Abstract

BACKGROUND Osteonecrosis of the jaw (ONJ) has a frequent adverse effect after the administration of nitrogenous bisphosphonates, as non-nitrogenous bisphosphonates are metabolized more rapidly and would produce this effect to a lesser extent. The objective of this study is to analyze the results obtained in the literature with the use of L-PRF in the treatment of ONJ through a systematic review and meta-analysis. MATERIAL AND METHODS Medline (via PubMed), Cochrane, Web of Science and Grey Literature Database was screened from which 10 were selected. RESULTS In the meta-analysis with full resolution, combining the use of L-PRF in the treatment of ONJ, a weighted proportion (PP) of 94.3% of complete resolution is obtained (95% CI: 91.2-97.4, p<0.001), with a low degree of heterogeneity, statistically significant (I2 = 29.02%; p<0.001). When analyzing the non-resolution data, a weighted proportion (PP) of 7.7% (95% CI: 3.6-11.9; p<0.001) was obtained with moderate heterogeneity (I2: 41.87%; p=0.112). In the meta-regression, no significant correlation was found between complete resolution and year of publication (intercept = 2.88, p=0.829). In consistency analysis no major changes in PP are identified when any of the studies are eliminated, demonstrating a high reliability in the combined results. CONCLUSION L-PRF alone or in combination with other therapies in treatment of ONJ achieved high percentages of complete lesion resolution (94.3%). In studies where L-PRF is combined with other therapies, and where the effectiveness of the other therapy alone is analyzed, L-PRF has been shown higher percentages of resolution.

Abstract

PURPOSE To evaluate the role of platelet-rich plasma (PRP) for adhesive capsulitis (AC) as compared to other injectables. METHODS A literature search was performed on PubMed and Embase online databases identifying articles evaluating injection therapy for the treatment of AC. Inclusion criteria included prospective studies comparing PRP against alternative injectables with a minimum 15 patients in each treatment arm and a minimum 12-week follow-up. Pain scores, range of motion, and function scores were the primary outcomes assessed. RESULTS Five articles met inclusion criteria comparing PRP to corticosteroid or saline injections. There were 157 patients treated with PRP with follow-up duration ranging from three to six months. All five studies demonstrated statistically significant improvement in pain scores, motion, and function scores for patients receiving PRP, corticosteroid, and saline injections. However, PRP was consistently superior on intergroup analyses in all but one study. In four studies, pain and function scores favored PRP over control at final follow-up (range in mean difference for VAS pain score: -2.2 - 0.69, n=5 and SPADI score: -50.5 - -4.0, n=3) while three studies found greater improvement in shoulder motion after PRP (range in mean difference for forward flexion: 0.7 - 34.3 degrees and external rotation -2.3 - 20.4 degrees, n=4). One study found no significant difference between PRP and corticosteroid injections, but noted results were comparable. CONCLUSIONS According to a limited number of prospective studies, PRP injections for AC is at least equivalent to corticosteroid or saline injections and often leads to improved pain, motion, and functional outcomes at 3-6-month follow-up. Given the small number of studies, with design heterogeneity, there is insufficient evidence to routinely recommend PRP for AC. However, the results are promising and do support considering PRP as an adjunct treatment option for AC, especially for patients refractory and/or averse to corticosteroids or alternative treatment modalities.

