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Medicine Mar 2023Shuxuening injection (SXN) is a traditional Chinese medicine used in the treatment of cardiovascular diseases. Whether it can provide better outcomes when combined with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Shuxuening injection (SXN) is a traditional Chinese medicine used in the treatment of cardiovascular diseases. Whether it can provide better outcomes when combined with edaravone injection (ERI) for the treatment of acute cerebral infarction is not well determined. Therefore, we evaluated the efficacy of ERI combined with SXN versus that of ERI alone in patients with acute cerebral infarction.
METHODS
PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang electronic databases were searched up to July 2022. Randomized controlled trials comparing the outcomes of efficacy rate, neurologic impairment, inflammatory factors, and hemorheology were included. Odds ratio or standard mean difference (SMD) with corresponding 95% confidence intervals (CIs) were used to present the overall estimates. The quality of the included trials was evaluated by the Cochrane risk of bias tool. The study was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses.
RESULTS
Seventeen randomized controlled trials were included consisting of 1607 patients. Compared to ERI alone, treatment with ERI plus SXN had a greater effective rate than ER alone (odds ratio = 3.94; 95% CI: 2.85, 5.44; I2 = 0%, P < .00001), a lower National Institute of Health Stroke Scale (SMD= -1.39; 95% CI: -1.73, -1.05; I2 = 71%, P < .00001), lower neural function defect score (SMD= -0.75; 95% CI: -1.06,-0.43; I2 = 67%, P < .00001), and lower level of neuron-specific enolase (SMD= -2.10; 95% CI: -2.85, -1.35; I2 = 85%, P < .00001). ERI plus SXN treatment provided significant improvements in whole blood high shear viscosity (SMD = -0.87; 95% CI: -1.17, -0.57; I2 = 0%, P < .00001), and whole blood low shear viscosity (SMD = -1.50; 95% CI: -1.65, -1.36; I2 = 0%, P < .00001) compared to ERI alone.
CONCLUSION
ERI plus SXN showed better efficacy than ERI alone for patients with acute cerebral infarction. Our study provides evidence supporting the application of ERI plus SXN for acute cerebral infarction.
Topics: Humans; Edaravone; Stroke; Brain Ischemia; Acute Disease; Cerebral Infarction
PubMed: 36862906
DOI: 10.1097/MD.0000000000032929 -
Journal of Cutaneous Medicine and... 2023Lichen Planus (LP) is a dermatological disorder characterized by violaceous papules that affect the cutaneous region, nails, scalp, and mucous membranes. Current... (Review)
Review
BACKGROUND
Lichen Planus (LP) is a dermatological disorder characterized by violaceous papules that affect the cutaneous region, nails, scalp, and mucous membranes. Current molecular and clinical studies point to the Janus Kinase-signal transducer and activator of transcription (JAK-STAT) pathway as a potential effector of LP pathology.
OBJECTIVE
This systematic review summarizes the current reported literature outcomes for patients receiving JAK inhibitors to treat LP.
METHODS
MEDLINE and Embase were searched on 16 October, 2022, and 15 original articles were included, with 56 LP patients.
RESULTS
(mean age: 54.5 years, range: 26-81 years, male: 26.8%). The treatment outcomes were included for the following JAK inhibitors: tofacitinib ( = 30), baricitinib ( = 16), ruxolitinib ( = 12), and upadacitinib ( = 2). Patient outcomes were classified into complete resolution, partial resolution, and no resolution. Patients achieving complete resolution represented 25% ( = 4/16) in the baricitinib group, 10% ( = 3/30) in the tofacitinib group, 16.7% ( = 2/12) in the ruxolitinib group, and 100% (2/2) in the upadacitinib group. Partial resolution patients represented 31.3% ( = 5/16) of baricitinib patients, 60% ( = 18/30) of tofacitinib patients, and 83% ( = 10/12) of ruxolitinib patients. 43.8% ( = 7/16) of baricitinib patients and 10% ( = 9/30) of tofacitinib patients had no resolution of lesions.
