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BACKGROUND AND OBJECTIVE: Systemic corticosteroids have a long history of use in the treatment of autoimmune and inflammatory diseases. Both efficacy and safety show large interindividual variability (IIV), suggesting that corticosteroids may have the potential for individualised dosing strategies to optimise therapy. This systematic review aims to provide an overview of current evidence on the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of systemic corticosteroids in patients with autoimmune and inflammatory diseases. METHODS: A systematic literature search was conducted in PubMed and Embase for PK/PD studies of systemic corticosteroids in autoimmune and inflammatory diseases in humans published until December 2023. Studies were scored from 1 to 5 according to criteria for the levels of evidence, as inspired by the Oxford Centre for Evidence-Based Medicine. RESULTS: Twelve studies (1981-2016) were included. The majority of these studies had a small sample size. The corticosteroids involved were prednisone, prednisolone, methylprednisolone and budesonide. Substantial IIV of corticosteroid PK was described in all studies. Evidence for a relationship between the PK of corticosteroids and efficacy was inconclusive and limited. However, there was some evidence for a relationship between the PK of prednisolone and the severity of Cushingoid features. CONCLUSION: There is insufficient evidence to draw firm conclusions on the potential associations between PK and clinical outcome of systemic corticosteroid treatment in autoimmune and inflammatory diseases. This is remarkable given the many decades that steroid drugs have been used in clinical care. Prospective research is recommended with robust and well-defined cohorts to fully quantify the PK/PD associations of corticosteroids.
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Background: Subjects with ankylosing spinal disorders, including diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS) are more prone to vertebral fractures and frequently present with neurological deficit compared to the patients without an ankylosed spine. Moreover, prevalent vertebral fractures are an important predictor for subsequent fracture risk. However, the pooled fracture prevalence for DISH is unknown and less recent for AS. We aimed to systematically investigate the prevalence and risk of vertebral fractures in DISH and AS populations. Methods: Publications in Medline and EMBASE were searched from January 1980 until July 2023 for cohort studies reporting vertebral fractures in AS and DISH. Data on prevalence were pooled with random effects modeling after double arcsine transformation. Heterogeneity was assessed with I2 statistics and we performed subgroup analysis and meta-regression to explore sources of heterogeneity. Results: We included 7 studies on DISH (n = 1,193, total fractures = 231) with a pooled vertebral fracture prevalence of 22.6% (95%CI: 13.4%-33.4%). For AS, 26 studies were included (n = 2,875, total fractures = 460) with a pooled vertebral fracture prevalence of 15.2% (95%CI: 11.6%-19.1%). In general, fracture prevalence for AS remained similar for several study-level and clinically relevant characteristics, including study design, diagnostic criteria, spine level, and patient characteristics in subgroup analysis. AS publications from 2010 to 2020 showed higher fracture prevalence compared to 1990 to 2010 (18.6% vs. 11.6%). Fractures in DISH were most common at the thoracolumbar junction, whereas for AS, the most common location was the mid-thoracic spine. Conclusions: Vertebral fractures are prevalent in AS and DISH populations. Differences in fracture distribution along the spinal axis exist between the 2 disorders. Additional longitudinal studies are needed for incident fracture assessment in patients with ankylosing spinal disorders.
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PURPOSE: Revisions for periprosthetic joint infection of knee and hip arthroplasty can be performed following one- or two-stage treatment protocols. Current literature is inconclusive whether one protocol is superior to the other, as prior literature reported similar reinfection rates for both treatment options. We aimed to provide a systematic review and meta-analysis of current literature on septic arthroplasty revisions. METHODS: Between April 2015 and December 2020, Medline, Embase, and The Cochrane Library were searched for studies reporting reinfection outcomes in patients treated with one-stage and two-stage knee or hip revision arthroplasty. Two reviewers independently extracted data and disagreements were resolved by a third investigator. We utilized a double arcsine transformation, prior to pooling using a random-effects model. RESULTS: For hip revision arthroplasty, we identified 14 one-stage studies (n = 1237) with a pooled reinfection rate of 5.7% (95% CI 3.7-8.1%), and 46 two-stage studies (n = 5009) with a reinfection rate of 8.4% (95% CI 6.9-9.9%). For knee revision arthroplasty, 6 one-stage studies (n = 527) and 48 two-stage studies (n = 4344) were identified with reinfection rates of 12.7% (7.0-19.7%) and 16.2% (13.7-19.0%), respectively. Overall, reinfection rates did not vary substantially after subgroup analysis. Limitations of our study are the limited amount of one-stage studies that introduce a potential bias. CONCLUSION: The reinfection rates following one- and two-stage hip and knee arthroplasty revisions were similar. Knee reinfection rates have increased compared to the previous analysis. Individual patient characteristics and adequate treatment algorithms are needed for a more individual selection approach, until a randomized trial is performed.