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Arthritis Research & Therapy Dec 2015Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib modulates the signaling of cytokines that are integral to... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials.
BACKGROUND
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib modulates the signaling of cytokines that are integral to lymphocyte activation, proliferation, and function. Thus, tofacitinib therapy may result in suppression of multiple elements of the immune response. Serious infections have been reported in tofacitinib RA trials. However, limited head-to-head comparator data were available within the tofacitinib RA development program to directly compare rates of serious infections with tofacitinib relative to biologic agents, and specifically adalimumab (employed as an active control agent in two randomized controlled trials of tofacitinib).
METHODS
A systematic literature search of data from interventional randomized controlled trials and long-term extension studies with biologics in RA was carried out. Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) consensus was followed for reporting results of the review and meta-analysis. Incidence rates (unique patients with events/100 patient-years) for each therapy were estimated based on data from randomized controlled trials and long-term extension studies using a random-effects model. Relative and absolute risk comparisons versus placebo used Mantel-Haenszel methods.
RESULTS
The search produced 657 hits. In total, 66 randomized controlled trials and 22 long-term extension studies met the selection criteria. Estimated incidence rates (95% confidence intervals [CIs]) for abatacept, rituximab, tocilizumab, and tumor necrosis factor inhibitors were 3.04 (2.49, 3.72), 3.72 (2.99, 4.62), 5.45 (4.26, 6.96), and 4.90 (4.41, 5.44), respectively. Incidence rates (95% CIs) for tofacitinib 5 and 10 mg twice daily (BID) in phase 3 trials were 3.02 (2.25, 4.05) and 3.00 (2.24, 4.02), respectively. Corresponding incidence rates in long-term extension studies were 2.50 (2.05, 3.04) and 3.19 (2.74, 3.72). The risk ratios (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 2.21 (0.60, 8.14) and 2.02 (0.56, 7.28), respectively. Risk differences (95% CIs) versus placebo for tofacitinib 5 and 10 mg BID were 0.38% (-0.24%, 0.99%) and 0.40% (-0.22%, 1.02%), respectively.
CONCLUSIONS
In interventional studies, the risk of serious infections with tofacitinib is comparable to published rates for biologic disease-modifying antirheumatic drugs in patients with moderate to severely active RA.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Communicable Diseases; Humans; Janus Kinase 3; Piperidines; Pyrimidines; Pyrroles; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 26669566
DOI: 10.1186/s13075-015-0880-2 -
European Journal of Medical Research Aug 2023To evaluate the efficacy and safety of vonoprazan-amoxicillin (VA) dual therapy for radically eradicating Helicobacter pylori (H. pylori). (Meta-Analysis)
Meta-Analysis Review
AIM
To evaluate the efficacy and safety of vonoprazan-amoxicillin (VA) dual therapy for radically eradicating Helicobacter pylori (H. pylori).
METHODS
The PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched up to July 7, 2022, to identify clinical trials comparing the efficacy of VA dual therapy and triple therapy for H. pylori eradication. After evaluating the quality of the included studies, random effects models were conducted, and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to estimate the efficacy and safety of each approach.
RESULTS
Six publications (including four randomized controlled trials) involving 2019 patients were included in this meta-analysis. Overall, the eradication rate for VA dual therapy was 89.9%, while it was 85.2% for triple therapy based on other acid inhibitors. The eradication rate of H. pylori in the VA dual regimen group was higher than that in the PPI-based (omeprazole or lansoprazole) triple therapy group (RR = 1.15, 95% CI 1.07-1.23, p < 0.0001). However, the efficacy of VA dual therapy was comparable with VA-Clarithromycin (VAC) triple therapy (RR = 0.97, 95% CI 0.93-1.02). Besides, the incidence of adverse reactions in VA dual therapy was also lower than that in triple therapy (RR = 0.80, 95% CI 0.70-0.91, p = 0.0009).
