-
1.
Red Cell Exchange as Adjunctive Therapy for Babesiosis: Is it Really Effective?
Tannous T, Cheves TA, Sweeney JD
Transfusion medicine reviews. 2021
Abstract
Human babesiosis is a parasitic disease prevalent in the Northeastern and Midwestern United States (US). Treatment with antibiotics is the standard of care but red cell exchange (RCE) has been used as an adjunctive treatment in more severe disease. Data for the efficacy of RCE in the treatment of babesiosis has been based on case reports and case series. An English language literature search was conducted for cases of babesiosis treated with RCE since 1980 and relevant laboratory and clinical outcome data were extracted. Similar data were obtained on severe cases of babesiosis referred for RCE in our hospitals in the time period 2000 to 2020. Fifty reports including forty-one individual case reports and nine case series were retrieved. There were 108 patients that underwent RCE with an overall mortality rate of 20%. Some patients had more than one RCE. The patients varied in the level of anemia and evidence of compromise of renal or pulmonary function. The pre-RCE level of parasitemia varied between 1.7% to 85% with the vast majority >10%. The post-RCE level of parasitemia varied between 1% to 10%. Since 2000, 32 patients were referred for RCE in our hospitals and RCE was performed on 23 of 32. There were more patients treated with RCE in the second decade as compared to the first decade, 19 versus 4 respectively. The overall mortality was 22% similar to the national data. Comparing the cohort treated with RCE to the 9 patients who were treated only with antibiotics, there were similar levels of parasitemia and laboratory parameters. The overall number of days needed to achieve a parasite count <1% was similar between the two cohorts and mortality for the antibiotics only cohort was 0%. More than 40 years after the first reported case of RCE in severe babesiosis it cannot be concluded that this adjunctive therapy favorably influences the clinical outcome. Since there is largely equipoise, a registry of severe patients treated with or without RCE could identify a benefit or otherwise.
-
2.
Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19 : a living systematic review.
Chai, K. L., Valk, S. J., Piechotta, V., Kimber, C., Monsef, I., Doree, C., Wood, E. M., Lamikanra, A. A., Roberts, D. J., McQuilten, Z., et al
The Cochrane Database of Systematic Reviews.. 2020;10:CD013600
Abstract
BACKGROUND Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with viral respiratory diseases, and are currently being investigated in trials as potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding the benefits and risks is required. OBJECTIVES To continually assess, as more evidence becomes available, whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in treatment of people with COVID-19. SEARCH METHODS We searched the World Health Organization (WHO) COVID-19 Global Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, Centers for Disease Control and Prevention COVID-19 Research Article Database and trial registries to identify completed and ongoing studies on 19 August 2020. SELECTION CRITERIA We followed standard Cochrane methodology. We included studies evaluating convalescent plasma or hyperimmune immunoglobulin for people with COVID-19, irrespective of study design, disease severity, age, gender or ethnicity. We excluded studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)) and studies evaluating standard immunoglobulin. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane 'Risk of bias' 2.0 tool for randomised controlled trials (RCTs), the Risk of Bias in Non-randomised Studies - of Interventions (ROBINS-I) tool for controlled non-randomised studies of interventions (NRSIs), and the assessment criteria for observational studies, provided by Cochrane Childhood Cancer for non-controlled NRSIs. We rated the certainty of evidence using the GRADE approach for the following outcomes: all-cause mortality at hospital discharge, mortality (time to event), improvement of clinical symptoms (7, 15, and 30 days after transfusion), grade 3 and 4 adverse events (AEs), and serious adverse events (SAEs). MAIN RESULTS This is the second living update of our review. We included 19 studies (2 RCTs, 8 controlled NRSIs, 9 non-controlled NRSIs) with 38,160 participants, of whom 36,081 received convalescent plasma. Two completed RCTs are awaiting