Abstract

Background: Many studies demonstrated that roxadustat (FG-4592) could increase hemoglobin (Hb) levels effectively in anemia patients with chronic kidney disease (CKD). However, its safety remains controversial. This study aims to explore the risk of infection for CKD patients treated with roxadustat, especially focused on sepsis. Methods: We thoroughly searched for the randomized controlled trials (RCTs) comparing treatment with roxadustat versus erythropoiesis stimulating agents (ESAs) or placebo in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, European Union Clinical Trials Register. Both on and not on dialysis anemia patients with CKD were included. Primary outcomes contained the incidence rates of sepsis. Secondary outcomes included infection-related consequences (septic shock and other infection events), general safety outcomes [all-cause mortality, treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)] and iron parameters. Moreover, a trial sequential analysis (TSA) was conducted to assess if the results were supposed to be a robust conclusion. Results: Eighteen RCTs (n = 11,305) were included. Overall, the incidence of sepsis (RR: 2.42, 95% CI [1.50, 3.89], p = 0.0003) and cellulitis (RR: 2.07, 95% CI [1.24, 3.44], p = 0.005) were increased in the roxadustat group compared with placebo group. In non-dialysis-dependent (NDD) CKD patients, the incidence of cellulitis (RR 2.01, 95% CI [1.23, 3.28], p = 0.005) was significantly higher in roxadustat group than that in the ESAs or placebo group. Both groups showed similar results in the incidence of septic shock (RR 1.29, 95% CI [0.86, 1.94], p = 0.22). A significant increased risk of all-cause mortality [risk ratios (RR): 1.15, 95% confidence interval (CI) [1.05, 1.26], p = 0.002] was found in roxadustat treatment, and TSA confirmed the result. Compared with ESAs or placebo, both the incident rates of TEAEs (RR:1.03, 95% CI [1.01, 1.04], p = 0.008) and TESAEs (RR: 1.06, 95% CI [1.02, 1.11], p = 0.002) were significantly increased in roxadustat group. As for iron parameters, changes from baseline (Δ) of hepcidin (MD: -26.46, 95% CI [-39.83, -13.09], p = 0.0001), Δ ferritin and Δ TSAT were remarkably lower in the roxadustat group, while Δ Hb, Δ iron and Δ TIBC increased significantly versus those in ESAs or placebo group. Conclusion: We found evidence that incidence rates of sepsis and cellulitis are higher in roxadustat group compared with placebo. This may be the result of improved iron homeostasis. The risk of all-cause mortality, TEAEs and TESAEs in CKD patients also increased in patients treated with roxadustat. We need more clinical and mechanistic studies to confirm whether roxadustat really causes infection.

Abstract

OBJECTIVE To compare the short-term effectiveness of corticosteroids, 5% dextrose(D5W), and platelet-rich plasma (PRP) injections for treating carpal tunnel syndrome (CTS). DATA SOURCES Four databases (MEDLINE (PubMed), Embase, the Cochrane Controlled Trials Register, and Web of Science (WOS)) were researched from inception to the 1st of April 2022. STUDY SELECTION Two authors independently screened the literature to identify the RCTs meeting the included criteria, which involved comparing corticosteroid, 5% dextrose water (D5W), and platelet-rich plasma (PRP) injection with each other or placebo-controlled for treating CTS. DATA EXTRACTION The two reviewers independently conducted information extraction, the outcomes included were the changes in Symptom Severity Scale (SSS), Function Status Scale (FSS), and Visual Analogue Scale (VAS) at short-term follow-up after drug injection treatment and any adverse events reported. DATA SYNTHESIS Twelve randomized controlled trials with 749patients (817 hands) were included. The results of this study suggested that PRP injection was the most likely to relieve symptoms, improve functions and alleviate pain, with the SUCRA being 91.5%, 92.7%, and 80.8%, respectively, followed by D5W injection (74.4%, 72.2%, 72.1%), and corticosteroid injection (33.7%, 31.9%, 46.2%). The injection of three drugs was significantly better than that of a placebo. CONCLUSION From the results of the network meta-analysis, PRP injection is the most recommended treatment among the injection of corticosteroid, D5W, and PRP. The protocol of this network meta-analysis has been registered in PROSPERO with registration number CRD42022325228.

