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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 We wrote to authors and pharmaceutical companies for information on other published, unpublished, or ongoing trials.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 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 -
Cureus Jan 2024There are no guidelines for the most effective medication to reduce hepatic encephalopathy (HE) or the associated mortality. The purpose of this study is to determine... (Review)
Review
There are no guidelines for the most effective medication to reduce hepatic encephalopathy (HE) or the associated mortality. The purpose of this study is to determine the most effective possible treatment among the single treatment options or the combined treatment options for decreasing the morbidity and mortality of HE. We evaluated the outcomes by various parameters such as the quality of life, reduction in ammonia, all causes of mortality, adverse events, reversal of minimal HE, and development of overt HE. We systematically searched PubMed, Cochrane, Web of Science, and Scopus till the 19th of January 2023 for studies that assess various treatment options for HE. Data were extracted from eligible studies and pooled in a frequentist network meta-analysis as standardized mean difference (SMD) and their 95% confidence interval (CI) using the MetaInsight web-based tool. The Cochrane Tool was used to assess the randomized controlled trials' quality (RCT), while the NIH tool was used to assess the quality of the included cohort studies. Utilizing the R software, the network meta-analysis was conducted. In addition to a significant variation in cases of (Lactulose and Rifaximin) compared with Rifaximin (RR= 0.39, 95% CI [0.17; 0.89]), the results demonstrated a significantly lower incidence of overt HE in (Lactulose and Rifaximin) compared with placebo (RR=0.19, 95% CI [0.09; 0.40]). Most arms demonstrated a statistically significant reduction in the incidence of overt HE compared to albumin and placebo. The results also demonstrated a significant reduction in ammonia between L-ornithine-L-aspartate (LOLA) and probiotics (MD= -19.17, 95% CI [-38.01; -0.32]), as well as a significant difference in the incidence of LOLA compared to placebo (MD= -22.62, 95% CI [-39.16; -6.07]). This network meta-analysis has significant data for managing subclinical HE in people without a history of overt HE. Our analysis showed that (Lactulose and Rifaximin), followed by (Rifaximin and L-carnitine), followed by (Lactulose and Rifaximin with zinc) were the best combinations regarding overt HE. LOLA reduced ammonia best, followed by Nitazoxanide and finally Lactulose. (Lactulose and Nitazoxanide) have the least adverse effects, followed by (Rifaximin and L-carnitine), then Probiotics. Yet, all mortality outcomes and quality of life changes yielded no useful findings. Future studies like RCTs must be done to compare our therapies directly.
PubMed: 38435950
DOI: 10.7759/cureus.53341 -
Journal of Critical Care Jun 2024Acute liver failure (ALF) is a rare syndrome leading to significant morbidity and mortality. An important cause of mortality is cerebral edema due to hyperammonemia.... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Acute liver failure (ALF) is a rare syndrome leading to significant morbidity and mortality. An important cause of mortality is cerebral edema due to hyperammonemia. Different therapies for hyperammonemia have been assessed including continuous renal replacement therapy (CRRT). We conducted a systematic review and meta-analysis to determine the efficacy of CRRT in ALF patients.
MATERIALS AND METHODS
We searched MEDLINE, EMBASE, Cochrane Library, and Web of Science. Inclusion criteria included adult patients admitted to an ICU with ALF. Intervention was the use of CRRT for one or more indications with the comparator being standard care without the use of CRRT. Outcomes of interest were overall survival, transplant-free survival (TFS), mortality and changes in serum ammonia levels.
RESULTS
In total, 305 patients underwent CRRT while 1137 patients did not receive CRRT. CRRT was associated with improved overall survival [risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70-0.99, p-value 0.04, I = 50%] and improved TFS (RR 0.65, 95% CI 0.49-0.85, p-value 0.002, I = 25%). There was a trend towards higher mortality with no CRRT (RR 1.24, 95% CI 0.84-1.81, p-value 0.28, I = 37%). Ammonia clearance data was unable to be pooled and was not analyzable.
