-
Nutrients Mar 2023Chronic pain is a major source of morbidity for which there are limited effective treatments. Palmitoylethanolamide (PEA), a naturally occurring fatty acid amide, has... (Meta-Analysis)
Meta-Analysis Review
Chronic pain is a major source of morbidity for which there are limited effective treatments. Palmitoylethanolamide (PEA), a naturally occurring fatty acid amide, has demonstrated utility in the treatment of neuropathic and inflammatory pain. Emerging reports have supported a possible role for its use in the treatment of chronic pain, although this remains controversial. We undertook a systematic review and meta-analysis to examine the efficacy of PEA as an analgesic agent for chronic pain. A systematic literature search was performed, using the databases MEDLINE and Web of Science, to identify double-blind randomized controlled trials comparing PEA to placebo or active comparators in the treatment of chronic pain. All articles were independently screened by two reviewers. The primary outcome was pain intensity scores, for which a meta-analysis was undertaken using a random effects statistical model. Secondary outcomes including quality of life, functional status, and side effects are represented in a narrative synthesis. Our literature search identified 253 unique articles, of which 11 were ultimately included in the narrative synthesis and meta-analysis. Collectively, these articles described a combined sample size of 774 patients. PEA was found to reduce pain scores relative to comparators in a pooled estimate, with a standard mean difference of 1.68 (95% CI 1.05 to 2.31, = 0.00001). Several studies reported additional benefits of PEA for quality of life and functional status, and no major side effects were attributed to PEA in any study. The results of this systematic review and meta-analysis suggest that PEA is an effective and well-tolerated treatment for chronic pain. Further study is warranted to determine the optimal dosing and administration parameters of PEA for analgesic effects in the context of chronic pain.
Topics: Humans; Chronic Pain; Quality of Life; Randomized Controlled Trials as Topic; Analgesics; Amides
PubMed: 36986081
DOI: 10.3390/nu15061350 -
The Journal of Allergy and Clinical... 2019There is no recent systematic review on the risk of cross-reactivity to cephalosporins and carbapenems in penicillin-allergic patients despite many new studies on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is no recent systematic review on the risk of cross-reactivity to cephalosporins and carbapenems in penicillin-allergic patients despite many new studies on the subject. All past reviews have several limitations such as not including any patient with a T-cell-mediated penicillin allergy.
OBJECTIVES
To determine the risk of cross-reactivity to cephalosporins and carbapenems in patients with a proven IgE- or T-cell-mediated penicillin allergy. To measure the association between R1 side chain similarity on cephalosporins and penicillins and the risk of cross-reactivity.
METHODS
MEDLINE and EMBASE were searched from January 1980 to March 2019. Studies had to include at least 10 penicillin-allergic subjects whose allergy had been confirmed by a positive skin test (ST) or drug provocation test (DPT) result. Cross-reactivity had to be assessed to at least 1 cephalosporin or carbapenem through ST or DPT. Both random-effects and fixed-effect models were used to combine data. A bioinformatic model was used to quantify the similarity between R1 side chains.
RESULTS
Twenty-one observational studies on cephalosporin cross-reactivity involving 1269 penicillin-allergic patients showed that the risk of cross-reactivity varied with the degree of similarity between R1 side chains: 16.45% (95% CI, 11.07-23.75) for aminocephalosporins, which share an identical side chain with a penicillin (similarity score = 1), 5.60% (95% CI, 3.46-8.95) for a few cephalosporins with an intermediate similarity score (range, 0.563-0.714), and 2.11% (95% CI, 0.98-4.46) for all those with low similarity scores (below 0.4), irrespective of cephalosporin generation. The higher risk associated with aminocephalosporins was observed whether penicillin allergy was IgE- or T-cell-mediated. Eleven observational studies on carbapenem cross-reactivity involving 1127 penicillin-allergic patients showed that the risk of cross-reactivity to any carbapenem was 0.87% (95% CI, 0.32-2.32).