Abstract

Iron deficiency (ID) is a common co-morbidity in patients with heart failure (HF). The present meta-analysis evaluates the effect of intravenous (IV) iron-carbohydrate complex supplementation in patients with HF with reduced ejection fraction (HFrEF) and ID/iron deficiency anaemia (IDA). Randomized controlled trials (RCTs) comparing IV iron-carbohydrate complexes with placebo/standard of care in patients with HFrEF with ID/IDA were identified using Embase (from 1957) and PubMed (from 1989) databases through 25 May 2021. Twelve RCTs including 2381 patients were included in this analysis. The majority (90.8%) of patients receiving IV iron-carbohydrate therapy were administered ferric carboxymaltose (FCM); 7.5% received iron sucrose and 1.6% received iron isomaltoside. IV iron-carbohydrate therapy significantly reduced hospitalization for worsening HF [0.53 (0.42-0.65); P < 0.0001] and first hospitalization for worsening HF or death [0.75 (0.59-0.95); P = 0.016], but did not significantly impact all-cause mortality, compared with control. IV iron-carbohydrate therapy significantly improved functional and exercise capacity compared with the control. There was no significant difference in outcome between IV iron-carbohydrate formulations when similar endpoints were measured. No significant difference in adverse events (AE) was observed between the treatment groups. IV iron-carbohydrate therapy resulted in improvements in a range of clinical outcomes and increased functional and exercise capacity, whereas AEs were not significantly different between IV iron-carbohydrate and placebo/standard of care arms. These findings align with the European Society of Cardiology's 2021 HF guidelines, which recommend the consideration of FCM in symptomatic patients with a left ventricular ejection fraction < 45% and ID.

Abstract

BACKGROUND Platelet-rich plasma (PRP) is reported as an effective treatment for lateral epicondylitis (LE). Theoretically, different types of PRP have different therapeutic effects. However, there is controversy on the effects of different types of PRP in the treatment of LE. PURPOSE To systematically compare the pain relief, functional improvement and successful rates on treatment of two different types of PRP, by reviewing and summarizing the data available in the current literature on LE after PRP injection. METHODS The PubMed, Medline, Embase, Cochrane Library and Web of science were reviewed. A computerized literature search was performed for related studies published from inception to August 2021 by terms of lateral epicondylitis, tennis elbow, tendinopathy, lateral elbow pain, PRP. PRP involved in present study were divided into leukocyte-poor PRP and leukocyte-rich PRP groups according to different preparation methods. Outcomes of interest included characteristics of the subjects, types and preparations of PRP, clinical outcomes, successful rate and safety of treatment of short-term and long-term follow-up. RESULTS A total of 33 studies included 2420 LE patients. There were 19 studies with LP-PRP, 13 studies with LR-PRP and 1 study involved both LP-PRP and LR-PRP. Patients had significant improved clinical outcomes post-treatment compared to pre-treatment in both groups of PRP. The mean of VAS was ranged from 6.1 to 8.0 before the treatment, 1.5 to 4.0 at short-term and 0.6 to 3.3 at the long-term follow-up in LR-PRP group. The mean of VAS was ranged from 4.2 to 8.4 before the treatment, 1.6 to 5.9 at short-term and 0.7 to 2.7 in the long-term follow-up in LP-PRP group. The DASH score of LR-PRP and LP-PRP were ranged from 47.0 to 54.3 and 30.0 to 67.7 separately before the treatment and 20.0 to 22.0 and 5.5 to 19.0 separately at long-term follow-up. LR-PRP and LP-PRP groups reflected successful rate ranged from 70%-100% and 36%-100% respectively. The complication rate lower in LP-PRP group (3.9%) than LR-PRP group (6.4%), with the major complication was temporary pain after PRP treatment (P = 0.029). CONCLUSION PRP treatment demonstrated a significant improvement with pain relief and functional improvement on lateral epicondylitis regardless types of PRP. There was no significant difference between LR-PRP and LP-PRP in pain relief and functional improvement. The major complication was temporary pain after PRP injection and the complication rate in LP-PRP was lower than LR-PRP.

