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Effectiveness and safety of autologous platelet-rich plasma therapy with total contact casting versus total contact casting alone in treatment of trophic ulcer in leprosy: An observer-blind, randomized controlled trial
Saha S, Patra AC, Gowda SP, Mondal N, Rahaman S, Ahmed SK, Debbarma S, Kumar Vitthal KP, Sarkar S, Sil A, et al
Indian journal of dermatology, venereology and leprology. 2020
Abstract
Background: Trophic ulcers secondary to leprosy pose a great stigma to patients and remain a challenge to the treating dermatologists. Platelet-rich plasma (PRP) introduces growth factors directly into the wound and aids in rapid healing. The role of PRP in the treatment of trophic ulcers in leprosy patients has not yet been established by randomized controlled trials. Aims: To study the effectiveness and safety of autologous PRP therapy with total contact casting versus total contact casting alone in the treatment of trophic ulcers in leprosy. Methods: In an observer-blind, randomized (1:1) controlled study, 118 patients were enrolled. PRP was prepared by the manual double-spin method (1600 rpm for 10 min followed by 4000 rpm for 10 min). After wound bed preparation, activated PRP was injected intra- and perilesionally, and platelet-poor plasma gel was applied over the ulcer bed. Occlusive dressings and total contact casting were then applied in Group A, and only total contact casting was applied in Group B. The same procedure was repeated every 2 weeks for 8 weeks. Results: In all, 56 patients were analyzable in Group A and 52 in Group B. The surface area of the ulcer decreased significantly from first follow-up onward in both the groups (P < 0.001 in both the groups). Intergroup comparison showed that the reduction in the surface area of the ulcer was significantly more in Group A than in Group B from the first follow-up onward (P = 0.038) and the difference was maintained till the fifth follow-up (P < 0.001). At the end of the study, 91.10 +/- 9.65% ulcer surface area reduction had occurred in Group A, whereas it was 79.77 +/- 17.91% in Group B (P < 0.001). Trophic ulcers healed completely more often in paucibacillary leprosy patients (P < 0.001) and in those with a lower initial surface area of the ulcer (P < 0.001). Limitation: Short duration of treatment (8 weeks). Conclusion: PRP combined with total contact casting accelerates the healing of trophic ulcers of leprosy and is more effective than total contact casting alone. Complete remission is more likely to occur when the duration and surface area of ulcer are less and in the paucibacillary spectrum.
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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
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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.
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Anti-influenza immune plasma for the treatment of patients with severe influenza A: a randomised, double-blind, phase 3 trial
Beigel JH, Aga E, Elie-Turenne MC, Cho J, Tebas P, Clark CL, Metcalf JP, Ozment C, Raviprakash K, Beeler J, et al
The Lancet. Respiratory medicine. 2019
Abstract
BACKGROUND Infection with influenza virus causes substantial morbidity and mortality globally, although antiviral treatments are available. Previous studies have suggested that anti-influenza immune plasma could be beneficial as treatment, but they were not designed as randomised, blinded, placebo-controlled trials. Therefore, we aimed to prospectively evaluate the clinical efficacy of high-titre immune plasma compared with standard low-titre plasma to improve outcomes in patients with severe influenza A infection. METHODS We did this randomised, double-blind, phase 3 trial at 41 US medical centres to assess the efficacy of high-titre anti-influenza plasma (haemagglutination inhibition antibody titre ≥1:80) compared with low-titre plasma (≤1:10). Children and adults with PCR-confirmed influenza A infection, a National Early Warning score of 3 or greater, and onset of illness within 6 days before randomisation were eligible. Patients were randomly assigned (2:1) using an interactive web response system to receive either two units (or paediatric equivalent) of high-titre plasma (high-titre group) or low-titre plasma (low-titre group), and were followed up for 28 days from randomisation. High-titre and low-titre plasma had the same appearance. Randomisation was stratified by severity (in intensive care unit, not in intensive care but requiring supplemental oxygen, or not in intensive care and not requiring supplemental oxygen) and age (<18 years and ≥18 years). All participants, site staff, and the study team were masked to treatment allocation until after the final database lock. The primary endpoint was clinical status assessed by a six-point ordinal scale on day 7 (death, in intensive care, hospitalised but requiring supplemental oxygen, hospitalised not requiring supplemental