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The Clinical Journal of Pain Jul 2024This study aimed to systematically evaluate the clinical efficacy of gabapentin and pregabalin in the treatment of acute herpes zoster (HZ) neuralgia, including pain... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to systematically evaluate the clinical efficacy of gabapentin and pregabalin in the treatment of acute herpes zoster (HZ) neuralgia, including pain control and the occurrence of adverse effects.
METHODS
A systematic computerized search was conducted in October 2023 in PubMed, Embase, Web of Science, Cochrane Library, VIP, CNKI, and Wanfang databases. Data from randomized controlled trials (RCTs) comparing gabapentin analogs for the treatment of acute HZ neuralgia were searched. Endpoints were visual analog scores (Visual Analog Scale) and adverse effects at 1, 2, and 4 weeks. Data from studies that met the inclusion criteria were extracted for meta-analysis and sensitivity analysis using Revman 5.4 and Stata16.
RESULTS
The study included 292 patients from 6 RCTs. Of these, 118 were in the gabapentin-treated group, 37 were in the pregabalin-treated group, and 137 were in the placebo-controlled group. The gabapentin group showed superior pain reduction compared with the placebo group ( P < 0.05), but adverse events were more frequent.
CONCLUSION
Gabapentin can effectively reduce acute HZ neuralgia in patients. Pregabalin requires additional RCTs to supplement the analysis.
Topics: Humans; Gabapentin; Randomized Controlled Trials as Topic; Herpes Zoster; Analgesics; Pregabalin; Neuralgia, Postherpetic; Neuralgia
PubMed: 38651606
DOI: 10.1097/AJP.0000000000001218 -
Nanotoxicology Apr 2024Amphotericin B (AmB) is a broad-spectrum therapeutic and effective drug, but it has serious side effects of toxicity and solubility. Therefore, reducing its toxicity... (Review)
Review
Amphotericin B (AmB) is a broad-spectrum therapeutic and effective drug, but it has serious side effects of toxicity and solubility. Therefore, reducing its toxicity should be considered in therapeutic applications. Nanotechnology has paved the way to improve drug delivery systems and reduce toxicity. The present study, for the first time, comprehensively reviews the studies from 2011 to 2023 on reducing the toxicity of AmB. The findings showed that loading AmB with micellar structures, nanostructured lipid carriers, liposomes, emulsions, poly lactide-co-glycolide acid, chitosan, dendrimers, and other polymeric nanoparticles increases the biocompatibility and efficacy of the drug and significantly reduces toxicity. In addition, modified carbon nanoparticles (including graphene, carbon nanotubes, and carbon dots) with positively charged amine groups, PEI, and other components showed favorable drug delivery properties. Uncoated and coated magnetic nanoparticles and silver NPs-AmB composites had less cytotoxicity and more antifungal activity than free AmB. Citrate-reduced GNPs and lipoic acid-functionalized GNPs were also effective nanocarriers to reduce AmB cytotoxicity and improve anti-leishmania efficacy. In addition, zinc oxide-NPs and PEGylated zinc oxide-NPs showed favorable antifungal activity and negligible toxicity. According to a review study, carbon-based nanoparticles, metal nanoparticles, and especially polymer nanoparticles caused some reduction in the toxicity and improved solubility of AmB in water. Overall, considering the discussed nanocarriers, further research on the application of nanotechnology as a cost-effective candidate to improve the efficiency and reduce the cytotoxicity of AmB is recommended.
PubMed: 38646931
DOI: 10.1080/17435390.2024.2340467 -
PloS One 2024Hypertrophic Cardiomyopathy (HCM) is a complex cardiac condition characterized by hypercontractility of cardiac muscle leading to a dynamic obstruction of left... (Meta-Analysis)
Meta-Analysis
Evaluating the efficacy and safety of mavacamten in hypertrophic cardiomyopathy: A systematic review and meta-analysis focusing on qualitative assessment, biomarkers, and cardiac imaging.