CONCLUSIONS
Although it remains possible that these meta-analyses overestimated the risk of cross-reactivity, clinicians should consider the increased risk of cross-reactivity associated with aminocephalosporins, and to a lesser extent with intermediate-similarity-score cephalosporins, compared with the very low risk associated with low-similarity-score cephalosporins and all carbapenems when using beta-lactams in patients with a suspected or proven penicillin allergy.
Topics: Carbapenems; Cephalosporins; Cross Reactions; Drug Hypersensitivity; Humans; Penicillins
PubMed: 31170539
DOI: 10.1016/j.jaip.2019.05.038 -
Critical Care (London, England) Nov 2017Cefepime is a widely used antibiotic with neurotoxicity attributed to its ability to cross the blood-brain barrier and exhibit concentration-dependent ϒ-aminobutyric... (Review)
Review
BACKGROUND
Cefepime is a widely used antibiotic with neurotoxicity attributed to its ability to cross the blood-brain barrier and exhibit concentration-dependent ϒ-aminobutyric acid (GABA) antagonism. Neurotoxic symptoms include depressed consciousness, encephalopathy, aphasia, myoclonus, seizures, and coma. Data suggest that up to 15% of ICU patients treated with cefepime may experience these adverse effects. Risk factors include renal dysfunction, excessive dosing, preexisting brain injury, and elevated serum cefepime concentrations. We aimed to characterize the clinical course of cefepime neurotoxicity and response to interventions.
METHODS
A librarian-assisted search identified publications describing cefepime-associated neurotoxicity from January 1980 to February 2016 using the CINAHL and MEDLINE databases. Search terms included cefepime, neurotoxicity, encephalopathy, seizures, delirium, coma, non-convulsive status epilepticus, myoclonus, confusion, aphasia, agitation, and death. Two reviewers independently assessed identified articles for eligibility and used the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) for data reporting.
RESULTS
Of the 123 citations identified, 37 (representing 135 patient cases) were included. Patients had a median age of 69 years, commonly had renal dysfunction (80%) and required intensive care (81% of patients with a reported location). All patients exhibited altered mental status, with reduced consciousness (47%), myoclonus (42%), and confusion (42%) being the most common symptoms. All 98 patients (73% of cohort) with electroencephalography had abnormalities, including non-convulsive status epilepticus (25%), myoclonic status epilepticus (7%), triphasic waves (40%), and focal sharp waves (39%). As per Food and Drug Administration (FDA)-approved dosing guidance, 48% of patients were overdosed; however, 26% experienced neurotoxicity despite appropriate dosing. Median cefepime serum and cerebrospinal fluid (CSF) concentrations were 45 mg/L (n = 21) and 13 mg/L (n = 4), respectively. Symptom improvement occurred in 89% of patients, and 87% survived to hospital discharge. The median delay from starting the drug to symptom onset was 4 days, and resolution occurred a median of 2 days after the intervention, which included cefepime discontinuation, antiepileptic administration, or hemodialysis.
CONCLUSIONS
Cefepime-induced neurotoxicity is challenging to recognize in the critically ill due to widely varying symptoms that are common in ICU patients. This adverse reaction can occur despite appropriate dosing, usually resolves with drug interruption, but may require additional interventions such as antiepileptic drug administration or dialysis.
Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Consciousness Disorders; Drug-Related Side Effects and Adverse Reactions; Humans; Neurotoxicity Syndromes; Seizures
PubMed: 29137682
DOI: 10.1186/s13054-017-1856-1 -
Journal of Endodontics Feb 2022The aim of this study was to analyze and compare the efficacy of different bleaching agents typically used for internal bleaching of endodontically treated discolored... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The aim of this study was to analyze and compare the efficacy of different bleaching agents typically used for internal bleaching of endodontically treated discolored teeth.
METHODS
Electronic databases (PubMed, Web of Science, and Cochrane Library) were searched by 2 reviewers for clinical trials in which the color of endodontically treated discolored teeth before and after internal bleaching was examined using shade guide units (ΔSGU) or a spectrophotometer/colorimeter (ΔE). The efficacies of the bleaching agents were compared using subgroup analyses. Statistical heterogeneity was assessed with the Cochran Q test and I statistic. Publication bias was evaluated using funnel plots.
