Association of Convalescent Plasma Treatment With Clinical Status in Patients Hospitalized With COVID-19: A Meta-analysis
JAMA network open. 2022;5(1):e2147331
IMPORTANCE COVID-19 convalescent plasma (CCP) is a potentially beneficial treatment for COVID-19 that requires rigorous testing. OBJECTIVE To compile individual patient data from randomized clinical trials of CCP and to monitor the data until completion or until accumulated evidence enables reliable conclusions regarding the clinical outcomes associated with CCP. DATA SOURCES From May to August 2020, a systematic search was performed for trials of CCP in the literature, clinical trial registry sites, and medRxiv. Domain experts at local, national, and international organizations were consulted regularly. STUDY SELECTION Eligible trials enrolled hospitalized patients with confirmed COVID-19, not receiving mechanical ventilation, and randomized them to CCP or control. The administered CCP was required to have measurable antibodies assessed locally. DATA EXTRACTION AND SYNTHESIS A minimal data set was submitted regularly via a secure portal, analyzed using a prespecified bayesian statistical plan, and reviewed frequently by a collective data and safety monitoring board. MAIN OUTCOMES AND MEASURES Prespecified coprimary end points-the World Health Organization (WHO) 11-point ordinal scale analyzed using a proportional odds model and a binary indicator of WHO score of 7 or higher capturing the most severe outcomes including mechanical ventilation through death and analyzed using a logistic model-were assessed clinically at 14 days after randomization. RESULTS Eight international trials collectively enrolled 2369 participants (1138 randomized to control and 1231 randomized to CCP). A total of 2341 participants (median [IQR] age, 60 [50-72] years; 845 women [35.7%]) had primary outcome data as of April 2021. The median (IQR) of the ordinal WHO scale was 3 (3-6); the cumulative OR was 0.94 (95% credible interval [CrI], 0.74-1.19; posterior probability of OR <1 of 71%). A total of 352 patients (15%) had WHO score greater than or equal to 7; the OR was 0.94 (95% CrI, 0.69-1.30; posterior probability of OR <1 of 65%). Adjusted for baseline covariates, the ORs for mortality were 0.88 at day 14 (95% CrI, 0.61-1.26; posterior probability of OR <1 of 77%) and 0.85 at day 28 (95% CrI, 0.62-1.18; posterior probability of OR <1 of 84%). Heterogeneity of treatment effect sizes was observed across an array of baseline characteristics. CONCLUSIONS AND RELEVANCE This meta-analysis found no association of CCP with better clinical outcomes for the typical patient. These findings suggest that real-time individual patient data pooling and meta-analysis during a pandemic are feasible, offering a model for future research and providing a rich data resource.
Evaluation of efficacy of Valsalva for attenuating needle puncture pain in first time nonremunerated voluntary plateletpheresis donors: A prospective, randomized controlled trial
Asian journal of transfusion science. 2021;15(1):68-74
BACKGROUND Plateletpheresis is generally safe but may have adverse reactions. Adverse reactions can negatively influence donor recruitment and retention. Valsalva is a proven method of attenuating pain caused by venipuncture. AIMS The aim was to evaluate the efficacy of the Valsalva maneuver on the attenuation of needle pain and donor anxiety. SETTINGS AND DESIGN This prospective randomized controlled trial was conducted between November 2015 and April 2016 at the Department of Transfusion Medicine. SUBJECTS AND METHODS One-hundred and sixty consecutive donors were grouped into control group (C) and Valsalva group (V) each of sample size 80. The Valsalva group performed a Valsalva maneuver and control did nothing before the venipuncture. Anxiety and pain were scored using a 10 cm visual analog scale (VAS). Severity was graded as VAS = 0 defines no pain and anxiety, VAS = 1-3 as mild pain and anxiety, VAS = 4-6 as moderate pain and anxiety, VAS = 7-9 as severe pain and anxiety, whereas VAS = 10 denotes extreme pain and anxiety. STATISTICAL ANALYSIS Statistical Package for Social Sciences, version 23 was used for analysis. Independent samples t-test/Mann-Whitney U-test was used to compare between treatment and control group, whereas the Wilcoxon signed-rank test was used to test the difference between pre- and postobservations. RESULTS In the Valsalva group, post-Valsalva anxiety levels were significantly reduced to (1 [0-2]) from their pre-Valsalva values of (2 [0-3]); (P < 0.001). Pain was significantly lower (2[1-2]) in Valsalva group compared to control (4[2-5]); (P < 0.001). CONCLUSIONS Valsalva reduced both severity of venipuncture pain and anxiety. Valsalva can be performed by donors as it is an easy, painless, and nonpharmacological method of pain and anxiety attenuation.
