scholarly journals Janus Kinase-Inhibitor and Type I Interferon Ability to Produce Favorable Clinical Outcomes in COVID-19 Patients: A Systematic Review and Meta-Analysis

Author(s):  
Lucas Walz ◽  
Avi J. Cohen ◽  
Andre P. Rebaza ◽  
James Vanchieri ◽  
Martin D. Slade ◽  
...  

Background Novel coronavirus (SARS-CoV-2) has infected over 17 million. Novel therapies are urgently needed. Janus-kinase (JAK) inhibitors and Type I interferons have emerged as potential antiviral candidates for COVID-19 patients for their proven efficacy against diseases with excessive cytokine release and by their ability to promote viral clearance in past coronaviruses, respectively. We conducted a systemic review and meta-analysis to evaluate role of these therapies in COVID-19 patients. Methods MEDLINE and MedRxiv were searched until July 30th, 2020, including studies that compared treatment outcomes of humans treated with JAK-inhibitor or Type I interferon against controls. Inclusion necessitated data with clear risk estimates or those that permitted back-calculation. Results We searched 733 studies, ultimately including four randomized and eleven non-randomized clinical trials. JAK-inhibitor recipients had significantly reduced odds of mortality (OR, 0.12; 95%CI, 0.03-0.39, p=0.0005) and ICU admission (OR, 0.05; 95%CI, 0.01-0.26, p=0.0005), and had significantly increased odds of hospital discharge (OR, 22.76; 95%CI, 10.68-48.54, p<0.00001), when compared to standard treatment group. Type I interferon recipients had significantly reduced odds of mortality (OR, 0.19; 95%CI, 0.04-0.85, p=0.03), and increased odds of discharge bordering significance (OR, 1.89; 95%CI, 1.00-3.59, p=0.05). Conclusions JAK-inhibitor treatment is significantly associated with positive clinical outcomes regarding mortality, ICU admission, and discharge. Type I interferon treatment is associated with positive clinical outcomes regarding mortality and discharge. While these data show promise, additional randomized clinical trials are needed to further elucidate the efficacy of JAK-inhibitors and Type I interferons and clinical outcomes in COVID-19.

Author(s):  
Lucas Walz ◽  
Avi J. Cohen ◽  
Andre P. Rebaza ◽  
James Vanchieri ◽  
Martin D. Slade ◽  
...  

Abstract Background The spread of a highly pathogenic, novel coronavirus (SARS-CoV-2) has emerged as a once-in-a-century pandemic, having already infected over 17 million. Novel therapies are urgently needed. Janus kinase-inhibitors and Type I interferons have emerged as potential antiviral candidates for COVID-19 patients for their proven efficacy against diseases with excessive cytokine release and due to direct antiviral ability against viruses including coronaviruses, respectively. We conducted a systemic review and meta-analysis to evaluate the effect of Janus kinase-inhibitors and Type I interferons and their ability to produce positive patient outcomes in COVID-19 patients. Methods A search of MEDLINE and MedRxiv was conducted by three investigators from inception until July 30 th 2020, including any study type that compared treatment outcomes of humans treated with JAK-inhibitor or Type I interferon against controls. Inclusion necessitated data with clearly indicated risk estimates or those that permitted their back-calculation. Outcomes were synthesized using RevMan. Results Of 733 searched studies, we included four randomized and eleven non-randomized trials. Five of the studies were unpublished. Those who received Janus kinase-inhibitor had significantly reduced odds of mortality (OR, 0.12; 95% CI, 0.03 – 0.39, p<0.001) and ICU admission (OR, 0.05; 95% CI, 0.01 – 0.26, p<0.001), and had significantly increased odds of hospital discharge (OR, 22.76; 95% CI, 10.68 – 48.54, p<0.00001), when compared to standard treatment group. Type I interferon recipients had significantly reduced odds of mortality (OR, 0.19; 95% CI, 0.04 – 0.85, p<0.05), and increased odds of discharge bordering significance (OR, 1.89; 95% CI, 1.00 – 3.59, p=0.05). Conclusions Janus kinase-inhibitor treatment is significantly associated with positive clinical outcomes in terms of mortality, ICU admission, and discharge. Type I interferon treatment is associated with positive clinical outcomes in regard to mortality and discharge. While these data show promise, additional well-conducted RCTs are needed to further elucidate the relationship between clinical outcomes and Janus kinase-inhibitors and Type I interferons in COVID-19 patients.


