-
The International Journal of... Jan 2020Low serum concentrations of first-line tuberculosis (TB) drugs have been widely reported. However, the impact of low serum concentrations on treatment outcome is less... (Meta-Analysis)
Meta-Analysis
Low serum concentrations of first-line tuberculosis (TB) drugs have been widely reported. However, the impact of low serum concentrations on treatment outcome is less well studied. A systematic search of MEDLINE/Pubmed and the Cochrane Central Register of Controlled Trials up to 31 March 2018 was conducted for articles describing drug concentrations of first-line TB drugs and treatment outcome in adult patients with drug-susceptible TB. The search identified 3073 unique publication abstracts, which were reviewed for suitability: 21 articles were acceptable for inclusion in the qualitative analysis comprising 13 prospective observational cohorts, 4 retrospective observational cohorts, 1 case-control study and 3 randomised controlled trials. Data for meta-analysis were available for 15 studies, 13 studies of rifampicin (RMP), 10 of isoniazid (INH), 8 of pyrazinamide (PZA) and 4 of ethambutol (EMB). This meta-analysis revealed that low PZA concentration appears to increase the risk of poor outcomes (8 studies, = 2727; RR 1.73, 95%CI 1.10-2.72), low RMP concentrations may slightly increase the risk of poor outcomes (13 studies, = 2753; RR 1.40, 95%CI 0.91-2.16), whereas low concentrations of INH (10 studies, = 2640; RR 1.32, 95%CI 0.66-2.63) and EMB (4 studies, = 551; RR 1.12, 95%CI 0.41-3.05) appear to make no difference to treatment outcome. There was no significant publication bias or between-study heterogeneity in any of the analyses. The potential clinical impact of low concentrations of PZA and RMP warrants further evaluation. Also, comprehensive assessments of the complex pharmacokinetic-pharmacodynamic relationships in the treatment of TB are urgently needed.
Topics: Adult; Antitubercular Agents; Case-Control Studies; Humans; Isoniazid; Observational Studies as Topic; Pharmaceutical Preparations; Pyrazinamide; Retrospective Studies; Treatment Outcome; Tuberculosis
PubMed: 32005307
DOI: 10.5588/ijtld.19.0025 -
Journal of Ethnopharmacology Apr 2020Ligusticum wallichii has been used to treat renal diseases for thousands of years in China. Ligustrazine (Lig) is the active ingredient of Ligusticum wallichii that... (Meta-Analysis)
Meta-Analysis
Protective effect and possible mechanisms of ligustrazine isolated from Ligusticum wallichii on nephropathy in rats with diabetes: A preclinical systematic review and meta-analysis.
ETHNOPHARMACOLOGICAL RELEVANCE
Ligusticum wallichii has been used to treat renal diseases for thousands of years in China. Ligustrazine (Lig) is the active ingredient of Ligusticum wallichii that possesses a variety of biological activities against kidney disease.
AIM OF THE STUDY
The purpose of this review is to further evaluate whether the supplementation with Lig has an effect on improving renal pathology, renal function indexes and blood glucose levels in animal model of diabetic nephropathy (DN). Potential mechanisms of Lig for DN as well as the existing problems regarding the modeling method and limitations in this area of research were also summarized.
MATERIALS AND METHODS
The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist was used to organize the search of eight databases from inception to June 2019. We used Cochrane Collaboration's 10-item checklist and Rev-Man 5.3 software to analyze the data as well as risk of bias.
RESULTS
The study quality scores ranged from 2 to 6 points with an average of 4.471. Compared with the control group, Lig significantly improved pathological changes of kidney including glomeruli and tubules, and induced significant decreases in levels of blood urea nitrogen, serum creatinine, 24-h urinary albumin and HbA1c, as well as increasing creatinine clearance rates. In subgroup analysis, the groups of high-dose STZ (≥60 mg/kg) and longer period of Lig treatment (>8 w) showed better results than those of the control group. No difference was seen between the high (>150 mg/kg, QD) and low (≤150 mg/kg, QD) dose of Lig treatment groups.
