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Journal of Nephrology Mar 2022Besides reducing hyperphosphatemia in chronic kidney disease (CKD) patients, phosphate lowering agents might provide beneficial effects on clinical and laboratory... (Meta-Analysis)
Meta-Analysis
The impact of phosphate lowering agents on clinical and laboratory outcomes in chronic kidney disease patients: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Besides reducing hyperphosphatemia in chronic kidney disease (CKD) patients, phosphate lowering agents might provide beneficial effects on clinical and laboratory parameters. This meta-analysis was conducted to comprehensively examine the impact of all phosphate lowering agents on various aspects of clinical and laboratory outcomes in CKD patients.
METHOD
A systematic literature search was performed in MEDLINE, Scopus, and the Cochrane Register of Controlled Trials until July 2020 to identify randomized controlled trials (RCTs) which compared the effects of each phosphate lowering agent with controls, comprising placebo and all other phosphate lowering agents. Various clinical and laboratory outcomes were analyzed. Random effects model was used to compute the standardized mean difference for continuous variables and the risk ratio (RR) for binary variables.
RESULTS
This meta-analysis included 127 RCTs with 20,215 patients. Sevelamer and lanthanum significantly reduced all-cause mortality (RR 0.610, 95% CI 0.401-0.929 and 0.467, 95% CI 0.337-0.647, respectively) but not cardiovascular (CV) mortality or CV events. Hospitalization rates were significantly diminished by sevelamer (RR 0.527; 95% CI 0.308-0.902). Certain phosphate lowering agents improved biochemical parameters including serum phosphate, calcium, coronary artery calcium scores, fibroblast growth factor-23, bone biomarkers, and lipid profiles. Intact parathyroid hormone and bone mineral density were not significantly changed.
CONCLUSIONS
In addition to decreasing serum phosphate levels, various beneficial effects on clinical and laboratory parameters of phosphate lowering agents might play potential roles in diminishing morbidity and mortality in CKD patients.
Topics: Humans; Hyperphosphatemia; Phosphates; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Sevelamer
PubMed: 34061337
DOI: 10.1007/s40620-021-01065-3 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2020Paracetamol (acetaminophen) remains a leading cause of poisoning in Europe, North America, and Australia. For over four decades, acetylcysteine has been the antidote of...
BACKGROUND
Paracetamol (acetaminophen) remains a leading cause of poisoning in Europe, North America, and Australia. For over four decades, acetylcysteine has been the antidote of choice. However, despite the use of acetylcysteine, some patients who ingest very large doses of paracetamol or who reach hospital late in the course of their poisoning, develop acute liver failure. Some will develop metabolic acidosis indicating mitochondrial toxicity.
OBJECTIVE
We review the experimental and clinical data reported with the use of cimetidine, fomepizole, and calmangafodipir in the treatment of paracetamol toxicity to determine if these treatments alone or in combination with acetylcysteine might be of benefit.
METHODS
We searched Ovid Medline 1946-2020, Embase 1947-2020, Scopus 2004-2020, Cochrane Databases of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov 1997-2020 for records including the concepts of paracetamol poisoning and cimetidine, fomepizole, calmangafodipir, and acetylcysteine. We included basic science studies in animals and all available study types in humans. We reviewed the reference lists of included articles to search for references missed in the original search. We registered the protocol in PROSPERO.