Abstract

BACKGROUND Over the past few years, many studies have been conducted to evaluate the effectiveness of platelet-rich plasma (PRP) in treating musculoskeletal conditions. However, there is controversy about its benefits for patients with Achilles tendinopathy. OBJECTIVE This study aimed to investigate whether platelet-rich plasma injections can improve outcomes in patients with Achilles tendinopathy. METHODS A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, Web of Science, China Biomedical CD-ROM, and Chinese Science and Technology Journal databases to identify randomised controlled clinical trials that compared the efficacy of PRP injection in patients with Achilles tendinopathy (AT) versus placebo, published between 1 January 1966 and 1 December 2022. Review Manager 5.4.1 software was used for the statistical analysis, and the Jadad score was used to assess the included literature. Only 8 of the 288 articles found met the inclusion criteria. RESULTS Our work suggests that: The PRP treatment group had a slightly higher VISA-A score than the placebo group at 6 weeks [MD = 1.92, 95% CI (-0.54, 4.38), I(2) = 34%], at 12 weeks [MD = 0.20, 95% CI (-2.65 3.05), I(2) = 60%], and 24 weeks [MD = 2.75, 95% CI (-2.76, 8.26), I(2) = 87%]). However, the difference was not statistically significant. The Achilles tendon thickness was higher at 12 weeks of treatment in the PRP treatment group compared to the control group [MD = 0.34, 95% CI (-0.04, 0.71), p = 0.08], but the difference was not statistically significant. The VAS-improvement results showed no significant difference at 6 and 24 weeks between the two groups, respectively (MD = 6.75, 95% CI = (-6.12, 19.62), I(2) = 69%, p = 0.30), and (MD = 10.46, 95% CI = (-2.44 to 23.37), I(2) = 69%, p = 0.11). However, at 12 weeks of treatment, the PRP injection group showed a substantial VAS improvement compared to the control group (MD = 11.30, 95% CI = (7.33 to 15.27), I(2) = 0%, p < 0.00001). The difference was statistically significant. The return to exercise rate results showed a higher return to exercise rate in the PRP treatment group than the placebo group [RR = 1.11, 95% CI (0.87, 1.42), p = 0.40]; the difference was not statistically significant. CONCLUSION There is no proof that PRP injections can enhance patient functional and clinical outcomes for Achilles tendinopathy. Augmenting the frequency of PRP injections may boost the outcomes, and additionally, more rigorous designs and standardised clinical randomised controlled trials are needed to produce more reliable and accurate results.

Abstract

OBJECTIVE To investigate the effect of platelet-rich fibrin application on implant stability. STUDY DESIGN Five databases, namely, PubMed, Embase, Web of Science, Wiley, and China National Knowledge Infrastructure, were searched for reports published up to November 20, 2022. Randomized controlled trials (RCT), including parallel RCTs and split-mouth RCTs, with at least 10 patients/sites were considered for inclusion. RESULTS After screening based on the inclusion criteria, ten RCTs were included. Low heterogeneity was observed in study characteristics, outcome variables, and estimation scales (I(2) = 27.2%, P = 0.19). The qualitative and meta-analysis results showed that PRF increased the effect of implant stabilizers after implant surgery. CONCLUSIONS The results of the present systematic review and meta-analysis suggest that PRF can increase implant stability after implant surgery. PRF may also have a role in accelerating bone healing and tends to promote new bone formation at the implant site.

Abstract

BACKGROUND Outpatient monoclonal antibodies are no longer effective and antiviral treatments for COVID-19 disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma is promising, clinical trials among outpatients have shown mixed results. METHODS We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching MEDLINE, Embase, MedRxiv, World Health Organization, Cochrane Library, and Web of Science from January 2020 to September 2022. RESULTS Five included studies from four countries enrolled and transfused 2,620 adult patients. Comorbidities were present in 1,795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14,580 in diverse assays. 160 (12.2%) of 1315 control patients were hospitalized, versus 111 (8.5%) of 1305 COVID-19 convalescent plasma treated patients, yielding a 3.7% (95%CI: 1.3%-6.0%; p=.001) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titer with a 7.6% absolute risk reduction (95%CI: 4.0%-11.1%; p=.0001) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment > 5 days after symptom onset or in those receiving COVID-19 convalescent plasma with antibody titers below the median titer. CONCLUSIONS Among outpatients with COVID-19, treatment with COVID-19 convalescent plasma reduced the rate of all-cause hospitalization and may be most effective when given within 5 days of symptom onset and when antibody titer is higher.