CONCLUSION
This review also highlights the significance of utilizing a uniform outcome measure for LP, as it aids in reporting more generalizable results, reduces reporting bias, and ultimately lead to improved clinical outcomes for LP patients.
Topics: Humans; Male; Middle Aged; Janus Kinase Inhibitors; Pyrazoles; Lichen Planus
PubMed: 36815857
DOI: 10.1177/12034754231156100 -
Critical Care (London, England) Feb 2023Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically,...
Ethylene glycol (EG) is metabolized into glycolate and oxalate and may cause metabolic acidemia, neurotoxicity, acute kidney injury (AKI), and death. Historically, treatment of EG toxicity included supportive care, correction of acid-base disturbances and antidotes (ethanol or fomepizole), and extracorporeal treatments (ECTRs), such as hemodialysis. With the wider availability of fomepizole, the indications for ECTRs in EG poisoning are debated. We conducted systematic reviews of the literature following published EXTRIP methods to determine the utility of ECTRs in the management of EG toxicity. The quality of the evidence and the strength of recommendations, either strong ("we recommend") or weak/conditional ("we suggest"), were graded according to the GRADE approach. A total of 226 articles met inclusion criteria. EG was assessed as dialyzable by intermittent hemodialysis (level of evidence = B) as was glycolate (Level of evidence = C). Clinical data were available for analysis on 446 patients, in whom overall mortality was 18.7%. In the subgroup of patients with a glycolate concentration ≤ 12 mmol/L (or anion gap ≤ 28 mmol/L), mortality was 3.6%; in this subgroup, outcomes in patients receiving ECTR were not better than in those who did not receive ECTR. The EXTRIP workgroup made the following recommendations for the use of ECTR in addition to supportive care over supportive care alone in the management of EG poisoning (very low quality of evidence for all recommendations): i) Suggest ECTR if fomepizole is used and EG concentration > 50 mmol/L OR osmol gap > 50; or ii) Recommend ECTR if ethanol is used and EG concentration > 50 mmol/L OR osmol gap > 50; or iii) Recommend ECTR if glycolate concentration is > 12 mmol/L or anion gap > 27 mmol/L; or iv) Suggest ECTR if glycolate concentration 8-12 mmol/L or anion gap 23-27 mmol/L; or v) Recommend ECTR if there are severe clinical features (coma, seizures, or AKI). In most settings, the workgroup recommends using intermittent hemodialysis over other ECTRs. If intermittent hemodialysis is not available, CKRT is recommended over other types of ECTR. Cessation of ECTR is recommended once the anion gap is < 18 mmol/L or suggested if EG concentration is < 4 mmol/L. The dosage of antidotes (fomepizole or ethanol) needs to be adjusted during ECTR.
Topics: Humans; Antidotes; Fomepizole; Ethanol; Renal Dialysis; Glycolates; Ethylene Glycol; Poisoning
PubMed: 36765419
DOI: 10.1186/s13054-022-04227-2 -
Acta Dermato-venereologica Jan 2023The aim of this study was to compare the efficacy and safety of treatment with Janus kinase inhibitors for alopecia areata, measured by change in Severity of Alopecia... (Meta-Analysis)
Meta-Analysis
The aim of this study was to compare the efficacy and safety of treatment with Janus kinase inhibitors for alopecia areata, measured by change in Severity of Alopecia Tool (SALT) score. A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was performed using Medline, EMBASE and Cochrane library. All studies investigating the efficacy of treatments for alopecia areata were included. Primary outcomes were the proportion of patients with alopecia areata achieving 30%, 50%, 75%, 90% and 100% improvement in SALT score after treatment with a Janus kinase inhibitor. A meta-analysis was performed including all randomized controlled trials investigating Janus kinase inhibitors. A total of 37 studies matched the inclusion criteria and were included. Meta-analysis was performed based on 5 randomized studies. Regarding patients with alopecia areata defined as ≥ 50% scalp hair loss, baricitinib 4 mg once daily demonstrated the highest efficacy. However, among patients with alopecia areata defined as a SALT score ≥ 50, oral deuruxolitinib 12 mg twice daily demonstrated the highest efficacy. Deuruxolitinib and baricitinib appear to be promising drugs for the treatment of alopecia areata. However, the response depends on the dosage of the drug. More randomized trials, with identical inclusion criteria and dose and duration of treatment, are required to confirm these findings.
