Comparison of clinical outcome, cartilage turnover, and inflammatory activity following either intra-articular or a combination of intra-articular with intra-osseous platelet-rich plasma injections in osteoarthritis knee: A randomized, clinical trial
Barman A, Bandyopadhyay D, Mohakud S, Sahoo J, Maiti R, Mukherjee S, Prakash S, Roy SS, Viswanath A
BACKGROUND The objective of the study was to determine the changes in clinical outcome (pain and knee activity) and assess bone/ cartilage biomarkers and inflammatory activity in persons with osteoarthritis (OA) knee following a single injection of intra-articular platelet-rich plasma (IA-PRP) and combination of intra-articular, intraosseous PRP (IA+IO-PRP). METHODS This prospective, randomized, single-blind clinical trial was conducted at a tertiary care teaching hospital in India. Ninety-six persons with OA knee with a Kellgren-Lawrence score of 3 were randomized into three groups- Group-I (IA-PRP), Group-II (IA+IO-PRP)], Group-III, [intra-articular normal saline (IA-NS)]. The primary outcome was a visual analog scale (VAS) for pain. The secondary outcomes were the Knee Injury and Osteoarthritis Outcome Score (KOOS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), bone/ cartilage turnover biomarkers [C-telopeptide (CTX-II), N-telopeptide (NTX-I), cartilage oligomeric matrix protein (COMP), N-terminal propeptide of collagen type-IIA (PIIANP), and hyaluronic acid (HA)], ultrasonography (USG) findings of the knee joint. The outcome measures were assessed at baseline, 6, and 12 weeks of follow-up. RESULTS Compared to IA-NS injection, IA-PRP and IA+IO-PRP injections significantly improved VAS-pain and KOOS scores at 6 and 12 weeks. Furthermore, both PRP groups showed a significant reduction in ESR, CRP, and CTX-II at 12 weeks following PRP injections. In addition, at 12 weeks, the IA+IO-PRP group showed a significant reduction (p=0.009) in NTX-I level. Persons in the IA+IO-PRP group reported significant reductions in the synovial-effusion and infra-patellar bursitis. CONCLUSIONS Significant clinical improvements were noticed following IA-PRP and IA-IO-PRP injections compared to IA-NS injections. Both PRP groups reported a significant reduction in ESR, CRP, and CTX-II levels at 12 weeks. Persons in the IA+IO-PRP group reported significant changes in u-NTX-I level and knee-USG findings.
Single intra-articular injection with or without intra-osseous injections of platelet-rich plasma in the treatment of osteoarthritis knee: A single-blind, randomized clinical trial
Barman A, Prakash S, Sahoo J, Mukherjee S, Maiti R, Roy SS
BACKGROUND Subchondral bony structure damage plays an essential role in the pathogenesis of osteoarthritis (OA) knee. An intra-articular injection cannot reach the damaged subchondral bony structure and treat its pathologies effectively. The objective of the study was to compare the clinical effects of single intra-articular injection with or without intra-osseous injections of PRP in the treatment of osteoarthritis (OA) knee. METHODS This was a single-blind, parallel-group, randomized clinical trial. Fifty patients, with OA knee (K&L grade III), with ages between 50 and 65 years, were randomly allocated into 'intra-osseous, intra-articular PRP' ('IO+IA-PRP') (n = 25) or 'intra-articular PRP' group ('IA-PRP') (n = 25). Patients in the 'IO+IA-PRP' group received 18 ml PRP injection, and the 'IA-PRP' group received 8 ml PRP injection. Intra-osseous injections were given at the tibial plateau (5 ml) and femoral condyle (5 ml), along with intra-articular knee injection (8 ml), under fluoroscopic guidance. Outcomes were measured using VAS-pain, the knee injury and osteoarthritis outcome score (KOOS), and the treatment satisfaction scale. All patients (n = 50) were followed up till six months. RESULTS The mean age was 57.12(4.27) years and 57.00(4.96) years in the 'IO+IA-PRP' and 'IA-PRP' groups. Both groups showed significant improvement in pain relief (VAS pain) and KOOS parameters: pain, symptoms, ADL function, sport and recreation function, and quality of life. Compared to the 'IA-PRP' group, the 'IO+IA-PRP' group showed a greater reduction of VAS pain at six months. However, no significant difference was obtained in VAS pain-relief between these two groups (p = 0.422) at six months. Similarly, at 6 months, in inter-group comparison, except 'sport and recreation function' (p < 0.05), no significant differences were obtained in mean-scores of KOOS parameters: pain (p = 0.514); symptom (p = 0.148), ADL-function (p = 0.991), QoL-(p = 0.376). Patients in the 'IO+IA-PRP' group complained of significant 'injection-associated' adverse events and consumed a greater number of Acetaphenomen. CONCLUSIONS Both groups showed significant improvement following the intervention. Intra-osseous PRP injections did not provide any additional benefit over intra-articular PRP injection until six months regarding pain relief and functional improvement.