RESULTS
We completed all search strategies on 20 August 2019, 27 January 2020, and 15 June 2020. These produced 6,826 citations. We identified and deleted 2,843 duplicate resulting in a total of 3,856 unique citations. After applying inclusion and exclusion criteria, 89 studies remained. The largest numbers of studies described the past use of cimetidine, and the more recent use of fomepizole. There is good animal evidence that cimetidine blocks CYP 2E1 with the potential to inhibit the toxic metabolism of paracetamol. Early case reports were inconclusive regarding the benefit to humans in paracetamol poisoning. Two comparative trials found no benefit of cimetidine in paracetamol poisoning, but few patients had severe poisoning. There is good animal evidence that fomepizole blocks CYP 2E1 with the potential to inhibit the toxic metabolism of paracetamol. There are no comparative trials of fomepizole for acute paracetamol poisoning. Case reports are inconclusive due to multiple other interventions including the use of acetylcysteine in all cases. The benefit of fomepizole as adjunct treatment has not been demonstrated. Calmangafodipir, a drug mimicking superoxide dismutase, has emerged as a potential treatment for severe paracetamol toxicity because the formation of superoxide free radicals appears to explain part of the mitochondrial toxicity of extremely large paracetamol overdoses. Calmangafodipir has reached Phase I/II trial of safety in humans with acute paracetamol overdose. Planning for a Phase III study of efficacy is currently underway.
CONCLUSIONS
The vast majority of patients with acute paracetamol overdose enjoy excellent outcomes with acetylcysteine alone. Although cimetidine and fomepizole inhibit CYP 2E1 in animals, there is insufficient evidence to recommend their use either as a primary treatment or adjunct therapy in paracetamol poisoning. Calmangafodipir remains investigational.
Topics: Acetaminophen; Acetylcysteine; Acidosis; Animals; Antidotes; Cimetidine; Drug Overdose; Edetic Acid; Fomepizole; Humans; Mitochondria; Pyridoxal Phosphate
PubMed: 32762579
DOI: 10.1080/15563650.2020.1798979 -
AJR. American Journal of Roentgenology Mar 2021Early diagnosis is important in the overall management of prostate cancer (PCa). Gallium-68-labeled prostate-specific membrane antigen (PSMA) PET/CT has an established... (Meta-Analysis)
Meta-Analysis
Early diagnosis is important in the overall management of prostate cancer (PCa). Gallium-68-labeled prostate-specific membrane antigen (PSMA) PET/CT has an established role in the detection of recurrent disease and staging of patients with intermediate- to high-risk PCa. However, only a small number of studies have evaluated its role in the initial diagnosis of PCa. This systematic review was conducted to evaluate the diagnostic performance of Ga-PSMA PET/CT in the initial detection of PCa in patients with clinical or biochemical findings suspicious for PCa. This systematic review followed PRISMA guidelines. Searches in PubMed, Scopus, and Embase were conducted using relevant keywords, and articles published through April 30, 2020, were included. Using histopathology results as the reference standard, the numbers of true- and false-positives and true- and false-negatives were extracted. Pooled estimates of diagnostic test accuracy-including sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and summary ROC (SROC) curve-were generated using bivariate random-effects meta-analysis. Seven studies comprising 389 patients were included in the systematic review and meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for the initial diagnosis of PCa using Ga-PSMA PET/CT were 0.97 (95% CI, 0.90-0.99), 0.66 (95% CI, 0.52-0.78), 2.86 (95% CI, 1.95-4.20), and 0.05 (95% CI, 0.01-0.15), respectively. The test had high accuracy; the area under the SROC curve was 0.91 (95% CI, 0.88-0.93). Gallium-68-labeled PSMA PET/CT had excellent sensitivity and negative likelihood ratio in the initial diagnosis of PCa in patients with clinical or biochemical findings suspicious for PCa. Gallium-68-labeled PSMA PET/CT had high diagnostic accuracy for the initial detection of PCa in patients with clinical or biochemical findings suspicious for PCa and has potential utility as a rule-out test for these patients.
Topics: Adult; Aged; Aged, 80 and over; Edetic Acid; False Negative Reactions; False Positive Reactions; Gallium Isotopes; Gallium Radioisotopes; Humans; Likelihood Functions; Male; Middle Aged; Oligopeptides; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Publication Bias; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 32755196
DOI: 10.2214/AJR.20.23912 -
Leukemia Research Oct 2020Leukemia-initiating cells localize to bone marrow niches via cell surface CXCR4 binding to stromal-derived factor 1 (SDF-1). Plerixafor, a CXCR4 antagonist, can mobilize... (Meta-Analysis)
Meta-Analysis
Plerixafor in combination with chemotherapy and/or hematopoietic cell transplantation to treat acute leukemia: A systematic review and metanalysis of preclinical and clinical studies.
