scholarly journals Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis

BMJ ◽  
2021 ◽  
pp. n2321
Author(s):  
Bruno R da Costa ◽  
Tiago V Pereira ◽  
Pakeezah Saadat ◽  
Martina Rudnicki ◽  
Samir M Iskander ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Event ◽  
Adverse Events ◽  
Meta Analysis ◽  
Hip Osteoarthritis ◽  
Randomised Trials ◽  
Increased Risk ◽  
Inflammatory Drugs ◽  
Topical Nsaids ◽  
Topical Diclofenac

Abstract Objective To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose. Design Systematic review and network meta-analysis of randomised trials. Data sources Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021. Eligibility criteria for selecting studies Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis. Outcomes and measures The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed. Review methods Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo. Results 192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%). Conclusions Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis. Systematic review registration PROSPERO number CRD42020213656

scholarly journals Perioperative outcomes and adverse events of minimally invasive versus open posterior lumbar fusion: meta-analysis and systematic review

2016 ◽  
Vol 24 (3) ◽  
pp. 416-427 ◽  
Author(s):  
Christina L. Goldstein ◽  
Kevin Macwan ◽  
Kala Sundararajan ◽  
Y. Raja Rampersaud
Keyword(s):  
Systematic Review ◽  
Adverse Event ◽  
Adverse Events ◽  
Minimally Invasive ◽  
Comparative Effectiveness ◽  
Meta Analysis ◽  
Perioperative Outcomes ◽  
Estimated Blood Loss ◽  
Significant Difference ◽  
Patient Reported

OBJECT The objective of this study was to determine the clinical comparative effectiveness and adverse event rates of posterior minimally invasive surgery (MIS) compared with open transforaminal or posterior lumbar interbody fusion (TLIF/PLIF). METHODS A systematic review of the Medline, EMBASE, PubMed, Web of Science, and Cochrane databases was performed. A hand search of reference lists was conducted. Studies were reviewed by 2 independent assessors to identify randomized controlled trials (RCTs) or comparative cohort studies including at least 10 patients undergoing MIS or open TLIF/PLIF for degenerative lumbar spinal disorders and reporting at least 1 of the following: clinical outcome measure, perioperative clinical or process measure, radiographic outcome, or adverse events. Study quality was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. When appropriate, a meta-analysis of outcomes data was conducted. RESULTS The systematic review and reference list search identified 3301 articles, with 26 meeting study inclusion criteria. All studies, including 1 RCT, were of low or very low quality. No significant difference regarding age, sex, surgical levels, or diagnosis was identified between the 2 cohorts (856 patients in the MIS cohort, 806 patients in the open cohort). The meta-analysis revealed changes in the perioperative outcomes of mean estimated blood loss, time to ambulation, and length of stay favoring an MIS approach by 260 ml (p < 0.00001), 3.5 days (p = 0.0006), and 2.9 days (p < 0.00001), respectively. Operative time was not significantly different between the surgical techniques (p = 0.78). There was no significant difference in surgical adverse events (p = 0.97), but MIS cases were significantly less likely to experience medical adverse events (risk ratio [MIS vs open] = 0.39, 95% confidence interval 0.23–0.69, p = 0.001). No difference in nonunion (p = 0.97) or reoperation rates (p = 0.97) was observed. Mean Oswestry Disability Index scores were slightly better in the patients undergoing MIS (n = 346) versus open TLIF/PLIF (n = 346) at a median follow-up time of 24 months (mean difference [MIS – open] = 3.32, p = 0.001). CONCLUSIONS The result of this quantitative systematic review of clinical comparative effectiveness research examining MIS versus open TLIF/PLIF for degenerative lumbar pathology suggests equipoise in patient-reported clinical outcomes. Furthermore, a meta-analysis of adverse event data suggests equivalent rates of surgical complications with lower rates of medical complications in patients undergoing minimally invasive TLIF/PLIF compared with open surgery. The quality of the current comparative evidence is low to very low, with significant inherent bias.