Comparative evaluation of efficacy and safety of automated versus manual red cell exchange in sickle cell disease: A systematic review and meta-analysis
Mukherjee S, Sahu A, Ray GK, Maiti R, Prakash S
Vox sanguinis. 2022
BACKGROUND AND OBJECTIVES Exchange transfusion is a valuable treatment option in sickle cell disease (SCD) and is preferred over simple transfusion as it removes abnormal haemoglobin S (HbS) levels and reduces complications. This meta-analysis aims to evaluate the efficacy and safety profile of automated red cell exchange (aRBX) procedure over manual red cell exchange transfusion (MET) in SCD patients. MATERIALS AND METHODS A standard meta-analysis protocol was developed, and after performing a comprehensive literature search in PubMed/MEDLINE, Cochrane and International Clinical Trial Registry Platform (ICTRP), reviewers assessed eligibility and extracted data from nine relevant studies. A random effects model was used to estimate the pooled effect size calculated from the mean difference in HbS percentage, serum ferritin level and risk ratio for the adverse events. Quality assessment was done using the risk-of-bias assessment tool, and a summary of observations was prepared using standard Cochrane methodology with GradePro GDT. RESULTS The random-model analysis revealed a mean difference of 4.10 (95% CI: -3.29-11.49; Z = 1.09; p = 0.28) for HbS percentage, mean difference of 435.29 (95% CI: -73.74-944.32; Z = 1.68; p = 0.09) for serum ferritin and pooled risk ratio of 1.35 (95% CI: 0.63-2.87; Z = 0.77; p = 0.44) for adverse events. CONCLUSION This meta-analysis did not reveal any significant benefit of aRBX in reducing HbS percentage and attenuating the serum ferritin level when compared with MET. There was also no significant increased risk of adverse events detected in association with aRBX.
A phase 2 single center open label randomised control trial for convalescent plasma therapy in patients with severe COVID-19
Ray Y, Paul SR, Bandopadhyay P, D'Rozario R, Sarif J, Raychaudhuri D, Bhowmik D, Lahiri A, Vasudevan JS, Maurya R, et al
Nature communications. 2022;13(1):383
A single center open label phase 2 randomised control trial (Clinical Trial Registry of India No. CTRI/2020/05/025209) was done to assess clinical and immunological benefits of passive immunization using convalescent plasma therapy. At the Infectious Diseases and Beleghata General Hospital in Kolkata, India, 80 patients hospitalized with severe COVID-19 disease and fulfilling the inclusion criteria (aged more than 18 years, with either mild ARDS having PaO2/FiO2 200-300 or moderate ARDS having PaO2/FiO2 100-200, not on mechanical ventilation) were recruited and randomized into either standard of care (SOC) arm (N = 40) or the convalescent plasma therapy (CPT) arm (N = 40). Primary outcomes were all-cause mortality by day 30 of enrolment and immunological correlates of response to therapy if any, for which plasma abundance of a large panel of cytokines was quantitated before and after intervention to assess the effect of CPT on the systemic hyper-inflammation encountered in these patients. The secondary outcomes were recovery from ARDS and time taken to negative viral RNA PCR as well as to report any adverse reaction to plasma therapy. Transfused convalescent plasma was characterized in terms of its neutralizing antibody content as well as proteome. The trial was completed and it was found that primary outcome of all-cause mortality was not significantly different among severe COVID-19 patients with ARDS randomized to two treatment arms (Mantel-Haenszel Hazard Ratio 0.6731, 95% confidence interval 0.3010-1.505, with a P value of 0.3424 on Mantel-Cox Log-rank test). No adverse effect was reported with CPT. In severe COVID-19 patients with mild or moderate ARDS no significant clinical benefit was registered in this clinical trial with convalescent plasma therapy in terms of prespecified outcomes.
Efficacy of therapeutic plasma exchange in severe COVID-19 disease: A meta-analysis
Prakash S, Sahu A, Routray SS, Maiti R, Mitra JK, Mukherjee S
Vox sanguinis. 2022
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BACKGROUND AND OBJECTIVES Therapeutic plasma exchange (TPE) has been used in severe COVID-19 disease to eliminate the cytokine storm. This meta-analysis aims to assess the effectiveness of TPE in reducing mortality in severe COVID-19 disease compared to standard treatment. MATERIALS AND METHODS A comprehensive literature search was performed in PubMed, the Cochrane database and the International Clinical Trial Registry Platform (ICTRP). The random-effect model was used to calculate the risk ratio and standardized mean difference (SMD) as pooled effect size for the difference in mortality and length of the intensive care unit (ICU) stay. The risk of bias and publication bias were assessed in R version 4.1.0. The certainty of the evidence was calculated using the GradePro tool. RESULTS The database identified 382 participants from six studies, including one randomized control trial. Egger's test did not detect any publication bias (p = 0.178). The random model analysis for mortality evaluated a risk ratio of 0.38 (95% CI: 0.28-0.52) with a significant reduction in the TPE group. The certainty of the evidence was moderate, with a risk ratio of 0.34 (95% CI: 0.24-0.49). Length of ICU stays between TPE versus standard care showed an SMD of 0.08 (95% CI: -0.38, 0.55) and was not significant. CONCLUSION The length of ICU stay in the TPE group was not different from standard care. However, this meta-analysis revealed a significant benefit of TPE in reducing mortality in severe COVID-19 disease compared to standard treatment.