CONCLUSION
Lig exerts renoprotective functions in an animal model of DN mediated by antioxidant action, inhibition of apoptosis, anti-inflammatory action, reduction of renal fibrosis, reduction of the proliferation of mesangial cells, inhibition of endotheliosis, inhibition of atherosclerosis and promotion of renal autophagy. The positive conclusion should be treated cautiously because of various methodological flaws. Further studies are recommended according to ARRIVE guidelines. The method of modeling with high-dose STZ should be avoided and improved STZ modeling schemes are recommended. Considering the large dosage range of Lig used clinically and in animals, the future studies on the basis of animal renal histology are urgently needed to determine the optimal dosages to delay histological changes. Nevertheless, together, our findings suggest that Lig is a renoprotective candidate drug for treatment of DN.
Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Ligusticum; Protective Agents; Pyrazines; Rats
PubMed: 31978520
DOI: 10.1016/j.jep.2020.112568 -
American Journal of Hematology Jun 2024Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease... (Meta-Analysis)
Meta-Analysis Comparative Study
Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta-analysis.
Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease as well as the therapies themselves. Overall, available evidence is inconclusive about the differential thrombogenicity of carfilzomib/lenalidomide/dexamethasone (KRd) and bortezomib/lenalidomide/dexamethasone (VRd). This meta-analysis compares the risk for venous thromboembolism (VTE; including deep venous thrombosis and pulmonary embolism) and arterial thromboembolism (ATE; including myocardial infarction and ischemic stroke) with KRd versus VRd as primary therapy for newly diagnosed MM (NDMM). Out of 510 studies identified after deduplication, one randomized controlled trial and five retrospective cohort studies were included. We analyzed 2304 patients (VRd: 1380; KRd: 924) for VTE events and 2179 patients (VRd: 1316; KRd: 863) for ATE events. Lower rates of VTE were observed in the VRd group when compared with the KRd group (6.16% vs. 8.87%; odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.88; p = .01). Both treatment groups exhibited minimal ATE incidence, with no significant difference between them (0.91% vs. 1.16%; OR, 1.01; 95% CI, 0.24-4.20; p = .99). In view of potential biases from retrospective studies, heterogeneity of baseline population characteristics, and limited access to patient-level data (e.g., VTE risk stratification and type of thromboprophylaxis regimen used) inherent to this meta-analysis, additional research is warranted to further validate our findings and refine strategies for thrombosis prevention in MM.
Topics: Humans; Multiple Myeloma; Dexamethasone; Oligopeptides; Bortezomib; Antineoplastic Combined Chemotherapy Protocols; Lenalidomide; Thromboembolism; Venous Thromboembolism
PubMed: 38488702
DOI: 10.1002/ajh.27288 -
Journal of Infection in Developing... Sep 2022COVID-19 is a coronavirus-based infectious illness that was first detected at the end of 2019 in Wuhan, China. The novel virus induces severe acute respiratory syndrome... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
COVID-19 is a coronavirus-based infectious illness that was first detected at the end of 2019 in Wuhan, China. The novel virus induces severe acute respiratory syndrome (SARS-CoV-2) and has spread globally, resulting in an ongoing pandemic. There is still a lack of evidence for direct comparison of favipiravir therapy. Network meta-analysis (NMA), may incorporate direct and indirect comparisons in a pooled computation while depending on strong assumptions and premises. This study provides evidence-based recommendations on the safety of currently used clinical pharmacological treatments compared to favipiravir for COVID-19 patients.
METHODOLOGY
We conducted a systematic review and Bayesian NMA. We searched the primary databases and clinical trials center for reports of short-term, randomized controlled trials (RCTs) of favipiravir for COVID-19 treatment. The primary endpoints here considered were any adverse events observed or reported during the treatment cycle with estimates of odds ratio (OR) and 95% confidence interval (CI), until November 6, 2021.
RESULTS
Between January 2020 and July 2021, 908 individuals were randomly assigned to one of the seven active prescription medication regimens or placebo in this study, generating seven direct comparisons on 12 data points. The safety of favipiravir over the four clinically efficacious monotherapies or combinations including tocilizumab, arbidol, lopinavir + ritonavir, and chloroquine remained unknown due to the lack of a significant difference and the limited sample size.
CONCLUSIONS
Overall, comparative rankings could assist doctors and guideline developers in decision-making. We have also concluded that the safety of favipiravir requires further attention.
