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Reporting Bias is Highly Prevalent in Systematic Reviews and Meta-Analyses of Platelet Rich Plasma Injections for Hip Osteoarthritis
Kim, D., Bashrum, B. S., Kotlier, J. L., Mayfield, C. K., Thompson, A. A., Abu-Zahra, M., Hwang, M., Bolia, I. K., Petrigliano, F. A., Liu, J. N.
Arthroscopy, sports medicine, and rehabilitation. 2024;6(1):100851
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Abstract
PURPOSE To describe the incidence and types of spin in systematic reviews of platelet-rich plasma (PRP) injections for hip osteoarthritis (OA) and to determine whether patterns in study characteristics could be identified among studies with identifiable spin. METHODS The PubMed, Scopus, and SPORTDiscus databases were queried. Inclusion criteria were systematic reviews or meta-analyses that included an assessment of intra-articular PRP injections as a stand-alone treatment for hip OA. Two authors independently assessed the presence of spin in the included studies and recorded general study characteristics. The prevalence of the 15 different categories of spin was quantified using descriptive statistics. RESULTS Fifteen studies met inclusion criteria for this study. All studies contained at least two types of spin (range 2-9), with a median of 2. The most common type of spin was type 14 ("Failure to report a wide confidence interval of estimates"), which was observed in 10 studies. The second most common type of spin was type 13 ("Failure to specify the direction of the effect when it favors the control intervention"), found in 6 studies. CONCLUSIONS Spin is highly prevalent in abstracts of systematic reviews of PRP in the treatment of hip OA. Several associations were found between spin types and the study characteristics of AMSTAR 2 rating, Scopus CiteScore, journal impact factor, and PROSPERO preregistration. When present, spin in the abstracts of reviewed studies tended to favor the use of PRP in hip osteoarthritis. CLINICAL RELEVANCE It is important to understand the prevalence of spin in published abstracts, especially in areas of great impact or interest, so authors and readers can have a greater awareness of this potential form of bias.
PICO Summary
Population
Patients with hip osteoarthritis (15 systematic reviews).
Intervention
Systematic review to describe the incidence and types of spin bias in systematic reviews of platelet-rich plasma injections for hip osteoarthritis and to determine whether patterns in study characteristics could be identified among studies with identifiable spin.
Comparison
Outcome
All studies contained at least two types of spin (range 2-9), with a median of 2. The most common type of spin was type 14 ("Failure to report a wide confidence interval of estimates"), which was observed in 10 studies. The second most common type of spin was type 13 ("Failure to specify the direction of the effect when it favors the control intervention"), found in 6 studies. Several associations were found between spin types and the study characteristics of AMSTAR 2 rating, Scopus CiteScore, journal impact factor, and PROSPERO preregistration.
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Desmopressin to reduce periprocedural bleeding and transfusion: a systematic review and meta-analysis
Wang, C., Lebedeva, V., Yang, J., Anih, J., Park, L. J., Paczkowski, F., Roshanov, P. S.
Perioperative medicine (London, England). 2024;13(1):5
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Editor's Choice
Abstract
We systematically reviewed the literature to investigate the effects of peri-procedural desmopressin in patients without known inherited bleeding disorders undergoing surgery or other invasive procedures. We included 63 randomized trials (4163 participants) published up to February 1, 2023. Seven trials were published after a 2017 Cochrane systematic review on this topic. There were 38 trials in cardiac surgery, 22 in noncardiac surgery, and 3 in non-surgical procedures. Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95, 95% confidence interval [CI] 0.86 to 1.05) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75, 95% CI 0.47 to 1.19) when compared to placebo or usual care. However, we demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units, 95% CI - 0.94 to - 0.15), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI - 0.56 to - 0.23), and the risk of bleeding events (2 trials, RR 0.45, 95% CI 0.24 to 0.84). The certainty of evidence of these findings was generally low. Desmopressin increased the risk of clinically significant hypotension that required intervention (19 trials, RR 2.15, 95% CI 1.36 to 3.41). Limited evidence suggests that tranexamic acid is more effective than desmopressin in reducing transfusion risk (3 trials, RR 2.38 favoring tranexamic acid, 95% CI 1.06 to 5.39) and total volume of blood loss (3 trials, mean difference 391.7 mL favoring tranexamic acid, 95% CI - 93.3 to 876.7 mL). No trials directly informed the safety and hemostatic efficacy of desmopressin in advanced kidney disease. In conclusion, desmopressin likely reduces periprocedural blood loss and the number of units of blood transfused in small trials with methodologic limitations. However, the risk of hypotension needs to be mitigated. Large trials should evaluate desmopressin alongside tranexamic acid and enroll patients with advanced kidney disease.
