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Journal of Cachexia, Sarcopenia and... Dec 2023Cancer cachexia (CC) is a multifactorial syndrome driven by inflammation, defined by ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot... (Review)
Review
Cancer cachexia (CC) is a multifactorial syndrome driven by inflammation, defined by ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support. CC leads to progressive functional impairment, with its clinical management complicated and limited therapeutic options available. The objective of this review was to assess the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) on patient-centred outcomes in patients with CC. In 2013, two systematic reviews concluded that there was insufficient evidence to recommend NSAIDs for clinical management of CC outside of clinical trials. However, clinical trials of multi-component CC interventions have included NSAIDs as an intervention component, so an up-to-date assessment of the evidence for NSAIDs in the treatment of CC is warranted. Four databases (MEDLINE, EMBASE, CENTRAL and CINAHL) and three trial registers (clinicaltrials.gov, WHO ICTRP and ISRCTN) were searched on 16 December 2022. Randomized controlled trials (RCTs) comparing any NSAID (any dose or duration) with a control arm, in adult patients with CC, reporting measures of body weight, body composition, nutrition impact symptoms, inflammation, physical function or fatigue, were eligible for inclusion. Primary outcomes (determined with patient involvement) were survival, changes in muscle strength, body composition, body weight and quality of life. Included studies were assessed for risk of bias using the Revised Cochrane risk-of-bias tool for randomized trials. Five studies were included, which investigated Indomethacin (n = 1), Ibuprofen (n = 1) and Celecoxib (n = 3). Four studies were judged to be at high risk of bias for all outcomes, with one study raising concerns for most outcomes. Considerable clinical and methodological heterogeneity amongst the studies meant that meta-analysis was not appropriate. There was insufficient evidence to determine whether Indomethacin or Ibuprofen is effective or safe for use in patients with CC; RCTs with lower risk of bias are needed. Celecoxib studies indicated it was safe for use in this population at the doses tested (200-400 mg/day) but found contrasting results regarding efficacy, potentially reflecting heterogeneity amongst the studies. There is inadequate evidence to recommend any NSAID for CC. While current clinical trials for CC treatments are shifting towards multi-component interventions, further research to determine the efficacy and safety of NSAIDs alone is necessary if they are to be included in such multi-component interventions. Furthermore, the lack of data on patient-determined primary outcomes in this review highlights the need for patient involvement in clinical trials for CC.
Topics: Adult; Humans; Ibuprofen; Celecoxib; Cachexia; Anti-Inflammatory Agents, Non-Steroidal; Indomethacin; Inflammation; Neoplasms
PubMed: 37750475
DOI: 10.1002/jcsm.13327 -
Frontiers in Endocrinology 2023As a popular antidiabetic drug, teneligliptin has been used for over 10 years, but its efficacy and safety have rarely been systematically evaluated. Therefore, a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
As a popular antidiabetic drug, teneligliptin has been used for over 10 years, but its efficacy and safety have rarely been systematically evaluated. Therefore, a Bayesian network meta-analysis was conducted to evaluate the efficacy and safety of teneligliptin in patients with type 2 diabetes mellitus (T2DM).
METHODS
We systematically searched PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Randomized controlled trials (RCTs) comparing teneligliptin with placebo or active comparators in T2DM patients for at least 12 weeks were included in the study. Data analysis was performed using R 4.2.3 and Stata 17.0 software. Each outcome was presented as a mean difference (MD) or an odds ratio (OR) along with 95% confidence interval (CI) and the surface under the cumulative ranking curve value (SUCRA).