2021 ◽  
Vol 6 (9) ◽  
pp. 759-770
Author(s):  
Zeng Li ◽  
Shuai Xiang ◽  
Cuijiao Wu ◽  
Yingzhen Wang ◽  
Xisheng Weng

Vitamin E incorporation into highly cross-linked polyethylene (HXLPE) has been introduced to improve wear resistance, and vitamin E incorporated HXLPE (VEPE) has been used in total hip arthroplasty. The aim of this meta-analysis was to investigate the wear properties of VEPE in clinical practice by synthesizing the data provided in randomized clinical trials. The effects on implant stability, functional outcomes and revision rate of VEPE were also compared with those of HXPLE or ultra-high molecular weight polyethylene (UHMWPE). Literature searches were conducted on 1 January 2020 using MEDLINE, EMBASE, Cochrane and ClinicalTrials.gov databases. Randomized controlled trials (RCTs) comparing the aforementioned parameters between VEPE and standard HXPLE/UHMWPE liners were included. Methodological quality and the bias of the included studies were analysed. Meta-analyses were performed using the Review Manager software. Nine RCTs met the eligibility criteria and were included. At early and mid-term follow-up, the vertical penetration and the total penetration of the femoral head were both significantly reduced in the VEPE group. The steady state wear rate of the VEPE group was also remarkably lower. However, at two-year follow-up, significantly increased cup migration was observed in the VEPE group. Moreover, the mid-term clinical outcomes of the VEPE group were worse, while the total revision rates between the two groups were not significantly different. The limited number of included studies may compromise our conclusion regarding clinical outcomes of the VEPE bearing surface. More RCTs with longer follow-up periods are needed to further investigate the effects of VEPE in total hip arthroplasty. Cite this article: EFORT Open Rev 2021;6:759-770. DOI: 10.1302/2058-5241.6.200072


2020 ◽  
Vol 8 (10) ◽  
pp. 232596712096041
Author(s):  
Flávio Luís Garcia ◽  
Brady T. Williams ◽  
Evan M. Polce ◽  
Daniel B. Heller ◽  
Zachary S. Aman ◽  
...  

Background: Despite its increasing use in the management of musculoskeletal conditions, questions remain regarding the preparation methods of platelet-rich plasma (PRP) and its clinical applications for intra-articular hip disorders, including femoroacetabular impingement syndrome (FAIS), labral pathology, and osteoarthritis (OA). Purpose: To systematically review and assess the preparation methods and clinical outcomes from randomized clinical trials (RCTs) on the use of PRP for intra-articular hip disorders. Study Design: Systematic review; Level of evidence, 2. Methods: A systematic review in accordance with the 2009 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was performed in September 2019. The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, PubMed, Ovid Medline, and Embase were queried for studies regarding the use of PRP to treat intra-articular hip disorders. Qualifying articles were English-language RCTs describing the use of PRP for intra-articular hip disorders, either as standalone treatment or surgical augmentation. Two authors independently assessed article eligibility. Data pertaining to patient characteristics, indication for treatment, PRP preparation method, follow-up period, and clinical outcomes were extracted. Study results were qualitatively reported and quantitatively compared using meta-analysis when appropriate. Results: Seven RCTs met inclusion criteria. Four studies described the use of PRP for hip OA and 3 utilized PRP at arthroscopy for FAIS and labral tears. Outcomes after PRP for OA demonstrated improvement in validated patient-reported outcome measures for up to 1 year; however, pooled effect sizes found no statistically significant difference between PRP and hyaluronic acid (HA) regarding pain visual analog scale scores at short-term (≤2 months; P = .27), midterm (4-6 months; P = .85), or long-term (1 year; P = .42) follow-up. When injected at arthroscopy, 1 study reported improved outcomes, 1 reported no difference in outcomes, and 1 reported worse outcomes compared with controls. The meta-analysis demonstrated no statistically significant difference on the modified Harris Hip Score (mHHS) between PRP and control cohorts at a minimum 1-year follow-up. There were considerable deficiencies and heterogeneity in the reporting of PRP preparation methods for both indications. Conclusion: Treatment of OA with PRP demonstrated reductions in pain and improved patient-reported outcomes for up to 1 year. However, there was no statistically significant difference between PRP and HA in pain reduction. Likewise, for FAIS and labral surgery there was no statistically significant difference in mHHS outcomes between patients treated with PRP and controls. Given the limited number of studies and variability in PRP preparations, additional high-quality randomized trials are warranted.