Abstract

BACKGROUND Multifocal motor neuropathy (MMN) is a rare, probably immune-mediated disorder characterised by slowly progressive, asymmetric, distal weakness of one or more limbs with no objective loss of sensation. It may cause prolonged periods of disability. Treatment options for MMN are few. People with MMN do not usually respond to steroids or plasma exchange. Uncontrolled studies have suggested a beneficial effect of intravenous immunoglobulin (IVIg). This is an update of a Cochrane Review first published in 2005, with an amendment in 2007. We updated the review to incorporate new evidence. OBJECTIVES To assess the efficacy and safety of intravenous and subcutaneous immunoglobulin in people with MMN. SEARCH METHODS We searched the following databases on 20 April 2021: the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP for randomised controlled trials (RCTs) and quasi-RCTs, and checked the reference lists of included studies. SELECTION CRITERIA We considered RCTs and quasi-RCTs examining the effects of any dose of IVIg and subcutaneous immunoglobulin (SCIg) in people with definite or probable MMN for inclusion in the review. Eligible studies had to have measured at least one of the following outcomes: disability, muscle strength, or electrophysiological conduction block. We used studies that reported the frequency of adverse effects to assess safety. DATA COLLECTION AND ANALYSIS Two review authors independently reviewed the literature searches to identify potentially relevant trials, assessed risk of bias of included studies, and extracted data. We followed standard Cochrane methodology. MAIN RESULTS Six cross-over RCTs including a total of 90 participants were suitable for inclusion in the review. Five RCTs compared IVIg to placebo, and one compared IVIg to SCIg. Four of the trials comparing IVIg versus placebo involved IVIg-naive participants (induction treatment). In the other two trials, participants were known IVIg responders receiving maintencance IVIg at baseline and were then randomised to maintenance treatment with IVIg or placebo in one trial, and IVIg or SCIg in the other. Risk of bias was variable in the included studies, with three studies at high risk of bias in at least one risk of bias domain. IVIg versus placebo (induction treatment): three RCTs including IVIg-naive participants reported a disability measure. Disability improved in seven out of 18 (39%) participants after IVIg treatment and in two out of 18 (11%) participants after placebo (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.89 to 10.12; 3 RCTs, 18 participants; low-certainty evidence). The proportion of participants with an improvement in disability at 12 months was not reported. Strength improved in 21 out of 27 (78%) IVIg-naive participants treated with IVIg and one out of 27 (4%) participants who received placebo (RR 11.00, 95% CI 2.86 to 42.25; 3 RCTs, 27 participants; low-certainty evidence). IVIg treatment may increase the proportion of people with resolution of at least one conduction block; however, the results were also consistent with no effect (RR 7.00, 95% CI 0.95 to 51.70; 4 RCTs, 28 participants; low-certainty evidence). IVIg versus placebo (maintenance treatment): a trial that included participants on maintenance IVIg treatment reported an increase in disability in 17 out of 42 (40%) people switching to placebo and seven out of 42 (17%) remaining on IVIg (RR 2.43, 95% CI 1.13 to 5.24; 1 RCT, 42 participants; moderate-certainty evidence) and a decrease in grip strength in 20 out of 42 (48%) participants after a switch to placebo treatment compared to four out of 42 (10%) remaining on IVIg (RR 0.20, 95% CI 0.07 to 0.54; 1 RCT, 42 participants; moderate-certainty evidence). Adverse events, IVIg versus placebo (induction or maintenance): four trials comparing IVIg and placebo reported adverse events, of which data from two studies could be meta-analysed. Transient side effects were reported in 71% of IVIg-treated participants versus 4.8% of placebo-treated participants in these studies. The pooled RR for the development of side effects was 10.33 (95% CI 2.15 to 49.77; 2 RCTs, 21 participants; very low-certainty evidence). There was only one serious side effect (pulmonary embolism) during IVIg treatment. IVIg versus SCIg (maintenance treatment): the trial that compared continuation of IVIg maintenance versus SCIg maintenance did not measure disability. The evidence was very uncertain for muscle strength (standardised mean difference 0.08, 95% CI -0.84 to 1.00; 1 RCT, 9 participants; very low-certainty evidence). The evidence was very uncertain for the number of people with side effects attributable to treatment (RR 0.50, 95% CI 0.18 to 1.40; 1 RCT, 9 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS Low-certainty evidence from three small RCTs shows that IVIg may improve muscle strength in people with MMN, and low-certainty evidence indicates that it may improve disability; the estimate of the magnitude of improvement of disability has wide CIs and needs further studies to secure its significance. Based on moderate-certainty evidence, it is probable that most IVIg responders deteriorate in disability and muscle strength after IVIg withdrawal. SCIg might be an alternative treatment to IVIg, but the evidence is very uncertain. More research is needed to identify people in whom IVIg withdrawal is possible and to confirm efficacy of SCIg as an alternative maintenance treatment.