Leukemia-initiating cells localize to bone marrow niches via cell surface CXCR4 binding to stromal-derived factor 1 (SDF-1). Plerixafor, a CXCR4 antagonist, can mobilize and sensitize leukemia cells to cytotoxic therapy, and/or enhance the engraftment of healthy donor stem cells in the context of hematopoietic cell transplantation (HCT). A systematic review of preclinical and clinical studies was performed (updated May 1, 2020) to inform the design of definitive clinical trials and identified 19 studies. Pooled data from 10 preclinical in-vivo studies of AML and ALL in mouse models of leukemia revealed significant mobilization of leukemia cells into the peripheral circulation, decreased total blast burden and increased survival with plerixafor in addition to cytotoxic treatment compared to control animals. Two of 9 clinical studies compared outcomes to a control group. Plerixafor appears well tolerated and safe and can mobilize leukemia cells into the peripheral circulation. In patients with AML undergoing HCT, plerixafor given with the conditioning regimen appears safe and well tolerated. Engraftment, relapse and survival were not different from controls after limited follow-up. Studies in high risk patients with AML with longer follow-up are needed to understand the influence on relapse following treatment and on donor cell engraftment following HCT.
Topics: Animals; Anti-HIV Agents; Antineoplastic Combined Chemotherapy Protocols; Benzylamines; Cyclams; Drug Evaluation, Preclinical; Drug Therapy, Combination; Hematopoietic Stem Cell Transplantation; Heterocyclic Compounds; Humans; Leukemia, Myeloid, Acute; Prognosis
PubMed: 32877869
DOI: 10.1016/j.leukres.2020.106442 -
European Radiology Oct 2022To compare the performance of Liver Imaging Reporting and Data System category 5 (LR-5) for diagnosing HCC between CT and MRI using comparative studies. (Meta-Analysis)
Meta-Analysis
Diagnostic performance of CT versus MRI Liver Imaging Reporting and Data System category 5 for hepatocellular carcinoma: a systematic review and meta-analysis of comparative studies.
OBJECTIVE
To compare the performance of Liver Imaging Reporting and Data System category 5 (LR-5) for diagnosing HCC between CT and MRI using comparative studies.
METHODS
The MEDLINE and EMBASE databases were searched from inception to April 21, 2021, to identify studies that directly compare the diagnostic performance of LR-5 for HCC between CT and MRI. A bivariate random-effects model was fitted to calculate the pooled per-observation sensitivity and specificity of LR-5 of each modality, and compare the pooled estimates of paired data. Subgroup analysis was performed according to the MRI contrast agent.
RESULTS
Seven studies with 1145 observations (725 HCCs) were included in the final analysis. The pooled per-observation sensitivity of LR-5 for diagnosing HCC was higher using MRI (61%; 95% confidence interval [CI], 43-76%; I = 95%) than CT (48%; 95% CI, 31-65%; I = 97%) (p < 0.001). The pooled per-observation specificities of LR-5 did not show statistically significant difference between CT (96%; 95% CI, 92-98%; I = 0%) and MRI (93%; 95% CI, 88-96%; I = 16%) (p = 0.054). In the subgroup analysis, extracellular contrast agent-enhanced MRI showed significantly higher pooled per-observation sensitivity than gadoxetic acid-enhanced MRI for diagnosing HCC (73% [95% CI, 55-85%] vs. 55% [95% CI, 39-70%]; p = 0.007), without a significant difference in specificity (93% [95% CI, 80-98%] vs. 94% [95% CI, 87-97%]; p = 0.884).