assessment (published after 19 August 2020). We identified a further 138 ongoing studies evaluating convalescent plasma or hyperimmune immunoglobulin, of which 73 are randomised (3 reported in a study registry as already being completed, but without results). We did not identify any completed studies evaluating hyperimmune immunoglobulin. We did not include data from controlled NRSIs in data synthesis because of critical risk of bias. The overall certainty of evidence was low to very low, due to study limitations and results including both potential benefits and harms. Effectiveness of convalescent plasma for people with COVID-19 We included results from two RCTs (both stopped early) with 189 participants, of whom 95 received convalescent plasma. Control groups received standard care at time of treatment without convalescent plasma. We are uncertain whether convalescent plasma decreases all-cause mortality at hospital discharge (risk ratio (RR) 0.55, 95% confidence interval (CI) 0.22 to 1.34; 1 RCT, 86 participants; low-certainty evidence). We are uncertain whether convalescent plasma decreases mortality (time to event) (hazard ratio (HR) 0.64, 95% CI 0.33 to 1.25; 2 RCTs, 189 participants; low-certainty evidence). Convalescent plasma may result in little to no difference in improvement of clinical symptoms (i.e. need for respiratory support) at seven days (RR 0.98, 95% CI 0.30 to 3.19; 1 RCT, 103 participants; low-certainty evidence). Convalescent plasma may increase improvement of clinical symptoms at up to 15 days (RR 1.34, 95% CI 0.85 to 2.11; 2 RCTs, 189 participants; low-certainty evidence), and at up to 30 days (RR 1.13, 95% CI 0.88 to 1.43; 2 studies, 188 participants; low-certainty evidence). No studies repo ted on quality of life. Safety of convalescent plasma for people with COVID-19 We included results from two RCTs, eight controlled NRSIs and nine non-controlled NRSIs assessing safety of convalescent plasma. Reporting of safety data and duration of follow-up was variable. The controlled studies reported on AEs and SAEs only in participants receiving convalescent plasma. Some, but not all, studies included death as a SAE. The studies did not report the grade of AEs. Fourteen studies (566 participants) reported on AEs of possible grade 3 or 4 severity. The majority of these AEs were allergic or respiratory events. We are very uncertain whether convalescent plasma therapy affects the risk of moderate to severe AEs (very low-certainty evidence). 17 studies (35,944 participants) assessed SAEs for 20,622 of its participants. The majority of participants were from one non-controlled NRSI (20,000 participants), which reported on SAEs within the first four hours and within an additional seven days after transfusion. There were 63 deaths, 12 were possibly and one was probably related to transfusion. There were 146 SAEs within four hours and 1136 SAEs within seven days post-transfusion. These were predominantly allergic or respiratory, thrombotic or thromboembolic and cardiac events. We are uncertain whether convalescent plasma therapy results in a clinically relevant increased risk of SAEs (low-certainty evidence). AUTHORS' CONCLUSIONS We are uncertain whether convalescent plasma is beneficial for people admitted to hospital with COVID-19. There was limited information regarding grade 3 and 4 AEs to determine the effect of convalescent plasma therapy on clinically relevant SAEs. In the absence of a control group, we are unable to assess the relative safety of convalescent plasma therapy. While major efforts to conduct research on COVID-19 are being made, recruiting the anticipated number of participants into these studies is problematic. The early termination of the first two RCTs investigating convalescent plasma, and the lack of data from 20 studies that have completed or were due to complete at the time of this update illustrate these challenges. Well-designed studies should be prioritised. Moreover, studies should report outcomes in the same way, and should consider the importance of maintaining comparability in terms of co-interventions administered in all study arms. There are 138 ongoing studies evaluating convalescent plasma and hyperimmune immunoglobulin, of which 73 are RCTs (three already completed). This is the second living update of the review, and we will continue to update this review periodically. Future updates may show different results to those reported here.
-
3.