Abstract

AIM: Infliximab is a tumor necrosis factor-alpha inhibitor that is being used to treat children with refractory Kawasaki disease. Our purpose was to evaluate the safety and the impact of infliximab versus intravenous immunoglobulins on the incidence of coronary artery aneurysms (CAAs) and treatment resistance in children with refractory Kawasaki disease (KD). METHODS The Medline/PubMed, Embase, CINAHL, Cochrane Central Register of Controlled Trials and clinical trials registries were searched to December 2021. Randomized controlled trials (RCTs) comparing infliximab as second-line therapy to a second dose of intravenous immunoglobulin (IVIG) in children with refractory KD, reported in abstract or full text were included. Studies were selected and assessed for risk of bias by two reviewers. Data were extracted and pooled using conventional random-effects meta-analysis. The certainty of evidence was assessed using the GRADE system. RESULTS A total of 199 participants from 4 RCTs were included. Pooled risk ratio (RR) for the incidence of treatment resistance in patients treated with infliximab was RR=0.40 (95% CI 0.25-0.64). For incidence of CAAs RR was 1.20 (95% CI 0.54-2.63), the incidence of adverse effect 'infusion reactions' RR=0.48, (95% CI 0.12-1.92), and 'infections' RR=0.55 (95% CI 0.27-1.12). Overall, the GRADE strength of evidence for the primary outcomes was low. Evidence on the duration of fever and inflammatory biomarkers was sparse, heterogeneous, and inconclusive. CONCLUSION Moderate-certainty evidence indicates that infliximab may reduce the incidence of treatment resistance in children with refractory KD. However, the limited strength of evidence warrants further research.

Abstract

BACKGROUND Therapeutic apheresis has been used in treating hematological and non-hematological diseases. For a successful procedure, efficient vascular access is required. Presently, peripheral venous access (PVA), central venous catheterization (CVC), implantable ports, and arteriovenous fistulas (AVFs) are used. This review aims to evaluate different type of access and their pros and cons to help physicians determine the best venous access. METHODS The electronic search included PubMed and Google Scholar up to Nov. 2020. The Mesh terms were apheresis, peripheral catheterization, central catheterization, and arteriovenous fistula. RESULTS A total of 228 studies were found through database searching. Two independent authors reviewed the articles using their titles and abstracts; 88 articles were selected and the full text was reviewed. Finally, 25 were included. The inclusion criteria were studies incorporating patients with any indication for apheresis. CONCLUSION PVA has been promoted in recent years in many centers across the United States to lower the rate of complications associated with vascular access and to make this procedure more accessible. Several factors are involved in selecting appropriate venous access, such as the procedure's duration and frequency, patient's vascular anatomy, and staff's experience. In short-term procedures, temporary vascular access like PVA or CVC is preferred. Permanent vascular access such as AVF, tunneled cuffed central lines, and implantable ports are more beneficial in prolonged treatment period but each patient has to be evaluated individually by apheresis team for the most appropriate method.

Abstract

OBJECTIVES To evaluate the efficacy and safety of intravenous immunoglobulin (IVIG) in the treatment of dermatomyositis (DM) and polymyositis (PM). METHODS A comprehensive systematic review was conducted in accordance with the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews And Meta-analyses). PubMed, Embase, and China National Knowledge Infrastructure (CNKI) were searched to find articles published between July 1919 and May 2021 concerning IVIG therapy in PM/DM. We analyzed continuum data through mean difference and the estimated pooled improvement rate through Log transformation. We calculated all the effect measures with a 95% confidence interval. The I²statistic was calculated to assess statistical heterogeneity across the studies. I²values of 25%, 50% and 75% were defined as low, moderate and high, respectively. All analyses were conducted using R Studio, Version 3.6.3. RESULTS Seventeen papers pertinent to our questions were found: three case-control studies, fourteen non-randomized studies. We evaluated the efficacy of IVIG in DM/PM by the indicators of creatine kinase (CK), Manual Muscle Test (MMT) scores, Medical Research Council (MRC) scale, the Activities of Daily Living (ADL) scale and the pooled improvement rate. In a meta-analysis, we found that IVIG significantly improved the level of CK (SMD -0.69, 95%CI -0.93, -0.46; P<0.0001), MMT (SMD 1.12; 95%CI 0.77, 1.47; P<0.00001), MRC (SMD 1.59; 95%CI 0.86, 2.33; P<0.00001), ADL (SMD 1.07; 95%CI 0.59, 1.56; P<0.0001). The CK levels in DM and PM were also significantly improved after IVIG (SMD = -0.73, 95%CI -1.12, -0.34; P=0.0002; and SMD = -3.29, 95%CI -5.82, -0.76; P < 0.0001, respectively). The meta-analysis of three RCTs showed that there was a statistically significant improvement after IVIG (SMD 0.63; 95%CI 0.22, 1.03; P=0.002). In a random effects model pooled muscle power improvement rate was 77% (95% CI: 66.0-87.0%). Meta-analyses of IVIG as first-line therapy showed a significant improvement of CK level (SMD -0.71; 95%CI -1.12, -0.30; P=0.0007). In three studies, the polled improvement rate of esophageal disorders was 88% (95% CI: 80.0-95.0%). There was no statistically significant difference in the rate of improvement between the number of courses < 2 and ≥ 2 (0.80 vs. 0.80 %, P = 0.9). The corticosteroid-sparing effect of IVIG was also well demonstrated, with the proportion of corticosteroid-sparing success reaching 81.8% (72/88). Adverse reactions included headache, fever, Hypotension and dizzy and so on. Mild cortical stroke, staphylococcal septicaemia, asymptomatic myocardial infarction, cerebral infarction, deep vein thrombosis and subendocardial ischemia as severe adverse events were found in seven cases. CONCLUSION IVIG seems to be an effective drug for DM\PM, improving muscle strength, CK levels and esophageal involvement, and it is well tolerated by patients.