BACKGROUND
Hypertrophic Cardiomyopathy (HCM) is a complex cardiac condition characterized by hypercontractility of cardiac muscle leading to a dynamic obstruction of left ventricular outlet tract (LVOT). Mavacamten, a first-in-class cardiac myosin inhibitor, is increasingly being studied in randomized controlled trials. In this meta-analysis, we aimed to analyse the efficacy and safety profile of Mavacamten compared to placebo in patients of HCM.
METHOD
We carried out a comprehensive search in PubMed, Cochrane, and clinicaltrials.gov to analyze the efficacy and safety of mavacamten compared to placebo from 2010 to 2023. To calculate pooled odds ratio (OR) or risk ratio (RR) at 95% confidence interval (CI), the Mantel-Haenszel formula with random effect was used and Generic Inverse Variance method assessed pooled mean difference value at a 95% CI. RevMan was used for analysis. P<0.05 was considered significant.
RESULTS
We analyzed five phase 3 RCTs including 609 patients to compare mavacamten with a placebo. New York Heart Association (NYHA) grade improvement and KCCQ score showed the odds ratio as 4.94 and 7.93 with p<0.00001 at random effect, respectively. Cardiac imaging which included LAVI, LVOT at rest, LVOT post valsalva, LVOT post-exercise, and reduction in LVEF showed the pooled mean differences for change as -5.29, -49.72, -57.45, -36.11, and -3.00 respectively. Changes in LVEDV and LVMI were not statistically significant. The pooled mean difference for change in NT-proBNP and Cardiac troponin-I showed 0.20 and 0.57 with p<0.00001. The efficacy was evaluated in 1) A composite score, which was defined as either 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction, or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening and 2) changes in pVO2, which was not statistically significant. Similarly, any treatment-associated emergent adverse effects (TEAE), treatment-associated serious adverse effects (TSAE), and cardiac-related adverse effects were not statistically significant.
CONCLUSION
Mavacamten influences diverse facets of HCM comprehensively. Notably, our study delved into the drug's impact on the heart's structural and functional aspects, providing insights that complement prior findings. Further large-scale trials are needed to evaluate the safety profile of Mavacamten.
Topics: Humans; Cardiomyopathy, Hypertrophic; Heart; Benzylamines; Biomarkers; Uracil
PubMed: 38635724
DOI: 10.1371/journal.pone.0301704 -
Journal of Public Health Dentistry Jun 2024This systematic review aimed to review the safety and effectiveness of professionally applied fluorides for preventing and arresting dental caries in low- and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This systematic review aimed to review the safety and effectiveness of professionally applied fluorides for preventing and arresting dental caries in low- and middle-income countries (LMICs).
METHODS
Randomized controlled trials conducted in LMICs, in which professionally applied fluorides were compared with placebo/no treatment/health education only or usual care with a minimum one-year follow-up period, were included. Any topically applied fluoride agents such as sodium fluoride (NaF), acidulated phosphate fluoride, silver diamine fluoride (SDF), and nano silver fluoride (NSF) were included. Five databases (PubMed, Embase, Scopus, Web of Science, and Cochrane Library) were searched in May 2022. Meta-analysis was conducted using a random effect model.
RESULTS
This review included 33 studies for qualitative synthesis, encompassing 16,375 children aged between 1.5 and 14 years. Nevertheless, the meta-analysis focused on only 17 studies, involving 4067 children. Fourteen papers assessed potential adverse events, none of which was reported as major adverse events. SDF and NSF were identified as effective in arresting caries on primary teeth (p < 0.05) compared with a placebo or no treatment. Fluoride varnish and gel were identified as effective in reducing new caries development on primary teeth (p < 0.05) but not on permanent teeth (p > 0.05). The certainty of the generated evidence obtained is low.
CONCLUSION
The review provides valuable insights into the use of professionally applied fluorides in LMICs and contributes to recommendations for their use. However, the limited rigorous evidence suggests the need for further research to strengthen these findings and draw more robust conclusions.