oxygen, discharged but unable to resume normal activities, and discharged with full resumption of normal activities) analysed in a proportional odds model (an odds ratio [OR] >1 indicates improvement in clinical status across all categories for the high-titre vs the low-titre group). The primary analysis was done in the intention-to-treat population, excluding two participants who did not receive plasma. This trial is registered with ClinicalTrials.gov, NCT02572817. FINDINGS Participants were recruited between Jan 26, 2016, and April 19, 2018. Of 200 participants enrolled (177 adults and 23 children), 140 met the criteria for randomisation and were assigned to the high-titre group (n=92) or to the control low-titre group (n=48). One participant from each group did not receive plasma. At baseline, 60 (43%) of 138 participants were in intensive care and 55 (71%) of 78 participants who were not in intensive care required oxygen. 93% of planned plasma infusions were completed. The study was terminated in July, 2018, when independent efficacy analysis showed low conditional power to detect an effect of high-titre plasma even if full accrual (150 participants) was achieved. The proportional OR for improved clinical status on day 7 was 1.22 (95% CI 0.65-2.29, p=0.54). 47 (34%) of 138 participants experienced 88 serious adverse events: 32 (35%) with 60 events in the high-titre group and 15 (32%) with 28 events in the low-titre group. The most common serious adverse events were acute respiratory distress syndrome (ARDS; four [4%] vs two [4%]), allergic transfusion reactions (two [2%] vs two [4%]), and respiratory distress (three [3%] vs none). 65 (47%) participants experienced 183 adverse events: 42 (46%) with 126 events in the high-titre group and 23 (49%) with 57 events in the low-titre group. The most common adverse events were anaemia (four [3%] vs two [4%]) and ARDS (four [3%] vs three [5%]). Ten patients died during the study (six [7%] in the high-titre group vs four [9%] in the low-titre group, p=0.73). The most common cause of death was worsening of acute respiratory distress syndrome (two [2%] vs two [4%] patients). INTERPRETATION High-titre anti-influenza plasma conferred no significant benefit over non-immune plasma. Although our study did not have the precision to rule out a small, clinically relevant effect, the benefit is insufficient to justify the use of immune plasma for treating patients with severe influenza A. FUNDING National Institute of Allergy and Infectious Diseases of the National Institutes of Health (Bethesda, MD, USA).
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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.
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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.
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Effectiveness of platelet transfusion in dengue fever: a randomized controlled trial
Khan Assir MZ, Kamran U, Ahmad HI, Bashir S, Mansoor H, Anees SB, Akram J
Transfusion Medicine & Hemotherapy. 2013;40((5):):362-8.
Abstract
BACKGROUND Scientific data regarding effects of platelet transfusion on platelet count in dengue-related thrombocytopenia is scanty. METHODS A single center, randomized non-blinded trial was conducted on adult patients with dengue fever and platelet counts less than 30,000/mul. Patients were randomized to treatment and control group. Treatment group received single donor platelets. Patients with post-transfusion platelet increment (PPI) >=10,000/mul and/or corrected count increment (CCI) >=5,000/mul 1 h post-transfusion were considered responders. Primary outcome was platelet count increments at 24 and 72 h. RESULTS 87 patients were enrolled, and 43 (48.2%) received platelet transfusion. Mean PPI and CCI at 1 h post-transfusion in the treatment group were 18,800/mul and 7,000/mul respectively. 22 (53.6%) patients in the treatment group were non-responders. Mean platelet increments at 24 and 72 h were higher in the treatment group as compared to the control group. Responders showed significantly higher increments when compared to non-responders and the control group at 24 h (p = 0.004 and p <= 0.001, respectively) and 72 h (p = 0.001 and p <= 0.001, respectively). Significant differences were found between non-responders and the control group at 24 h (p <= 0.001), but not at 72 h (p = 0.104). Patients with lower baseline platelet count were more likely to be non-responders. Platelet transfusion neither prevented development of severe bleeding nor shortened time to cessation of bleeding. Three severe transfusion reactions and two deaths occurred in treatment group. CONCLUSION In this trial, almost half the patients showed no response to a high-dose platelet transfusion. Platelet transfusion did not prevent development of severe bleeding or shorten time to cessation of bleeding and was associated with significant side effects. Therefore, platelet transfusion should not be routinely done in the management of dengue fever.