scholarly journals Effects of dual blockade in heart failure and renal dysfunction: Systematic review and meta-analysis

2019 ◽  
Vol 20 (4) ◽  
pp. 147032031988265
Author(s):  
Alessandra Rodrigues Silva ◽  
Alexandre Goes Martini ◽  
Graziela De Luca Canto ◽  
Eliete Neves da Silva Guerra ◽  
Francisco de Assis Rocha Neves
Keyword(s):  
Heart Failure ◽  
Systematic Review ◽  
Adverse Events ◽  
Renal Dysfunction ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Renin Angiotensin System ◽  
Ras Inhibition ◽  
Increased Risk ◽  
Dual Blockade

Objective: The effect of dual renin–angiotensin system (RAS) inhibition in heart failure (HF) is still controversial. Systematic reviews have shown that dual RAS blockade may reduce mortality and hospitalizations, yet it has been associated with the increased risk of renal dysfunction (RD). Surprisingly, although RD in patients with HF is frequent, the effect of combining RAS inhibitors in HF patients with RD has never been studied in a meta-analysis. Methods: A systematic review and meta-analysis of randomized clinical trials involving HF patients with RD who received dual blockade analyzing death, cardiovascular (CV) death or HF hospitalization, and adverse events. Results: Out of 2258 screened articles, 12 studies were included (34,131 patients). Compared with monotherapy, dual RAS inhibition reduced hazard ratio of death to 0.94 ( p=0.07) and significantly reduced CV death or HF hospitalization to 0.89 ( p=0.0006) in all individuals, and to 0.86 ( p=0.005) in patients with RD and to 0.91 ( p=0.04) without RD. Nevertheless, dual RAS blockade significantly increased the risk of renal impairment (40%), hyperkalemia (44%), and hypotension (42%), although discontinuation of treatment occurs only in 3.68% versus 2.19% ( p=0.00001). Conclusions: Dual RAS inhibition therapy reduces the risk of CV death or HF hospitalization. However, cautions monitoring for specific adverse events may be warranted.

scholarly journals Association between NSAIDs andClostridium difficile-Associated Diarrhea: A Systematic Review and Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Nitipong Permpalung ◽  
Sikarin Upala ◽  
Anawin Sanguankeo ◽  
Suthanya Sornprom
Keyword(s):  
Systematic Review ◽  
Observational Studies ◽  
Meta Analysis ◽  
Developed Countries ◽  
Community Based ◽  
Nosocomial Diarrhea ◽  
Increased Risk ◽  
History Of ◽  
Inflammatory Drugs ◽  
Healthcare Associated

Objective. Clostridium difficileinfection is a leading cause of nosocomial diarrhea in developed countries. Studies evaluating the associations of increased risk of community-acquired CDAD and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) have yielded inconclusive results. We conducted a systematic review and meta-analysis to compare the odds of NSAID exposure in patients with CDAD versus patients without CDAD in both community-based and healthcare-associated settings.Methods.Relevant observational studies indexed in PubMed/MEDLINE and EMBASE up to February 2015 were analyzed and data were extracted from nine studies. Of these, eight studies were included in the meta-analysis.Results.A search of the databases resulted in 987 articles. The nine studies from which data were extracted involved over 39,000 subjects. The pooled odds ratio for history of NSAID use in participants with CDAD compared with controls was 1.41 (95% CI 1.06–1.87;p<0.01), indicating a significant increased odds of CDAD among patients exposed to NSAIDs.Conclusions.To the best of our knowledge, this is the first study of its nature to demonstrate the association between the use of NSAIDs and increased risk of CDAD. Further studies to evaluate if any specific types of NSAIDs can increase the risk of CDAD are warranted.

scholarly journals P01.06 Overweight and obesity as biomarkers for survival outcomes and immune related adverse events undergoing immunotherapy – a systematic review and meta-analysis

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A5.2-A6
Author(s):  
P Trinkner ◽  
S Günther ◽  
M von Bergwelt ◽  
D Cordas dos Santos ◽  
S Theurich
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
Obese Patients ◽  
Increased Risk ◽  
Underweight Patients ◽  
The Impact

