Abstract

BACKGROUND There is no clear consensus regarding the optimal approach for secondary prophylaxis of gastric variceal bleeding (GVB) in patients with cirrhosis. We conducted a systematic review and network metanalysis (NMA) to compare the efficacy of available treatments. METHODS A comprehensive search of several databases from each database's inception to March 23rd, 2021 was conducted to identify relevant randomized controlled trials (RCTs). Outcomes of interest were rebleeding and mortality. Results were expressed as relative risk (RR) and 95% confidence interval (CI). We followed the Grading of Recommendations Assessment, Development, and Evaluation approach to rate the certainty of evidence. RESULTS We included 9 RCTs with 579 patients, who had history of GVB and follow-up > 6 weeks. Nine interventions were included in the NMA. Balloon-occluded retrograde transvenous obliteration (BRTO) was associated with a lower risk of rebleeding when compared to beta-blockers (RR 0.04, 95%CI 0.01-0.26; low certainty), endoscopic injection sclerotherapy (EIS-CYA) (RR 0.18, 95%CI 0.04-0.77; low certainty). Beta-blockers were associated with a higher risk of rebleeding compared to most interventions and with increased mortality compared to EIS-CYA (RR 4.85, 95%CI 1.04-22.67; low certainty) and EIS-CYA+BB (RR 5.47, 95% CI 1.07-28.01; low certainty). CONCLUSION Analysis based on indirect comparisons suggests that BRTO may be the best intervention in preventing rebleeding whereas beta-blocker monotherapy is likely the worst in preventing rebleeding and mortality. Head-to-head RCTs are needed to validate these results.

Abstract

OBJECTIVE To evaluate the effectiveness and adverse events of autologous platelet-rich plasma (PRP) in individuals with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers. PATIENTS AND METHODS We searched multiple databases from database inception to June 11, 2020, for randomized controlled trials and observational studies that compared PRP to any other wound care without PRP in adults with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers. RESULTS We included 20 randomized controlled trials and five observational studies. Compared with management without PRP, PRP therapy significantly increased complete wound closure in lower-extremity diabetic ulcers (relative risk, 1.20; 95% CI, 1.09 to 1.32, moderate strength of evidence [SOE]), shortened time to complete wound closure, and reduced wound area and depth (low SOE). No significant changes were found in terms of wound infection, amputation, wound recurrence, or hospitalization. In patients with lower-extremity venous ulcers or pressure ulcers, the SOE was insufficient to estimate an effect on critical outcomes, such as complete wound closure or time to complete wound closure. There was no statistically significant difference in adverse events. CONCLUSION Autologous PRP may increase complete wound closure, shorten healing time, and reduce wound size in individuals with lower-extremity diabetic ulcers. The evidence is insufficient to estimate an effect on wound healing in individuals with lower-extremity venous ulcers or pressure ulcers. TRIAL REGISTRATION PROSPERO Identifier: CRD42020172817.

Abstract

A higher risk of thrombosis has been described as a prominent feature of coronavirus disease 2019 (COVID-19). This systematic review synthesizes current data on thrombosis risk, prognostic implications, and anticoagulation effects in COVID-19. We included 37 studies from 4070 unique citations. Meta-analysis was performed when feasible. Coagulopathy and thrombotic events were frequent among patients with COVID-19 and further increased in those with more severe forms of the disease. We also present guidance on the prevention and management of thrombosis from a multidisciplinary panel of specialists from Mayo Clinic. The current certainty of evidence is generally very low and continues to evolve.