Efficacy of convalescent plasma for the treatment of severe influenza
Xu Z, Zhou J, Huang Y, Liu X, Xu Y, Chen S, Liu D, Lin Z, Liu X, Li Y
Crit Care. 2020;24(1):469
-
-
-
Free full text
-
Editor's Choice
Abstract
BACKGROUND Convalescent plasma administration may be of clinical benefit in patients with severe influenza, but reports on the efficacy of this therapy vary. METHODS We conducted a systematic review and meta-analysis assessing randomized controlled trials (RCTs) involving the administration of convalescent plasma to treat severe influenza. Healthcare databases were searched in February 2020. All records were screened against eligibility criteria, and the risks of bias were assessed. The primary outcome was the fatality rate. RESULTS A total of 2861 studies were retrieved and screened. Five eligible RCTs were identified. Pooled analyses yielded no evidence that using convalescent plasma to treat severe influenza resulted in significant reductions in mortality (odds ratio, 1.06; 95% CI, 0.51-2·23; P = 0.87; I(2) = 35%), number of days in the intensive care unit, or number of days on mechanical ventilation. This treatment may have the possible benefits of increasing hemagglutination inhibition titers and reducing influenza B viral loads and cytokine levels. No serious adverse events were reported. The included studies were generally of high quality with a low risk of bias. CONCLUSIONS The administration of convalescent plasma appears safe but may not reduce the mortality, number of days in the intensive care unit, or number of days on mechanical ventilation in patients with severe influenza.
PICO Summary
Population
Patients hospitalized with severe influenza (5 studies, n= 598).
Intervention
Convalescent plasma or hyperimmune intravenous immunoglobulin (H-IVIG).
Comparison
Various comparators (normal intravenous immunoglobulin, standard care, low-titre anti-influenza, placebo).
Outcome
Pooled analyses yielded no evidence that using convalescent plasma to treat severe influenza resulted in significant reductions in mortality, number of days in the intensive care unit, or number of days on mechanical ventilation.
-
4.
Identification of the crucial parameters regarding the efficacy of ribavirin therapy in Crimean-Congo haemorrhagic fever (CCHF) patients: a systematic review and meta-analysis
Arab-Bafrani Z, Jabbari A, Mostakhdem Hashemi M, Arabzadeh AM, Gilanipour A, Mousavi E
The Journal of antimicrobial chemotherapy. 2019
Abstract
OBJECTIVES Recently, ribavirin has been suggested as a therapeutic approach in Crimean-Congo haemorrhagic fever (CCHF) patients; however, there are controversial findings about its efficacy. In the current study, a meta-analysis was systematically performed to assess the effectiveness of ribavirin administration regarding CCHF patient survival and to explore the most important influential parameters for its efficacy. METHODS All of the outcomes of the clinically studied CCHF patients who were treated with ribavirin were included in the meta-analysis. RESULTS Overall, 24 studies met our criteria. Although the studies did not have high quality there was no heterogeneity and publication bias across studies. The results indicated that the administration of ribavirin to CCHF patients significantly decreased the mortality rate (by 1.7-fold) compared with those who did not receive this medication. Furthermore, it was found that the prescription of ribavirin in the initial phase of disease was more effective, and a delay in the start of treatment resulted in a 1.6-fold increase in mortality rate. In addition, interventional therapy resulted in an approximately 2.3-fold reduction in the mortality rate of those who received ribavirin along with corticosteroids compared with those who were treated with ribavirin monotherapy. CONCLUSIONS This meta-analysis reveals that ribavirin should be considered as a crucial antiviral drug in the therapeutic approach used for CCHF patients, especially in early phases of the disease. Additionally, it seems that the administration of corticosteroids alongside ribavirin can play an effective role in alleviation of the disease status, particularly in haemorrhagic phases.
-
5.