Abstract

BACKGROUND Convalescent plasma may reduce mortality in patients with viral respiratory diseases, and is being investigated as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding benefits and risks of this intervention is required. OBJECTIVES To assess the effectiveness and safety of convalescent plasma transfusion in the treatment of people with COVID-19; and to maintain the currency of the evidence using a living systematic review approach. SEARCH METHODS To identify completed and ongoing studies, we searched the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, and the Epistemonikos COVID-19 L*OVE Platform. We searched monthly until 03 March 2022. SELECTION CRITERIA We included randomised controlled trials (RCTs) evaluating convalescent plasma for COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)), as well as studies evaluating standard immunoglobulin. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology. To assess bias in included studies we used RoB 2. We used the GRADE approach to rate the certainty of evidence for the following outcomes: all-cause mortality at up to day 28, worsening and improvement of clinical status (for individuals with moderate to severe disease), hospital admission or death, COVID-19 symptoms resolution (for individuals with mild disease), quality of life, grade 3 or 4 adverse events, and serious adverse events. MAIN RESULTS In this fourth review update version, we included 33 RCTs with 24,861 participants, of whom 11,432 received convalescent plasma. Of these, nine studies are single-centre studies and 24 are multi-centre studies. Fourteen studies took place in America, eight in Europe, three in South-East Asia, two in Africa, two in western Pacific and three in eastern Mediterranean regions and one in multiple regions. We identified a further 49 ongoing studies evaluating convalescent plasma, and 33 studies reporting as being completed. Individuals with a confirmed diagnosis of COVID-19 and moderate to severe disease 29 RCTs investigated the use of convalescent plasma for 22,728 participants with moderate to severe disease. 23 RCTs with 22,020 participants compared convalescent plasma to placebo or standard care alone, five compared to standard plasma and one compared to human immunoglobulin. We evaluate subgroups on detection of antibodies detection, symptom onset, country income groups and several co-morbidities in the full text. Convalescent plasma versus placebo or standard care alone Convalescent plasma does not reduce all-cause mortality at up to day 28 (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.92 to 1.03; 220 per 1000; 21 RCTs, 19,021 participants; high-certainty evidence). It has little to no impact on need for invasive mechanical ventilation, or death (RR 1.03, 95% CI 0.97 to 1.11; 296 per 1000; 6 RCTs, 14,477 participants; high-certainty evidence) and has no impact on whether participants are discharged from hospital (RR 1.00, 95% CI 0.97 to 1.02; 665 per 1000; 6 RCTs, 12,721 participants; high-certainty evidence). Convalescent plasma may have little to no impact on quality of life (MD 1.00, 95% CI -2.14 to 4.14; 1 RCT, 483 participants; low-certainty evidence). Convalescent plasma may have little to no impact on the risk of grades 3 and 4 adverse events (RR 1.17, 95% CI 0.96 to 1.42; 212 per 1000; 6 RCTs, 2392 participants; low-certainty evidence). It has probably little to no effect on the risk of serious adverse events (RR 1.14, 95% CI 0.91 to 1.44; 135 per 1000; 6 RCTs, 3901 participants; moderate-certainty evidence). Convalescent plasma versus standard plasma We are uncertain whether convalescent plasma reduces or increases all-cause mortality at up to day 28 (RR 0.73, 95% CI 0.45 to 1.19; 129 per 1000; 4 RCTs, 484 participants; very low-certainty evidence). We are uncertain whether convalescent plasma reduces or increases the need for invasive mechanical ventilation, or death (RR 5.59, 95% CI 0.29 to 108.38; 311 per 1000; 1 study, 34 participants; very low-certainty evidence) and whether it reduces or increases the risk of serious adverse events (RR 0.80, 95% CI 0.55 to 1.15; 236 per 1000; 3 RCTs, 327 participants; very low-certainty evidence). We did not identify any study reporting other key outcomes. Convalescent plasma versus human immunoglobulin Convalescent plasma may have little to no effect on all-cause mortality at up to day 28 (RR 1.07, 95% CI 0.76 to 1.50; 464 per 1000; 1 study, 190 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. Individuals with a confirmed diagnosis of SARS-CoV-2 infection and mild disease We identified two RCTs reporting on 536 participants, comparing convalescent plasma to placebo or standard care alone, and two RCTs reporting on 1597 participants with mild disease, comparing convalescent plasma to standard plasma. Convalescent plasma versus placebo or standard care alone We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (odds ratio (OR) 0.36, 95% CI 0.09 to 1.46; 8 per 1000; 2 RCTs, 536 participants; very low-certainty evidence). It may have little to no effect on admission to hospital or death within 28 days (RR 1.05, 95% CI 0.60 to 1.84; 117 per 1000; 1 RCT, 376 participants; low-certainty evidence), on time to COVID-19 symptom resolution (hazard ratio (HR) 1.05, 95% CI 0.85 to 1.30; 483 per 1000; 1 RCT, 376 participants; low-certainty evidence), on the risk of grades 3 and 4 adverse events (RR 1.29, 95% CI 0.75 to 2.19; 144 per 1000; 1 RCT, 376 participants; low-certainty evidence) and the risk of serious adverse events (RR 1.14, 95% CI 0.66 to 1.94; 133 per 1000; 1 RCT, 376 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. Convalescent plasma versus standard plasma We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (OR 0.30, 95% CI 0.05 to 1.75; 2 per 1000; 2 RCTs, 1597 participants; very low-certainty evidence). It probably reduces admission to hospital or death within 28 days (RR 0.49, 95% CI 0.31 to 0.75; 36 per 1000; 2 RCTs, 1595 participants; moderate-certainty evidence). Convalescent plasma may have little to no effect on initial symptom resolution at up to day 28 (RR 1.12, 95% CI 0.98 to 1.27; 1 RCT, 416 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. This is a living systematic review. We search monthly for new evidence and update the review when we identify relevant new evidence. AUTHORS' CONCLUSIONS For the comparison of convalescent plasma versus placebo or standard care alone, our certainty in the evidence that convalescent plasma for individuals with moderate to severe disease does not reduce mortality and has little to no impact on clinical improvement or worsening is high. It probably has little to no effect on SAEs. For individuals with mild disease, we have low certainty evidence for our primary outcomes. There are 49 ongoing studies, and 33 studies reported as complete in a trials registry. Publication of ongoing studies might resolve some of the uncertainties around convalescent plasma therapy for people with asymptomatic or mild disease.