Abstract

BACKGROUND AND AIMS We performed a systematic review with network meta-analysis (NMA) to compare the efficacy of different approaches in primary prevention of esophageal variceal bleeding and overall survival in cirrhotic patients with large varices. METHODS Thirty-two randomized clinical trials (RCT) with 3362 cirrhotic adults with large esophageal varices and no prior history of bleeding, with minimum 12m follow-up were included. Nonselective beta- blockers (NSBB), isosorbide-mononitrate (ISMN), carvedilol and variceal band ligation (VBL), alone or in combination, were compared to each other or placebo. Primary outcomes were reduction of all-cause mortality, and prevention of esophageal variceal bleeding. Random effects NMA was performed and summary estimates were expressed as odds ratio and 95% confidence intervals (OR; CI). Quality of evidence was critically appraised using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS Moderate quality evidence supports NSBB monotherapy (0.70; 0.49-1.00) or in combination with VBL (0.49; 0.23-1.02) or ISMN (0.44; 0.21-0.93) for decreasing mortality in cirrhotic patients with large esophageal varices and no prior history of bleeding. Moderate quality evidence supports carvedilol (0.21; 0.08-0.56) and VBL monotherapy (0.33; 0.19-0.55) or in combination with NSBB (0.34; 0.14-0.86), and low quality evidence supports NSBB monotherapy (0.64; 0.38-1.07) for primary prevention of variceal bleeding. VBL carries a higher risk of serious adverse events compared to NSBB. CONCLUSION NSBB monotherapy may decrease all-cause mortality and the risk of first variceal bleeding in cirrhotic patients with large esophageal varices. Additionally, NSBB carry a lower risk of serious complications compared to VBL. Therefore, NSBB may be the preferred initial approach for primary prophylaxis of esophageal variceal bleeding. This article is protected by copyright. All rights reserved.

Abstract

BACKGROUND Leukoreduced (LR) or cytomegalovirus (CMV)-seronegative cellular blood components are commonly used to reduce the risk of transfusion-transmitted CMV infection in high-risk patients. STUDY DESIGN AND METHODS We performed a systematic review and meta-analysis to evaluate the evidence for the use of LR cellular blood components with or without concurrent CMV testing of donor units in patients undergoing chemotherapy or solid organ and hematopoietic stem cell transplantation, in pregnant women, in very-low-birthweight infants, and in patients with primary immunodeficiency. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from 1980 through February 2015. Studies were included if they had a comparison group. Two independent reviewers selected and appraised studies. Meta-analysis was performed when appropriate. RESULTS Of 457 studies screened, 11 were eligible. One study was excluded from the meta-analysis because the comparison performed differed significantly from the others. Meta-analysis of five studies that compared leukoreduction to transfusing CMV-untested blood components showed no significant difference in clinical CMV infection (relative risk [RR], 0.26; 95% confidence interval [CI], 0.04-1.57) or laboratory CMV infection (RR, 0.33; 95% CI, 0.08-1.37). Meta-analysis of three studies that compared leukoreduction to transfusing CMV-seronegative cellular components showed no significant difference in laboratory CMV infection (RR, 2.18; 95% CI, 0.96-4.98). Meta-analysis of two studies that compared adding CMV testing to leukoreduction (vs. leukoreduction alone) showed no significant difference in clinical or laboratory CMV infection. The certainty in estimates was low for all comparisons. CONCLUSION At present, the scientific evidence does not favor a single strategy for reducing the risk of transfusion-related CMV infection in high-risk patients.

