Abstract

BACKGROUND Edema is one of the cardinal clinical features of nephrotic syndrome (NS). It may vary from mild periorbital edema to severe generalized edema (anasarca). In patients where edema does not improve with prednisone therapy, the most common supportive medications are diuretics and albumin. However, due to the complex pathophysiology of edema formation in NS patients resulting in intravascular normovolemia or hypovolemia, optimal therapy for edema is still debated. We conducted a systematic review with the objective of evaluating the change in urine volume and urine sodium excretion after treatment with furosemide only versus furosemide with albumin in edematous patients with NS. OBJECTIVES (1) To evaluate efficacy of furosemide alone versus furosemide with albumin in the treatment of nephrotic edema in adults and children. (2) To compare the harms and benefits of different doses of furosemide for treating nephrotic edema. SEARCH METHODS The search included all randomized or quasi-randomized controlled trials in English and French using MEDLINE, Embase, and CENTRAL Trials Registry of the Cochrane Collaboration using the Ovid interface. ClinicalTrials.gov and the International Clinical Trials Registry Platform were also searched. SELECTION CRITERIA We included all RCTs and randomized cross-over studies in which furosemide and furosemide plus albumin are used in the treatment of children or adults with nephrotic edema. We excluded patients with hypoalbuminemia of non-renal origin and severe chronic kidney disease (CKD) with a glomerular filtration rate below 30 ml/min/1.74 m(2) and patients with congenital NS. DATA COLLECTION AND ANALYSIS All abstracts were independently assessed by at least two authors to determine which studies met the inclusion criteria. Information on study design, methodology, and outcome data (urine volume, urine sodium excretion, adverse effects) from each identified study was entered into a separate data sheet. The differences in outcomes between the types of therapy were expressed as standardized mean difference (SMD) with 95% confidence intervals (CI). RESULTS The search yielded 525 records, and after screening, five studies were included in the systematic review and four of those studies in the meta-analysis. One study had high risk of bias and the remaining three studies were deemed to have some concerns. Urine excretion was greater after treatment with furosemide and albumin versus furosemide (SMD 0.85, 95% CI = 0.33 to 1.38). Results for sodium excretion were inconclusive (SMD 0.37, 95%CI =  - 0.28 to 1.02). AUTHORS' CONCLUSIONS The current evidence is not sufficient to make definitive conclusions about the role of albumin in treating nephrotic edema. High-quality randomized studies with adequate samples sizes are needed. Including an assessment of intravascular volume status may be helpful. TRIAL REGISTRATION Prospero: CRD4201808979. https://www.crd.york.ac.uk/PROSPERO A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

Abstract

BACKGROUND Anaemia is a common sequela of advanced disease and is associated with significant symptom burden. No specific guidance exists for the investigation and management of anaemia in palliative care patients. AIM: We aim to offer a pragmatic overview of the approaches to investigate and manage anaemia in advanced disease, based on guidelines and evidence in disease specific patient groups, including cancer, heart failure and chronic kidney disease. DESIGN Scoping review methodology was used to determine the strength of evidence supporting the investigation and management of anaemia in patients with advanced disease. DATA SOURCES A search for guidelines was performed in 2020. National or international guidelines were examined if they described the investigation or management of anaemia in adult patients with health conditions seen by palliative care services written within the last 5 years in the English language. Searches of MEDLINE, the Cochrane library and WHO guidance were made in 2019 to identify key publications that provided additional primary data. RESULTS Evidence supports patient-centred investigation of anaemia, results of which should guide targeted intervention. Blanket use of blood transfusion should be avoided, with evidence supporting a more restrictive approach to transfusion. Routine use of oral iron and erythropoetin stimulating agents (ESAs) are not recommended. Insufficient evidence exists to determine the effectiveness of IV iron in this patient group. CONCLUSION We advocate early consideration and investigation of anaemia, guided by symptom burden and patient preferences. Correction of reversible causes should be the mainstay of treatment, with a restrictive approach to blood transfusion. Research is required to evaluate the efficacy of IV iron in these patients.