Topics: Humans; Alopecia Areata; Janus Kinase Inhibitors; Alopecia; Pyrazoles
PubMed: 36695751
DOI: 10.2340/actadv.v103.4536 -
Medicine Dec 2022To estimate the acute analgesic efficacy of combined Pregabalin and Celecoxib after operation via a systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the acute analgesic efficacy of combined Pregabalin and Celecoxib after operation via a systematic review and meta-analysis.
METHODS
Studies for inclusion were randomized controlled trials, reporting on relevant outcomes (0-6 hours, 24 hours, 7 days pain scores) with treatment with combined Pregabalin and Celecoxib.
RESULTS
The pooled results from meta-analysis demonstrated that compared with placebo, combined Pregabalin and Celecoxib reduced pain scores at 0 to 6 hours in 3 articles, 24 hours in 5 articles, 7 days in 2 articles (standard mean difference [SMD], -3.10 at 0-6 hours, -2.80 at 24 hours, -1.32 at 7 days, respectively). Combined Pregabalin and Celecoxib could significantly reduce the postoperative narcotic consumption in 3 studies (SMD, -1.99 at 36 hour).
DISCUSSION
This work suggested that combined Pregabalin and Celecoxib were efficacious in reduction of postoperative pain and narcotic requirements after surgery, whereas more trials are needed to further identify the efficacy of combined Pregabalin and Celecoxib in the management of acute postoperative pain.
Topics: Humans; Pregabalin; Celecoxib; Analgesics; Narcotics; Pain, Postoperative
PubMed: 36596023
DOI: 10.1097/MD.0000000000032080 -
European Journal of Pharmaceutical... Apr 2023Malaria poses a severe public health risk and a significant economic burden in disease-endemic countries. One of the most severe issues in malaria control is the... (Review)
Review
Malaria poses a severe public health risk and a significant economic burden in disease-endemic countries. One of the most severe issues in malaria control is the development of drug resistance in malaria parasites. The standard treatment for malaria is artemisinin-combination therapy (ACT). Nevertheless, the Plasmodium parasite's extensive resistance to prior drugs and reduced ACT efficiency necessitates novel drug discovery. The progress in discovering novel, affordable, and effective antimalarial agents is significant in combating drug resistance, and the hybrid drug concept can be used to covalently link two or more active pharmacophores that may act on multiple targets. Pyrazole and pyrazoline derivatives are considered pharmacologically necessary active heterocyclic scaffolds that possess almost all types of pharmacological activities. This review summarized recent progress in antimalarial activities of synthesized pyrazole and pyrazoline derivatives. The studies published since 2000 are included in this systematic review. This review is anticipated to be beneficial for future study and new ideas in searching for rational development strategies for more effective pyrazole and pyrazoline derivatives as antimalarial drugs.
Topics: Humans; Antimalarials; Malaria; Pyrazoles; Drug Resistance; Folic Acid Antagonists; Plasmodium falciparum
PubMed: 36563914
DOI: 10.1016/j.ejps.2022.106365 -
The Canadian Journal of Infectious... 2022Since the beginning of the novel coronavirus (SARS-CoV-2) disease outbreak, there has been an increasing interest in discovering potential therapeutic agents for this... (Review)
Review
BACKGROUND
Since the beginning of the novel coronavirus (SARS-CoV-2) disease outbreak, there has been an increasing interest in discovering potential therapeutic agents for this disease. In this regard, we conducted a systematic review through an overview of drug development (in silico, in vitro, and in vivo) for treating COVID-19.
METHODS
A systematic search was carried out in major databases including PubMed, Web of Science, Scopus, EMBASE, and Google Scholar from December 2019 to March 2021. A combination of the following terms was used: coronavirus, COVID-19, SARS-CoV-2, drug design, drug development, In silico, In vitro, and In vivo. A narrative synthesis was performed as a qualitative method for the data synthesis of each outcome measure.