CONCLUSION
Use of CRRT in ALF patients is associated with improved overall and transplant-free survival compared to no CRRT.
Topics: Adult; Humans; Continuous Renal Replacement Therapy; Renal Replacement Therapy; Ammonia; Hyperammonemia; Liver Failure, Acute; Acute Kidney Injury
PubMed: 38194760
DOI: 10.1016/j.jcrc.2023.154513 -
Journal of Gastroenterology and... May 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 30% of the global population, with a significant risk of advancing to liver cirrhosis and... (Review)
Review
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 30% of the global population, with a significant risk of advancing to liver cirrhosis and hepatocellular carcinoma. The roles of ammonia and glutamine in MASLD's pathogenesis are increasingly recognized, prompting this systematic review. This systematic review was conducted through a meticulous search of literature on December 21, 2023, across five major databases, focusing on studies that addressed the relationship between ammonia or glutamine and MASLD. The quality of the included studies was evaluated using CASP checklists. This study is officially registered in the PROSPERO database (CRD42023495619) and was conducted without external funding or sponsorship. Following PRISMA guidelines, 13 studies were included in this review. The studies were conducted globally, with varying sample sizes and study designs. The appraisal indicated a mainly low bias, confirming the reliability of the evidence. Glutamine's involvement in MASLD emerged as multifaceted, with its metabolic role being critical for liver function and disease progression. Variable expressions of glutamine synthetase and glutaminase enzymes highlight metabolic complexity whereas ammonia's impact through urea cycle dysfunction suggests avenues for therapeutic intervention. However, human clinical trials are lacking. This review emphasizes the necessity of glutamine and ammonia in understanding MASLD and identifies potential therapeutic targets. The current evidence, while robust, points to the need for human studies to corroborate preclinical findings. A personalized approach to treatment, informed by metabolic differences in MASLD patients, is advocated, alongside future large-scale clinical trials for a deeper exploration into these metabolic pathways.
PubMed: 38763916
DOI: 10.1111/jgh.16603 -
Obesity Research & Clinical Practice 2023Nonhepatic Hyperammonemic encephalopathy (NHAE) following Bariatric Surgery (BS), mainly Roux-en-Y Gastric Bypass (RYGB) and Biliopancreatic Diversion (BPD) is a... (Review)
Review
BACKGROUND
Nonhepatic Hyperammonemic encephalopathy (NHAE) following Bariatric Surgery (BS), mainly Roux-en-Y Gastric Bypass (RYGB) and Biliopancreatic Diversion (BPD) is a potentially devastating condition if not diagnosed and managed promptly.
METHODS
A literature review was performed using PRISMA guidelines. Eighteen studies and 3 conference abstracts with a total of 33 patients were included in this review.
RESULTS
Majority (28 patients, 84.8 %) had RYGB. Seven patients (21.2 %) had associated metabolic disorders. 60 % of patients presented with neurological symptoms or signs such as confusion, cognitive and/or psychomotor changes, and decreased reflexes. Two patients presented with status epilepticus. In 30 of the 33 patients an elevated serum ammonia levels was reported (90.9 %). The overall mortality was 39.3 %.
CONCLUSION
NHAE is a rare condition following bariatric surgery (in particular bypass procedures), carrying a high mortality rate. The signs and symptoms are predominantly neurological and may be mistaken for Wernicke's encephalopathy or other more common neurological conditions. Serum ammonia levels should be checked in those who present with these symptoms and signs. Prompt treatment might be life saving in patients with NHAE.
Topics: Humans; Obesity, Morbid; Ammonia; Bariatric Surgery; Gastric Bypass; Brain Diseases; Retrospective Studies
PubMed: 38007358
DOI: 10.1016/j.orcp.2023.11.001 -
Przeglad Gastroenterologiczny 2024Because not all liver dysfunction patients are suitable for transplantations and there is a shortage of grafts, liver support therapies have gained interest. In this... (Review)
Review
Safety and efficacy of Single-Pass Albumin Dialysis (SPAD), Prometheus, and Molecular Adsorbent Recycling System (MARS) liver haemodialysis vs. Standard Medical Therapy (SMT): meta-analysis and systematic review.