Abstract

INTRODUCTION AND HYPOTHESIS Articles are getting published on the use of tissue adhesive for vesicovaginal fistula. The objective is to carry out a systematic review on their effectiveness and complications. METHODS A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Two reviewers screened abstracts and full-text and extracted data independently. A narrative synthesis was conducted given the heterogeneity of studies. RESULTS A total of 1032 studies were identified after searching the database, and 14 articles were included in this systematic review. Of the 84 women included, 12 (14.3%) presented failure or recurrence of their fistula tract. The mean time of follow-up was 11.46 months. The average size of the fistula was 1.05 (range 0.1 to 3.9) cm. Most fistulas (81) included were vesicovaginal fistulas. Nine papers reported the usage of fibrin glue in which only three (6.5%) women reported recurrence of the fistula in a delay of 2 weeks to 26 months. The other studies used cyanoacrylate (14 women) and autologous fibrin injection from the patients' blood (31 women). No significant complications were reported. Complications reported were urinary tract infections in 3 women (3.6%), hematuria in 2 women (2.4%), overactive bladder symptoms in 6 women (7.2%) and septic pelvic thrombosis in one woman (1.2%). CONCLUSIONS Tissue adhesive appears to be a promising alternative for management of urogenital fistulas without reported important complications.

Abstract

PURPOSE Platelet-rich plasma (PRP) represents a highly profitable biological therapy. Platelet-rich plasma is widely used to treat musculoskeletal disorders despite mixed evidence of its efficacy. As evidenced by literature from other domains, industry funding may influence the results of clinical trials. The objective of the current study was to determine the association between industry funding and positive results for randomized controlled trials (RCTs) assessing the efficacy of PRP in musculoskeletal disorders. METHODS A search of four databases was conducted. Included studies were RCTs comparing PRP to any non-PRP comparator in adults (18 years old or over) with musculoskeletal disorders and had full text available in English. Studies were excluded if they were published before 2016 or were non-human trials. A multivariate binomial logistic regression model was created to explore predictors of statistically significant findings. Covariates included the presence of industry funding, sample size, and length of study follow-up. 1440 records were screened with 87 trials included in the final analysis. RESULTS Of the 87 studies, 61 (70%) reported a statistically significant primary outcome. The presence of industry funding was not predictive of a statistically significant primary outcome [OR = 0.36, 95% CI 0.096-1.36, (n.s.)]. Studies that did not state whether industry funding was present had a higher chance of reporting a statistically significant primary outcome (OR = 3.61, 95% CI 1.1-11.9, p = 0.035). Sample size and length of follow-up were not predictive of a statistically significant primary outcome. CONCLUSION The results of the current study conclude that industry funding had no impact on the reporting of positive results for RCTs investigating PRP in musculoskeletal disorders. However, not disclosing sources of funding was associated with a higher likelihood of reporting positive results. The results of trials that fail to disclose funding sources should be interpreted with caution in the PRP literature. LEVEL OF EVIDENCE I.