RESULTS
Eight studies were included in the systematic review, 6 of which could be included in the meta-analyses. Internal bleaching led to a significant change in tooth shade (ΔSGU: 6.27 [95% confidence interval, 5.36-7.17], ΔE: 12.83 [95% confidence interval, 9.46-16.20]). With regard to ΔSGU, the use of carbamide peroxide (35% or 37%), hydrogen peroxide (35%), and the combination of sodium perborate and hydrogen peroxide (3% or 30%) led to a better bleaching effect than sodium perborate (adjusted P value ≤ .026). Regarding ΔE, there were no significant differences between carbamide peroxide (37%), hydrogen peroxide (35%), and sodium perborate mixed with hydrogen peroxide (P = .051). The risk of bias of the included studies was classified as moderate to high.
CONCLUSIONS
Carbamide peroxide, hydrogen peroxide, and sodium perborate have a significant bleaching effect on discolored, root canal-treated teeth. For a valid assessment of shade stability and a comparison of bleaching agents and their concentrations, further studies with long-term recalls are necessary.
Topics: Carbamide Peroxide; Humans; Hydrogen Peroxide; Peroxides; Tooth Bleaching; Tooth Bleaching Agents; Tooth Discoloration; Urea
PubMed: 34762968
DOI: 10.1016/j.joen.2021.10.011 -
Critical Care Medicine Jan 2018The objective of this systematic review and meta-analysis was to assess acute kidney injury with combination therapy of vancomycin plus piperacillin-tazobactam, in... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVES
The objective of this systematic review and meta-analysis was to assess acute kidney injury with combination therapy of vancomycin plus piperacillin-tazobactam, in general, adult patients and in critically ill adults. Rates of acute kidney injury, time to acute kidney injury, and odds of acute kidney injury were compared with vancomycin monotherapy, vancomycin plus cefepime or carbapenem, or piperacillin-tazobactam monotherapy.
DATA SOURCES
Studies were identified by searching Pubmed, Embase, Web of Science, and Cochrane from inception to April 2017. Abstracts from selected conference proceedings were manually searched.
STUDY SELECTION
Articles not in English, pediatric studies, and case reports were excluded.
DATA EXTRACTION
Two authors independently extracted data on study methods, rates of acute kidney injury, and time to acute kidney injury. Effect estimates and 95% CIs were calculated using the random effects model in RevMan 5.3.
DATA SYNTHESIS
Literature search identified 15 published studies and 17 conference abstracts with at least 24,799 patients. The overall occurrence rate of acute kidney injury was 16.7%, with 22.2% for vancomycin plus piperacillin-tazobactam and 12.9% for comparators. This yielded an overall number needed to harm of 11. Time to acute kidney injury was faster for vancomycin plus piperacillin-tazobactam than vancomycin plus cefepime or carbapenem, but not significantly (mean difference, -1.30; 95% CI, -3.00 to 0.41 d). The odds of acute kidney injury with vancomycin plus piperacillin-tazobactam were increased versus vancomycin monotherapy (odds ratio, 3.40; 95% CI, 2.57-4.50), versus vancomycin plus cefepime or carbapenem (odds ratio, 2.68; 95% CI, 1.83-3.91), and versus piperacillin-tazobactam monotherapy (odds ratio, 2.70; 95% CI, 1.97-3.69). In a small subanalysis of 968 critically ill patients, the odds of acute kidney injury were increased versus vancomycin monotherapy (odds ratio, 9.62; 95% CI, 4.48-20.68), but not significantly different for vancomycin plus cefepime or carbapenem (odds ratio, 1.43; 95% CI, 0.83-2.47) or piperacillin-tazobactam monotherapy (odds ratio, 1.35; 95% CI, 0.86-2.11).
CONCLUSIONS
The combination of vancomycin plus piperacillin-tazobactam increased the odds of acute kidney injury over vancomycin monotherapy, vancomycin plus cefepime or carbapenem, and piperacillin-tazobactam monotherapy. Limited data in critically ill patients suggest the odds of acute kidney injury are increased versus vancomycin monotherapy, and mitigated versus the other comparators. Further research in the critically ill population is needed.