RESULTS
A total of 2168 articles were identified through searching databases. Finally, 315 studies (266 in silico, 34 in vitro, and 15 in vivo) were included. In studies with in silico approach, 98 article study repurposed drug and 91 studies evaluated herbal medicine on COVID-19. Among 260 drugs repurposed by the computational method, the best results were observed with saquinavir ( = 9), ritonavir ( = 8), and lopinavir ( = 6). Main protease ( = 154) following spike glycoprotein ( = 62) and other nonstructural protein of virus ( = 45) was among the most studied targets. Doxycycline, chlorpromazine, azithromycin, heparin, bepridil, and glycyrrhizic acid showed both in silico and in vitro inhibitory effects against SARS-CoV-2.
CONCLUSION
The preclinical studies of novel drug design for COVID-19 focused on main protease and spike glycoprotein as targets for antiviral development. From evaluated structures, saquinavir, ritonavir, eucalyptus, Tinospora cordifolia, aloe, green tea, curcumin, pyrazole, and triazole derivatives in in silico studies and doxycycline, chlorpromazine, and heparin from in vitro and human monoclonal antibodies from in vivo studies showed promised results regarding efficacy. It seems that due to the nature of COVID-19 disease, finding some drugs with multitarget antiviral actions and anti-inflammatory potential is valuable and some herbal medicines have this potential.
PubMed: 36199815
DOI: 10.1155/2022/2044282 -
Respiratory Medicine Oct 2022There are conflicting reports on the results of several of the latest clinical trials related to the use of baricitinib in the management of COVID-19 patients. The aim... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are conflicting reports on the results of several of the latest clinical trials related to the use of baricitinib in the management of COVID-19 patients. The aim of the current systematic review and meta-analysis was to evaluate the efficacy of baricitinib in COVID-19 patients.
METHODS
Databases like ScienceDirect, PubMed/Medline, Publons, Google Scholar and other sources like ClinicalTrials.gov, Cochrane, medRxiv, Research Square and reference lists were thoroughly searched.
RESULTS
Fifteen (15) articles which met the inclusion criteria were qualitatively and quantitatively analysed. Based on Cochrane and Newcastle-Ottawa Scale (NOS) risk of bias (RoB) analyses, 14/15 articles are grouped as high-quality. Meta-analyses revealed that randomised control trials (RCTs) and non-randomised control trials (nRCTs) statistically significantly reduced the mortality rate in COVID-19 patients, with a risk ratio (RR) in the fixed-effect model was RR = 0.64 [95% CI: 0.51 to 0.79; p < 0.0001] and RR = 0.58 [95% CI: 0.45 to 0.73; p < 0.00001], respectively, with insignificant heterogeneity and no publication bias found. For block/reduce disease progression (BDP), baricitinib did not statistically significantly reduce disease progression for RCTs. The RR in the random effect model was RR = 0.80 [95% CI: 0.58 to 1.10: p = 0.17], with significant heterogeneity, where I was 60%. On the other hand, baricitinib statistically significantly reduced disease progression in nRCTs, as the RR of the fixed effect model was RR = 0.54 [95% CI: 0.37 to 0.78; p = 0.001] with insignificant heterogeneity.
CONCLUSION
The current meta-analyses revealed that baricitinib statistically significantly reduced mortality rate and disease progression in COVID-19 patients.
PROSPERO REGISTRATION NUMBER
CRD42021281556.