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The effect of blood storage age on treatment of lactic acidosis by transfusion in children with severe malarial anaemia: a pilot, randomized, controlled trial
Dhabangi A, Mworozi E, Lubega IR, Cserti-Gazdewich CM, Maganda A, Dzik WH
Malaria Journal. 2013;12:55
Abstract
BACKGROUND Severe malarial anaemia requiring blood transfusion is a life-threatening condition affecting millions of children in sub-Saharan Africa. Up to 40% of children with severe malarial anaemia have associated lactic acidosis. Lactic acidosis in these children is strongly associated with fatal outcomes and is corrected by blood transfusion. However, it is not known whether the storage age of blood for transfusion affects resolution of lactic acidosis. The objective of this pilot study was to evaluate the effect of blood storage age on resolution of lactic acidosis in children with severe malarial anaemia and demonstrate feasibility of conducting a large trial. METHODS Children aged six to 59 months admitted to Acute Care Unit of Mulago Hospital (Kampala, Uganda) with severe malarial anaemia (haemoglobin<=5g/dL) and lactic acidosis (blood lactate >=5mmol/L), were randomly assigned to receive either blood of short storage age (one to 10 days) or long storage age (21-35days) by gravity infusion. Seventy-four patients were enrolled and randomized to two equal-sized study arms. Physiological measurements, including blood lactate, oxygen saturation, haemoglobin, and vital signs, were taken at baseline, during and after transfusion. The primary outcome variable was the proportion of children whose lactic acidosis resolved by four hours after transfusion. RESULTS Thirty-four of 37 (92%) of the children in the short storage treatment arm compared to 30/37 (81%) in the long storage arm achieved a blood lactate <5mmol/L by four hours post transfusion (p value=0.308). The mean time to lactic acidosis resolution was 2.65hours (95% CI; 2.25-3.05) in the short storage arm, compared to 3.35hours (95% CI; 2.60-4.10) in the long storage arm (p value=0.264). CONCLUSION Pilot data suggest that among children with severe malarial anaemia and lactic acidosis transfused with packed red blood cells, the storage age of blood does not affect resolution of lactic acidosis. The results support a larger and well-powered study which is under way. TRIAL REGISTRATION clinicaltrials.gov NCT01580111.
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Is fresh frozen plasma effective for thrombocytopenia in adults with dengue fever? A prospective randomised double blind controlled study
Sellahewa KH, Samaraweera N, Thusita KP, Fernando JL
The Ceylon Medical Journal. 2008;53((2):):36-40.
Abstract
RATIONALE Thrombocytopenia is a common problem which causes concern and complications in dengue fever. If proven effective, intravenous fresh frozen plasma is a simple and widely available therapeutic option to manage thrombocytopenia. OBJECTIVE To test the efficacy of fresh frozen plasma (FFP) on thrombocytopenia in patients with dengue fever. DESIGN 109 serologically confirmed dengue patients with platelet counts <40 000/mm3 were randomised into two groups. Group A (treatment) comprised 53 patients and group B (control) 56 patients. Group A received an intravenous infusion of 3 units (600 ml) of FFP over 90 minutes. Group B received an intravenous infusion of an equal volume of isotonic saline over the same period. The primary outcome measure was the difference between pre- and post-interventional platelet counts at 12, 24 and 48 hours. RESULTS Following Intervention, the mean platelet count was significantly higher in Group Athan in Group B at 12 hours (p=0. 04; t-test). The mean platelet counts continued to be higher in Group A than in Group B at 24 and 48 hours post-intervention, but the differences were not statistically significant. CONCLUSIONS In dengue patients with thrombocytopenia, infusion of 600 ml FFP may contribute to a significant increase in platelet count in the first 12 hours, but not thereafter.