Abstract

OBJECTIVE The aim of this systematic scoping review is to identify and categorize the outcome measures that have been reported in clinical studies, where therapeutic plasma exchange (TPE) has been used as an intervention in any clinical settings, excluding thrombotic thrombocytopenic purpura (TTP). METHODS We searched electronic databases using a predefined search strategy from inception to October 9, 2020. Two reviewers independently screened and extracted data. RESULTS We included 42 studies (37 RCTs and 5 prospective cohort studies) grouped into six main categories (neurology, immunology, renal, rheumatology, hematology, and dermatology). Primary outcomes were defined in eight studies (19%, 8/42) and were categorized as efficacy (five studies) or patient reported outcomes (three studies). A power calculation was reported in six studies (75%, 6/8): five neurology studies (mainly patient reported outcomes) and a single immunological study (efficacy outcome). Disease-specific efficacy outcomes were dependent on the clinical setting of the population receiving TPE. Most of the trials (43%, 18/42) were undertaken in patients with neurology conditions where clear, disease-specific, clinical outcome measures were used, including neurological disability scales (11/18, 61%), change in neurological examination (9/18, 50%), and functional improvement scores (7/18, 39%). For other conditions, the reporting of disease-specific outcomes was poorly reported. Safety outcomes were mainly related to replacement fluid type rather than being disease-specific. The most common outcome reported was hypotension (19%, 8/42), and this was primarily in patients exchanged with albumin. CONCLUSION Future clinical studies to determine which fluid replacement option is most efficacious and safe should use disease-specific outcomes, as a trial in one therapeutic area may not necessarily translate to another therapeutic area. Patient reported outcomes are not universally reported for all disease areas. Safety measures focused primarily on fluid safety.

Abstract

BACKGROUND Although the current consensus recommends a standard treatment of high-dose intravenous immunoglobulin with high-dose aspirin to manage Kawasaki disease (KD), the use of different adjunctive therapies remains controversial. The aim of the current network meta-analysis (NMA) was to compare the efficacy and tolerability of different existing interventions for the initial and refractory stages of KD. METHODS An NMA of randomised controlled trials (RCTs) was conducted using the frequentist model applied after electronic searches in PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov, ClinicalKey, Cochrane CENTRAL, and Web of Science. The main outcomes were reduced fever duration/diminished severity of fever subsided. The initial stage of KD was defined as the first stage to treat patients with KD; the refractory stage of KD represents KD patients who failed to respond to standard KD treatment. The cut-off points for intravenous immunoglobulin (IVIG) were low (100-400 mg), medium (1 g), and high (at least 2 g). FINDINGS A total of fifty-six RCTs with 6486 participants were included. NMA demonstrated that the medium-dosage IVIG + aspirin + infliximab [mean difference=-1.76 days (95% confidence intervals (95% CIs): -3.65 to 0.13 days) compared to high-dosage IVIG + aspirin] exhibited the shortest fever duration; likewise, the medium-dosage IVIG + aspirin + infliximab [odds ratio (OR)=0.50, 95% CIs: 0.18-1.37 compared to high-dosage IVIG + aspirin] exhibited the smallest incidence of coronary artery lesion (CAL) in the initial-stage KD. In the refractory-stage KD, the high-dosage IVIG + pulse steroid therapy (OR=0.04, 95% CIs: 0.00-0.43 compared to the high-dosage IVIG only) had the best rate of decline of fever; likewise, the high-dosage IVIG + ciclosporin [OR=0.05 (95% CIs: 0.00-1.21) compared to the high-dosage IVIG only] exhibited the smallest incidence of CAL. Infliximab significantly improved resolution compared to the high-dosage IVIG only group (OR=0.20, 95%CIs: 0.07-0.62) in refractory-stage KD. INTERPRETATION The NMA demonstrated that the combination therapy with the standard therapy of IVIG and aspirin might have an additional effect on shortening the duration of fever and lowering the CAL incidence rate in patients with acute KD. Moreover, the combination therapy with high-dose IVIG and pulse steroid therapy or cyclosporine therapy might have an additional effect on improving the rate of decline of fever and lowering the incidence rate of CAL in children with refractory KD. Because some of the findings of this NMA should be considered hypothesis-generating rather than confirmatory, further evidence from de novo randomised trials is needed to support our results. FUNDING None.