CONCLUSION
Compared with PPI-based triple therapy, VA dual therapy showed a better therapeutic effect, safety and patient compliance rate for eradicating H. pylori, which should be used as a novel curative strategy in the future.
Topics: Humans; Amoxicillin; Helicobacter pylori; Anti-Bacterial Agents; Helicobacter Infections; Proton Pump Inhibitors; Drug Therapy, Combination; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37550781
DOI: 10.1186/s40001-023-01249-6 -
Current Reviews in Clinical and... 2023A subpopulation of statin users such as subjects with chronic kidney disease (CKD), Human Immune virus (HIV), acute coronary syndrome (ACS), revascularization, metabolic...
BACKGROUND
A subpopulation of statin users such as subjects with chronic kidney disease (CKD), Human Immune virus (HIV), acute coronary syndrome (ACS), revascularization, metabolic syndrome, and/or diabetes may particularly benefit from pitavastatin pharmacotherapy.
AIM
The current systematic review aimed systematically to evaluate the effect of pitavastatin on primary cardiac events in subjects receiving pitavastatin in comparison to the other four statin members.
METHODS
We conducted a systematic review on phases III and IV of randomized controlled trials (RCT-s, 11 trials) for subjects with primary cardiac events who received pitavastatin. Subjects diagnosed with any type of dyslipidemia (population 4804) and received pitavastatin (interventions) versus comparator (comparison) with the primary efficacy endpoint of minimization of LDL-C and non- HDL-C, had an increase in HDL-C and/or reduction in major adverse cardiac events (MACE, cardiovascular death, myocardial infarction (fatal/nonfatal), and stroke (fatal/nonfatal) and/or their composite (outcomes). The secondary safety endpoint was the development of any adverse effects.
RESULTS
In the included trials (11), participants (4804) were randomized for pitavastatin or its comparators such as atorvastatin, pravastatin, rosuvastatin, simvastatin and followed up for 12 to 52 weeks. In terms of the primary outcome (reduction in LDL-C), pitavastatin 4 mg was superior to pravastatin 40 mg in three trials, while the 2 mg pitavastatin was comparable to atorvastatin 10 mg in four trials and simvastatin 20 and 40 mg in two 2 trials. However, rosuvastatin 2.5 mg was superior to pitavastatin 2 mg in two trials. Pitavastatin increased HDL-C and reduced non-HDL-C in eleven trials. Regarding the safety profile, pitavastatin has proved to be tolerated and safe.
CONCLUSION
The FDA-approved indications for pitavastatin included primary dyslipidemia and mixed dyslipidemia as a supplementary therapy to dietary changes to lower total cholesterol, LDL-C, apolipoprotein B (Apo B), triglycerides (TG), and enhance HDL-C. Pitavastatin might be suitable for subjects with diabetes, ACS (reduced revascularization), metabolic syndrome, CKD, HIV, and subjects with low levels of HDL-C. We highly recommend rational individualization for the selection of statin.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium; Pravastatin; Cholesterol, LDL; Metabolic Syndrome; Cholesterol, HDL; Randomized Controlled Trials as Topic; Simvastatin; Dyslipidemias; Cardiovascular Diseases; HIV Infections
PubMed: 35642121
DOI: 10.2174/2772432817666220531115314 -
Nutrients Nov 2023Pooled data from published reports on infants with clinically diagnosed vitamin B12 (B12) deficiency were analyzed with the purpose of describing the presentation,... (Review)
Review
Pooled data from published reports on infants with clinically diagnosed vitamin B12 (B12) deficiency were analyzed with the purpose of describing the presentation, diagnostic approaches, and risk factors for the condition to inform prevention strategies. An electronic (PubMed database) and manual literature search following the PRISMA approach was conducted (preregistration with the Open Science Framework, accessed on 15 February 2023). Data were described and analyzed using correlation analyses, Chi-square tests, ANOVAs, and regression analyses, and 102 publications (292 cases) were analyzed. The mean age at first symptoms (anemia, various neurological symptoms) was four months; the mean time to diagnosis was 2.6 months. Maternal B12 at diagnosis, exclusive breastfeeding, and a maternal diet low in B12 predicted infant B12, methylmalonic acid, and total homocysteine. Infant B12 deficiency is still not easily diagnosed. Methylmalonic acid and total homocysteine are useful diagnostic parameters in addition to B12 levels. Since maternal B12 status predicts infant B12 status, it would probably be advantageous to target women in early pregnancy or even preconceptionally to prevent infant B12 deficiency, rather than to rely on newborn screening that often does not reliably identify high-risk children.