Prognostic factors for VTE and Bleeding in Hospitalized Medical Patients: a systematic review and meta-analysis
Many predictors for venous thromboembolism (VTE) and bleeding in hospitalized medical patients may exist but until now systematic reviews and assessments of the certainty of the evidence do not exist. We conducted a systematic review to identify prognostic factors for VTE and bleeding in hospitalized medical patients and searched Medline and EMBASE from inception to May 2018. We considered studies that identified potential prognostic factors for VTE and bleeding in hospitalized adult medical patients. Reviewers extracted data in duplicate and independently and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Of 69,410 citations, we included 17 studies; 14 that reported on VTE and identified 29 candidate prognostic factors and three that reported on bleeding and identified 17 candidate factors. For VTE, moderate certainty evidence shows a probable association with older age, elevated CRP, D-dimer, fibrinogen levels, heart rate, thrombocytosis, leukocytosis, fever, leg edema, lower Barthel Index score, immobility, paresis, previous history of VTE, thrombophilia, malignancy, critical illness and infections. For bleeding, moderate certainty evidence shows a probable association with older age, sex, anemia, obesity, low hemoglobin, gastroduodenal ulcers, rehospitalization, critical illness, thrombocytopenia, blood dyscrasias, hepatic disease, renal failure, antithrombotic medication and central venous catheter (CVC). Elevated CRP, a lower Barthel Index, history of malignancy and elevated heart rate are not included in most VTE risk assessment models (RAMs). This study informs risk prediction in the management of hospitalized medical patients for VTE and bleeding, related research and guidelines for VTE prevention.
Hospitalized adult medical patients (17 studies).
Systematic review to identify prognostic factors for venous thromboembolism (VTE) and bleeding.
Fourteen studies that reported on VTE identified 29 candidate prognostic factors and three that reported on bleeding identified 17 candidate factors. For VTE, moderate certainty evidence shows a probable association with older age, elevated CRP, D-dimer, fibrinogen levels, heart rate, thrombocytosis, leukocytosis, fever, leg edema, lower Barthel Index score, immobility, paresis, previous history of VTE, thrombophilia, malignancy, critical illness and infections. For bleeding, moderate certainty evidence shows a probable association with older age, sex, anemia, obesity, low hemoglobin, gastroduodenal ulcers, rehospitalization, critical illness, thrombocytopenia, blood dyscrasias, hepatic disease, renal failure, antithrombotic medication and central venous catheter. Elevated CRP, a lower Barthel Index, history of malignancy and elevated heart rate are not included in most VTE risk assessment models.
Risk models for VTE and bleeding in medical inpatients: systematic identification and expert assessment
Blood Adv. 2020;4(12):2557-2566
Risk assessment models (RAMs) for venous thromboembolism (VTE) and bleeding in hospitalized medical patients inform appropriate use of thromboprophylaxis. Our aim was to use a novel approach for selecting risk factors for VTE and bleeding to be included in RAMs. First, we used the results of a systematic review of all candidate factors. Second, we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of the evidence for the identified factors. Third, we using a structured approach to select factors to develop the RAMs, by building on clinical and methodological expertise. The expert panel made judgments on whether to include, potentially include, or exclude risk factors, according to domains of the GRADE approach and the Delphi method. The VTE RAM included age >60 years, previous VTE, acute infections, immobility, acute paresis, active malignancy, critical illness, and known thrombophilia. The bleeding RAM included age >=65 years, renal failure, thrombocytopenia, active gastroduodenal ulcers, hepatic disease, recent bleeding, and critical illness. We identified acute infection as a factor that was not considered in widely used RAMs. Also, we identified factors that require further research to confirm or refute their importance in a VTE RAM (eg, D-dimer). We excluded autoimmune disease which is included in the IMPROVE (International Medical Prevention Registry on Venous Thromboembolism) bleeding RAM. Our results also suggest that sex, malignancy, and use of central venous catheters (factors in the IMPROVE bleeding RAM) require further research. In conclusion, our study presents a novel approach to systematically identifying and assessing risk factors to be included or further explored during RAM development.