Dermatology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Chenyang Li ◽  
Xun Sun ◽  
Kun Zhao ◽  
Fanxiang Meng ◽  
Lin Li ◽  
...  

<b><i>Background:</i></b> Current therapeutic options for atopic dermatitis (AD) are limited. Janus kinase (JAK) inhibitors may be viable alternatives. <b><i>Objectives:</i></b> To assess the efficacy and safety of JAK inhibitors for AD treatment. <b><i>Methods:</i></b> We searched PubMed, Embase, the Cochrane Controlled Register of Trials, Web of Science, Global Resource of Eczema Trials database, and ClinicalTrials.gov from inception to September 1, 2020. Randomized clinical trials (RCTs) comparing JAK inhibitors with placebo/vehicle treatment for AD patients were included. The primary study outcomes included (1) the change (%) from the Eczema Area and Severity Index (EASI) baseline expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI), and (2) the Investigator’s Global Assessment (IGA) response and safety outcomes expressed as relative risk (RR) and 95% CI. <b><i>Results:</i></b> We included 14 RCTs published in 13 studies (3,822 patients). Treatment with JAK inhibitors significantly improved IGA response (RR 2.83, 95% CI 2.25–3.56, <i>p</i> &#x3c; 0.001) and EASI score (WMD –28.82, 95% CI –34.48 to −23.16, <i>p</i> &#x3c; 0.001). JAK inhibitor treatment achieved the largest improvement in both IGA response (RR 3.59, 95% CI 2.66–4.84, <i>p</i> &#x3c; 0.001) and EASI score (WMD –42.00, 95% CI –48.64 to −35.36, <i>p</i> &#x3c; 0.001) by week 4 of treatment. Topical JAK inhibitors were significantly more efficacious than oral inhibitors. Upadacitinib treatment for 4 weeks was most effective in reducing EASI score (WMD –53.92, 95% CI –69.26 to −38.58, <i>p</i> &#x3c; 0.001), while abrocitinib for 4 weeks led to the most effective IGA response (RR 5.47, 95% CI 2.74–10.93, <i>p</i> &#x3c; 0.001). There was no difference in the frequency of adverse events (AEs) leading to discontinuation; however, JAK inhibitors use, especially abrocitinib, led to a higher incidence of treatment-emergent AEs (RR 1.25, 95% CI 1.10–1.42, <i>p</i> = 0.001). <b><i>Conclusion:</i></b> Our results imply that JAK inhibitors are an effective and safe AD treatment. Nevertheless, further trials with longer duration and head-to-head comparisons of different JAK inhibitors are needed.


2017 ◽  
pp. 598-606 ◽  
Author(s):  
Rugheed Ghadban ◽  
Tariq Enezate ◽  
Jad Omran ◽  
Rajaa Almourani ◽  
Atul Singla ◽  
...  

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