Topics: Amides; Chloroquine; Humans; Lopinavir; Network Meta-Analysis; Pyrazines; Ritonavir; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 36223614
DOI: 10.3855/jidc.16083 -
PloS One 2024To evaluate the efficacy and safety of multi-drug therapy based on eszopiclone in the treatment of insomnia after stroke using a network meta-analysis method and to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of multi-drug therapy based on eszopiclone in the treatment of insomnia after stroke using a network meta-analysis method and to provide evidence for clinical practice.
METHOD
Computer searches of PubMed, Excerpt Medica Database (Embase), Cochrane Library Central Register of Controlled Trials, APA PsycInfo, CNKI, WanFang, Sinomed and other databases were performed to search for clinical randomized controlled studies (RCTs) on multi-drug therapy based on eszopiclone in the treatment of insomnia patients after stroke. The search time was from the establishment of each database until July 2023. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included RCTs. Stata 14.0 was applied to perform network meta-analysis using Review Manager 5.3 software for traditional meta-analysis.
RESULT
Eighteen RCTs and 1646 patients were ultimately included, involving 11 treatment options. The results of the network meta-analysis showed that the ranking of Pittsburgh Sleep Quality Index (PSQI) decline was eszopiclone combined with sweet dream oral liquid (ESZ+SDOL)>eszopiclone combined with a shugan jieyu capsule (ESZ+SGJYC)>eszopiclone combined with agomelatine (ESZ+AGO)>eszopiclone combined with flupentixol and melitracen tablets (ESZ+FMT)>eszopiclone combined with yangxue qingnao granules (ESZ+YXQNG)>eszopiclone combined with mirtazapine (ESZ+MIR)>ESZ>FMT; the modified Edinburgh Scandinavia Stroke Scale (MESSS) decline ranking was ESZ+SDOL>ESZ+AGO>ESZ; and the clinical total effective rate ranking was eszopiclone combined with a xuefu zhuyu capsule (ESZ+XFZYC)>ESZ+MIR>ESZ+SGJYC>ESZ+SDOL> ESZ+FMT>ESZ+YXQNG>ESZ>FMT. In terms of clinical adverse reactions, in addition to ESZ therapy, ESZ+ESC had the highest number of adverse reactions, with abdominal pain being the most common. ESZ+YXQNG had the most types of adverse reactions, with 8 types.
CONCLUSION
Multi-drug therapy based on eszopiclone can effectively improve the sleep quality of patients with insomnia after stroke, and ESZ+SDOL has significant efficacy and safety. However, due to the limitations of this study, efficacy ranking cannot fully explain the superiority or inferiority of clinical efficacy. In the future, more multicentre, large sample, double-blind randomized controlled trials are needed to supplement and demonstrate the results of this study.
Topics: Humans; Eszopiclone; Sleep Initiation and Maintenance Disorders; Network Meta-Analysis; Stroke; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 38315683
DOI: 10.1371/journal.pone.0297064 -
Sleep May 2021To compare the efficacy and safety of various hypnotics for identifying the best treatments for insomnia in older adults. (Meta-Analysis)
Meta-Analysis
STUDY OBJECTIVES
To compare the efficacy and safety of various hypnotics for identifying the best treatments for insomnia in older adults.
METHODS
We searched the EMBASE, PubMed, ClinicalTrials.gov, and ProQuest Dissertations and Theses A&I databases from the inception to September 12, 2020. Only randomized controlled trials comparing hypnotics with either another hypnotic or placebo for insomnia treatment in elderly people were included. Sleep outcomes, including total sleep time, sleep onset latency, wake after sleep onset, sleep efficiency, were derived from polysomnography, valid questionnaires, or sleep diaries.
RESULTS
We identified 24 articles with 5917 older adults. Eszopiclone and low-dose doxepin were ranked the optimal therapy for prolonging objective and subjective total sleep time (26.69 and 28.19 min), respectively, compared to placebo. Zaleplon was the most effective therapy in reducing objective and subjective sleep onset latency (-21.63 and -15.86 min) compared with control. Temazepam was the best treatment for objective and subjective wake after sleep onset (-25.29 and -22.25 min) compared with control. Low-dose doxepin appeared to be the effective treatment for increasing objective sleep efficiency (6.08%) Triazolam showed the higher risk of overall adverse events (odds ratio, 1.96, 95% confidence interval 1.03-3.74) when compared to zaleplon.
