scholarly journals POS0665 TRAJECTORIES OF GLUCOCORTICOID-THERAPY IN EARLY RHEUMATOID ARTHRITIS: FIRST RESULTS OF A SCOPING SYSTEMATIC REVIEW AND META-ANALYSIS OF OBSERVATIONAL COHORT STUDIES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 575.1-575
Author(s):  
A. Palmowski ◽  
F. Buttgereit
Keyword(s):  
Rheumatoid Arthritis ◽  
Early Rheumatoid Arthritis ◽  
Search Strategy ◽  
Meta Analysis ◽  
Term Treatment ◽  
Sensitivity Analyses ◽  
Published Data ◽  
Glucocorticoid Treatment ◽  
Long Term Treatment ◽  
Meta Analyses

Background:Glucocorticoids (GCs) are regularly used as a bridging therapy in early rheumatoid arthritis (eRA). As long-term treatment, especially at higher dosages, may lead to undesirable adverse events, GCs should be tapered as rapidly as clinically feasible.Objectives:To assess real-world trajectories of GC-therapy initiated in patients with eRA and in methotrexate-naïve RA patients.Methods:We conducted a scoping search in MEDLINE (via PubMed) to find articles (years 2005 – 2020) reporting on eRA (or methotrexate-naïve RA) patients from observational cohorts who start or take GCs at baseline. Articles had to describe either dosages or proportions of patients who took GCs or were able to taper GCs at two (minimum) pre-specified time points. The articles were screened by one reviewer (AP). Random-effects meta-analyses pooled results per outcome and time point if ≥3 studies were available. R software with package metafor was used for statistical analyses. A research protocol was published with protocols.io (10.17504/protocols.io.bpyfmptn).Results:Our highly specific search strategy yielded 165 results. Twelve articles on nine cohorts were finally included. Eight cohorts originated in Europe, one in Africa. At baseline, about half of the patients with eRA were prescribed GCs with a mean dosage of 8mg/d prednisone equivalent (fig 1). Over time, both the proportion taking GCs and the mean dosage declined. There was substantial heterogeneity between studies.Conclusion:Our results indicate that GCs remain regularly used drugs in eRA patients and in methotrexate-naïve patients with RA. While about 40% of patients still receive GCs after 24 months, mean dosages were tapered to “low” dosages (≤7.5mg/d prednisone equivalent)1 in all cohorts that reported respective data. Heterogeneity might be caused by country-specific differences. Unfortunately, the validity of sensitivity analyses would be poor due to the paucity of published data regarding GC dosages and proportions of patients taking GCs in observational RA cohorts. Major limitations of this scoping review are the very specific (and consequently less sensitive) search strategy and that the screening was conducted by one reviewer only.References:[1]Buttgereit F, Da Silva JAP, Boers M, et al. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis 2002;61(8):718-22. doi: 10.1136/ard.61.8.718.Figure 1.Meta-analyses of proportions taking glucocorticoids and mean dosages at baseline and 24 months. GCs: Glucocorticoids; CI: Confidence interval.Disclosure of Interests:None declared

scholarly journals What does the latest meta-analysis really tell us about antidepressants?

2018 ◽  
Vol 27 (5) ◽  
pp. 430-432 ◽  
Author(s):  
J. Moncrieff
Keyword(s):  
Meta Analysis ◽  
Term Treatment ◽  
Significant Other ◽  
Brain Abnormality ◽  
Antidepressant Effects ◽  
Long Term Treatment ◽  
Clinically Significant ◽  
Meta Analyses ◽  
Chemical Imbalance

A recent meta-analysis of antidepressant trials is the largest conducted to date. Although it claims to prove antidepressant effectiveness beyond dispute, the main outcome is response rates, which are derived from continuous data in a process that can inflate differences between groups. The standardised mean difference of 0.3 is in line with other meta-analyses that show small differences between antidepressants and placebo that are unlikely to be clinically significant. Other factors likely to exaggerate the effects are discussed, and evidence on associations between antidepressant effects and severity and outcomes of long-term treatment is considered. Clinicians need to have open discussions with patients about the limitations of antidepressant research, the lack of evidence that antidepressants correct a chemical imbalance or other brain abnormality, and the range of adverse effects and mental and physical alterations they can produce.