Topics: Acute Kidney Injury; Adult; Critical Care; Drug Therapy, Combination; Humans; Observational Studies as Topic; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Randomized Controlled Trials as Topic; Vancomycin
PubMed: 29088001
DOI: 10.1097/CCM.0000000000002769 -
Journal of Back and Musculoskeletal... 2023Cupping therapy has been used to treat musculoskeletal impairments for about 4000 years. Recently, world athletes have provoked an interest in it, however, the evidence... (Review)
Review
BACKGROUND
Cupping therapy has been used to treat musculoskeletal impairments for about 4000 years. Recently, world athletes have provoked an interest in it, however, the evidence to support its use in managing musculoskeletal and sports conditions remains unknown.
OBJECTIVE
To evaluate the evidence level of the effect of cupping therapy in managing common musculoskeletal and sports conditions.
METHODS
2214 studies were identified through a computerized search, of which 22 met the inclusion criteria. The search involved randomized and case series studies published between 1990 and 2019. The search involved five databases (Scopus, MEDLINE (PubMed), Web of Science, Academic Search Complete PLUS (EBSCO), and CrossRef) and contained studies written in the English language. Three analyses were included: the quality assessment using the PEDro scale, physical characteristic analysis, and evidence-based analysis.
RESULTS
The results showed that most studies used dry cupping, except five which used wet cupping. Most studies compared cupping therapy to non-intervention, the remaining studies compared cupping to standard medical care, heat, routine physiotherapy, electrical stimulation, active range of motion and stretching, passive stretching, or acetaminophen. Treatment duration ranged from 1 day to 12 weeks. The evidence of cupping on increasing soft tissue flexibility is moderate, decreasing low back pain or cervical pain is low to moderate, and treating other musculoskeletal conditions is very low to low. The incidence of adverse events is very low.
CONCLUSION
This study provides the first attempt to analyze the evidence level of cupping therapy in musculoskeletal and sports rehabilitation. However, cupping therapy has low to moderate evidence in musculoskeletal and sports rehabilitation and might be used as a useful intervention because it decreases the pain level and improves blood flow to the affected area with low adverse effects.
Topics: Humans; Acetaminophen; Cupping Therapy; Low Back Pain; Physical Therapy Modalities; Sports
PubMed: 35848010
DOI: 10.3233/BMR-210242 -
International Journal of Antimicrobial... May 2021The superiority of combination therapy for carbapenem-resistant Gram-negative bacilli (CR-GNB) infections remains controversial. In vitro models may predict the efficacy... (Meta-Analysis)
Meta-Analysis
The superiority of combination therapy for carbapenem-resistant Gram-negative bacilli (CR-GNB) infections remains controversial. In vitro models may predict the efficacy of antibiotic regimens against CR-GNB. A systematic review and meta-analysis was performed including pharmacokinetic/pharmacodynamic (PK/PD) and time-kill (TK) studies examining the in vitro efficacy of antibiotic combinations against CR-GNB [PROSPERO registration no. CRD42019128104]. The primary outcome was in vitro synergy based on the effect size (ES): high, ES ≥ 0.75, moderate, 0.35 < ES < 0.75; low, ES ≤ 0.35; and absent, ES = 0). A network meta-analysis assessed the bactericidal effect and re-growth rate (secondary outcomes). An adapted version of the ToxRTool was used for risk-of-bias assessment. Over 180 combination regimens from 136 studies were included. The most frequently analysed classes were polymyxins and carbapenems. Limited data were available for ceftazidime/avibactam, ceftolozane/tazobactam and imipenem/relebactam. High or moderate synergism was shown for polymyxin/rifampicin against Acinetobacter baumannii [ES = 0.91, 95% confidence interval (CI) 0.44-1.00], polymyxin/fosfomycin against Klebsiella pneumoniae (ES = 1.00, 95% CI 0.66-1.00) and imipenem/amikacin against Pseudomonas aeruginosa (ES = 1.00, 95% CI 0.21-1.00). Compared with monotherapy, increased bactericidal activity and lower re-growth rates were reported for colistin/fosfomycin and polymyxin/rifampicin in K. pneumoniae and for imipenem/amikacin or imipenem/tobramycin against P. aeruginosa. High quality was documented for 65% and 53% of PK/PD and TK studies, respectively. Well-designed in vitro studies should be encouraged to guide the selection of combination therapies in clinical trials and to improve the armamentarium against carbapenem-resistant bacteria.