RESULTS
A total of 18 RCTs with 3,290 participants with T2DM were included in this study. Generally, compared to placebo, sitagliptin, vildagliptin, metformin, and bromocriptine, 20 mg of teneligliptin showed better efficacy in reducing HbA1c (MD [95% CI], -0.78 [-0.86 to -0.70], -0.08 [-0.36 to 0.19], -0.04 [-0.72 to 0.60], -0.12 [-0.65 to 0.42], and -0.50 [-0.74 to -0.26], respectively) and fasting plasma glucose (FPG) (MD [95% CI], -18.02 [-20.64 to -15.13], 1.17 [-9.39 to 11.70], -8.06 [-30.95 to 14.35], -2.75 [-18.89 to 13.01], and -34.23 [-45.93 to -22.96], respectively), and 40 mg of teneligliptin also showed better efficacy in reducing HbA1c (MD [95% CI], -0.84 [-1.03 to -0.65], -0.15 [-0.49 to 0.19], -0.10 [-0.81 to 0.57], -0.18 [-0.76 to 0.39], and -0.56 [-0.88 to -0.26], respectively) and FPG (MD [95% CI], -20.40 [-26.07 to -14.57], -1.20 [-13.21 to 10.38], -10.43 [-34.16 to 12.65], -5.13 [-22.21 to 11.66], and -36.61 [-49.33 to -24.01], respectively). Compared to placebo, 20 mg of teneligliptin showed no significant difference in incidences of hypoglycemia and gastrointestinal adverse events (OR [95% CI], 1.30 [0.70 to 2.19] and 1.48 [0.78 to 2.98], respectively), and 40 mg of teneligliptin showed no significant difference in incidence of hypoglycemia (OR [95% CI], 2.63 [0.46 to 8.10]). Generally, antidiabetic effect and hypoglycemia risk of teneligliptin gradually increased as its dose increased from 5 mg to 40 mg. Compared to 20 mg of teneligliptin, 40 mg of teneligliptin showed superior efficacy and no-inferior safety, which was considered as the best option in reducing HbA1c, FPG, and 2h PPG and increasing proportion of the patients achieving HbA1c < 7% (SUCRA, 85.51%, 84.24%, 79.06%, and 85.81%, respectively) among all the included interventions.
CONCLUSION
Compared to sitagliptin, vildagliptin, metformin, bromocriptine, and placebo, teneligliptin displayed favorable efficacy and acceptable safety in treating T2DM. Twenty milligrams or 40 mg per day was the optimal dosage regimen of teneligliptin. The results of this study will provide important evidence-based basis for rational use of teneligliptin and clinical decision-making of T2DM medication.
Topics: Humans; Bromocriptine; Glycated Hemoglobin; Network Meta-Analysis; Vildagliptin; Diabetes Mellitus, Type 2; Metformin; Sitagliptin Phosphate; Hypoglycemic Agents; Hypoglycemia
PubMed: 38189048
DOI: 10.3389/fendo.2023.1282584 -
Pharmaceuticals (Basel, Switzerland) Mar 2023Natural product derivatives are essential in searching for compounds with important chemical, biological, and medical applications. Naphthoquinones are secondary... (Review)
Review
Natural product derivatives are essential in searching for compounds with important chemical, biological, and medical applications. Naphthoquinones are secondary metabolites found in plants and are used in traditional medicine to treat diverse human diseases. Considering this, the synthesis of naphthoquinone derivatives has been explored to contain compounds with potential biological activity. It has been reported that the chemical modification of naphthoquinones improves their pharmacological properties by introducing amines, amino acids, furan, pyran, pyrazole, triazole, indole, among other chemical groups. In this systematic review, we summarized the preparation of nitrogen naphthoquinones derivatives and discussed their biological effect associated with redox properties and other mechanisms. Preclinical evaluation of antibacterial and/or antitumoral naphthoquinones derivatives is included because cancer is a worldwide health problem, and there is a lack of effective drugs against multidrug-resistant bacteria. The information presented herein indicates that naphthoquinone derivatives could be considered for further studies to provide drugs efficient in treating cancer and multidrug-resistant bacteria.
PubMed: 37111253
DOI: 10.3390/ph16040496 -
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 -
Annals of Palliative Medicine Oct 2021Riociguat therapy has been recommended for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), and it might have therapeutic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Riociguat therapy has been recommended for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), and it might have therapeutic significance for other types of pulmonary hypertension (PH). Our purpose was to evaluate the specific impact of riociguat on all types of PH.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the safety and efficacy of riociguat treatment for PH through databases of the Cochrane Library, PubMed, Embase, and Web of Science from inception to the present. Duplicate publications, studies with no full text, incomplete information or inability to extract data, animal experiments and reviews, and systematic reviews were excluded. The software RevMan 5.4 was used for data synthesis.
RESULTS
There were 8 RCTs included in our study, involving 1,606 participants. For PAH and CTEPH patients, riociguat treatment extended 6-minute walk distance (6MWD) by 39.84 meters, decreased mean pulmonary arterial pressure (PAP) by 4.20 mmHg, lowered pulmonary vascular resistance (PVR) by 218.76 dynes/sec/cm-5, cut down right atrial pressure (RAP) by 0.9 mmHg, increased cardiac index (CI) by 0.49 L/min/m2, improved cardiac output (CO) by 0.89 L/min, reduced N-terminal pro-type B natriuretic peptide (NT-proBNP) by 436.21 pg/mL, and decreased adverse events and clinical worsening as compared with placebo. For other types of PH including PH due to left heart disease and PH due to lung disease, riociguat was reported as having improved CI by 0.42 L/min/m2 and CO was increased by 0.92 L/min compared with placebo. Other efficacy outcomes and safety outcomes did not attain statistical difference in other types of PH.