Topics: Humans; Dental Caries; Developing Countries; Fluorides, Topical; Child; Child, Preschool; Adolescent; Cariostatic Agents; Infant; Fluorides; Silver Compounds; Randomized Controlled Trials as Topic; Quaternary Ammonium Compounds
PubMed: 38623701
DOI: 10.1111/jphd.12617 -
Journal of Cystic Fibrosis : Official... May 2024Cystic Fibrosis (CF) liver disease progresses to liver failure requiring transplantation in about 3 % of patients, 0.7 % of CF patients are post liver transplant. The...
BACKGROUND & AIMS
Cystic Fibrosis (CF) liver disease progresses to liver failure requiring transplantation in about 3 % of patients, 0.7 % of CF patients are post liver transplant. The prognosis of CF has improved with the introduction of elexacaftor/tezacaftor/ivacaftor (ETI). Due to the paucity of data and concerns regarding interactions with immunosuppressive drug regimens, there is no general consensus on use of ETI post liver transplantation. The aim of this review is to report the safety and efficacy of ETI in CF patients who underwent liver transplantation.
METHODS
A systematic review was conducted through MEDLINE/Pubmed and EMBASE databases. English-written articles reporting clinical data on liver transplanted CF patients treated with ETI were included. Article quality was evaluated using the Critical Appraisal Checklist for Case Reports.
RESULTS
Twenty cases were retrieved from 6 reports. Temporary discontinuation and/or dose reduction due to elevated transaminases was required in 5 cases. ETI restarted on a reduced dose was tolerated in 3 out of 5 patients, 1 patient tolerated full dose. Tacrolimus dose change was required in 14 cases, in 1 case ETI was discontinued due to tacrolimus toxicity. Improvement in percentage predicted FEV1 was noted in 15/19 patients (median +17 %, range 8 %-38 %).
CONCLUSIONS
In the majority of liver transplanted patients ETI is well tolerated, although adverse events and liver function abnormalities may occur. Close monitoring of liver function and tacrolimus level is warranted. Significant improvement in lung function after ETI initiation is confirmed, highlighting the importance of accessing this medication for this group of patients.
Topics: Humans; Aminophenols; Benzodioxoles; Chloride Channel Agonists; Cystic Fibrosis; Drug Combinations; Indoles; Liver Transplantation; Pyrazoles; Pyridines; Pyrroles; Pyrrolidines; Quinolones
PubMed: 38614868
DOI: 10.1016/j.jcf.2024.04.006 -
Medicine Apr 2024Tyrosine kinase inhibitors (TKIs) have been approved for treating patients with clinically advanced metastatic thyroid cancer. However among the many TKIs, it remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tyrosine kinase inhibitors (TKIs) have been approved for treating patients with clinically advanced metastatic thyroid cancer. However among the many TKIs, it remains unknown which regimen is the best choice for these patients.
METHODS
We conducted a systematic review and network meta-analysis to compare the survival benefits and efficacy of the available first-line regimens. We conducted an active search for phase II, III, or IV randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to compare the effects of at least 2 drugs in the systemic treatment of advanced or metastatic thyroid cancer up to May 2023. The network meta-analysis model was adjusted using Bayesian Network model. Twelve trials with 2535 patients were included in our meta-analysis. The overall survival (OS), progression-free survival (PFS), and serious adverse events (SAEs) were taken as reference indicators. We also performed subgroup analyses of OS and PFS in medullary thyroid cancer (MTC) and radioiodine-refractory differentiated thyroid cancer (RR-DTC) to explore the variations of TKIs in different groups.
RESULTS
As a result, apatinib had the best effect on overall survival (OS) (hazards ratio [HR] = 0.42, 95% confidence interval [CI] = 0.18-0.98), lenvatinib 18 mg/d has the best effect on progression-free survival (PFS) (HR = 0.13, 95% CI = 0.064-0.27), and cabozantinib 60 mg/d has the best safety profile.
CONCLUSIONS
Our network meta-analysis showed that we believe that cabozantinib has the potential to become a widely used drug in clinical practice.