PICO Summary
Population
Children or adults without known inherited bleeding disorders undergoing surgery or other invasive procedures (63 randomised controlled trials, n= 4,163).
Intervention
Desmopressin administered intravenously or subcutaneously before, during, or immediately after a surgical or interventional procedure.
Comparison
Placebo, usual care, or antifibrinolytic agents.
Outcome
Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95; 95% confidence interval (CI) [0.86, 1.05]) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75; 95% CI [0.47, 1.19]) when compared to placebo or usual care. However, the authors demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units; 95% CI [-0.94, -0.15]), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI [-0.56, -0.23]), and the risk of bleeding events (2 trials, RR 0.45; 95% CI [0.24, 0.84]). The certainty of evidence of these findings was generally low.
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Reported outcomes in patients with iron deficiency or iron deficiency anemia undergoing major surgery: a systematic review of outcomes
Stangl, S., Popp, M., Reis, S., Sitter, M., Saal-Bauernschubert, L., Schießer, S., Kranke, P., Choorapoikayil, S., Weibel, S., Meybohm, P.
Systematic reviews. 2024;13(1):5
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Abstract
BACKGROUND Iron deficiency (ID) is the leading cause of anemia worldwide. The prevalence of preoperative ID ranges from 23 to 33%. Preoperative anemia is associated with worse outcomes, making it important to diagnose and treat ID before elective surgery. Several studies indicated the effectiveness of intravenous iron supplementation in iron deficiency with or without anemia (ID(A)). However, it remains challenging to establish reliable evidence due to heterogeneity in utilized study outcomes. The development of a core outcome set (COS) can help to reduce this heterogeneity by proposing a minimal set of meaningful and standardized outcomes. The aim of our systematic review was to identify and assess outcomes reported in randomized controlled trials (RCTs) and observational studies investigating iron supplementation in iron-deficient patients with or without anemia. METHODS We searched MEDLINE, CENTRAL, and ClinicalTrials.gov systematically from 2000 to April 1, 2022. RCTs and observational studies investigating iron supplementation in patients with a preoperative diagnosis of ID(A), were included. Study characteristics and reported outcomes were extracted. Outcomes were categorized according to an established outcome taxonomy. Quality of outcome reporting was assessed with a pre-specified tool. Reported clinically relevant differences for sample size calculation were extracted. RESULTS Out of 2898 records, 346 underwent full-text screening and 13 studies (five RCTs, eight observational studies) with sufficient diagnostic inclusion criteria for iron deficiency with or without anemia (ID(A)) were eligible. It is noteworthy to mention that 49 studies were excluded due to no confirmed diagnosis of ID(A). Overall, 111 outcomes were structured into five core areas including nine domains. Most studies (92%) reported outcomes within the 'blood and lymphatic system' domain, followed by "adverse event" (77%) and "need for further resources" (77%). All of the latter reported on the need for blood transfusion. Reported outcomes were heterogeneous in measures and timing. Merely, two (33%) of six prospective studies were registered prospectively of which one (17%) showed no signs of selective outcome reporting. CONCLUSION This systematic review comprehensively depicts the heterogeneity of reported outcomes in studies investigating iron supplementation in ID(A) patients regarding exact definitions and timing. Our analysis provides a systematic base for consenting to a minimal COS. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42020214247.
PICO Summary
Population
Patients with iron deficiency or iron deficiency anaemia undergoing major surgery (13 studies: 5 randomised controlled trials and 8 observational studies).
Intervention
Systematic review to identify and appraise outcomes reported for preoperative or perioperative treatment of iron deficiency, with or without anemia.
Comparison
Outcome
Overall, 111 outcomes were structured into five core areas including nine domains. Most studies (92%) reported outcomes within the 'blood and lymphatic system' domain, followed by ‘adverse event’ (77%) and ‘need for further resources’ (77%). All of the latter reported on the need for blood transfusion. Reported outcomes were heterogeneous in measures and timing. Merely, two (33%) of six prospective studies were registered prospectively of which one (17%) showed no signs of selective outcome reporting.
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Evaluation of Spin Bias in Systematic Reviews and Meta-analyses of Rotator Cuff Repair With Platelet-Rich Plasma
Moulton, S. G., Hartwell, M. J., Feeley, B. T.