CONCLUSIONS
For PAH and CTEPH, riociguat treatment is safe and effective, but for other types of PH, it can only improve some hemodynamic parameters.
Topics: Chronic Disease; Humans; Hypertension, Pulmonary; Pyrazoles; Pyrimidines
PubMed: 34763472
DOI: 10.21037/apm-21-2656 -
International Journal of Clinical... Jun 2024Zuranolone, an oral version of allopregnanolone and neurosteroid, is a novel drug for the treatment of major depressive disorder (MDD) and postpartum depression (PPD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Zuranolone, an oral version of allopregnanolone and neurosteroid, is a novel drug for the treatment of major depressive disorder (MDD) and postpartum depression (PPD).
AIM
The purpose of this systematic review and meta-analysis was to assess the efficacy of zuranolone in the treatment of MDD and PPD.
METHOD
A systematic search was conducted using EBSCOhost to simultaneously search Academic Search Premier, APA PsycArticles, APA PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL Ultimate, and MEDLINE with Full Text. Two independent reviewers screened the articles and completed a full-text review using Covidence. The quality of each study was assessed using the Cochrane Risk of Bias tool for randomized trials (RoB 2). A meta-analysis was then conducted using Review Manager (RevMan v5.4) software.
RESULTS
The initial search yielded 127 results, with 6 articles fitting our inclusion and exclusion criteria. All 6 studies, comprising 1707 participants, had an overall low risk of bias. There was a significant decrease in HAM-D scores for MDD at 15 days versus placebo (MD - 2.40, 95% CI - 3.07 to - 1.63; p < .001). When pooling data for PDD, there was an overall significant decrease in HAM-D scores at 15 days versus placebo (MD - 4.06, 95% CI - 4.25 to - 3.87; p < .001).
CONCLUSION
The results suggest that zuranolone can improve symptoms of PPD at 15 days; however, results were not clinically significant for MDD. Future research is needed to evaluate the long-term efficacy of zuranolone in PPD and the treatment efficacy in MDD.
Topics: Humans; Depression, Postpartum; Depressive Disorder, Major; Female; Pregnanolone; Antidepressive Agents; Randomized Controlled Trials as Topic; Treatment Outcome; Pyrazoles
PubMed: 38489051
DOI: 10.1007/s11096-024-01714-0 -
Jornal Brasileiro de Pneumologia :... 2024To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor (ETI)-on important clinical endpoints in individuals with cystic fibrosis.
METHODS
This was a systematic review and meta-analysis of randomized clinical trials that compared the use of ETI in individuals with CF and at least one F508del allele with that of placebo or with an active comparator such as other combinations of CFTR modulators, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) methodology. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to December 26th, 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS
We retrieved 54 studies in the primary search. Of these, 6 met the inclusion criteria and were analyzed (1,127 patients; 577 and 550 in the intervention and control groups, respectively). The meta-analysis revealed that the use of ETI increased FEV1% [risk difference (RD), +10.47%; 95% CI, 6.88-14.06], reduced the number of acute pulmonary exacerbations (RD, -0.16; 95% CI, -0.28 to -0.04), and improved quality of life (RD, +14.93; 95% CI, 9.98-19.89) and BMI (RD, +1.07 kg/m2; 95% CI, 0.90-1.25). Adverse events did not differ between groups (RD, -0.03; 95% CI, -0.08 to 0.01), and none of the studies reported deaths.
CONCLUSIONS
Our findings demonstrate that ETI treatment substantially improves clinically significant, patient-centered outcomes.