BackgroundThe impact of overweight/obesity in cancer patients treated with immune checkpoint inhibitors (ICIs) is controversial. To further contribute to this debate, we performed a systematic review and meta-analysis of published articles evaluating the effects of overweight/obesity on survival and immune-related adverse events (irAEs).Materials and MethodsIn analogy to Cochrane recommendations, systematic literature searches included all published articles in PubMed until February 2021 with key terms ‘obesity’ and ‘overweight’ and ICI treatment irrespective of cancer entity and ICI used. Further selection criteria for meta-analysis included WHO cut-offs for overweight/obesity. For the random effects meta-analysis, we used Hazard Ratios (HR) for overall and progression-free survival (OS, PFS) and Odds Ratios (OR) for occurrence of irAEs with corresponding 95% confidence intervals (95%CI), respectively.ResultsA total of 30 studies (12,895 patients, 38% female) selected for meta-analysis revealed a superior survival of overweight/obese patients (PFS: HR 0.9, 95%CI 0.77-1.04, p = 0.11; OS: 0.74, 95%CI 0.63-0.92, p = 0.0005) compared to normal weight patients. In subgroup analyses based on sex, overweight/obese male patients showed increased survival (PFS: HR 0.79, 95%CI 0.63-1.00, p = 0.05; OS: 0.71, 95%CI 0.58-0.86, p = 0.0005), whereas overweight/obese female patients had similar survival probabilities compared to their normal weight counterparts (PFS: HR 1.01, 95%CI 0.69-1.47, p = 0.96; OS: HR 0.73, 95%CI 0.48-1.10, p = 0.13). Underweight patients showed inferior survival (PFS: HR 1.48, 95%CI 1.07-2.04, p = 0.02; OS: HR 1.86, 95%CI 1.13-3.04, p = 0.01). In addition, overweight/obese patients had a higher risk of developing irAEs with grade ≥ 3 (OR 1.91, 95%CI 1.18-3.10, p = 0.008).ConclusionsOur meta-analysis revealed that overweight/obesity is a beneficial factor for PFS and OS in a mixed cohort of cancer patients undergoing ICI treatment accompanied by an increased risk of severe irAEs. The differences between overweight/obese males and overweight/obese females might point to sex specific adipose distribution patterns and interactions of sex steroids on a molecular level. A significant number of studies included underweight patients into normal weight control groups which led to a compromised interpretation of the data and should be addressed in future studies.Disclosure InformationP. Trinkner: None. S. Günther: None. M. von Bergwelt: None. D. Cordas dos Santos: None. S. Theurich: None.

scholarly journals Enough with the madness: a systematic review and meta-analysis of hydroxychloroquine for COVID-19

2021 ◽  
Vol 13 (2) ◽  
pp. 186-220
Author(s):  
André Santos ◽  
◽  
Érica Gonçalves ◽  
Ananda Oliveira ◽  
Douglas Lima ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Meta Analysis ◽  
Standard Of Care ◽  
P Value ◽  
Serious Adverse Events ◽  
Risk Of Death ◽  
Increased Risk ◽  
Significant Difference

Objective: Because of preliminary results from in vitro studies, hydroxychloroquine (HCQ) and chloroquine (CQ) have been proposed as possible treatments for COVID-19, but the clinical evidence is discordant. This study aims to evaluate the safety and efficacy of CQ and HCQ for the treatment of COVID-19. Methods: A systematic review with meta-analysis was performed. An electronic search was conducted in four databases for randomized controlled trials that compared HCQ or CQ with standard-of-care. A complementary search was performed. A quantitative synthesis of clinical outcomes was performed using the inverse variance method adjusting for a random-effects model. Results: In total, 16 studies were included. The meta-analysis found no significant difference between intervention and control groups in terms of mortality at the most extended follow-up (RR = 1.09, CI95% = 0.99-1.19, p-value = 0.08), patients with negative PCR results (RR = 0.99, CI95% = 0.89-1.10, p-value = 0.86), or serious adverse events (RR = 2.21, CI95% = 0.89-5.47, p-value = 0.09). HCQ was associated with an increased risk of adverse events (RR = 2.28, CI95% = 1.36-2.83, p-value < 0.01). The quality of evidence varied from very low to high. Conclusion: There is no evidence that HCQ reduces the risk of death or improves cure rates in patients with COVID-19, but it might be associated with an increased risk of adverse events