The American journal of sports medicine. 2024;:3635465231213039
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Abstract
BACKGROUND The use of platelet-rich plasma (PRP) in orthopaedics continues to increase. One common use of PRP is as an adjunct in rotator cuff repair surgery. Multiple systematic reviews and meta-analyses have summarized the data on PRP use in rotator cuff repair surgery. However, systematic reviews and meta-analyses are subject to spin bias, where authors' interpretations of results influence readers' interpretations. PURPOSE To evaluate spin in the abstracts of systematic reviews and meta-analyses of PRP with rotator cuff repair surgery. STUDY DESIGN Systematic review; Level of evidence, 3. METHODS A PubMed and Embase search was conducted using the terms rotator cuff repair and PRP and systematic review or meta-analysis. After review of 74 initial studies, 25 studies met the inclusion criteria. Study characteristics were documented, and each study was evaluated for the 15 most common forms of spin and using the AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews, Version 2) rating system. Correlations between spin types and study characteristics were evaluated using binary logistic regression for continuous independent variables and a chi-square test or Fisher exact test for categorical variables. RESULTS At least 1 form of spin was found in 56% (14/25) of the included studies. In regard to the 3 different categories of spin, a form of misleading interpretation was found in 56% (14/25) of the studies. A form of misleading reporting was found in 48% (12/25) of the studies. A form of inappropriate extrapolation was found in 16% (4/25) of the studies. A significant association was found between misleading interpretation and publication year (odds ratio [OR], 1.41 per year increase in publication; 95% CI, 1.04-1.92; P = .029) and misleading reporting and publication year (OR, 1.41 per year increase in publication; 95% CI, 1.02-1.95; P = .037). An association was found between inappropriate extrapolation and journal impact factor (OR, 0.21 per unit increase in impact factor; 95% CI, 0.044-0.99; P = .048). CONCLUSION A significant amount of spin was found in the abstracts of systematic reviews and meta-analyses of PRP use in rotator cuff repair surgery. Given the increasing use of PRP by clinicians and interest among patients, spin found in these studies may have a significant effect on clinical practice.
PICO Summary
Population
Patients undergoing arthroscopic rotator cuff repair surgery with platelet-rich plasma (PRP) (25 studies).
Intervention
Systematic review to evaluate the presence of spin bias in the abstracts of systematic reviews and meta-analyses of PRP with rotator cuff repair surgery.
Comparison
Outcome
Each included study was evaluated for the 15 most common forms of spin. Correlations between spin types and study characteristics were evaluated. At least 1 form of spin bias was found in 56% (14/25) of the included studies. In regard to the 3 different categories of spin, a form of misleading interpretation was found in 56% (14/25) of the studies. A form of misleading reporting was found in 48% (12/25) of the studies. A form of inappropriate extrapolation was found in 16% (4/25) of the studies. A significant association was found between misleading interpretation and publication year (odds ratio (OR) 1.41 per year increase in publication; 95% CI [1.04, 1.92]) and misleading reporting and publication year (OR 1.41 per year increase in publication; 95% CI [1.02, 1.95]). An association was found between inappropriate extrapolation and journal impact factor (OR 0.21 per unit increase in impact factor; 95% CI [0.044, 0.99]).
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Kidney disease in trials of perioperative tranexamic acid
Liu, C. W., Anih, J., Lebedeva, V., Gungor, A., Wang, C., Park, L., Roshanov, P. S.
Journal of clinical anesthesia. 2024;94:111417
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Abstract
STUDY OBJECTIVE To assess how kidney disease is handled in randomized trials evaluating the safety and efficacy of perioperative tranexamic acid, and to evaluate its effects across levels of kidney function. DESIGN Systematic review and meta-analysis of randomized controlled trials. SETTING We screened studies from a previous comprehensive systematic review, and updated its search of PubMed, Embase, and Cochrane CENTRAL to July 31, 2023. PATIENTS Patients undergoing non-obstetric surgery. INTERVENTIONS Intravenous tranexamic acid compared to placebo or usual care without tranexamic acid. MEASUREMENT We summarized the handling of kidney disease in eligibility criteria, dose adjustments for kidney function, and effects of tranexamic acid on thrombotic events, seizures, and bleeding by subgroups of kidney function. MAIN RESULTS We evaluated 300 trials with 53,085 participants; 45,958 participants (86.6%) were enrolled in 228 trials (76.0%) that explicitly excluded patients with kidney disease. Definitions of kidney diseased used for exclusion varied widely. Most were non-specific and some corresponded to mild disease. Only 5 trials adjusted dosing for kidney function. Meta-analysis of two large trials found tranexamic acid unlikely to substantially increase or decrease the occurrence of thrombotic events in patients with eGFR <60 mL/min/1.73m(2) (RR, 0.95; 95% CI: 0.83 to 1.07) or ≥ 60 mL/min/1.73m(2) (RR, 1.00; 95% CI, 0.91 to 1.11; P for subgroup difference = 0.47), but both trials excluded patients with severe kidney disease. No analysis could be performed regarding seizure risk. One large trial in noncardiac surgery reported similar reduction in bleeding across subgroups of kidney function but excluded patients with creatinine clearance <30 mL/min. CONCLUSIONS The large evidence base supporting perioperative tranexamic acid suffers from broad and unjustified exclusion of patients with kidney disease. Typical perioperative dosing of tranexamic acid is likely safe and effective in patients with creatinine clearance >30 mL/min, but effects in more severe kidney disease are unknown.