INTRODUCTION
Because not all liver dysfunction patients are suitable for transplantations and there is a shortage of grafts, liver support therapies have gained interest. In this regard, extracorporeal albumin dialysis devices such as single-pass albumin dialysis (SPAD), Prometheus, and molecular adsorbent recycling system (MARS) have been valuable in supplementing standard medical therapy (SMT). However, the efficacy and safety of these devices is often questioned.Aim: We performed a systematic review to summarize the efficacy and safety of MARS, SPAD, and Prometheus as supportive treatments for liver dysfunction.
MATERIAL AND METHODS
PubMed, Medline, Cochrane Library, Web of Science, and Google Scholar electronic databases were extensively searched for all randomized trials published in English. In addition, meta-analytic analyses were performed with Review Manager software, and Cochrane's risk of bias tool embedded in this software was used for bias assessment.
RESULTS
Twelve trials including a total of 653 patients were eligible for inclusion. Subgroup analyses of data from these trials revealed that MARS and Prometheus were associated with significant removal of bilirubin (MD = -5.14 mg/dl; 95% CI: -7.26 - -3.02; < 0.00001 and MD = -8.11 mg/dl; 95% CI: -12.40 - -3.82; = 0.0002, respectively) but not bile acids and ammonia when compared to SMT. Furthermore, MARS was as effective as Prometheus and SPAD in the reduction of bilirubin (MD = 2.98 mg/dl; 95% CI: -4.26 - 10.22; = 0.42 and MD = 0.67 mg/dl; 95% CI: -2.22 - 3.56; = 0.65), bile acids (MD = -17.06 µmol/l; 95% CI: -64.33 - 30.20; = 0.48 and MD = 16.21 µmol/l; 95% CI: -17.26 - 49.68; = 0.34), and ammonia (MD = 26 µmol/l; 95% CI: -12.44 - 64.44; = 0.18). In addition, MARS had a considerable effect in improving hepatic encephalopathy (HE) (RR = 1.54; 95% CI: 1.15-2.05; = 0.004). However, neither MARS nor Prometheus had a mortality benefit compared to SMTRR (0.86; 95% CI: 0.71-1.03; = 0.11 and RR = 0.87; 95% CI: 0.66-1.14; = 0.31, respectively).
CONCLUSIONS
MARS, SPAD, and Prometheus, as liver support therapies, are equally effective in reducing albumin-bound and water-soluble substances. Moreover, MARS is associated with HE improvement. However, none of the therapies was associated with a significant reduction in mortality or adverse events.
PubMed: 38939063
DOI: 10.5114/pg.2024.139297 -
The Science of the Total Environment May 2024Ammonia, a significant precursor for secondary inorganic aerosols, plays a pivotal role in new particle formation. Inventories and source apportionment studies have...
Ammonia, a significant precursor for secondary inorganic aerosols, plays a pivotal role in new particle formation. Inventories and source apportionment studies have identified vehicular exhaust as a primary source of atmospheric ammonia in urban regions. Existing research on the factors influencing ammonia emissions from gasoline vehicles exhibits substantial inconsistencies in both test results and analyses. The lack of a uniform pattern in ammonia emissions across different standard vehicles and the significant overlap in test results across diverse operational conditions highlight the complexities in this field of study. While individual results can be interpreted through a mechanistic lens, disparate studies often lack a common explanatory framework. To address this gap, our study leverages the robust and comprehensive approach of meta-analysis to reconcile these inconsistencies and provide a more precise understanding of the factors influencing ammonia emissions from gasoline vehicles. A large number (N = 537) of ammonia emission factors were extracted after screening >1628 publications. The combined ammonia emission factor was 23.57 ± 24.94 mg/km. Emission standards, engine type, ambient temperatures, mileage, vehicle speed, and engine displacement have a significant impact on ammonia emission factors, explaining the ammonia emission factor by up to 50.63 %, with speed being the most significant factor. All these factors are attributed to the interplay of catalyst properties, lambda, and residence time (space velocity). In the current fleet, ammonia emission control is relatively insufficient under low-speed and ultra-high speed, low temperature, and ultra-high mileage conditions. Since ammonia emission factors do not monotonically decrease with the upgrading of motor vehicle emission standards, it is called for the addition of ammonia emission factors indicators in motor vehicle emission standards, and stipulation of targeted testing procedures and testing instruments.