Topics: Infant; Infant, Newborn; Pregnancy; Child; Humans; Female; Methylmalonic Acid; Vitamin B 12 Deficiency; Vitamin B 12; Breast Feeding; Homocysteine
PubMed: 38068819
DOI: 10.3390/nu15234960 -
Psychiatry Research May 2022Nutritional supplementations have been widely used as adjunctive treatments for schizophrenia. However, among these supplementations, of which the most beneficial is... (Meta-Analysis)
Meta-Analysis Review
Nutritional supplementations have been widely used as adjunctive treatments for schizophrenia. However, among these supplementations, of which the most beneficial is currently unknown. This study aimed to compare and rank the effectiveness of nutritional supplementations in the adjunctive treatments of schizophrenia. The four nutritional supplementations evaluated were: 1) folate acid or vitamin B12; 2) vitamin D; 3) N-acetyl cysteine (NAC); 4) Omega-3 polyunsaturated fatty acid, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). 17 eligible RCTs with 1165 participants were included in this network meta-analysis based on study criteria. NAC supplementation was significantly more efficacious than folic acid or vitamin B12 [MD (95% CI): -6.6 (-10.8, -2.4)] and omega-3 polyunsaturated fatty acid [MD (95% CI): -5.1(-9.9, -0.8)] supplementation in the term of PANSS score changes. There were no significant differences in the PANSS score changes between NAC and vitamin D [MD (95% CI): -5.2 (-10.9, 0.5)] supplementations. The estimated ranking probabilities of treatments showed that NAC might be the most effective adjunctive intervention over all nutritional supplementations. These results indicate that NAC could improve PANSS score and it may be among the most effective nutritional supplementations in schizophrenia patients.
Topics: Acetylcysteine; Dietary Supplements; Fatty Acids, Omega-3; Humans; Network Meta-Analysis; Schizophrenia; Vitamin B 12; Vitamin D; Vitamins
PubMed: 35287043
DOI: 10.1016/j.psychres.2022.114500 -
Critical Reviews in Oncology/hematology Dec 2023The advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has been transformative for the treatment of advanced renal cell carcinoma (RCC).... (Review)
Review
The advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has been transformative for the treatment of advanced renal cell carcinoma (RCC). Their efficacy post-surgical resection remains a contentious point. Various phase 3 RCTs have assessed their potency. Amongst evaluated agents, sunitinib and pembrolizumab have demonstrated notable disease-free survival benefits. Sunitinib's potential is diminished due to absence of clear overall survival (OS) benefits and side-effect profile. Pembrolizumab shows better tolerance, conclusive OS data are forthcoming. This scenario underscores the pressing need for advanced risk stratification methods and discovery of novel biomarkers. Existing strategies, largely pre-dating TKI and ICI therapeutic era, lack sufficient accuracy in predicting relapse-risk. Our review offers a comprehensive analysis of key phase 3 RCTs, focusing on TKIs, mTOR-inhibitors, and ICIs for adjuvant RCC treatment. The intent is to shed light on the intricate landscape of RCC treatment, guiding future research directions for optimizing patient outcomes.