CONCLUSIONS
The LR-5 of MRI showed significantly higher pooled per-observation sensitivity than CT for diagnosing HCC. The pooled per-observation specificities of LR-5 were comparable between the two modalities.
KEY POINTS
• The pooled sensitivity of LR-5 using MRI was higher than that using CT (61% versus 48%), but the pooled specificities of LR-5 were not significantly different between CT and MRI (96% versus 93%). • Subgroup analysis according to the MRI contrast media showed a significantly higher pooled per-observation sensitivity using ECA-enhanced MRI than with EOB-enhanced MRI (73% versus 55%), and comparable specificities (93% versus 94%). • Although LI-RADS provides a common diagnostic algorithm for CT or MRI, the per-observation performance of LR-5 can be affected by the imaging modality as well as the MRI contrast agent.
Topics: Carcinoma, Hepatocellular; Contrast Media; Gadolinium DTPA; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Retrospective Studies; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 35849177
DOI: 10.1007/s00330-022-08985-z -
Clinical Radiology Apr 2020To identify and evaluate the efficiency of the most commonly used parameters applied to gadoxetate disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for... (Meta-Analysis)
Meta-Analysis
AIM
To identify and evaluate the efficiency of the most commonly used parameters applied to gadoxetate disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for liver fibrosis (LF) staging.
MATERIALS AND METHODS
Literature searches of PubMed, Web of Science, Embase, and MEDLINE databases from January 2004 to August 2018 were conducted. The applied parameters during imaging were noted and summarised. Studies using the most commonly used parameter were included. Extractive data were combined as pooled weighted mean difference (WMD) to determine the benefits in LF staging. The pooled sensitivity, specificity, and summary receiver operating characteristics (SROC) curve were calculated.
RESULTS
Among 57 relevant studies, the contrast enhancement index (CEI) was a relatively commonly used parameter. It was calculated as SI/SI, where SI and SI are the liver-to-muscle signal intensity ratios in the hepatocyte phase and pre-enhanced images, respectively. Six studies were included. F0 was regarded as normal liver, F1 as mild LF, F2 as moderate LF, and F3 and F4 as advanced LF. Comparisons of WMD revealed significant differences between F1-2 and F3-4. For stage ≥F1, the pooled sensitivity, specificity, and areas under SROC curve were 0.58, 0.84, and 0.85, respectively; the corresponding values for ≥F2 were 0.57, 0.68, and 0.76, while those for ≥F3 were 0.61, 0.75, and 0.72.
CONCLUSION
The methodology and parameters used for Gd-EOB-DTPA-enhanced MRI for LF staging are diverse, but the CEI was a relatively common parameter. Overall, there is evidence to support use of CEI, but more evidence from larger studies is needed.