Topics: Amikacin; Anti-Bacterial Agents; Azabicyclo Compounds; Carbapenems; Ceftazidime; Cephalosporins; Colistin; Drug Combinations; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Imipenem; In Vitro Techniques; Microbial Sensitivity Tests; Polymyxins; Rifampin; Tazobactam; Tobramycin
PubMed: 33857539
DOI: 10.1016/j.ijantimicag.2021.106344 -
Microbial Pathogenesis Jun 2023Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a significant public health issue. CRKP infections can increase the mortality of severely ill... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of ceftazidime-avibactam compared to other antimicrobials for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae strains, a systematic review and meta-analysis.
INTRODUCTION
Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a significant public health issue. CRKP infections can increase the mortality of severely ill hospitalised patients and elevate the financial burden of their hospitalisation globally. Colistin and tigecycline are the main antimicrobials which have been widely used for the treatment of CRKP infections. However, novel antimicrobials have been recently launched. Ceftazidime-avibactam (CAZ-AVI) seems one of the most efficient ones.
AIM
The aim of the current systematic literature review and meta-analysis is to assess the efficacy and safety of CAZ-AVI compared to other antimicrobials in adult patients (aged >18) with CRKP infection.
METHODS
All data were retrieved using PubMed/Medline, the Web of Science and Cochrane library. The main outcome was the effective treatment of CRKP infection or the microbiological eradication of CRKP in the culture of biological samples. Secondary outcomes included the impact on 28- or 30-day mortality and adverse effects, if available. Pooled analysis was conducted using Review Manager v. 5.4.1 software (RevMan). The level of statistical significance was set at p < 0.05.
RESULTS
CAZ-AVI was proved more effective than other antimicrobials against CRKP infections and CRKP bloodstream infections (p < 0.00001 and p < 0.0001, respectively). Patients in the CAZ-AVI arm displayed statistically lower 28- and 30-day mortality rates (p = 0.002 and p < 0.00001, respectively). Concerning the microbiological eradication, no meta-analysis was feasible due to high heterogeneity.
CONCLUSION
The promotion of CAZ-AVI for treating CRKP infections over other antimicrobials seems favourable. However, there is a long way ahead to reveal additional scientific findings to further strengthen this statement.
Topics: Adult; Humans; Anti-Bacterial Agents; Klebsiella pneumoniae; Ceftazidime; Drug Combinations; Carbapenem-Resistant Enterobacteriaceae; Anti-Infective Agents; Carbapenems; Microbial Sensitivity Tests; Klebsiella Infections; beta-Lactamases
PubMed: 37004964
DOI: 10.1016/j.micpath.2023.106090 -
JAMA Surgery Apr 2021Cefazolin is the preoperative antibiotic of choice because it is safer and more efficacious than second-line alternatives. Surgical patients labeled as having penicillin... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Cefazolin is the preoperative antibiotic of choice because it is safer and more efficacious than second-line alternatives. Surgical patients labeled as having penicillin allergy are less likely to prophylactically receive cefazolin and more likely to receive clindamycin or vancomycin, which results in higher rates of surgical site infections.
OBJECTIVE
To examine the incidence of dual allergy to cefazolin and natural penicillins.
DATA SOURCES
MEDLINE/PubMed, Web of Science, and Embase were searched without language restrictions for relevant articles published from database inception until July 31, 2020.
STUDY SELECTION
In this systematic review and meta-analysis, a search of MEDLINE/PubMed, Web of Science, and Embase was performed for articles published from database inception to July 31, 2020, for studies that included patients who had index allergies to a natural penicillin and were tested for tolerability to cefazolin or that included patients who had index allergies to cefazolin and were tested for tolerability to a natural penicillin. A total of 3228 studies were identified and 2911 were screened for inclusion.