Topics: Humans; Carcinoma, Renal Cell; Sunitinib; Kidney Neoplasms; Neoplasm Recurrence, Local; Disease-Free Survival
PubMed: 37748694
DOI: 10.1016/j.critrevonc.2023.104144 -
Surgical Endoscopy Mar 2017Acute appendicitis is the most common surgical emergency and can represent a challenging diagnosis, with a negative appendectomy rate as high as 20 %. This review aimed... (Review)
Review
BACKGROUND
Acute appendicitis is the most common surgical emergency and can represent a challenging diagnosis, with a negative appendectomy rate as high as 20 %. This review aimed to evaluate the clinical utility of individual biomarkers in the diagnosis of appendicitis and appraise the quality of these studies.
METHODS
A systematic review of the literature between January 2000 and September 2015 using of PubMed, OvidMedline, EMBASE and Google Scholar was conducted. Studies in which the diagnostic accuracy, statistical heterogeneity and predictive ability for severity of several biomarkers could be elicited were included. Information regarding costs and process times was retrieved from the regional laboratory. European surgeons blinded to these reviews were independently asked to rank which characteristics of biomarkers were most important in acute appendicitis to inform a cost-benefit trade-off. Sensitivity testing and the QUADAS-2 tool were used to assess the robustness of the analysis and study quality, respectively.
RESULTS
Sixty-two studies met the inclusion criteria and were assessed. Traditional biomarkers (such as white cell count) were found to have a moderate diagnostic accuracy (0.75) but lower costs in the diagnosis of acute appendicitis. Conversely, novel markers (pro-calcitonin, IL 6 and urinary 5-HIAA) were found to have high process-related costs including analytical times, but improved diagnostic accuracy. QUADAS-2 analysis revealed significant potential biases in the literature.
CONCLUSION
When assessing biomarkers, an appreciation of the trade-offs between the costs and benefits of individual biomarkers is needed. Further studies should seek to investigate new biomarkers and address concerns over bias, in order to improve the diagnosis of acute appendicitis.
Topics: Acute Disease; Appendectomy; Appendicitis; Bilirubin; Biomarkers; C-Reactive Protein; Calcitonin; Cost-Benefit Analysis; Emergencies; Humans; Hydroxyindoleacetic Acid; Interleukin-6; Leukocyte Count; Sensitivity and Specificity
PubMed: 27495334
DOI: 10.1007/s00464-016-5109-1 -
Digestive Diseases and Sciences Mar 2024Low-dose aspirin (LDA) administration is associated with an elevated risk of recurring peptic ulcer (PU) and gastrointestinal (GI) hemorrhage. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Low-dose aspirin (LDA) administration is associated with an elevated risk of recurring peptic ulcer (PU) and gastrointestinal (GI) hemorrhage.
AIMS
This systematic review and Bayesian network meta-analysis aimed to comprehensively assess the effectiveness of diverse medications in preventing the recurrence of PU and GI hemorrhage in patients with a history of PU receiving long-term LDA therapy.
METHODS
This systematic review and network meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered on PROSPERO (CRD42023406550). We searched relevant studies in main databases from inception to March 2023. All statistical analyses were performed using R (version 4.1.3), with the "Gemtc" (version 1.0-1) package. The pooled risk ratio (RR), corresponding 95% credible interval (95% CrI), and the surface under the cumulative ranking curve (SUCRA) were calculated.
RESULTS
11 Randomized clinical trials (RCTs) were included. The analysis underscored pantoprazole was the most efficacious for reducing the risk of PU recurrence (RR [95% CrI] = 0.02 [0, 0.28]; SUCRA: 90.76%), followed by vonoprazan (RR [95% CrI] = 0.03 [0, 0.19]; SUCRA: 86.47%), comparing with the placebo group. Pantoprazole also performed well in preventing GI hemorrhage (RR [95% CrI] = 0.01[0, 0.42]; SUCRA: 87.12%) compared with Teprenone.