Prophylactic and therapeutic interventions for bleeding in dengue: a systematic review
Rajapakse S, de Silva N L, Weeratunga P, Rodrigo C, Fernando S D
Transactions of the Royal Society of Tropical Medicine and Hygiene. 2018;111((10):):433-439
Abstract
The global incidence of dengue has increased sevenfold between 1990 and 2013. Despite a low case fatality rate (<1%), during epidemics, due to the large number of people affected, overall mortality rates can be significant. The risk of clinically significant bleeding in dengue is unpredictable and often contributes to an adverse outcome. This systematic review focuses on the evidence for prophylactic and therapeutic interventions for bleeding in dengue infection. PubMed, CINAHL, Cochrane Library, Embase and Google Scholar were searched for randomized, quasi-randomized and non-randomized, prospective or retrospective studies that had a control group alongside an intervention aimed at stopping or preventing bleeding in dengue infection. Eleven studies that included 1904 patients in 12 study arms were eligible. These assessed the role of platelet transfusion [two randomized controlled trials (RCTs) and three non-randomized studies], plasma transfusion (one RCT), recombinant activated factor VII (one RCT), anti-D globulin (two RCTs), immunoglobulin (one RCT) and interleukin 11 (one RCT) as prevention or treatment for bleeding. Due to significant heterogeneity in study design and outcome reporting, a meta-analysis was not performed. Currently there is no evidence that any of the above interventions would have a beneficial effect in preventing or treating clinically significant bleeding in dengue.
-
6.
Antifibrinolytic therapy to reduce haemoptysis from any cause
Prutsky G, Domecq JP, Salazar CA, Accinelli R
The Cochrane Database of Systematic Reviews. 2016;((11)):CD008711.
Abstract
BACKGROUND Haemoptysis is a common pathology around the world, occurring with more frequency in low-income countries. It has different etiologies, many of which have infectious characteristics. Antifibrinolytic agents are commonly used to manage bleeding from different sources, but their usefulness in pulmonology is unclear. OBJECTIVES To evaluate the effectiveness and safety of antifibrinolytic agents in reducing the volume and duration of haemoptysis in adult and paediatric patients. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library, EMBASE and LILACS for publications that describe randomized controlled trials (RCTs) of antifibrinolytic therapy in patients presenting with haemoptysis. We also performed an independent search in MEDLINE for relevant trials not yet included in CENTRAL or DARE. Searches are up to date to the 19th September 2016. We conducted electronic and manual searches of relevant national and international journals. We reviewed the reference lists of included studies to locate relevant randomized controlled trials (RCTs). An additional search was carried out to find unpublished RCTs. SELECTION CRITERIA We included RCTs designed to evaluate the effectiveness and safety of antifibrinolytic agents in reducing haemoptysis in adult and paediatric patients of both genders presenting with haemoptysis of any etiology and severity. The intervention of interest was the administration of antifibrinolytic agents compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS All reviewers independently assessed methodological quality and extracted data tables pre-designed for this review. MAIN RESULTS The electronic literature search identified 1 original study that met the eligibility criteria. One unpublished study was also identified through manual searches. Therefore two randomized controlled trials met the inclusion criteria: Tscheikuna 2002 (via electronic searches) and Ruiz 1994 (via manual searches). Tscheikuna 2002, a double-blind RCT performed in Thailand, evaluated the effectiveness of tranexamic acid (TXA, an antifibrinolytic agent) administered orally in 46 hospital in- and outpatients with haemoptysis of various etiologies. Ruiz 1994, a double-blind RCT performed in Peru, evaluated the effectiveness of intravenous TXA in 24 hospitalised patients presenting with haemoptysis secondary to tuberculosis.Pooled together, results demonstrated a significant reduction in bleeding time between patients receiving TXA and patients receiving placebo with a weighted mean difference (WMD) of -19.47 (95% CI -26.90 to -12.03 hours), but with high heterogeneity (I(2) = 52%). TXA did not affect remission of haemoptysis evaluated at seven days after the start of treatment. Adverse effects caused by the drug's mechanism of action were not reported. There was no significant difference in the incidence of mild side effects between active and placebo groups (OR 3.13, 95% CI 0.80 to 12.24). AUTHORS' CONCLUSIONS There is insufficient evidence to judge whether antifibrinolytics should be used to treat haemoptysis from any cause, though limited evidence suggests they may reduce the duration of bleeding.