Abstract

BACKGROUND Immunotherapy has been shown to reduce relapses in patients with myelin oligodendrocyte glycoprotein antibody-associated disorder (MOG-AD); however, the superiority of specific treatments remains unclear. AIM: To identify the efficacy and tolerability of different treatments for MOG-AD. METHODS Systematic search in Pubmed, Embase, Web of Science, and Cochrane Library databases from inception to March 1, 2021, were performed. Published articles including patients with MOG-AD and reporting the efficacy or tolerability of two or more types of treatment in preventing relapses were included. Reported outcomes including incidence of relapse, annualized relapse rate (ARR), and side effects were extracted. Network meta-analysis with a random-effect model within a Bayesian framework was conducted. Between group comparisons were estimated using Odds ratio (OR) or mean difference (MD) with 95% credible intervals (CrI). RESULTS Twelve studies that compared the efficacy of 10 different treatments in preventing MOG-AD relapse, including 735 patients, were analyzed. In terms of incidence of relapse, intravenous immunoglobulins (IVIG), oral corticosteroids (OC), mycophenolate mofetil (MMF), azathioprine (AZA), and rituximab (RTX) were all significantly more effective than no treatment (ORs ranged from 0.075 to 0.34). On the contrary, disease-modifying therapy (DMT) (OR=1.3, 95% CrI: 0.31 to 5.0) and tacrolimus (TAC) (OR=5.9, 95% CrI: 0.19 to 310) would increase the incidence of relapse. Compared with DMT, IVIG significantly reduced the ARR (MD=-0.85, 95% CrI: -1.7 to -0.098). AZA, MMF, OC and RTX showed a trend to decrease ARR, but those results did not reach significant differences. The combined results for relapse rate and adverse events, as well as ARR and adverse events showed that IVIG and OC were the most effective and tolerable therapies. CONCLUSIONS Whilst DMT should be avoided, IVIG and OC may be suited as first-line therapies for patients with MOG-AD. RTX, MMF, and AZA present suitable alternatives.

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

BACKGROUND Kawasaki disease (KD), or mucocutaneous syndrome, is the leading cause of childhood-acquired heart disease in high-income countries. There is much controversy on how best to treat children with KD and in particular who may benefit from additional treatment beyond the standard intravenous immunoglobulin (IVIG) and aspirin, such as the addition of corticosteroids. This is an update of the review first published in 2017. OBJECTIVES To assess the impact of corticosteroid use on the incidence of coronary artery abnormalities in KD as either first-line or second-line treatment. SEARCH METHODS The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and two trials registers to 8 February 2021. We searched the reference lists of relevant articles for additional studies. SELECTION CRITERIA We selected randomised controlled trials involving children with all severities of KD who were treated with corticosteroids, including different types of corticosteroids, different durations of treatment, and where corticosteroids were used alone or in conjunction with other accepted KD treatments. We included trials using corticosteroids for both first- and second-line treatment. DATA COLLECTION AND ANALYSIS Two review authors independently selected studies, assessed study quality and extracted data using standard Cochrane methods. We performed fixed-effect model meta-analyses with odds ratios (ORs) or mean difference (MD) with 95% confidence intervals (CIs). We used a random-effects model when there was heterogeneity. We assessed the certainty of the evidence using GRADE. The outcomes of interest were incidence of coronary artery abnormalities, serious adverse events, mortality, duration of acute symptoms (such as fever), time for laboratory parameters to normalise, length of hospital stay and longer-term coronary morbidity. MAIN RESULTS This update identified one new study, therefore the analysis included eight trials consisting of 1877 participants. Seven trials investigated the use of corticosteroids in first-line treatment and one investigated second-line treatment. The trials were all of good methodological quality. On pooled analysis, corticosteroid treatment reduced the subsequent occurrence of coronary artery abnormalities (OR 0.32, 95% CI 0.14 to 0.75; 8 studies, 986 participants; moderate-certainty evidence), without resultant serious adverse events (0 events; 6 studies, 737 participants; moderate-certainty) and mortality (0 events; 8 studies, 1075 participants; moderate-certainty evidence). In addition, corticosteroids reduced the duration of fever (MD -1.34 days, 95% CI -2.24 to -0.45; 3 studies, 290 participants; low-certainty evidence), time for laboratory parameters (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) to normalise (MD -2.80 days, 95% CI -4.38 to -1.22; 1 study, 178 participants; moderate-certainty evidence), and length of hospital stay (MD -1.01 days, 95% CI -1.72 to -0.30; 2 studies, 119 participants; moderate-certainty evidence). None of the included studies reported long-term (greater than one year after disease onset) coronary morbidity. AUTHORS' CONCLUSIONS Moderate-certainty evidence shows that use of steroids in the acute phase of KD can be associated with reduced coronary artery abnormalities, reduced inflammatory markers and shorter duration of hospital stay when compared to no corticosteroids. There were no serious adverse events or deaths reported with or without corticosteroid use. Low-certainty evidence shows use of corticosteroids can reduce duration of clinical symptoms (fever and rash). None of the included studies reported on long-term (greater than one year after disease onset) coronary morbidity. Evidence presented in this systematic review agrees with current clinical guidelines on the use of corticosteroids in the first-line treatment in KD.

