and psychomotor deficits have been shown to negatively affect their daily functioning and quality of life. Treatment with probiotics has shown benefit in some clinical trials. This review aimed to systematically analyze the efficacy of probiotics in the treatment of MHE.
MATERIAL AND METHODS
A systematic search of the electronic databases PubMed, Science Direct, and Cochrane Library was conducted for randomized controlled trials (RCTs) in adult patients with MHE who had been given probiotics intervention. The primary outcomes were reversal of MHE and improvement of neuropsychometric tests, while the secondary outcome was the reduction of serum ammonia.
RESULTS
Nine RCTs involving 776 MHE patients were included, consisting of 311 patients receiving probiotics and 465 patients receiving comparator (placebo or no treatment, lactulose, L-ornithine L-aspartate [LOLA], or rifaximin). The meta-analysis showed that probiotics significantly reversed MHE (OR = 3.95, < 0.0001, 95% CI: 2.05 to 7.60) compared with placebo or no treatment. Probiotics also significantly reduced serum ammonia compared with placebo (pooled mean difference -25.94, = 0.04, 95% CI: -50.21 to -1.66). However when compared to lactulose and LOLA, probiotics did not show a significant difference in reversal of MHE or reduction of serum ammonia levels.
CONCLUSIONS
Probiotics were more effective in reversal of MHE and reduced serum ammonia levels in patients with MHE compared to placebo or no treatment, but not more effective than lactulose or LOLA.
PubMed: 37502435
DOI: 10.5114/ceh.2023.128768 -
Neurosurgical Review Jul 2023While magnetic resonance imaging (MRI) is the current standard imaging method for diagnosing and localizing corticotropinomas in Cushing disease, it can fail to detect... (Review)
Review
While magnetic resonance imaging (MRI) is the current standard imaging method for diagnosing and localizing corticotropinomas in Cushing disease, it can fail to detect adenomas in up to 40% of cases. Recently, positron emission tomography (PET) has shown promise as a diagnostic tool to detect pituitary adenomas in Cushing disease. We perform a scoping review to characterize the uses of PET in diagnosing Cushing disease, with a focus on describing the types of PET investigated and defining PET-positive disease. A scoping review was conducted following the PRISMA-ScR guidelines. Thirty-one studies fulfilled our inclusion criteria, consisting of 10 prospective studies, 8 retrospective studies, 11 case reports, and 2 illustrative cases with a total of 262 patients identified. The most commonly utilized PET modalities in prospective/retrospective studies were FDG PET (n = 5), MET PET (n = 5), 68 Ga-DOTATATE PET (n = 2), 13N-ammonia PET (n = 2), and 68 Ga-DOTA-CRH PET (n = 2). MRI positivity ranged from 13 to 100%, while PET positivity ranged from 36 to 100%. In MRI-negative disease, PET positivity ranged from 0 to 100%. Five studies reported the sensitivity and specificity of PET, which ranged from 36 to 100% and 50 to 100%, respectively. PET shows promise in detecting corticotropinomas in Cushing disease, including MRI-negative disease. MET PET has been highly investigated and has demonstrated excellent sensitivity and specificity. However, preliminary studies with FET PET and 68 Ga-DOTA-CRH PET show promise for achieving high sensitivity and specificity and warrant further investigation.
Topics: Humans; Pituitary ACTH Hypersecretion; Nitrogen Radioisotopes; Prospective Studies; Retrospective Studies; Positron-Emission Tomography
PubMed: 37393399
DOI: 10.1007/s10143-023-02077-2 -
Journal of Vector Borne Diseases 2021This study aimed to review the effectiveness of lactic acid when combined with other types of attractants for Aedes spp. (Review)
Review
BACKGROUND & OBJECTIVES
This study aimed to review the effectiveness of lactic acid when combined with other types of attractants for Aedes spp.
METHODS
A systematic review was conducted according to the protocol for a systematic review and meta-analysis (PRISMA). Literature search used Cinahl, Medline/PubMed, ScienceDirect, ProQuest and Ebsco electronic databases. Research articles used in the systematic review were experimental articles that reported the effectiveness of mosquito traps using lactic acid or a combination of lactic acid with other attractants.
RESULTS
From a total of 42 articles reviewed, there were 6 articles fulfilling the inclusion criteria. The highest synergistic combination of lactic acid in the ketone group was shown in the acetone compound, in the sulfides class, dimethyl sulfides, and in the chloroalkanes group, chloroform. The combination of lactic acid with two effective attractants can be seen in the incorporation of ammonia + caproic acid, and for the incorporation of lactic acid with three other effective attractants illustrated by combining ammonia + caproic acid + CO.
INTERPRETATION & CONCLUSION
Lactic acid as an attractant can be combined with other various compounds (ketone compounds, sulfides and chloroalkanes). Lactic acid increases its effectiveness in trapping Ae. aegypti and/or Ae. albopictus if combined with acetone, dimethyl sulfides, and/or chloroform.
Topics: Aedes; Animals; Dengue; Lactic Acid; Meta-Analysis as Topic; Mosquito Control; Mosquito Vectors
PubMed: 35074942
DOI: 10.4103/0972-9062.316276 -
Transplant Infectious Disease : An... Dec 2022Hyperammonemia syndrome (HS) is a rare post-transplant complication associated with high morbidity and mortality. Its incidence appears to be higher in lung transplant... (Review)
Review
BACKGROUND
Hyperammonemia syndrome (HS) is a rare post-transplant complication associated with high morbidity and mortality. Its incidence appears to be higher in lung transplant recipients and its pathophysiology is not well understood. In addition to underlying metabolic abnormalities, it is postulated that HS may be associated with Ureaplasma or Mycoplasma spp. lung infections. Management of this condition is not standardized and may include preemptive antimicrobials, renal replacement, nitrogen scavenging, and bowel decontamination therapies, as well as dietary modifications.
METHODS
In this case series, we describe seven HS cases, five of whom had metabolic deficiencies ruled out. In addition, a literature review was performed by searching PubMed following PRISMA-P guidelines. Articles containing the terms "hyperammonemia" and "lung" were reviewed from 1 January 1997 to 31 October 2021.
RESULTS
All HS cases described in our center had positive airway samples for Mycoplasmataceae, neurologic abnormalities and high ammonia levels post-transplant. Mortality in our group (57%) was similar to that published in previous cases. The literature review supported that HS is an early complication post-transplant, associated with Ureaplasma spp. and Mycoplasma hominis infections and of worse prognosis in patients presenting cerebral edema and seizures.
CONCLUSION
This review highlights the need for rapid testing for Ureaplasma spp. and M. hominis after lung transplant, as well as the necessity for future studies to explore potential therapies that may improve outcomes in these patients.
Topics: Humans; Meta-Analysis as Topic; Lung Transplantation; Hyperammonemia; Ureaplasma
PubMed: 36039822
DOI: 10.1111/tid.13940