Abstract

BACKGROUND While early evidence concluded a lack of clinical benefit of convalescent plasma therapy (CPT) in COVID-19 management, recent trials demonstrate the therapeutic potential of CPT in ambulatory care. CPT may also potentiate thromboembolic events given the presence of coagulation factors and the prothrombotic state of COVID-19. OBJECTIVE The present study aims to assess and compare the clinical efficacy and the risk of venous/arterial thromboembolism (VTE, ATE) of CPT in ambulatory vs hospitalized COVID-19 patients. METHODS MEDLINE, Embase, and Cochrane CENTRAL were searched from December 2019 to December 2022 for randomized controlled trials that investigated the use of CPT against placebo or standard of care in adult COVID-19 patients. The primary outcome was non-mortality disease progression. Secondary outcomes include VTE, ATE, 28-day mortality, clinical improvement, length of hospitalization (LOH), sepsis/fever, and major adverse cardiovascular events (MACE). RESULTS Twenty randomized controlled trials, with 21340 patients, were included. CPT significantly reduced non-mortality disease progression in ambulatory patients (OR 0.72, 0.56-0.92, P = 0.009) but not in hospitalized patients (1.03, 0.94-1.12, P = 0.58). The risk of VTE and ATE did not differ between the CPT and the control group (1.15, 0.81 to 1.64, P = 0.44; 1.01, 0.37 to 2.79, P = 0.98). No conclusive differences between CPT and control were noted in 28-day mortality, clinical improvement, LOH, risk of sepsis/fever, and MACE. CONCLUSIONS In conclusion, treatment of COVID-19 with CPT prevents the progression of COVID-19 in the ambulatory care. It is not associated with an increased risk of VTE, ATE, or other adverse events.

Abstract

The aim of this review was to update evidence for benefit of convalescent plasma transfusion (CPT) in patients with coronavirus disease 2019 (COVID-19). Databases were searched for randomized controlled trials (RCT) comparing CPT plus standard treatment versus standard treatment only in adults with COVID-19. Primary outcome measures were mortality and need for invasive mechanical ventilation (IMV). Twenty-Six RCT involving 19,816 patients were included in meta-analysis for mortality. Quantitative synthesis showed no statistically significant benefit of adding CPT to standard treatment (RR = 0.97, 95% CI = 0.92 to 1.02) with unimportant heterogeneity (Q(25) = 26.48, p = .38, I(2) = 0.00%). Trim-and-fill-adjusted effect size was unimportantly changed and level of evidence was graded as high. Trial sequential analysis (TSA) indicated information size was adequate and CPT was futile. Seventeen trials involving 16,083 patients were included in meta-analysis for need of IMV. There was no statistically significant effect of CPT (RR = 1.02, 95% CI = 0.95 to 1.10) with unimportant heterogeneity (Q(16) = 9.43, p = .89, I(2) = 3.30%). Trim-and-fill-adjusted effect size was trivially changed and level of evidence was graded as high. TSA showed information size was adequate and indicated futility of CPT. It is concluded with high level of certainty that CPT added to standard treatment of COVID-19 is not associated with reduced mortality or need of IMV compared with standard treatment alone. In view of these findings, further trials on efficacy of CPT in COVID-19 patients are probably not needed.