CONCLUSIONS
For patients with a history of PU receiving LDA, pantoprazole and vonoprazan might be the optimal choices to prevent PU recurrence and GI hemorrhage.
Topics: Humans; Pantoprazole; Peptic Ulcer; Aspirin; Gastrointestinal Hemorrhage; Pyrroles; Sulfonamides
PubMed: 38252210
DOI: 10.1007/s10620-023-08233-4 -
Frontiers in Endocrinology 2023Numerous studies have found an association between vitamin deficiency and thyroid disorders (TD). The presence of anti-parietal cell antibodies is indicative of reduced... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Numerous studies have found an association between vitamin deficiency and thyroid disorders (TD). The presence of anti-parietal cell antibodies is indicative of reduced ability to absorb vitamin B12. Thus, this study reviewed the existing studies with the objective of assessing differences in the serum levels of vitamin B12 among patients with and without TD, the frequency of vitamin B12 deficiency in patients with TD, and the presence of anti-parietal cell antibodies in patients with TD.
METHODS
A meta-analysis of random-effects model was conducted to calculate pooled frequencies, mean differences (MD), and their respective 95% confidence intervals (CI). We identified 64 studies that met our inclusion criteria (n = 28597).
RESULTS
We found that patients with hypothyroidism had lower vitamin B12 levels than healthy participants (MD: -60.67 pg/mL; 95% CI: -107.31 to -14.03 pg/mL; p = 0.01). No significant differences in vitamin B12 levels were observed between healthy participants and patients with hyperthyroidism (p = 0.78), autoimmune thyroid disease (AITD) (p = 0.22), or subclinical hypothyroidism (SH) (p = 0.79). The frequencies of vitamin B12 deficiency among patients with hypothyroidism, hyperthyroidism, SH, and AITD were 27%, 6%, 27%, and 18%, respectively.
CONCLUSIONS
Patients with hypothyroidism had lower levels of vitamin B12 than healthy participants. No significant differences were observed between vitamin B12 levels and hyperthyroidism, AITD, or SH.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=324422, identifier (CRD42022324422).
Topics: Humans; Hypothyroidism; Hyperthyroidism; Vitamin B 12; Vitamin B 12 Deficiency; Hashimoto Disease; Autoantibodies
PubMed: 36909313
DOI: 10.3389/fendo.2023.1070592 -
Folate-Methionine Cycle Disruptions in ASD Patients and Possible Interventions: A Systematic Review.Genes Mar 2023Autism Spectrum Disorder (ASD) has become a major public health concern due to its rapidly rising incidence over the past few years. Disturbances in folate or methionine... (Review)
Review
Autism Spectrum Disorder (ASD) has become a major public health concern due to its rapidly rising incidence over the past few years. Disturbances in folate or methionine metabolism have been identified in many individuals with ASD, suggesting that the folate-methionine cycle may play an essential role in the pathogenesis of autism. Thus, changes in metabolite concentrations associated with this cycle could be used as potential biomarkers and therapeutic targets for ASD. The aim of this systematic review is to elucidate the perturbations of this cycle and the possible interventions that may be proposed in this context. Several studies have shown that high levels of homocysteine and low levels of vitamins B12 and folate are associated with ASD. These changes in serum metabolites are influenced by poor diet. In fact, children with ASD tend to eat selectively, which could compromise the quality of their diet and result in nutrient deficiencies. Moreover, these disturbances may also be caused by genetic predispositions such as polymorphisms of the gene. Few studies have demonstrated the beneficial effects of the use of nutritional supplements in treating ASD children. Therefore, larger, well-structured studies are recommended to examine the impact of vitamin B12 and folate supplementation on homocysteine levels.
Topics: Child; Humans; Folic Acid; Methionine; Autism Spectrum Disorder; Vitamin B 12; Dietary Supplements; Racemethionine
PubMed: 36980981
DOI: 10.3390/genes14030709