Topics: Contrast Media; Gadolinium DTPA; Humans; Liver Cirrhosis; Magnetic Resonance Imaging
PubMed: 31831141
DOI: 10.1016/j.crad.2019.11.001 -
Radiology Dec 2020Background Gadoxetic acid is classified by the American College of Radiology as a group III gadolinium-based contrast agent (GBCA), which indicates that there are... (Meta-Analysis)
Meta-Analysis
Background Gadoxetic acid is classified by the American College of Radiology as a group III gadolinium-based contrast agent (GBCA), which indicates that there are limited data regarding nephrogenic systemic fibrosis (NSF) risk, but there are few if any unconfounded cases of NSF. Purpose To perform a systematic review and meta-analysis of gadoxetic acid adverse events, including immediate hypersensitivity reactions, NSF, and intracranial gadolinium retention. Materials and Methods Original research studies, case series, and case reports that reported adverse events in patients undergoing gadoxetic acid-enhanced MRI were searched in MEDLINE (1946-2019), Embase (1947-2019), CENTRAL (March 2019), and Scopus (1946-2019). The study protocol was registered at Prospero (number 162811). Risk of bias was evaluated by using Quality Assessment of Diagnostic Accuracy Studies-2, or QUADAS-2. Meta-analysis of proportions was performed by using random-effects modeling. Upper bound of 95% confidence interval (CI) for risk of NSF was determined. Results Seventy-one studies underwent full-text review. From 17 studies reporting 14 850 administrations, hypersensitivity reactions occurred in 0.3% (31 of 14 850; 95% CI: 0.2%, 0.4%) with zero deaths. From four studies reporting 106 administrations in patients with stage 4 or 5 chronic kidney disease or undergoing dialysis, the upper bound 95% CI for the risk of NSF was 2.8%. Five studies evaluating intracranial retention of gadolinium after gadoxetic acid administration were at high risk of bias. Conclusion Gadoxetic acid had a similar safety profile to American College of Radiology group 2 gadolinium-based contrast agents for hypersensitivity reactions and nephrogenic systemic fibrosis (NSF) but had lower confidence for risk of NSF because of fewer administrations in patients with severe kidney impairment. There is incomplete information documenting intracranial gadolinium retention in patients administered gadoxetic acid. © RSNA, 2020
Topics: Contrast Media; Drug Hypersensitivity; Gadolinium DTPA; Humans; Hypersensitivity, Immediate; Magnetic Resonance Imaging; Nephrogenic Fibrosing Dermopathy; Renal Insufficiency
PubMed: 32452732
DOI: 10.1148/radiol.2020200073 -
The British Journal of General Practice... Jul 2021Urinary tract infections (UTIs) are often treated with antibiotics and are a source of antibiotic overuse. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Urinary tract infections (UTIs) are often treated with antibiotics and are a source of antibiotic overuse.
AIM
To systematically review randomised controlled trials (RCTs) of adult women in the community with a history of recurrent UTIs and who use methenamine hippurate prophylactically.
DESIGN AND SETTING
Systematic review of women in the UK, Australia, Norway, and US (aged ≥18 years) with recurrent UTIs receiving methenamine hippurate against placebo or no treatment, and antibiotics.
METHOD
The authors searched three databases, clinical trial registries, and performed forward-backward citation analysis on references of included studies.
RESULTS
Six studies involving 557 participants were included (447 were analysed). Of the six studies, five were published and one was an unpublished trial record with results, three compared methenamine hippurate against placebo or control, and three compared methenamine hippurate with antibiotics. For the number of patients who remained asymptomatic, methenamine hippurate showed a non-statistically significant trend of benefit versus antibiotics over 12 months (risk ratio [RR] 0.65, 95% confidence interval [CI] = 0.40 to 1.07, 49%), versus control over 6 or 12 months (RR 0.56, 95% CI = 0.13 to 2.35, 93%), and a non-statistically significant trend versus any antibiotic for abacteruria (RR 0.80, 95% CI = 0.62 to 1.03, 23%). A similar non-statistically significant trend of benefits for methenamine hippurate for the number of UTI or bacteriuric episodes was found, and a non-statistically significant difference in the number of patients experiencing adverse events between methenamine hippurate and any comparator, with a trend towards benefit for the methenamine hippurate, was identified. Antibiotic use and resistance were not consistently reported.
CONCLUSION
There is insufficient evidence to be certain of the benefits of methenamine hippurate to prevent UTI. Further research is needed to test the drug's effectiveness in preventing UTIs and as an alternative for antibiotic treatment for UTI.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Female; Hippurates; Humans; Methenamine; Pharmaceutical Preparations; Urinary Tract Infections
PubMed: 34001538
DOI: 10.3399/BJGP.2020.0833 -
Academic Radiology Feb 2022To perform a systematic review and meta-analysis to determine risk factors for hypervascularization in hepatobiliary phase (HBP) hypointense nodules without arterial... (Meta-Analysis)
Meta-Analysis
RATIONALE AND OBJECTIVES
To perform a systematic review and meta-analysis to determine risk factors for hypervascularization in hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) in patients with hepatocellular carcinoma (HCC).