scholarly journals How safe is TDF/FTC as PrEP? A systematic review and meta-analysis of the risk of adverse events in 13 randomised trials of PrEP

2018 ◽  
Vol 4 (4) ◽  
pp. 215-224 ◽  
Author(s):  
Victoria Pilkington ◽  
Andrew Hill ◽  
Sophie Hughes ◽  
Nneka Nwokolo ◽  
Anton Pozniak
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Meta Analysis ◽  
Randomised Trials

scholarly journals Association of Sports Participation With Osteoarthritis: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 9 (6) ◽  
pp. 232596712110045
Author(s):  
Thomas Bestwick-Stevenson ◽  
Onosi S. Ifesemen ◽  
Richard G. Pearson ◽  
Kimberley L. Edwards
Keyword(s):  
Systematic Review ◽  
Knee Osteoarthritis ◽  
Meta Analysis ◽  
Hip Osteoarthritis ◽  
Case Control ◽  
Ice Hockey ◽  
Case Control Studies ◽  
Ankle Osteoarthritis ◽  
Speed Skating ◽  
Increased Risk

Background: The association between participating in sport and osteoarthritis is not fully understood. Purpose: To investigate the association between osteoarthritis and participating in sports not listed in previous reviews: American football, archery, baseball, bobsleigh, curling, handball, ice hockey, shooting, skeleton, speed skating, and wrestling. Study Design: Systematic review; Level of evidence, 3. Methods: We searched 4 electronic databases and hand searched recent/in-press editions of relevant journals. The criteria for study selection were case-control studies, cohort studies, nested case-control studies, and randomized trials with a control group that included adults to examine the effect of exposure to any of the included sports on the development of osteoarthritis. Results: The search returned 6197 articles after deduplication. Nine studies were included in the final review, covering hip, knee, and ankle osteoarthritis. There were no studies covering archery, baseball, skeleton, speed skating, or curling. The 6 sports included in the review were analyzed as a collective; the results of the meta-analysis indicated that participation in the sports analyzed was associated with an increased risk of developing osteoarthritis of the hip (relative risk [RR] = 1.67 [95% confidence interval (CI), 1.15-2.41]; P = .04), knee (RR = 1.60 [95% CI, 1.23-2.08]; P < .001), and ankle (RR = 7.08 [95% CI, 1.24-40.51]; P = .03) as compared with controls. Meta-analysis suggested a significantly increased likelihood of developing hip osteoarthritis through participating in wrestling (RR = 1.78 [95% CI, 1.20-2.64]; P = .004) and ice hockey (RR = 1.70 [95% CI, 1.27-2.29]; P < .001), while there was no significant difference through participating in handball (RR = 2.50 [95% CI, 0.85-7.36]; P = .10). Likelihood of developing knee osteoarthritis was significantly increased in wrestling (RR = 2.22 [95% CI, 1.59-3.11]) and ice hockey (RR = 1.52 [95% CI, 1.18-1.96]; both P < .002). According to the meta-analysis, shooting did not have a significant effect on the RR of knee osteoarthritis as compared with other sports (RR = 0.43 [95% CI, 0.06-2.99]; P = .39). Conclusion: The likelihood of developing hip and knee osteoarthritis was increased for ice hockey and wrestling athletes, and the risk of developing hip osteoarthritis was increased for handball athletes. The study also found that participation in the sports examined, as a collective, resulted in an increased risk of developing hip, knee, and ankle osteoarthritis.

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