CONCLUSIONS
Considering study quality and the potential adverse effects of benzodiazepines and nonbenzodiazepines, low-dose doxepin seems to be the optimal pharmacotherapy for the improvements in total sleep time and sleep efficiency. Future RCTs investigating the treatment effects of hypnotics, particularly low-dose doxepin, on insomnia in older adults are warranted. PROSPERO Registration number: CRD42016046301.
Topics: Aged; Eszopiclone; Humans; Hypnotics and Sedatives; Network Meta-Analysis; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 33249496
DOI: 10.1093/sleep/zsaa260 -
Journal of Chemotherapy (Florence,... Nov 2023Pyrazinamide (PZA) is an essential first-line tuberculosis drug for its unique mechanism of action active against multidrug-resistant-TB (MDR-TB). Thus, the aim of... (Meta-Analysis)
Meta-Analysis Review
Pyrazinamide (PZA) is an essential first-line tuberculosis drug for its unique mechanism of action active against multidrug-resistant-TB (MDR-TB). Thus, the aim of updated meta-analysis was to estimate the PZA weighted pooled resistance (WPR) rate in M. tuberculosis isolates based on publication date and WHO regions. We systematically searched the related reports in PubMed, Scopus, and Embase (from January 2015 to July 2022). Statistical analyses were performed using STATA software. The 115 final reports in the analysis investigated phenotypic PZA resistance data. The WPR of PZA was 57% (95% CI 48-65%) in MDR-TB cases. According to the WHO regions, the higher WPRs of PZA were reported in the Western Pacific (32%; 95% CI 18-46%), South East Asian region (37%; 95% CI 31-43%), and the Eastern Mediterranean (78%; 95% CI 54-95%) among any-TB patients, high risk of MDR-TB patients, and MDR-TB patients, respectively. A negligible increase in the rate of PZA resistance were showed in MDR-TB cases (55% to 58%). The rate of PZA resistance has been rising in recent years among MDR-TB cases, underlines the essential for both standard and novel drug regimens development.
Topics: Humans; Pyrazinamide; Mycobacterium tuberculosis; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Drug Resistance, Multiple, Bacterial; Amidohydrolases; Mutation; Microbial Sensitivity Tests; Tuberculosis
PubMed: 37211822
DOI: 10.1080/1120009X.2023.2214473 -
BMC Infectious Diseases May 2021Favipiravir possesses high utility for treating patients with COVID-19. However, research examining the efficacy and safety of favipiravir for patients with COVID-19 is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Favipiravir possesses high utility for treating patients with COVID-19. However, research examining the efficacy and safety of favipiravir for patients with COVID-19 is limited.
METHODS
We conducted a systematic review of published studies reporting the efficacy of favipiravir against COVID-19. Two investigators independently searched PubMed, the Cochrane Database of Systematic Reviews, MedRxiv, and ClinicalTrials.gov (inception to September 2020) to identify eligible studies. A meta-analysis was performed to measure viral clearance and clinical improvement as the primary outcomes.
RESULTS
Among 11 eligible studies, 5 included a comparator group. Comparing to the comparator group, the favipiravir group exhibited significantly better viral clearance on day 7 after the initiation of treatment (odds ratio [OR] = 2.49, 95% confidence interval [CI] = 1.19-5.22), whereas no difference was noted on day 14 (OR = 2.19, 95% CI = 0.69-6.95). Although clinical improvement was significantly better in the favipiravir group on both days 7 and 14, the improvement was better on day 14 (OR = 3.03, 95% CI = 1.17-7.80) than on day 7 (OR = 1.60, 95% CI = 1.03-2.49). The estimated proportions of patients with viral clearance in the favipiravir arm on days 7 and 14 were 65.42 and 88.9%, respectively, versus 43.42 and 78.79%, respectively, in the comparator group. The estimated proportions of patients with clinical improvement on days 7 and 14 in the favipiravir group were 54.33 and 84.63%, respectively, compared with 34.40 and 65.77%, respectively, in the comparator group.
CONCLUSIONS
Favipiravir induces viral clearance by 7 days and contributes to clinical improvement within 14 days. The results indicated that favipiravir has strong possibility for treating COVID-19, especially in patients with mild-to-moderate illness. Additional well-designed studies, including examinations of the dose and duration of treatment, are crucial for reaching definitive conclusions.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amides; Antiviral Agents; Female; Humans; Male; Middle Aged; Pyrazines; SARS-CoV-2; Treatment Outcome; Viral Load; Young Adult; COVID-19 Drug Treatment
PubMed: 34044777
DOI: 10.1186/s12879-021-06164-x -
Expert Review of Anti-infective Therapy Oct 2021: Currently, there is no approved therapeutic entity for coronavirus disease 2019 (COVID-19) and clinicians are primarily relying on drug repurposing. However, findings...