PICO Summary
Population
Patients undergoing non-obstetric surgery (300 trials, n= 53,085).
Intervention
Intravenous tranexamic acid.
Comparison
Placebo or usual care without tranexamic acid.
Outcome
From all the included studies, 45,958 participants (86.6%) were enrolled in 228 trials (76.0%) that explicitly excluded patients with kidney disease. Definitions of kidney diseased used for exclusion varied widely. Most were non-specific and some corresponded to mild disease. Only 5 trials adjusted dosing for kidney function. Meta-analysis of two large trials found tranexamic acid unlikely to substantially increase or decrease the occurrence of thrombotic events in patients with estimated glomerular filtration rate <60 mL/min/1.73m(2) (RR 0.95; 95% CI [0.83, 1.07]) or ≥ 60 mL/min/1.73m(2) (RR 1.00; 95% CI [0.91, 1.11], but both trials excluded patients with severe kidney disease. No analysis could be performed regarding seizure risk. One large trial in non-cardiac surgery reported similar reduction in bleeding across subgroups of kidney function but excluded patients with creatinine clearance <30 mL/min.
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Erythropoiesis-stimulating agents and cardiovascular mortality: A systematic review and meta-analysis of 17 studies and 372,156 hemodialysis patients
Karimi, Z., Raeisi Shahraki, H., Mohammadian-Hafshejani, A.
International journal of cardiology. Cardiovascular risk and prevention. 2023;19:200220
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Editor's Choice
Abstract
INTRODUCTION Prior studies on the association between erythropoiesis-stimulating agents (ESAs) and cardiovascular mortality in hemodialysis patients have yielded conflicting findings. We aimed to clarify this relationship through a systematic review and meta-analysis of current evidence. METHODS We comprehensively searched major databases for observational and interventional studies on ESA use and cardiovascular mortality in hemodialysis patients published from 1980 to September 2023. Pooled risk ratios (RR) with 95 % confidence intervals (CI) were calculated using random-effects models. Sources of heterogeneity were explored through subgroup analyses and meta-regression. The study data were analyzed using Stata 15 software. FINDINGS Upon conducting the initial search, we extracted 792 articles and, after screening and considering the research criteria, 17 studies with 372,156 participants were included in the meta-analysis. Overall, ESA use was associated with a 27 % increased risk of cardiovascular mortality (RR 1.27, 95 % CI: 1.15-1.40, p < 0.001). This risk varied by geographical location, with RRs of 1.27 (95 % CI: 1.14-1.41; p-value≤0.001) for America, 1.33 (95 % CI: 1.12-1.58; p-value = 0.001) for Asia, and 1.23 (95 % CI: 1.02-1.49; p-value = 0.028) for Europe. Importantly, a gender disparity was revealed, with studies involving a higher proportion of males showing greater risks (RR 1.51, 95 % CI: 1.25-1.83, p < 0.001) than female-predominant studies (RR 1.08, 95 % CI: 0.86-1.36, p < 0.001). CONCLUSION Our meta-analysis indicates ESA use is associated with heightened cardiovascular mortality in hemodialysis patients, especially in males. These findings have implications for optimizing dosing strategies while balancing efficacy and safety. Further research is warranted, particularly randomized controlled trials, to establish definitive ESA dosing guidelines.
PICO Summary
Population
Haemodialysis patients (17 studies, n= 372,156).
Intervention
Systematic review and meta-analysis evaluating the relationship between erythropoiesis-stimulating agents (ESAs) use and cardiovascular mortality.