Topics: Humans; Alleles; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis; Quality of Life; Pyridines; Indoles; Pyrazoles; Aminophenols; Quinolones; Pyrrolidines; Benzodioxoles
PubMed: 38198345
DOI: 10.36416/1806-3756/e20230187 -
Critical Reviews in Oncology/hematology Mar 2021The use of ibrutinib is hampered by major bleeding events and atrial fibrillation. Speculating whether randomized controlled trials might underestimate the risk of... (Meta-Analysis)
Meta-Analysis Review
The use of ibrutinib is hampered by major bleeding events and atrial fibrillation. Speculating whether randomized controlled trials might underestimate the risk of adverse events in clinical practice, we conducted a systematic review and meta-analysis studying patients treated in any setting and indication. We systematically searched the literature using MEDLINE and EMBASE databases for case series, cohort studies, or randomized controlled trials and retrieved all data in parallel. Proportions of patients with adverse events were pooled in relevant subgroups using the binominal distribution and Freeman-Tukey double arcsine transformation. Among 2'537 records screened, 85 were finally included, comprising 7'317 patients. Methodological quality according to the Newcastle-Ottawa Scale was rated as moderate to poor with regard to bleeding events and atrial fibrillation; 106 studies were excluded because of missing data at all. Reported events varied substantially between 0 % and 78 % (any bleedings), 0 % and 25 % (major bleedings), and 0 % and 38 % (new-onset atrial fibrillation). Pooled estimates were 28 % (95 % confidence interval 22 %, 34 %), 3 % (2 %, 4 %), and 8 % respectively (7 %, 10 %). The risk of events was higher in studies with an older population, high ibrutinib dosage, thrombocytopenia, antithrombotic treatment, and retrospective studies. In conclusions, reporting of bleeding events and atrial fibrillation varied substantially among studies. These observations, in combination with the estimates obtained, suggest a relevant risk in clinical practice.
Topics: Adenine; Atrial Fibrillation; Humans; Piperidines; Pyrazoles; Pyrimidines; Retrospective Studies
PubMed: 33515702
DOI: 10.1016/j.critrevonc.2021.103238 -
Mayo Clinic Proceedings Jul 2020To assess the efficacy and safety profiles of different dosing regimens of tofacitinib, baricitinib, and upadacitinib, novel selective oral Janus activated kinase... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the efficacy and safety profiles of different dosing regimens of tofacitinib, baricitinib, and upadacitinib, novel selective oral Janus activated kinase inhibitors, in rheumatoid arthritis (RA).
METHODS
Randomized controlled trials of tofacitinib (5 and 10 mg twice daily) baricitinib (2 and 4 mg daily), and upadacitinib (15 and 30 mg daily) in RA were identified from MEDLINE, EMBASE, and Cochrane databases through December 11, 2019. Random-effects models were used to estimate pooled mean differences and relative risks (RRs). American College of Rheumatology 20%, Health Assessment Questionnaire-Disability Index, adverse events, risk for infection, venous thromboembolic events, and malignancy were calculated.
RESULTS
Twenty trials with an overall low risk of bias involving 8982 patients were identified. Tofacitinib, baricitinib, and upadacitinib improved RA control as determined by American College of Rheumatology 20% (RR, 2.03; 95% CI, 1.87 to 2.20) and Health Assessment Questionnaire-Disability Index scores (mean differences, -0.31; 95% CI, -0.34 to -0.28) compared with placebo. Adverse events were more frequent with upadacitinib, 30 mg, daily (RR, 1.15; 95% CI, 1.02 to 1.30); upadacitinib, 15 mg, daily (RR, 1.14; 95% CI, 1.02 to 1.27); and baricitinib, 4 mg, daily (RR, 1.13; 95% CI, 1.02 to 1.24). The risk for infection was highest with tofacitinib, 10 mg, twice daily (RR, 2.75; 95% CI, 1.72 to 4.41), followed by upadacitinib, 15 mg, daily (RR, 1.35; 95% CI, 1.14 to 1.60) and baricitinib, 4 mg, daily (RR, 1.28; 95% CI, 1.12 to 1.45). Data for venous thromboembolic events were not available for tofacitinib or baricitinib, but there was no increase in risk with upadacitinib (15 mg daily: RR, 2.34; 95% CI, 0.34 to 15.92).
CONCLUSION
Tofacitinib, baricitinib, and upadacitinib significantly improve RA control. Head-to-head Janus activated kinase inhibitor clinical trials are needed to further inform decision making.
Topics: Arthritis, Rheumatoid; Azetidines; Dose-Response Relationship, Drug; Drug Administration Schedule; Heterocyclic Compounds, 3-Ring; Humans; Janus Kinase Inhibitors; Piperidines; Purines; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; Sulfonamides
PubMed: 32499126
DOI: 10.1016/j.mayocp.2020.01.039 -
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