Topics: Humans; Tyrosine Kinase Inhibitors; Network Meta-Analysis; Randomized Controlled Trials as Topic; Anilides; Neoplasms; Pyridines
PubMed: 38608050
DOI: 10.1097/MD.0000000000037655 -
Clinical Therapeutics May 2024L-carnitine supplementation has been recommended to improve cardiometabolic health markers in diabetic patients. Our purpose was to assess the dose-dependent effects of... (Meta-Analysis)
Meta-Analysis Review
The Effects of L-Carnitine Supplementation on Weight Loss, Glycemic Control, and Cardiovascular Risk Factors in Patients With Type 2 Diabetes: A Systematic Review and Dose-response Meta-Analysis of Randomized Controlled Trials.
PURPOSE
L-carnitine supplementation has been recommended to improve cardiometabolic health markers in diabetic patients. Our purpose was to assess the dose-dependent effects of l-carnitine supplementation on cardiometabolic risk factors in patients with type 2 diabetes.
METHODS
PubMed/Medline, Scopus, and Web of Science were searched until May 2022 for randomized controlled trials that examined the impact of l-carnitine supplementation on cardiometabolic risk factors in adults with type 2 diabetes. The mean difference (MD) and its 95% confidence interval (CI) were estimated utilizing a random-effects model. Nonlinear dose-response associations were modeled with restricted cubic splines. The certainty of evidence was rated using the GRADE approach.
FINDINGS
Twenty-one randomized trials with 2041 patients with type 2 diabetes were included. We found that every 1 g/d supplementation with l-carnitine significantly reduced body mass index (MD: -0.37 kg/m, 95% CI: -0.59, -0.15; I =93%, n=13, GRADE=low), HbA (MD: -0.16%, 95% CI: -0.32, -0.01; I = 94%, n = 18, GRADE = moderate), and low-density lipoprotein cholesterol (MD: -0.11 mmol/L, 95% CI: -0.16, -0.05; I = 91%, n = 11, GRADE = high). There were also reductions in serum triglycerides (MD: 0.07 mmol/L), total cholesterol (MD: -0.13 mmol/L), and fasting plasma glucose (MD: -0.17 mmol/L). A U-shaped effect was demonstrated for body mass index, with the largest reduction at 2 g/d. A linear reduction was seen for serum triglycerides, total cholesterol, and fasting plasma glucose up to l-carnitine supplementation of 4 g/d.
IMPLICATIONS
L-carnitine supplementation resulted in a small reduction in serum lipids and plasma glucose in patients with type 2 diabetes. However, due to high statistical heterogeneity, the results should be interpreted very cautiously.
Topics: Carnitine; Diabetes Mellitus, Type 2; Humans; Randomized Controlled Trials as Topic; Dietary Supplements; Glycemic Control; Blood Glucose; Weight Loss; Dose-Response Relationship, Drug; Cardiovascular Diseases; Heart Disease Risk Factors; Glycated Hemoglobin
PubMed: 38594107
DOI: 10.1016/j.clinthera.2024.03.002 -
Anesthesiology May 2024Liposomal bupivacaine is reported to prolong the duration of analgesia when used for abdominal fascial plane blocks compared to plain local anesthetics; however,... (Meta-Analysis)
Meta-Analysis
Analgesic Effectiveness of Liposomal Bupivacaine versus Plain Local Anesthetics for Abdominal Fascial Plane Blocks: A Systematic Review and Meta-analysis of Randomized Trials.
BACKGROUND
Liposomal bupivacaine is reported to prolong the duration of analgesia when used for abdominal fascial plane blocks compared to plain local anesthetics; however, evidence from randomized trials is mixed. This meta-analysis aims to compare the analgesic effectiveness of liposomal bupivacaine to plain local anesthetics in adults receiving abdominal fascial plane blocks.