Risk-assessment models for VTE and bleeding in hospitalized medical patients: an overview of systematic reviews
Blood advances. 2020;4(19):4929-4944
Multiple risk-assessment models (RAMs) for venous thromboembolism (VTE) in hospitalized medical patients have been developed. To inform the 2018 American Society of Hematology (ASH) guidelines on VTE, we conducted an overview of systematic reviews to identify and summarize evidence related to RAMs for VTE and bleeding in medical inpatients. We searched Epistemonikos, the Cochrane Database, Medline, and Embase from 2005 through June 2017 and then updated the search in January 2020 to identify systematic reviews that included RAMs for VTE and bleeding in medical inpatients. We conducted study selection, data abstraction and quality assessment (using the Risk of Bias in Systematic Reviews [ROBIS] tool) independently and in duplicate. We described the characteristics of the reviews and their included studies, and compared the identified RAMs using narrative synthesis. Of 15 348 citations, we included 2 systematic reviews, of which 1 had low risk of bias. The reviews included 19 unique studies reporting on 15 RAMs. Seven of the RAMs were derived using individual patient data in which risk factors were included based on their predictive ability in a regression analysis. The other 8 RAMs were empirically developed using consensus approaches, risk factors identified from a literature review, and clinical expertise. The RAMs that have been externally validated include the Caprini, Geneva, IMPROVE, Kucher, and Padua RAMs. The Padua, Geneva, and Kucher RAMs have been evaluated in impact studies that reported an increase in appropriate VTE prophylaxis rates. Our findings informed the ASH guidelines. They also aim to guide health care practitioners in their decision-making processes regarding appropriate individual prophylactic management.
Adult patients hospitalized for an acute, critical, or chronic medical illness. (2 systematic reviews).
Overview of systematic reviews to identify and describe multiple risk-assessment models (RAMs) and their clinical utility for venous thromboembolism (VTE) and bleeding.
Standard care without the use of RAMs or a different RAM from the one used in the intervention.
Fifteen unique RAMs for VTE were identified, seven were derived from individual participant data and eight were developed empirically using consensus approaches, risk factors identified from a literature review, and clinical expertise. Five systematic reviews described RAMs that have been externally validated and three systematic reviews described RAMs evaluated in terms of thromboprophylaxis rates or clinical outcomes.
Platelet-rich fibrin in combination with decalcified freeze-dried bone allograft for the management of mandibular degree II furcation defect: A randomised controlled clinical trial
Singapore dental journal. 2020;:1-8
Background: Treatment of furcation involvement of molars with periodontal disease remains challenging and unpredictable. Platelet-rich fibrin (PRF) has received the attention of researchers due to its pleiotropic properties essential for periodontal wound healing. The osteoinductive property of demineralized freeze-dried bone allograft (DFDBA) has been successfully used in periodontal regeneration. Aim: The present study aimed to explore the effectiveness of PRF alone and with DFDBA in the treatment of mandibular degree II furcation defects in subjects with chronic periodontitis. Material and Methods: Patients treated were from the Department of Periodontology and Implantology, Institute of Dental Sciences, Bareilly. A total of 60 mandibular molars were treated with either open flap debridement (OFD) alone, PRF+OFD combination or OFD+PRF+DFDBA combination. The soft and hard tissue parameters such as vertical probing depth (VPD), vertical clinical attachment level (VCAL), gingival marginal level (GML), horizontal probing depth (HPD), vertical bone fill (VBF), horizontal bone fill (HBF) and furcation width (FW) were determined at baseline and 9 months postoperatively. A paired t-test was conducted to assess the statistical significance between time period within each group for clinical and radiographic parameters. ANOVA and post-hoc Tukey's tests were also conducted for intergroup comparison of soft and hard tissue parameters. Statistical significance was set at p<0.05. Results and Discussion: After 9 months, all treatment groups showed significant (p<0.001) improvement in soft and hard tissue parameters, except GML in all the three groups and HBF and FW in the OFD group as compared to baseline. The mean VBF change was highest in the OFD+PRF+DFDBA group (1.90+0.45) mm, followed by that in the PRF+OFD and OFD groups (1.60+0.88 and 0.45+0.51mm, respectively). Conclusions: It was shown that both PRF+OFD and PRF+DFDBA+OFD combinations were significantly advantageous for the management of mandibular degree II furcation defects. However, the PRF+DFDBA+OFD combination has significantly greater benefits than PRF+OFD combination in terms of VBF.
Efficacy and safety of blood transfusion in obstetric patients: systematic review of the literature
Ginekologia Polska. 2017;88((8)):446-452.