Comparison
Outcome
Overall, ESA use was associated with a 27% increased risk of cardiovascular mortality (RR, 1.27; 95% CI [1.15, 1.40]). This risk varied by geographical location, with RRs of 1.27; 95% CI [1.14, 1.41] for America, 1.33; 95% CI [1.12, 1.58] for Asia, and 1.23; 95% CI [1.02, 1.49] for Europe. A gender disparity was revealed, with studies involving a higher proportion of males showing greater risks RR, 1.51; 95% CI [1.25, 1.83] than female-predominant studies RR, 1.08; 95% CI [0.86, 1.36].
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Perioperative transfusion and long-term mortality after cardiac surgery: a meta-analysis
Woldendorp K, Manuel L, Srivastava A, Doane M, Bassin L, Marshman D
General thoracic and cardiovascular surgery. 2023
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Abstract
OBJECTIVES Cardiac surgical procedures are associated with a high incidence of periprocedural blood loss and blood transfusion. Although both may be associated with a range of postoperative complications there is disagreement on the impact of blood transfusion on long-term mortality. This study aims to provide a comprehensive review of the published outcomes of perioperative blood transfusion, examined as a whole and by index procedure. METHODS A systematic review of perioperative blood transfusion cardiac surgical patients was conducted. Outcomes related to blood transfusion were analysed in a meta-analysis and aggregate survival data were derived to examine long-term survival. RESULTS Thirty-nine studies with 180,074 patients were identified, the majority (61.2%) undergoing coronary artery bypass surgery. Perioperative blood transfusions were noted in 42.2% of patients and was associated with significantly higher early mortality (OR 3.87, p < 0.001). After a median of 6.4 years (range 1-15), mortality remained significantly higher for those who received a perioperative transfusion (OR 2.01, p < 0.001). Pooled hazard ratio for long-term mortality similar for patients who underwent coronary surgery compared to isolated valve surgery. Differences in long-term mortality for all comers remained true when corrected for early mortality and when only including propensity matched studies. CONCLUSIONS Perioperative red blood transfusion appears to be associated with a significant reduction in long-term survival for patients after cardiac surgery. Strategies such as preoperative optimisation, intraoperative blood conservation, judicious use of postoperative transfusions, and professional development into minimally invasive techniques should be utilised where appropriate to minimise the need for perioperative transfusions.
PICO Summary
Population
Patients undergoing cardiac surgery (39 studies, n= 180,074).
Intervention
Red blood cell (RBC) transfusion.
Comparison
No RBC transfusion.
Outcome
The meta-analysis identified 180,074 patients with follow-up data ranging from 1 to 15 years. The majority (61.2%) of patients underwent coronary artery bypass surgery. Perioperative blood transfusions were noted in 42.2% of patients and was associated with significantly higher early mortality (OR= 3.87). After a median of 6.4 years (range 1, 15), mortality remained significantly higher for those who received a perioperative transfusion (OR= 2.01). Pooled hazard ratio for long-term mortality was similar for patients who underwent coronary surgery compared to isolated valve surgery. Differences in long-term mortality for all comers remained true when corrected for early mortality and when only including propensity matched studies.
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Cryotherapy following total knee replacement
Aggarwal, A., Adie, S., Harris, I. A., Naylor, J.