-
7.
The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis
Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Beck CR, Convalescent PlasmaStudy Group
Journal of Infectious Diseases. 2015;211((1):):80-90.
-
-
Free full text
-
Abstract
BACKGROUND Administration of convalescent plasma, serum, or hyperimmune immunoglobulin may be of clinical benefit for treatment of severe acute respiratory infections (SARIs) of viral etiology. We conducted a systematic review and exploratory meta-analysis to assess the overall evidence. METHODS Healthcare databases and sources of grey literature were searched in July 2013. All records were screened against the protocol eligibility criteria, using a 3-stage process. Data extraction and risk of bias assessments were undertaken. RESULTS We identified 32 studies of SARS coronavirus infection and severe influenza. Narrative analyses revealed consistent evidence for a reduction in mortality, especially when convalescent plasma is administered early after symptom onset. Exploratory post hoc meta-analysis showed a statistically significant reduction in the pooled odds of mortality following treatment, compared with placebo or no therapy (odds ratio, 0.25; 95% confidence interval, .14-.45; I(2) = 0%). Studies were commonly of low or very low quality, lacked control groups, and at moderate or high risk of bias. Sources of clinical and methodological heterogeneity were identified. CONCLUSIONS Convalescent plasma may reduce mortality and appears safe. This therapy should be studied within the context of a well-designed clinical trial or other formal evaluation, including for treatment of Middle East respiratory syndrome coronavirus CoV infection. The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
-
8.
Treatment for anemia in people with AIDS
Marti-Carvajal AJ, Sola I
Cochrane Database of Systematic Reviews. 2011;((10):):CD004776.
Abstract
BACKGROUND Anemia is common in persons with HIV infection and is associated with poor prognosis. There is a need to assess the effects of anemia treatments, and to determine whether these interventions are beneficial. OBJECTIVES To determine the efficacy and safety of treatments for anemia in people with HIV infection and AIDS. SEARCH STRATEGY The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 10, 2010), MEDLINE (1980-November 25, 2010), EMBASE (1980-November 25, 2010), LlLACS (1982 to November 25, 2010), Africa Index Medicus (up to November 9, 2010), ISI Web of Knowledge (2005 to October 9, 2010), Scirus (October 9, 2010) reference lists of relevant articles. We asked the Cochrane HIV/AIDS and Pregnancy and Childbirth Groups to check their Specialised Registers. We also checked the reference lists of all trials identified by the above methods. SELECTION CRITERIA Randomized trials assessing the effects of treatments for anemia in people diagnosed with HIV infection. There were no age restrictions. DATA COLLECTION AND ANALYSIS Two authors independently assessed relevant studies for inclusion. Data extraction and quality assessment of relevant studies was performed by two authors and checked by the other two authors. MAIN RESULTS Six trials with a high risk of bias, including 537 patients, met the inclusion criteria. These trials only covered recombinant Human erythropoietin alfa (rHuEPO). Two of them including adult and paediatric participants (84 participants and 4 events) comparing rHuEPO to placebo did not reduce the risk of mortality with a follow up to 12 weeks (pooled RR 0.56, 95% confidence interval (CI) 0.08 to 4.05, I(2) = 0%). Any trials that compared rHuEPO to placebo did not show any benefit on hematological values response, number of patients transfused, or number of packed red cell transfused. Two trial compared the effects of two rHuEPO dosing regimens on hemoglobin value and quality of life, but the effects are unclear. Three RCT reported high risk of attrition bias; therefore, were not included in a meta-analysis. AUTHORS' CONCLUSIONS This updated Cochrane review provides evidence that rHuEPO compared with placebo does not reduce mortality, does not reduce transfusion requirements, did not increase hemoglobin levels, and did not improve quality of life in HIV-infected patients with anemia. The results are based on six RCTs with high risk of bias. Therefore prescription of this intervention for treating anemia in patients with AIDS is not justified, unless new evidence from a large high quality trial alters this conclusion.