scholarly journals A Network Meta-Analysis to Compare Effectiveness of Baricitinib and Other Treatments in Rheumatoid Arthritis Patients with Inadequate Response to Methotrexate

2020 ◽  
Vol 7 (1) ◽  
pp. 10-23
Keyword(s):  
Rheumatoid Arthritis ◽  
Meta Analysis ◽  
Patient Characteristics ◽  
Janus Kinase ◽  
Sensitivity Analyses ◽  
Baseline Risk ◽  
Inadequate Response ◽  
Primary Analysis ◽  
American College Of Rheumatology ◽  
Meta Analyses

Background/Objectives: This article compares the effectiveness of baricitinib (BARI) 4 mg (oral, Janus kinase [JAK] 1/2 inhibitor) versus other targeted synthetic/biologic disease-modifying antirheumatic drugs, in combination with methotrexate (MTX), in moderate-to-severe rheumatoid arthritis patients with inadequate response (IR) to MTX. Methods: A systematic literature review was conducted to identify randomized controlled trials (RCTs) of the interventions of interest. Bayesian network meta-analyses (NMA) were used to compare American College of Rheumatology (ACR) responses at 24 weeks. A series of prespecified sensitivity analyses addressed the potential impact of, among others, baseline risk, treatment effect modifiers, and trial design on treatment response. Results: Nineteen RCTs were included in the NMA (primary analysis). For ACR20, BARI 4 mg + MTX was found to be more effective than adalimumab (ADA) 40 mg + MTX (Odds Ratio [OR] 1.33), abatacept (ABA) 10 mg + MTX (IV/4 weeks) (OR 1.45), infliximab (IFX) 3 mg + MTX (IV/8 wks) (OR 1.63), and rituximab (RTX) 1000 mg + MTX (OR 1.63). No differences were found on ACR50. For ACR70, BARI 4 mg + MTX was more effective than ADA 40 mg + MTX (OR 1.37), ABA 10 mg + MTX (OR 1.86), and RTX 1000 mg + MTX (OR 2.26). Sensitivity analysis including 10 additional RCTs with up to 20% of patients with prior biologic use showed BARI 4 mg + MTX to be more effective than tocilizumab (TCZ) 8 mg + MTX on ACR20 (OR 1.44). Results for all sensitivity analyses were consistent with the direction and magnitude of the primary results. Key limitations include the time span in which trials were conducted (1999–2017), during which patient characteristics and treatment approaches might have changed. Conclusion: This NMA suggests that BARI 4 mg + MTX is an efficacious treatment option in the MTX-IR population as evidenced by the robustness of results.

Serum concentrations of piroxicam in patients with rheumatoid arthritis on long-term treatment with ampiroxicam.

Ensho ◽  
1991 ◽  
Vol 11 (6) ◽  
pp. 597-605
Author(s):  
Sachiko Sugawara ◽  
Shoichiro Irimajiri ◽  
Torakichi Aoki ◽  
Shuichi Yokoyama ◽  
Sanae Ida ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Term Treatment ◽  
Serum Concentrations ◽  
Long Term Treatment

scholarly journals Cardiovascular and cerebrovascular risk with nonsteroidal anti-inflammatory drugs and cyclooxygenase 2 inhibitors: latest evidence and clinical implications

2017 ◽  
Vol 8 (6) ◽  
pp. 173-182 ◽  
Author(s):  
Andrea Fanelli ◽  
Daniela Ghisi ◽  
Pierangelo Lora Aprile ◽  
Francesco Lapi
Keyword(s):  
Term Treatment ◽  
Cyclooxygenase 2 ◽  
Thrombotic Risk ◽  
Long Term Treatment ◽  
Pressure Development ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
High Doses ◽  
The Right ◽  
Meta Analyses