Abstract

PURPOSE Multiple preparation protocols for platelet-rich fibrin (PRF) are in use today, and clinical results are often heterogeneous. This study analyzes the impact of the chosen PRF preparation protocol on 1) wound healing and 2) alveolar ridge preservation. METHODS For this systematic review and meta-analysis, eligible studies were identified in PubMed and Cochrane databases. Included were randomized controlled and controlled clinical trials with healthy patients treated with PRF after atraumatic tooth extraction compared to untreated socket(s), reporting at least one of the following outcome variables: pain, swelling, soft tissue healing, alveolar osteitis risk, horizontal and vertical bone loss, socket fill, and new bone formation. Main predictor variable was relative centrifugal force (RCF) comparing high RCF (high PRF), intermediate RCF (standard [S-PRF]), low RCF (advanced PRF), and various RCF settings (concentrated growth factor preparation [CGF]). The type of centrifugation tubes (silica-coated plastic and glass) was a secondary predictor. Weighted or standardized mean differences, risk ratio and corresponding 95% confidence intervals were calculated. RESULTS Forty studies published between 2012 and 2022 were selected. The pooled effects of all outcomes were significant against untreated sockets. Within the subgroups high PRF or advanced PRF had the lowest efficacy for many outcome parameters. Pain reduction (in visual analog scale units) was highest for S-PRF (-1.18 [-1.48, -0.88], P < .00001) and CGF (-1.03 [-1.16, -0.90], P < .001). The relative risk of alveolar osteitis (0.09 [0.01, 0.69], P < .02) and soft tissue healing (standardized mean difference = 2.55 [2.06, 3.03], P < .001) were best for CGF. No subgroup differences were found for bone-related outcomes. No meaningful analysis of the tube material effect was possible. CONCLUSION This study confirms that PRF is associated with reduced postoperative complications but indicates that preparation protocol influences clinical outcomes. S-PRF and CGF protocols appear to be superior for several outcome parameters.

Abstract

OBJECTIVES The objective of this study was to critically appraise and synthesise evidence for blood conservation strategies in intensive care. Blood sampling is a critical aspect of intensive care to guide clinical decision-making. Repeated blood sampling can result in blood waste and contamination, leading to iatrogenic anaemia and systemic infection. REVIEW METHOD USED Cochrane systematic review methods were used including meta-analysis, and independent reviewers. DATA SOURCES A systematic search was conducted in Medline, CINAHL, PUBMED and EMBASE databases. The search was limited to randomised controlled trials (RCTs) and cluster RCTs, published in English between 2000 and 2021. REVIEW METHODS Paired authors independently assessed database search results and identified eligible studies. Trials comparing any blood conservation practice or product in intensive care were included. Primary outcomes were blood sample volumes and haemoglobin change. Secondary outcomes included proportion of patients receiving transfusions and infection outcomes. Quality appraisal employed the Cochrane Risk of Bias tool. Meta-analysis using random effects approach and narrative synthesis summarised findings. RESULTS Eight studies (n = 1027 patients), all RCTs were eligible. Six studies included adults, one studied paediatrics and one studied preterm infants. Seven studies evaluated a closed loop blood sampling system, and one studied a conservative phlebotomy protocol. Studies were of low to moderate quality. Meta-analysis was not possible for interventions targeting blood sample volumes or haemoglobin. Decreased blood sample volumes reported in four studies were attributable to a closed loop system or conservative phlebotomy. No study reported a significant change in haemoglobin. Meta-analysis demonstrated that use of a closed system (compared to open system) reduced the proportion of patients receiving transfusion [Risk Ratio (RR) 0.65, 95% CI 0.46-0.92; 287 patients] and reduced intraluminal fluid colonisation [RR 0.25, 95% CI 0.07-0.58; 500 patients]. CONCLUSIONS Limited evidence demonstrates closed loop blood sampling systems reduced transfusion use and fluid colonisation. Simultaneous effectiveness-implementation evaluation of these systems and blood conservation strategies is urgently required. PROSPERO PROTOCOL REGISTRATION REFERENCE CRD42019137227.