OBJECTIVES To evaluate the efficacy of blood transfusion compared to no intervention in obstetric patients. MATERIAL AND METHODS A systematic review was performed with Cochrane Database of Clinical Trials, PubMed, EMBASE and LILACS databases searched as of September, 2016. Two authors independently selected relevant clinical trials, assessed their methodological quality and extracted data, using the GRADE approach. RESULTS Five studies within a total of 6,297 met the inclusion criteria, with women generally aged 20-40 years. Three included studies allocated women to receive blood transfusion or no intervention. Two other studies allocated women with either restricted or full blood supplies. The major issue regarding risk of bias was the extent of concealment of randomization and blinding. There was no statistically significant difference between blood transfusion versus no transfusion or restricted blood supply on mortality (relative risk 0.82 [95% confidential interval 0.32 to 2.09], p = 0.68; two studies; I2 = not applicable). CONCLUSIONS Very low-quality evidence suggests no significant difference between blood transfusion and no intervention in obstetric patients, underlining the need for more robust clinical trials evaluating this area.
Platelet rich fibrin combined with decalcified freeze-dried bone allograft for the treatment of human intrabony periodontal defects: a randomized split mouth clinical trail
Acta Odontologica Scandinavica. 2016;74((1)):36-43.
OBJECTIVE Polypeptide growth factors of platelet rich fibrin (PRF) have the potential to regenerate periodontal tissues. Osteoinductive property of demineralized freeze-dried bone allograft (DFDBA) has been successfully utilized in periodontal regeneration. The aim of the present randomized, split mouth, clinical trial was to determine the additive effects of PRF with a DFDBA in the treatment of human intrabony periodontal defects. MATERIALS AND METHODS Sixty interproximal infrabony defects in 30 healthy, non-smoker patients diagnosed with chronic periodontitis were randomly assigned to PRF/DFDBA group or the DFDBA/saline. Clinical [pocket depth (PD), clinical attachment level (CAL) and gingival recession (REC)] and radiographic (bone fill, defect resolution and alveolar crest resorption) measurements were made at baseline and at a 12-month evaluation. RESULTS Compared with baseline, 12-month results indicated that both treatment modalities resulted in significant changes in all clinical and radiographic parameters. However, the PRP/DFDBA group exhibited statistically significantly greater changes compared with the DFDBA/saline group in PD (4.15 +/- 0.84 vs 3.60 +/- 0.51 mm), CAL (3.73 +/- 0.74 vs 2.61 +/- 0.68 mm), REC (0.47 +/- 0.56 vs 1.00 +/- 0.61 mm), bone fill (3.50 +/- 0.67 vs 2.49 +/- 0.64 mm) and defect resolution (3.73 +/- 0.63 vs 2.75 +/- 0.57 mm). CONCLUSION Observations indicate that a combination of PRF and DFDBA is more effective than DFDBA with saline for the treatment of infrabony periodontal defects.
Platelet-rich plasma combined with decalcified freeze-dried bone allograft for the treatment of noncontained human intrabony periodontal defects: a randomized controlled split-mouth study
International Journal of Periodontics & Restorative Dentistry. 2014;34((5):):705-11.
The aim of the present randomized split-mouth clinical trial was to compare plateletrich plasma (PRP) combined with a demineralized freeze-dried bone allograft (DFDBA) to DFDBA with a saline solution in the treatment of noncontained human periodontal intrabony defects. Forty-eight noncontained interproximal intrabony defects in 24 healthy nonsmoking patients diagnosed with chronic periodontitis were randomly assigned to the test group (PRP/DFDBA) or the control group (DFDBA/saline). Clinical (probing pocket depth, clinical attachment level [CAL], and gingival recession [REC]) and radiographic (bone fill, defect resolution, and alveolar crest resorption) measurements were made at baseline and at a 12-month evaluation. Compared with baseline, 12-month results indicated that both treatment modalities resulted in significant changes in all clinical and radiographic parameters. However, the test group exhibited statistically significantly greater changes compared with the control group in CAL (3.15 + 0.50 versus 2.40 + 0.61 mm), REC (0.54 + 0.59 versus 1.23 + 0.47 mm), bone fill (3.02 + 0.50 versus 2.37 + 0.47 mm), and defect resolution (3.29 + 0.53 versus 2.69 + 0.38 mm). Findings indicate that a combination of PRP and DFDBA is more effective than DFDBA with saline for the treatment of noncontained intrabony defects.