Observational studies and meta-analyses have shown that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs), especially when prescribed at high doses for long periods of time, can potentially increase the risk of cardiovascular diseases. The increased thrombotic risk related to the use of NSAIDs is mainly due to their cyclooxygenase 2 selectivity. The dosage use, the formulation selected and the duration of the therapy are other factors that can significantly impact on the cardiovascular risk. In order to minimize the risk, prescription of the right drug based on the patient’s features and the different safety profiles of several NSAIDs that are available on the market is key for their appropriate administration. Despite the baseline cardiovascular and gastrointestinal risk of each patient, monitoring of patients is suggested for increases in blood pressure, development of edema, deterioration of renal function, or gastrointestinal bleeding during long-term treatment with NSAIDs.

scholarly journals Relationship between hospital or surgeon volume and outcomes in joint arthroplasty: protocol for a suite of systematic reviews and dose–response meta-analyses

BMJ Open ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. e022797 ◽  
Author(s):  
Xiang-Dong Wu ◽  
Meng-Meng Liu ◽  
Ya-Ying Sun ◽  
Zhi-Hu Zhao ◽  
Quan Zhou ◽  
...  
Keyword(s):  
Systematic Reviews ◽  
Dose Response ◽  
Data Extraction ◽  
Meta Analysis ◽  
High Volume ◽  
Joint Arthroplasty ◽  
Surgeon Volume ◽  
Published Data ◽  
Records Management ◽  
Meta Analyses

IntroductionJoint arthroplasty is a particularly complex orthopaedic surgical procedure performed on joints, including the hip, knee, shoulder, ankle, elbow, wrist and even digit joints. Increasing evidence from volume–outcomes research supports the finding that patients undergoing joint arthroplasty in high-volume hospitals or by high-volume surgeons achieve better outcomes, and minimum case load requirements have been established in some areas. However, the relationships between hospital/surgeon volume and outcomes in patients undergoing arthroplasty are not fully understood. Furthermore, whether elective arthroplasty should be restricted to high-volume hospitals or surgeons remains in dispute, and little is known regarding where the thresholds should be set for different types of joint arthroplasties.Methods and analysesThis is a protocol for a suite of systematic reviews and dose–response meta-analyses, which will be amended and updated in conjunction with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Electronic databases, including PubMed and Embase, will be searched for observational studies examining the relationship between the hospital or surgeon volume and clinical outcomes in adult patients undergoing primary or revision of joint arthroplasty. We will use records management software for study selection and a predefined standardised file for data extraction and management. Quality will be assessed using the Newcastle-Ottawa Scale, and the meta-analysis, subgroup analysis and sensitivity analysis will be performed using Stata statistical software. Once the volume–outcome relationships are established, we will examine the potential non-linear relationships between hospital/surgeon volume and outcomes and detect whether thresholds or turning points exist.Ethics and disseminationEthical approval is not required, because these studies are based on aggregated published data. The results of this suite of systematic reviews and meta-analyses will be submitted to peer-reviewed journals for publication.PROSPERO registration numberCRD42017056639.

scholarly journals Do antipsychotic drugs lose their efficacy for relapse prevention over time?

2017 ◽  
Vol 211 (3) ◽  
pp. 127-129 ◽  
Author(s):  
Stefan Leucht ◽  
John M. Davis
Keyword(s):  
Relapse Prevention ◽  
Antipsychotic Drugs ◽  
Meta Analysis ◽  
Term Treatment ◽  
First Episode ◽  
Brain Volume Loss ◽  
New Findings ◽  
Long Term Treatment ◽  
Long Term Follow Up

SummaryThere is a debate about long-term treatment of schizophrenia with antipsychotic drugs, with some experts suggesting that these drugs should be discontinued. In this issue, Takeuchi et al demonstrated by a meta-analysis of 11 trials that antipsychotic drugs maintained their efficacy for relapse prevention for 1 year, whereas patients on placebo kept getting worse. We consider these findings in the light of the current discussion about possible dose-related brain volume loss, supersensitivity psychosis, the high variability of results in long-term follow-up studies and recent approaches to discontinue antipsychotics in patients with a first-episode. The new findings speak in favour of continuing antipsychotics at the same dose, at least in patients whose condition is chronic, but the topic is complex.