MATERIALS AND METHODS
Pubmed and EMBASE databases were searched up to May 7, 2020. Studies which evaluated radiologic and clinical risk factors for hypervascularization in HBP hypointense nodules without APHE were included. Hazard ratios were meta-analytically pooled using random-effects model. Methodological quality of included studies was assessed using Quality in Prognostic Studies (QUIPS) tool.
RESULTS
Sixteen studies with 934 patients were included. HBP hypointense nodules without APHE with baseline size greater than 10 mm, T2 hyperintensity, and restricted diffusion showed risk for hypervascularization with pooled HRs of 2.95 (95% confidence interval [CI], 1.94-4.20), 4.21 (95% CI, 1.15-15.40), 5.83 (95% CI, 1.42-23.95), respectively. Previous HCC history contributed to hypervascularization of the nodules with hazard ratio of 2.06 (95% CI, 1.23-3.44). T1 hyperintensity, intralesional fat, Child-Pugh Class B, sex, alfa-fetoprotein, hepatitis B or C infection were not significant risk factors for hypervascularization (p ≥0.05). Study quality was generally moderate.
CONCLUSION
HBP hypointense nodules without APHE on gadoxetic acid-enhanced MRI with baseline size greater than 10 mm, T2 hyperintensity, restricted diffusion and previous hepatocellular carcinoma history pose higher risk for hypervascularization. Proper patient management in patients with HBP hypointense nodules without APHE on gadoxetic acid-enhanced MRI may need to be tailored according to these risk factors.
Topics: Carcinoma, Hepatocellular; Contrast Media; Gadolinium DTPA; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Retrospective Studies; Risk Factors
PubMed: 32962925
DOI: 10.1016/j.acra.2020.08.031 -
Abdominal Radiology (New York) Mar 2023This study aimed to systematically determine the inter-reader reliability of the functional liver imaging score (FLIS) and explore the factors affecting it. (Meta-Analysis)
Meta-Analysis
PURPOSE
This study aimed to systematically determine the inter-reader reliability of the functional liver imaging score (FLIS) and explore the factors affecting it.
METHODS
Original articles reporting the inter-reader reliability of FLIS derived from gadoxetic acid-enhanced magnetic resonance imaging (MRI) were systematically searched in the MEDLINE and EMBASE databases from January 2013 to June 2022. Data synthesis was performed to calculate the meta-analytic pooled estimates of the FLIS and its three subcategories, including enhancement quality score (EnQS), excretion quality score (ExQS), and portal vein sign quality score (PVsQS) using the DerSimonian-Laird random-effects model. To explore any cause of study heterogeneity, we conducted a meta-regression analysis.
RESULTS
Six studies with data from 1419 patients were included. The meta-analytic pooled inter-reader reliability of FLIS was 0.93 (95% confidence interval [CI], 0.88-0.98). That of the three FLIS subcategories were 0.93 (95% CI, 0.85-1.00), 0.95 (95% CI, 0.91-1.00), and 0.90 (95% CI, 0.81-0.99) for EnQS, ExQS, and PVsQS, respectively. The pooled FLIS data was moderately heterogenous, but heterogeneity was not associated with the study methodology, MRI-related factors, and reader experience.
CONCLUSION
The FLIS and its three subcategories showed almost perfect inter-reader reliability. Therefore, FLIS may be a reliable imaging parameter that reflects liver function and outcomes in patients with chronic liver disease. Further studies should be conducted to confirm any factors affecting the inter-reader reliability of FLIS.
Topics: Humans; Contrast Media; Reproducibility of Results; Retrospective Studies; Gadolinium DTPA; Liver; Magnetic Resonance Imaging; Liver Neoplasms
PubMed: 36576517
DOI: 10.1007/s00261-022-03785-x