Abstract

Background: Recently, there was a series of clinical studies focusing on local injection of platelet-rich plasma (PRP) for treatment of patients with carpal tunnel syndrome (CTS). However, the safety and efficacy of PRP in these CTS patients remains controversial. Therefore, we performed a systematic review to compare PRP with other conservative treatments in treatment of CTS patients. Methods: We systematically searched from electronic databases (Cochrane, PubMed, Web of Science, and EMBASE) up to 10 December 2021. The data of clinical results were extracted and analyzed by RevMan Manager 5.4. Results: Finally, eight randomized controlled studies, involving 220 CTS patients undergoing local injection of PRP were enrolled in this systematic review. All enrolled trials were considered to be of high quality. In the short-term efficacy, the PRP group was significantly lower in symptom severity scale (SSS) compared with the control group (MD = -2.00; 95% CI, -3.15 to -0.85; p = 0.0007; I(2) = 0%). In the mid-term efficacy, the PRP group was significantly effective than the control group in the visual analogue scale (MD = -0.63; 95% CI, -1.22 to -0.04; p = 0.04; I(2) = 61%), SSS (MD = -3.56; 95% CI, -4.93 to -2.18; p < 0.00001; I(2) = 0%), functional status scale (MD = -2.29; 95% CI, -3.03 to -1.56; p < 0.00001; I(2) = 45%), sensory peak latency (MD = -0.39; 95% CI, -0.58 to -0.19; p = 0.0001; I(2) = 0%) and cross-sectional area of median nerve (MD = -0.20; 95% CI, -0.31 to -0.10; p = 0.0002; I(2) = 0%). In the mid-long-term efficacy, the PRP group was only significantly lower in SSS compared with the control group (MD = -2.71; 95% CI, -4.33 to -1.10; p = 0.001; I(2) = 38%). Conclusion: Local PRP injection is more effective than other conservative treatments in terms of mid-term efficacy in relieving pain, improving wrist function and symptoms, reducing MN swelling, and partially improving electrophysiological indicators. However, the long-term adverse side and consensus on standardization of PRP in CTS patients still need further large-scale trials.

Abstract

Tennis elbow (TE) is a painful and debilitating condition of the elbow. Recently, the use of orthobiologics, such as platelet-rich-plasma (PRP), has been proposed to promote tendon regeneration. Despite their popularity, there is a paucity of updated reviews on the use of PRP compared with other treatment modalities for treating TE. The aim of this review is to summarise high quality studies that compare the use of PRP therapy with other therapies for TE and to identify areas where further research is warranted. This systematic review was performed in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A comprehensive literature search of PubMed, Scopus and Cochrane Library databases was undertaken in May 2021. Articles were screened for the following criteria: randomised control trials (RCTs) involving PRP in at least one of the treatment arms for tennis elbow. The quality of the RCTs included were analysed for their risk of bias using the modified Cochrane Collaboration Risk of Bias Assessment Tool for randomised trials. A total of 20 RCTs of which 1520 TE patients were analysed. The RCTs included in this review compared PRP with various treatment modalities routinely used in clinical practice such as physiotherapy, steroid injections, Autologous Whole Blood (AWB) and surgical interventions. With regards to the quality of RCTs, collectively, selection bias was found to be low risk however, performance bias in terms of blinding of participants and personnel performed poorly. Of the 20 RCTs, only 5 studies were classified as low risk of bias. In these 5 studies, 2 RCTs compared PRP with steroids and reported contrasting results, 1 RCT compared PRP with AWB injections which reported both to be similarly efficacious, 3 RCTs included a placebo group and only 1 reported superior effects with PRP. There are 2 main types of PRP classified according to the number of pro-inflammatory leukocyte i.e. leukocyte-rich and leukocyte-poor PRP. However, only 8 studies documented the formulation of PRP used. While the heterogeneity of PRP formulations could in-part explain the reported differences in outcomes, overall there is limited robust evidence to recommend PRP therapy for TE. Further research is required to establish the optimal formulation and administration of PRP injections. Proper documentation of TE patients need to be standardised before concrete recommendations on the use of PRP therapy may be offered.