DATA EXTRACTION AND SYNTHESIS
Data were independently extracted by 2 authors. Bayesian meta-analysis was used to estimate the frequency of allergic reactions.
MAIN OUTCOMES AND MEASURES
Dual allergy to cefazolin and a natural penicillin.
RESULTS
Seventy-seven unique studies met the eligibility criteria, yielding 6147 patients. Cefazolin allergy was identified in 44 participants with a history of penicillin allergy, resulting in a dual allergy meta-analytical frequency of 0.7% (95% credible interval [CrI], 0.1%-1.7%; I2 = 74.9%). Such frequency was lower for participants with unconfirmed (0.6%; 95% CrI, 0.1%-1.3%; I2 = 54.3%) than for those with confirmed penicillin allergy (3.0%; 95% CrI, 0.01%-17.0%; I2 = 88.2%). Thirteen studies exclusively assessed surgical patients (n = 3884), among whom 0.7% (95% CrI, 0%-3.3%; I2 = 85.5%) had confirmed allergy to cefazolin. Low heterogeneity was observed for studies of patients with unconfirmed penicillin allergy who had been exposed to perioperative cefazolin (0.1%; 95% CrI, 0.1%-0.3%; I2 = 13.1%). Penicillin allergy was confirmed in 16 participants with a history of cefazolin allergy, resulting in a meta-analytical frequency of 3.7% (95% CrI, 0.03%-13.3%; I2 = 64.4%). The frequency of penicillin allergy was 4.4% (95% CrI, 0%-23.0%; I2 = 75%) for the 8 studies that exclusively assessed surgical patients allergic to cefazolin.
CONCLUSIONS AND RELEVANCE
These findings suggest that most patients with a penicillin allergy history may safely receive cefazolin. The exception is patients with confirmed penicillin allergy in whom additional care is warranted.
Topics: Humans; Anti-Bacterial Agents; Antibiotic Prophylaxis; Cefazolin; Drug Hypersensitivity; Incidence; Penicillins; Surgical Wound Infection
PubMed: 33729459
DOI: 10.1001/jamasurg.2021.0021 -
Heart Failure Reviews Jan 2021Diuretics have an essential role in the management of heart failure (HF). However, each drug has its own benefit and side effect. Side effects include fluid, electrolyte... (Meta-Analysis)
Meta-Analysis Review
Diuretics have an essential role in the management of heart failure (HF). However, each drug has its own benefit and side effect. Side effects include fluid, electrolyte abnormalities, and acid-base disturbance. These adverse effects of diuretics predispose patients to serious cardiac arrhythmias and may increase the risk of arrhythmic mortality. Herein, we aim to summarize the relative efficacy and safety of all available diuretics used in the treatment of patients with HF. In June 2017, a systematic electronic database search was conducted in nine databases. All randomized controlled trials (RCTs) comparing the different diuretics used in HF were included for meta-analysis. The protocol was registered in Prospero with CRD42018084819. Among the included 54 studies (10,740 patients), 34 RCTs were eligible for quantitative network meta-analysis (NMA) and traditional meta-analysis while the other 20 studies were qualitatively analyzed. Our results showed that azosemide and torasemide caused a significant reduction in brain natriuretic peptide (BNP) level. Torasemide also caused a significant decrease in collagen volume fraction (CVF) and edema. No significant difference between the agents concerning glomerular filtration rate (GFR), water extraction, and sodium excretion was demonstrated. Regarding side effects, no significant difference among diuretics was observed in terms of hospital readmission and mortality rates. Diuretics are the main treatment of hypervolemia in HF patients. The choice of appropriate diuretic is essential for successful management and is mainly guided by patient clinical situations and the presence of other co-morbidities.
Topics: Diuretics; Furosemide; Heart Failure; Humans; Randomized Controlled Trials as Topic; Torsemide
PubMed: 32783109
DOI: 10.1007/s10741-020-10003-7