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Survival of transfused donor white blood cells in HIV-infected recipients
Kruskall MS, Lee TH, Assmann SF, Laycock M, Kalish LA, Lederman MM, Busch MP, Viral Activation Transfusion Study Group
Blood. 2001;98((2):):272-9.
Abstract
The appearance and expansion of donor white blood cells in a recipient after transfusion has many potential biologic ramifications. Although patients with HIV infection are ostensibly at high risk for microchimerism, transfusion-associated graft-versus-host disease (TA-GVHD) is rare. The purpose of this study was to search for sustained microchimerism in such patients. Blood samples were collected from 93 HIV-infected women (a subset from the Viral Activation Transfusion Study, an NHLBI multicenter randomized trial comparing leukoreduced versus unmodified red blood cell [RBC] transfusions) before and after transfusions from male donors. Donor lymphocytes were detected in posttransfusion specimens using a quantitative Y-chromosome-specific polymerase chain reaction (PCR) assay, and donor-specific human leukocyte antigen (HLA) alleles were identified with allele-specific PCR primers and probes. Five of 47 subjects randomized to receive nonleukoreduced RBCs had detectable male lymphocytes 1 to 2 weeks after transfusion, but no subject had detectable male cells more than 4 weeks after a transfusion. In 4 subjects studied, donor-specific HLA haplotypes were detected in posttransfusion specimens, consistent with one or more donors' cells. None of 46 subjects randomized to receive leukoreduced RBCs had detectable male lymphocytes in the month after transfusion. Development of sustained microchimerism after transfusion in HIV-infected patients is rare; HIV-infected patients do not appear to be at risk for TA-GVHD.
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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.
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10.
Passive immunotherapy in AIDS: a double-blind randomized study based on transfusions of plasma rich in anti-human immunodeficiency virus 1 antibodies vs. transfusions of seronegative plasma
Vittecoq D, Chevret S, Morand-Joubert L, Heshmati F, Audat F, Bary M, Dusautoir T, Bismuth A, Viard JP, Barre-Sinoussi F,, et al
Proceedings of the National Academy of Sciences of the United States of America. 1995;92((4):):1195-9.
Abstract
A randomized double-blind controlled trial was conducted to determine the efficacy of passive immunotherapy in the treatment of symptomatic human immunodeficiency virus (HIV) infection. This trial included 86 symptomatic patients randomized to receive plasma rich in anti-HIV-1 antibody or standard seronegative plasma. Each patient in both groups received a 300-ml infusion every 14 days over a 1-year period, and every 28 days thereafter, in addition to zidovudine and other conventional prophylactic treatments. Plasma donors were selected among symptomless seropositive individuals with a CD4 lymphocyte count > or = 400 x 10(6) cells per liter, a negative p24 antigen assay, and a high concentration of anti-p24 antibody. The plasmas were heat-inactivated before infusion. During the study period (day 28-day 365) scheduled by the protocol, clinical benefit from passive immunotherapy was observed in delaying the appearance of the first AIDS-defining event (P < 0.009) and reducing the cumulative incidence of such events, which was estimated 3-fold higher in the control group compared to the treatment group. Seven deaths occurred in the treatment group vs. 11 in the control group (P = 0.27). A total of 47 patients died or exhibited new AIDS-defining events, 18 in the treatment group and 29 in the control group (P = 0.009). No clinical benefit was observed after the 1-year period with infusions performed every 4 weeks. These results indicate a favorable effect of passive immunotherapy on the evolution of advanced AIDS.