Abstract

OBJECTIVES To assess 1) the effectiveness of male-predominant plasma transfusion strategy for preventing transfusion-related acute lung injury and related mortality; and 2) whether this effect varies across different patient subgroups. DESIGN Systematic Review and meta-analysis: Data were identified by querying MEDLINE and EMBASE (including proceedings of major conferences on blood transfusions), searching the Internet for hemovigilance reports, reviewing reference lists of eligible articles and contacting experts in the field. Eligible were all studies reporting transfusion-related acute lung injury incidence, all-cause mortality (primary outcomes), hospital length of stay, time to extubation, PaO2/FIO2-ratio or blood pressure changes (secondary outcomes) in recipients of plasma transfusions containing relatively more plasma from individuals at low risk of carrying leukocyte-antibodies ("male plasma") than those receiving comparator plasma ("control plasma"). No limits were placed on study design, population or language. The only exclusion criteria were non-human subjects and lack of control group. Prespecified study quality indicators (including risk of bias assessment) and potential effect modifiers were tested using Cochran's Q Test. Final analyses using random-effects models and I2 to assess heterogeneity were performed in the subset of studies judged to provide the best evidence and separately for significantly different subgroups using STATA 12.1 (StataCorp, College Station, TX). SETTING As per primary studies. PATIENTS/SUBJECTS As per primary studies. INTERVENTIONS As per primary studies (generally: exposure to plasma containing relatively more male plasma than comparator plasma). MEASUREMENTS AND MAIN RESULTS From a total of 850 retrieved records, we identified 45 eligible studies. For transfusion-related acute lung injury incidence, final analysis was restricted to 13 cohort studies and one randomized controlled trial in which transfusion-related acute lung injury cases only involved plasma transfusions. Risk of transfusion-related acute lung injury and mortality in plasma recipients exposed to men when compared with control plasma were 0.27 (95% CI, 0.20-0.38; p < 0.001; I = 0%; n = 14; 286 events) and 0.89 (95% CI, 0.80-1.00; p = 0.04; I = 79%; n = 7; 5, 710 events), respectively. No other significant interactions were found. Secondary outcomes showed similar results but were less reported and the studies were more heterogeneous. Sensitivity analyses did not alter the results. There was no evidence of publication bias. DISCUSSION More than 800 million people in 17 countries are subject to male-predominant plasma transfusion policy and at least three more countries are planning or considering adoption of this strategy. On the basis of most observational data, judged to be of high quality, male-predominant plasma transfusion strategy reduces plasma-related transfusion-related acute lung injury incidence and possibly mortality. There was no evidence that the effect differs across patient subgroups, but power to detect such differences was low.

Abstract

IMPORTANCE Sickle cell disease (SCD) is a life-threatening genetic disorder affecting nearly 100,000 individuals in the United States and is associated with many acute and chronic complications requiring immediate medical attention. Two disease-modifying therapies, hydroxyurea and long-term blood transfusions, are available but underused. OBJECTIVE To support and expand the number of health professionals able and willing to provide care for persons with SCD. EVIDENCE REVIEW Databases of MEDLINE (including in-process and other nonindexed citations), EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, TOXLINE, and Scopus were searched using prespecified search terms and keywords to identify randomized clinical trials, nonrandomized intervention studies, and observational studies. Literature searches of English-language publications from 1980 with updates through April 1, 2014, addressed key questions developed by the expert panel members and methodologists. FINDINGS Strong recommendations for preventive services include daily oral prophylactic penicillin up to the age of 5 years, annual transcranial Doppler examinations from the ages of 2 to 16 years in those with sickle cell anemia, and long-term transfusion therapy to prevent stroke in those children with abnormal transcranial Doppler velocity (=200 cm/s). Strong recommendations addressing acute complications include rapid initiation of opioids for treatment of severe pain associated with a vasoocclusive crisis, and use of incentive spirometry in patients hospitalized for a vasoocclusive crisis. Strong recommendations for chronic complications include use of analgesics and physical therapy for treatment of avascular necrosis, and use of angiotensin-converting enzyme inhibitor therapy for microalbuminuria in adults with SCD. Strong recommendations for children and adults with proliferative sickle cell retinopathy include referral to expert specialists for consideration of laser photocoagulation and for echocardiography to evaluate signs of pulmonary hypertension. Hydroxyurea therapy is strongly recommended for adults with 3 or more severe vasoocclusive crises during any 12-month period, with SCD pain or chronic anemia interfering with daily activities, or with severe or recurrent episodes of acute chest syndrome. A recommendation of moderate strength suggests offering treatment with hydroxyurea without regard to the presence of symptoms for infants, children, and adolescents. In persons with sickle cell anemia, preoperative transfusion therapy to increase hemoglobin levels to 10 g/dL is strongly recommended with a moderate strength recommendation to maintain sickle hemoglobin levels of less than 30% prior to the next transfusion during long-term transfusion therapy. A strong recommendation to assess iron overload is accompanied by a moderate strength recommendation to begin iron chelation therapy when indicated. CONCLUSIONS AND RELEVANCE Hydroxyurea and transfusion therapy are strongly recommended for many individuals with SCD. Many other recommendations are based on quality of evidence that is less than high due to the paucity of clinical trials regarding screening, management, and monitoring for individuals with SCD.