Patients with severe COVID-19 disease (6 studies, n= 382).
Therapeutic plasma exchange (TPE).
The random model analysis for mortality evaluated a risk ratio of 0.38 (95% CI: 0.28-0.52) with a significant reduction in the TPE group. The certainty of the evidence was moderate, with a risk ratio of 0.34 (95% CI: 0.24-0.49). Length of intensive care unit stays between TPE versus standard care showed a standardized mean difference of 0.08 (95% CI: -0.38-0.55) and was not significant.
Can platelet-rich plasma injections provide better pain relief and functional outcomes in persons with common shoulder diseases: a meta-analysis of randomized controlled trials
Barman A, Mishra A, Maiti R, Sahoo J, Thakur KB, Sasidharan SK
Clinics in shoulder and elbow. 2021
BACKGROUND To evaluate the efficacy of autologous platelet-rich plasma (PRP) injections in the treatment of common shoulder diseases. METHODS The PubMed, Medline, and Central databases and trial registries were searched from their inception to October 2020 for randomized controlled trials of autologous PRP injections for shoulder diseases versus placebo or any control intervention. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed in the selection, analysis, and reporting of findings. The primary outcome was pain intensity (visual analog scale), and secondary outcomes were changes in function and quality of life (QoL). RESULTS A total of 17 randomized controlled trials of PRP versus control were analyzed. From 8-12 weeks to ≥1 year, PRP injections were associated with better pain relief and functional outcomes than control interventions. PRP injections were also associated with greater QoL, with an effect size of 2.61 (95% confidence interval, 2.01-14.17) at medium-term follow-up. Compared with placebo and corticosteroid injections, PRP injections provided better pain relief and functional improvement. In subgroup analyses, trials in which PRP was prepared by the double centrifugation technique, the platelet concentration in the PRP was enriched ≥5 times, leucocyte-rich PRP was used, or an activating agent was used before application reported the most effective pain relief at 6-7 months. CONCLUSIONS PRP injections could provide better pain relief and functional outcomes than other treatments for persons presenting with common shoulder diseases. PRP injections have a greater capacity to improve shoulder-related QoL than other interventions.
Recurrence rate and graft stability with fibrin glue compared with suture and autologous blood coagulum for conjunctival autograft adherence in pterygium surgery: a meta-analysis
Maiti R, Mukherjee S, Hota D
PURPOSE To minimize recurrence and improve graft stability after pterygium surgery, conjunctival autograft adherence is done using fibrin glue (FG) or autologous blood coagulum (ABC). But there are studies that have reported conflicting or inconclusive results. This meta-analysis was conducted to evaluate the postoperative recurrence rate and graft stability after using FG, sutures, and ABC. METHODS MEDLINE, Cochrane databases, and ICTRP were searched and PRISMA guidelines as well as recommended meta-analysis practices were followed. The odds ratio was calculated to estimate the effect size to assess the difference in recurrence and graft stability between the groups. Heterogeneity across the studies was explored using subgroup analyses and quality assessment using the Cochrane risk of bias tool and sensitivity analysis. RESULTS After screening, 30 studies were included for meta-analysis. The random model analysis for recurrence revealed an effect size of 0.44 [95% confidence interval (CI), 0.32-0.60], and subgroup analysis for studies comparing FG and sutures showed an effect size of 0.38 (95% CI, 0.27-0.53). In case of studies comparing FG and ABC, the random model analysis revealed an effect size of 1.01 (95% CI, 0.45-2.26). The random model analysis for graft stability revealed an effect size of 0.87 (95% CI, 0.57-1.31). In subgroup analysis, the random model revealed an effect size of 0.39 (95% CI, 0.17-0.88) indicating significant better graft stability with FG over ABC. CONCLUSIONS This meta-analysis reveals the superiority of FG over sutures as the use of FG can significantly reduce the recurrence rate, but no significant difference in graft stability was found between FG and sutures. No significant difference was found in the recurrence rate between FG and ABC, but graft stability was found to be better with FG compared with ABC.