Topics: Azetidines; Disease Progression; Humans; Purines; Pyrazoles; SARS-CoV-2; Sulfonamides; COVID-19 Drug Treatment
PubMed: 36150282
DOI: 10.1016/j.rmed.2022.106986 -
Current Oncology (Toronto, Ont.) Aug 2022The purpose of this meta-analysis was to evaluate the efficacy and safety of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in addition to standard... (Meta-Analysis)
Meta-Analysis Review
The purpose of this meta-analysis was to evaluate the efficacy and safety of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in addition to standard anticancer therapy. Randomized controlled trials (RCTs) that evaluated the efficacy and safety of celecoxib-combined cancer therapy were systematically searched in PubMed and Embase databases. The endpoints were overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR), and adverse events (AEs). The results of 30 RCTs containing 9655 patients showed limited benefits in celecoxib-combined cancer therapy. However, celecoxib-combined palliative therapy prolonged PFS in epidermal growth factor receptor (EGFR) wild-type patients (HR = 0.57, 95%CI = 0.35-0.94). Moreover, despite a slight increase in thrombocytopenia (RR = 1.35, 95%CI = 1.08-1.69), there was no increase in other toxicities. Celecoxib combined with adjuvant therapy indicated a better OS (HR = 0.850, 95%CI = 0.725-0.996). Furthermore, celecoxib plus neoadjuvant therapy improved the ORR in standard cancer therapy, especially neoadjuvant therapy (overall: RR = 1.13, 95%CI = 1.03-1.23; neoadjuvant therapy: RR = 1.25, 95%CI = 1.09-1.44), but not pCR. Our study indicated that adding celecoxib to palliative therapy prolongs the PFS of EGFR wild-type patients, with good safety profiles. Celecoxib combined with adjuvant therapy prolongs OS, and celecoxib plus neoadjuvant therapy improves the ORR. Thus, celecoxib-combined cancer therapy may be a promising therapy strategy.
Topics: Carcinoma, Non-Small-Cell Lung; Celecoxib; Cyclooxygenase 2; ErbB Receptors; Humans; Lung Neoplasms; Randomized Controlled Trials as Topic
PubMed: 36135051
DOI: 10.3390/curroncol29090482 -
BMJ Open Sep 2022To systematically evaluate the efficacy and safety of anaplastic lymphoma kinase (ALK) inhibitors in ALK-rearranged positive non-small cell lung cancer (NSCLC) with... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically evaluate the efficacy and safety of anaplastic lymphoma kinase (ALK) inhibitors in ALK-rearranged positive non-small cell lung cancer (NSCLC) with brain metastases, and update the overall survival (OS) outcomes of the second-generation and third-generation ALK (ALK-2G/3G) inhibitors versus first-generation (ALK-1G) inhibitors.
DESIGN
The study is in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Randomised controlled trials (RCTs) published up to 3 November 2021 were retrieved from PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov.
SETTING
RCTs from any country and healthcare setting.
PARTICIPANTS
Patients with advanced ALK-positive NSCLC with or without brain metastases.
INTERVENTIONS AND COMPARISONS
The interventions were ALK-2G/3G; the control arm was ALK-1G or crizotinib.
PRIMARY AND SECONDARY OUTCOME MEASURES
Primary outcomes included median progression-free survival and median OS. Secondary outcomes included systemic objective response rate, intracranial response rate and rate of grade ≥3 adverse events (AEs).
RESULTS
A total of 12 RCTs involving 3156 patients were analysed. Compared with ALK-1G (crizotinib), ALK-2G (alectinib, brigatinib, ceritinib and ensartinib) significantly improved the OS (HR: 0.72, 95% CI: 0.57 to 0.90, p=0.004) and intracranial response of patients with any brain metastases, especially with measurable (diameter ≥10 mm) brain metastases. Network meta-analysis demonstrated that ALK-3G (lorlatinib) had superior efficacy for patients with brain lesions, but performed a distinct side-effect profile. Moreover, alectinib showed superior efficacy and lower toxicity in ALK-positive NSCLC.
CONCLUSION
Treatment with ALK-2G inhibitors significantly improved OS compared with crizotinib, and alectinib has less severe AEs than any other ALK inhibitors with moderate-high efficacy. The limited OS follow-up and inadequate sample sizes might contribute to having no statistically significant difference in OS of lorlatinib versus crizotinib. More high-quality and longer follow-up RCTs are warranted to prove our findings.
PROSPERO REGISTRATION NUMBER
CRD42021292245.
Topics: Aminopyridines; Anaplastic Lymphoma Kinase; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Crizotinib; Humans; Lactams; Lactams, Macrocyclic; Lung Neoplasms; Network Meta-Analysis; Protein Kinase Inhibitors; Pyrazoles
PubMed: 36123063
DOI: 10.1136/bmjopen-2022-060782