: Currently, there is no approved therapeutic entity for coronavirus disease 2019 (COVID-19) and clinicians are primarily relying on drug repurposing. However, findings across studies are widely disparate, making it difficult to draw firm conclusions. Since clinicians need accurate evidence to treat COVID-19, this manuscript systematically analyzed the published and ongoing studies evaluating the pharmacological interventions for COVID-19.: A systematic search of observational studies and Clinical Trials on the treatment and prevention of COVID-19 was performed by using various databases from inception to 2 December 2020.: A total of 460 studies met the inclusion criteria. Of these, 37 were research studies, 386 were ongoing trials, and 37 were completed trials. Anti-virals, steroids, anti-malarial, plasma exchange, and monoclonal antibodies were the most common treatment modalities used alone or in combination in these studies. However, tocilizumab, plasma exchange, and steroids have shown significant improvements in patient's clinical and radiological status. Tocilizumab reported minimum hospital stay of 2 days along with maximum recovery and patient's stability rate. Existing literature demonstrate promising results of tocilizumab, plasma exchange, and steroids among COVID-19 patients. Nevertheless, these studies are accompanied by several methodological disparities which should be considered while interpreting the results.
Topics: Adenosine Monophosphate; Alanine; Amides; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antimalarials; Antiviral Agents; COVID-19; Chloroquine; Clinical Trials as Topic; Humans; Hydroxychloroquine; Immunization, Passive; Indoles; Intensive Care Units; Length of Stay; Lopinavir; Methylprednisolone; Observational Studies as Topic; Patient Admission; Pyrazines; Ritonavir; SARS-CoV-2; Survival Rate; COVID-19 Drug Treatment; COVID-19 Serotherapy
PubMed: 33719819
DOI: 10.1080/14787210.2021.1902805 -
Indian Journal of Pharmacology 2020Multiple options are being tried for the management of 2019-nCoV infection since its pandemic started. Favipiravir (FPV) is one of drugs, which is also being tried for... (Meta-Analysis)
Meta-Analysis
Multiple options are being tried for the management of 2019-nCoV infection since its pandemic started. Favipiravir (FPV) is one of drugs, which is also being tried for the management of 2019-nCoV infection. The present study aimed to evaluate the efficacy and safety of FPV in published literature. Comparative randomized or nonrandomized controlled clinical trials comparing FPV to the standard of care (SOC)/control or other antiviral agent/combinations were included. A total of 12 databases were searched and identify four studies which were further used for final analysis. The data analysis was done as pooled prevalence using a random effect model by "RevMan manager version 5.4.1 and "R" software. The point estimate, odds ratio (OR) with 95% confidence interval (CI) was calculated for dichotomous data. In the present study, the marginal beneficial effect was seen in the FPV group in overall clinical improvement comparison to SOC/control, i.e., (4 studies, log OR [95% CI] (-0.19 [-0.51, 0.13]). However, in all other outcomes, it was found to be comparable to the SOC/control arm namely "clinical improvement on day 7-10" (3 studies, OR [95% CI] 1.63 [1.07, 2.48]) while "clinical improvement on day 10-14" (3 studies, OR [95% CI] 1.37 [0.24, 7.82]) and viral negativity was seen (4 studies, OR [95% CI] 1.91 [0.91, 4.01]). No difference in efficacy was found between FPV versus lopinavir/ritonavir or arbidol groups. Regarding adverse effects, except for the occurrence of rash (higher in the FPV group), safety was comparable to SOC. In our study, there was a marginal difference between the FPV and the SOC arm in terms of "clinical improvement" on day 7-10 or 10-14, and "virological negativity" on day 10-14." However, some benefit was observed in a few studies, but it was also comparable to the control drugs or SOC.
Topics: Amides; Antiviral Agents; Humans; Pyrazines; Randomized Controlled Trials as Topic; COVID-19 Drug Treatment
PubMed: 33283773
DOI: 10.4103/ijp.ijp_998_20