scholarly journals Comparative efficacy and safety of oral or transdermal opioids in the treatment of knee or hip osteoarthritis: a systematic review and Bayesian network meta-analysis protocol

BMJ Open ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. e022142
Author(s):  
Jun Wang ◽  
Yin Wang ◽  
Hui Zhang ◽  
Ming Lu ◽  
Weilu Gao ◽  
...  
Keyword(s):  
Bayesian Network ◽  
Meta Analysis ◽  
Hip Osteoarthritis ◽  
Sensitivity Analyses ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Meta Analyses ◽  
Transdermal Opioids ◽  
And Function

IntroductionOsteoarthritis is a common degenerative joint disease that eventually leads to disability and poor quality of life. The main symptoms are joint pain and mobility disorders. If the patient has severe pain or other analgesics are contraindicated, opioids may be a viable treatment option. To evaluate and compare the efficacy and safety of opioids in the treatment of knee or hip osteoarthritis, we will integrate direct and indirect evidence using a Bayesian network meta-analysis to establish hierarchies of these drugs.Methods and analysisWe will search the Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Web of Science and PsycINFO databases as well as published and unpublished research in international registries and regulatory agency websites for osteoarthritis reports published prior to 5 January 2018. There will be no restrictions on the language. Randomised clinical trials that compare oral or transdermal opioids with other various opioids, placebo or no treatment for patients with knee or hip osteoarthritis will be included. The primary outcomes of efficacy will be pain and function. We will use pain and function scales to evaluate the main outcomes. The secondary outcomes of safety will be defined as the proportion of patients who have stopped treatment due to side effects. Pairwise meta-analyses and Bayesian network meta-analyses will be performed for all related outcome measures. We will conduct subgroup analyses and sensitivity analyses to assess the robustness of our findings. The Grading of Recommendations, Assessment, Development and Evaluations framework will be used to assess the quality of the evidence contributing to each network assessment.Ethics and disseminationThis study does not require formal ethical approval because individual patient data will not be included. The findings will be disseminated through peer-reviewed publications or conference presentations.PROSPERO registration numberCRD42018085503.

scholarly journals Pharmacogenetic association between NAT2 gene polymorphisms and isoniazid induced hepatotoxicity: trial sequence meta-analysis as evidence

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Saif Khan ◽  
Raju K. Mandal ◽  
Abdulbaset Mohamed Elasbali ◽  
Sajad A. Dar ◽  
Arshad Jawed ◽  
...  
Keyword(s):  
Gene Polymorphisms ◽  
Meta Analysis ◽  
Term Treatment ◽  
Wild Type ◽  
Severe Problem ◽  
Trial Sequence ◽  
Increased Risk ◽  
Long Term Treatment ◽  
Nat2 Gene

Abstract Hepatotoxicity is a severe problem generally faced by tuberculosis (TB) patients. It is a well-known adverse reaction due to anti-TB drugs in TB patients undergoing long-term treatment. The studies published previously have explored the connection of N-acetyltransferase 2 (NAT2) gene polymorphisms with isoniazid-induced hepatotoxicity, but the results obtained were inconsistent and inconclusive. A comprehensive trial sequence meta-analysis was conducted employing 12 studies comprising 3613 controls and 933 confirmed TB cases using the databases namely, EMBASE, PubMed (Medline) and Google Scholar till December 2017. A significant association was observed with individuals carrying variant allele at position 481C>T (T vs. C: P = 0.001; OR = 1.278, 95% CI = 1.1100–1.484), at position 590G>A (A vs. G: P = 0.002; OR = 1.421, 95% CI = 1.137–1.776) and at position 857G>A (A vs. G: P = 0.0022; OR = 1.411, 95% CI = 1.052–1.894) to higher risk of hepatotoxicity vis-à-vis wild-type allele. Likewise, the other genetic models of NAT2 gene polymorphisms have also shown increased risk of hepatotoxicity. No evidence of publication bias was observed. These results suggest that genetic variants of NAT2 gene have significant role in isoniazid induced hepatotoxicity. Thus, NAT2 genotyping has the potential to improve the understanding of the drug–enzyme metabolic capacity and help in early predisposition of isoniazid-induced hepatotoxicity.

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