-
9.
Effect of Helicobacter pylori eradication on platelet count in idiopathic thrombocytopenic purpura: a systematic review and meta- analysis
Franchini M, Cruciani M, Mengoli C, Pizzolo G, Veneri D
Journal of Antimicrobial Chemotherapy. 2007;60((2):):237-246.
Abstract
Background: There is a debate in the recent literature about the effect of Helicobacter pylori eradication on platelet count in patients with idiopathic thrombocytopenic purpura (ITP). In order to clarify this controversial issue, we performed a systematic review with meta-analysis of the available literature. Methods: The meta-analytic comparison was focused on the difference in the platelet count increase between the experimental arm (H. pylori- infected patients who responded to eradication therapy) and each control arm (H. pylori -infected patients who failed to respond to eradication therapy; H. pylori -infected patients who did not receive eradication therapy and H. pylori-negative patients) and was expressed as weighted mean difference (WMD). Moreover, in order to explain the heterogeneity, a meta-regression model was fitted with arm-level covariates. Results: Data involving 788 ITP patients were collected from 17 articles (16 studies with a prospective cohort design and 1 randomized trial). There was a statistically significant difference in the increase in platelet count in patients in whom eradication was successful compared with control groups (WMD, 40.77 × 10(9)/L (95% CI, 20.92-60.63) compared with untreated patients; 52.16 (95% CI, 34.26-70.05) compared with patients who failed eradication and 46.35 (95% CI, 27.79-64.91) compared with H. pylori -negative patients). Moreover, in the meta-regression model, the success of H. pylori eradication was highly significant as an explanatory variable for platelet count increase. Conclusions: Our analysis shows a strict correlation between H. pylori eradication and increase in platelet count. However, due to intrinsic limits in the design of the studies analysed, further evidence from randomized clinical trials is required to confirm the effect of eradication treatment on platelet count.
-
10.
Blood transfusion for treating malarial anaemia
Meremikwu M, Smith HJ
Cochrane Database of Systematic Reviews. 1999;((4):):CD001475.
Abstract
BACKGROUND Blood transfusion is used in patients with severe malarial anaemia, but risks adverse reactions, transmission of disease, and is complicated to organise in developing countries. OBJECTIVES This review evaluates the effects of routine blood transfusion for severe anaemia on death and adverse outcomes in malarious areas. SEARCH STRATEGY We searched the Cochrane Infectious Diseases Group Specialized Register (July 2006), CENTRAL (The Cochrane Library Issue 3, 2006), MEDLINE (1966 to July 2006), EMBASE (1980 to July 2006), LILACS (July 2006), and reference lists of relevant articles. We contacted researchers and organizations working in the field. SELECTION CRITERIA Randomised and quasi-randomised trials of blood transfusion compared with conservative management in malaria-associated severe anaemia. DATA COLLECTION AND ANALYSIS Trials were identified and data extracted by a single reviewer (MM) and checked by a second (HS). Inclusion criteria were applied and data were extracted independently by both reviewers. MAIN RESULTS Two randomised trials of 230 children were included. In the transfusion group, there was a non-signficant tendency towards fewer deaths (RR 0.41, 95% CI 0.06 to 2.70), but a trend towards more severe adverse events (RR 8.60, 95% CI 1.11 to 66.43). In one trial by Bojang (1997a) respiratory distress was less common and hospital stay was shorter in the transfusion group (WMD 1.88 days, 95% CI 2.41 to 1.35). Subsequent need for urgent blood transfusion was less common in the transfusion group (RR 0.12, 95% CI 0.02 to 0.68). Day 28 packed cell volume was less in the transfusion group (WMD -1.34, 95% CI -2.57 to -0.11). There was no information on HIV or Hepatitis B virus transmission. AUTHORS' CONCLUSIONS There is insufficient data to be sure whether routinely giving blood to clinically stable children with severe anaemia in endemic malarious areas reduces death, or results in higher haematocrit measured at one month.