PubMed: 38447721
DOI: 10.1016/j.scitotenv.2024.171467 -
Veterinary Journal (London, England :... 2023Bovine respiratory disease (BRD) is one of the leading causes of mortality and morbidity in calves across diverse management systems. Despite expert opinion often citing...
A systematic review of the relationship between housing environmental factors and bovine respiratory disease in preweaned calves - Part 1: Ammonia, air microbial count, particulate matter and endotoxins.
Bovine respiratory disease (BRD) is one of the leading causes of mortality and morbidity in calves across diverse management systems. Despite expert opinion often citing the influence of housing environment on the level of respiratory disease in calf groups, there have been few reviews of environmental factors that predispose to BRD. This systematic review was undertaken to identify the measurable environmental variables associated with respiratory disease in housed preweaned calves. To achieve this Pubmed, CAB Direct and Scopus databases were searched. To be considered for inclusion, publications had to be fully published in English, published before 24 November, 2022 and include at least one measurable/ manipulated environmental variable and a standardized method of BRD detection. Twelve publications were included in this review. These examined a wide range of risk factors including air microbial count (four publications), air particulate matter (one publication); air endotoxins (one publication) and air ammonia (four publications). From the included publications, a statistically significant relationship to BRD was identified in 2/4 examining air microbial count, 1/1 examining air particulate matter, 1/1 examining air endotoxins and 2/4 examining air ammonia. This review indicated a paucity of evidence from the peer-review literature demonstrating a significant association between the many investigated exposure factors and BRD occurrence. An optimal environment for housed calves could not be clearly identified in this review.
Topics: Animals; Cattle; Ammonia; Housing; Cattle Diseases; Respiratory Tract Diseases; Risk Factors; Respiration Disorders; Bovine Respiratory Disease Complex
PubMed: 37778652
DOI: 10.1016/j.tvjl.2023.106031 -
Journal of Environmental Management Mar 2024Global sustainable development faces several challenges in addressing the needs of a growing population. Regarding food industries, the heightening pressure to meet... (Review)
Review
Global sustainable development faces several challenges in addressing the needs of a growing population. Regarding food industries, the heightening pressure to meet these needs has resulted in increased waste generation. Thus, recognising these wastes as valuable resources is crucial to integrating sustainable models into current production systems. For instance, the current 24 billion tons of nutrient-rich livestock wastewater (LW) generated yearly could be recovered and valorised via biological uptake through microalgal biomass. Microalgae-based livestock wastewater treatment (MbLWT) has emerged as an effective technology for nutrient recovery, specifically targeting carbon, nitrogen, and phosphorus. However, the viability and efficacy of these systems rely on the characteristics of LW, including organic matter and ammonium concentration, content of suspended solids, and microbial load. Thus, this systematic literature review aims to provide guidance towards implementing an integral MbLWT system for nutrient control and recovery, discussing several pre-treatments used in literature to overcome the challenges regarding LW as a suitable media for microalgae cultivation.
Topics: Animals; Microalgae; Livestock; Wastewater; Nutrients; Technology; Biomass; Nitrogen; Phosphorus; Water Purification
PubMed: 38387343
DOI: 10.1016/j.jenvman.2024.120258