METHODS
Randomized trials comparing liposomal bupivacaine and plain (nonliposomal) local anesthetics in abdominal fascial plane blocks were sought. The primary outcome was area under the curve rest pain between 24 to 72 h postoperatively. Secondary outcomes included rest pain at individual timepoints (1, 6, 12, 24, 48, and 72 h); analgesic consumption at 0 to 24, 25 to 48, and 49 to 72 h; time to analgesic request; hospital stay duration; and opioid-related side effects. Data were pooled using the Hartung-Knapp-Sidik-Jonkman random effects method.
RESULTS
Sixteen trials encompassing 1,287 patients (liposomal bupivacaine, 667; plain local anesthetics, 620) were included. The liposomal bupivacaine group received liposomal bupivacaine mixed with plain bupivacaine in 10 studies, liposomal bupivacaine alone in 5 studies, and both preparations in 1 three-armed study. No difference was observed between the two groups for area under the curve pain scores, with a standardized mean difference (95% CI) of -0.21 cm.h (-0.43 to 0.01; P = 0.058; I2 = 48%). Results were robust to subgroup analysis based on (1) potential conflict of interest and (2) mixing of plain local anesthetics with liposomal bupivacaine. The two groups were not different for any of the day 2 or day 3 secondary outcomes.
CONCLUSIONS
This systematic review and meta-analysis suggests similar analgesic effectiveness between liposomal bupivacaine and plain local anesthetics when used for fascial plane block of the abdominal wall. The authors' analysis does not support an evidence-based preference for liposomal bupivacaine compared to plain local anesthetics for abdominal fascial plane blocks.
Topics: Adult; Humans; Anesthetics, Local; Randomized Controlled Trials as Topic; Analgesics; Bupivacaine; Pain
PubMed: 38592360
DOI: 10.1097/ALN.0000000000004932 -
Inhaled bronchodilators for the prevention and treatment of chronic lung disease in preterm infants.The Cochrane Database of Systematic... Apr 2024Chronic lung disease (CLD) occurs frequently in preterm infants and is associated with respiratory morbidity. Bronchodilators have the potential effect of dilating small... (Review)
Review
BACKGROUND
Chronic lung disease (CLD) occurs frequently in preterm infants and is associated with respiratory morbidity. Bronchodilators have the potential effect of dilating small airways with muscle hypertrophy. Increased compliance and tidal volume, and decreased airway resistance, have been documented with the use of bronchodilators in infants with CLD. Therefore, bronchodilators are widely considered to have a role in the prevention and treatment of CLD, but there remains uncertainty as to whether they improve clinical outcomes. This is an update of the 2016 Cochrane review.
OBJECTIVES
To determine the effect of inhaled bronchodilators given as prophylaxis or as treatment for chronic lung disease (CLD) on mortality and other complications of preterm birth in infants at risk for or identified as having CLD.
SEARCH METHODS
An Information Specialist searched CENTRAL, MEDLINE, Embase, CINAHL and three trials registers from 2016 to May 2023. In addition, the review authors undertook reference checking, citation searching and contact with trial authors to identify additional studies.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials involving preterm infants less than 32 weeks old that compared bronchodilators to no intervention or placebo. CLD was defined as oxygen dependency at 28 days of life or at 36 weeks' postmenstrual age. Initiation of bronchodilator therapy for the prevention of CLD had to occur within two weeks of birth. Treatment of infants with CLD had to be initiated before discharge from the neonatal unit. The intervention had to include administration of a bronchodilator by nebulisation or metered dose inhaler. The comparator was no intervention or placebo.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. Critical outcomes included: mortality within the trial period; CLD (defined as oxygen dependency at 28 days of life or at 36 weeks' postmenstrual age); adverse effects of bronchodilators, including hypokalaemia (low potassium levels in the blood), tachycardia, cardiac arrhythmia, tremor, hypertension and hyperglycaemia (high blood sugar); and pneumothorax. We used the GRADE approach to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We included two randomised controlled trials in this review update. Only one trial provided useable outcome data. This trial was conducted in six neonatal intensive care units in France and Portugal, and involved 173 participants with a gestational age of less than 31 weeks. The infants in the intervention group received salbutamol for the prevention of CLD. The evidence suggests that salbutamol may result in little to no difference in mortality (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.50 to 2.31; risk difference (RD) 0.01, 95% CI -0.09 to 0.11; low-certainty evidence) or CLD at 28 days (RR 1.03, 95% CI 0.78 to 1.37; RD 0.02, 95% CI -0.13 to 0.17; low-certainty evidence), when compared to placebo. The evidence is very uncertain about the effect of salbutamol on pneumothorax. The one trial with usable data reported that there were no relevant differences between groups, without providing the number of events (very low-certainty evidence). Investigators in this study did not report if side effects occurred. We found no eligible trials that evaluated the use of bronchodilator therapy for the treatment of infants with CLD. We identified no ongoing studies.