Abstract

BACKGROUND Plasma transfusion is increasingly performed without clear consensus on indications. We systematically reviewed the literature to summarize the available evidence regarding the benefits and harms of plasma transfusion in common clinical settings. STUDY DESIGN AND METHODS We searched electronic databases from inception through August 2009. Eligible studies enrolled adult patients transfused with plasma and compared to a control group. Paired reviewers independently assessed studies for eligibility and extracted quality and outcome data. RESULTS Thirty-seven studies met eligibility criteria, most of which were observational. In patients undergoing massive transfusion, plasma infusion at high plasma : red blood cell ratios was associated with a significant reduction in the risk of death (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.24-0.60) and multiorgan failure (OR, 0.40; 95% CI, 0.26-0.60). However, the quality of this evidence was very low due to significant unexplained heterogeneity and several other biases. In a single retrospective study, plasma transfusion was associated with reduced mortality in anticoagulated patients with intracranial hemorrhage (OR, 0.29; 95% CI, 0.09-0.98). In patients undergoing surgery without massive transfusion, plasma infusion was associated with a trend toward increased mortality (OR, 1.22; 95% CI, 0.73-2.03). Plasma transfusion was associated with increased risk of developing acute lung injury (OR, 2.92; 95% CI, 1.99-4.29). CONCLUSIONS Very-low-quality evidence suggests that plasma infusion in the setting of massive transfusion for trauma patients may be associated with a reduction in the risk of death and multiorgan failure. A survival benefit was not demonstrated in most other transfusion populations.

Abstract

Objective: Although recent trial results of anti-CD3 therapy are promising, there have been conflicting results of various immunotherapeutic agents used in patients with type 1 diabetes. We conducted a systematic review and meta-analysis to determine the efficacy of nonantigen-based immunotherapeutic approaches for preservation of beta-cell function in patients with type 1 diabetes. Methods: We searched MEDLINE, EMBASE, Cochrane CENTRAL, reference lists, and content expert files up to September 2006. Eligible studies were randomized controlled trials (RCTs) of antiproliferative agents (methotrexate, azathioprine), monoclonal antibodies (CD3, CD4), T-cell inhibitors (cyclosporin) and other immunotherapeutic agents (photopheresis, linomide, fusidin, buffy coat, intravenous immunoglobulin, BCG, nicotinamide) in patients with newly diagnosed type 1 diabetes followed for [greater-than or equal to] 6 months. Pairs of reviewers working independently and with adequate reliability assessed the trials' methodological quality, collected data, and conducted random-effects meta-analyses on measures of preservation of beta-cell function (e.g. C-peptide secretion, insulin independence). Results: Of the 299 potentially relevant articles identified after an initial search, 20 trials met selection criteria. Meta-analysis of 20 trials (n = 1187 patients) found a small to moderate improvement in beta-cell function with immunotherapy [vs. placebo, effect size 0.37, 95% confidence interval (CI) 0.14-0.6] but there was moderate inconsistency in results across trials (I² 65%, 95% CI 39-77%). Subgroup analysis suggested a greater effect of cyclosporin and antiproliferative agents on beta-cell function when used for [greater-than or equal to] 6 months (pooled effect size 0.77 vs. -0.11, respectively; P _interaction = 0.002). Conclusions: Long-term immunotherapy may preserve beta-cell function in newly diagnosed patients with type 1 diabetes. Patients and clinicians must await the conduct of rigorous trials reporting on diabetes resolution, adverse events, and other patient-important outcomes.