AUTHORS' CONCLUSIONS
Low-certainty evidence from one trial showed that inhaled bronchodilator prophylaxis may result in little or no difference in the incidence of mortality or CLD in preterm infants, when compared to placebo. The evidence is very uncertain about the effect of salbutamol on pneumothorax, and neither included study reported on the incidence of serious adverse effects. We identified no trials that studied the use of bronchodilator therapy for the treatment of CLD. Additional clinical trials are necessary to assess the role of bronchodilator agents in the prophylaxis or treatment of CLD. Researchers studying the effects of inhaled bronchodilators in preterm infants should include relevant clinical outcomes in addition to pulmonary mechanical outcomes.
Topics: Infant; Female; Infant, Newborn; Humans; Infant, Premature; Bronchodilator Agents; Pneumothorax; Chronic Disease; Premature Birth; Infant, Premature, Diseases; Albuterol; Lung Diseases; Oxygen
PubMed: 38591664
DOI: 10.1002/14651858.CD003214.pub4 -
World Journal of Urology Apr 2024Fosfomycin has been used more frequently in managing uncomplicated urinary tract infections (UTIs) due to decreased compliance and increased multidrug-resistant... (Meta-Analysis)
Meta-Analysis
PURPOSE
Fosfomycin has been used more frequently in managing uncomplicated urinary tract infections (UTIs) due to decreased compliance and increased multidrug-resistant bacteria. The aim of this network meta-analysis was to assess the efficacy of Fosfomycin compared to Nitrofurantoin, Trimethoprim-Sulfamethoxazole (TMP-SMX), and Ciprofloxacin in terms of clinical and microbiological cure alongside with other measurements.
MATERIALS AND METHODS
We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). We included randomized control trials (RCTs) with uncomplicated UTI patients who received Fosfomycin, Nitrofurantoin, TMP-SMX, or Ciprofloxacin and reported the clinical or microbiological cure. We used Cochrane Risk of Bias Assessment Tool to assess the included studies' quality. R-software was used for all statistical analysis. We ranked all antibiotics using the netrank function which yielded P scores. Frequentist network meta-analysis was used to assess the efficacy of all outcomes.
RESULTS
We included 13 RCTs with a total number of 3856 patients that showed Fosfomycin ranked the highest among the other antibiotics with respect to clinical cure (P-score = 0.99) and microbiological cure (P-score = 0.99) while Ciprofloxacin ranked the lowest (P-score = 0.11 and 0.02, respectively). Moreover, Ciprofloxacin yielded the highest relapse rate (P-score = 1), whereas TMP-SMX had the lowest relapse rate (P-score = 0.07). As for the adverse events, Ciprofloxacin demonstrated the highest adverse events as opposed to Fosfomycin (P-score = 0.98 and 0.05, respectively).
CONCLUSION
The network meta-analysis demonstrated that Fosfomycin is the most effective antibiotic in treating uncomplicated UTIs with respect to clinical cure, microbiological cure, and adverse events profile.
Topics: Humans; Anti-Bacterial Agents; Fosfomycin; Nitrofurantoin; Trimethoprim, Sulfamethoxazole Drug Combination; Network Meta-Analysis; Urinary Tract Infections; Ciprofloxacin; Recurrence
PubMed: 38587648
DOI: 10.1007/s00345-024-04922-5