The Cochrane database of systematic reviews. 2023;9(9):Cd007911
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Abstract
BACKGROUND Total knee replacement (TKR) is a common intervention for people with end-stage symptomatic knee osteoarthritis, resulting in significant improvements in pain, function and quality of life within three to six months. It is, however, acutely associated with pain, local oedema and blood loss. Post-operative management may include cryotherapy. This is the application of low temperatures to the skin surrounding the surgical site, through ice or cooled water, often delivered using specialised devices. This is an update of a review published in 2012. OBJECTIVES To evaluate the effect of cryotherapy in the acute phase after TKR (within 48 hours after surgery) on blood loss, pain, transfusion rate, range of motion, knee function, adverse events and withdrawals due to adverse events. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers, as well as reference lists, related links and conference proceedings on 27 May 2022. SELECTION CRITERIA We included randomised controlled trials or controlled clinical trials comparing cryotherapy with or without other treatments (such as compression, regional nerve block or continuous passive motion) to no treatment, or the other treatment alone, following TKR for osteoarthritis. DATA COLLECTION AND ANALYSIS Two review authors independently selected studies for inclusion, extracted data and assessed risk of bias and certainty of evidence using GRADE. We discussed any disagreements and consulted another review author to resolve them, if required. Major outcomes were blood loss, pain, transfusion rate, knee range of motion, knee function, total adverse events and withdrawals from adverse events. Minor outcomes were analgesia use, knee swelling, length of stay, quality of life, activity level and participant-reported global assessment of success. MAIN RESULTS We included 22 trials (20 randomised trials and two controlled clinical trials), with 1839 total participants. The mean ages reflected the TKR population, ranging from 64 to 74 years. Cryotherapy with compression was compared to no treatment in four studies, and to compression alone in nine studies. Cryotherapy without compression was compared to no treatment in eight studies. One study compared cryotherapy without compression to control with compression alone. We combined all control interventions in the primary analysis. Certainty of evidence was low for blood loss (downgraded for bias and inconsistency), pain (downgraded twice for bias) and range of motion (downgraded for bias and indirectness). It was very low for transfusion rate (downgraded for bias, inconsistency and imprecision), function (downgraded twice for bias and once for inconsistency), total adverse events (downgraded for bias, indirectness and imprecision) and withdrawals from adverse events (downgraded for bias, indirectness and imprecision). The nature of cryotherapy made blinding difficult and most studies had a high risk of performance and detection bias. Low-certainty evidence from 12 trials (956 participants) shows that cryotherapy may reduce blood loss at one to 13 days after surgery. Blood loss was 825 mL with no cryotherapy and 561 mL with cryotherapy: mean difference (MD) 264 mL less (95% confidence interval (CI) 7 mL less to 516 mL less). Low-certainty evidence from six trials (530 participants) shows that cryotherapy may slightly improve pain at 48 hours on a 0- to 10-point visual analogue scale (lower scores indicate less pain). Pain was 4.8 points with no cryotherapy and 3.16 points with cryotherapy: MD 1.6 points lower (95% CI 2.3 lower to 1.0 lower). We are uncertain whether cryotherapy improves transfusion rate at zero to 13 days after surgery. The transfusion rate was 37% with no cryotherapy and 79% with cryotherapy (risk ratio (RR) 2.13, 95% CI 0.04 to 109.63; 2 trials, 91 participants; very low-certainty evidence). Low-certainty evidence from three trials (174 participants) indicates cryotherapy may improve range of motion at discharge: it was 62.9 degrees with no cryotherapy and 71.2 degrees with cryotherapy: MD 8.3 degrees greater (95% CI 3.6 degrees more to 13.1 degrees more). We are uncertain whether cryotherapy improves function two weeks after surgery. Function was 75.4 points on the 0- to 100-point Dutch Western Ontario and McMaster Universities Arthritis Index (WOMAC) scale (lower score indicates worse function) in the control group and 88.6 points with cryotherapy (MD 13.2 points better, 95% CI 0.5 worse to 27.1 improved; 4 trials, 296 participants; very low-certainty evidence). We are uncertain whether cryotherapy reduces total adverse events: the risk ratio was 1.30 (95% CI 0.53 to 3.20; 16 trials, 1199 participants; very low-certainty evidence). Adverse events included discomfort, local skin reactions, superficial infections, cold-induced injuries and thrombolytic events. We are uncertain whether cryotherapy reduces withdrawals from adverse events (RR 2.71, 95% CI 0.42 to 17.38; 19 trials, 1347 participants; very low-certainty evidence). No significant benefit was found for secondary outcomes of analgesia use, length of stay, activity level or quality of life. Evidence from seven studies (403 participants) showed improved mid-patella swelling between two and six days after surgery (MD 7.32 mm less, 95% CI 11.79 to 2.84 lower), though not at six weeks and three months after surgery. The included studies did not assess participant-reported global assessment of success. AUTHORS' CONCLUSIONS The certainty of evidence was low for blood loss, pain and range of motion, and very low for transfusion rate, function, total adverse events and withdrawals from adverse events. We are uncertain whether cryotherapy improves transfusion rate, function, total adverse events or withdrawals from adverse events. We downgraded evidence for bias, indirectness, imprecision and inconsistency. Hence, the potential benefits of cryotherapy on blood loss, pain and range of motion may be too small to justify its use. More well-designed randomised controlled trials focusing especially on clinically meaningful outcomes, such as blood transfusion, and patient-reported outcomes, such as knee function, quality of life, activity level and participant-reported global assessment of success, are required.
PICO Summary
Population
People undergoing total knee replacement (22 trials, n= 1,839).
Intervention
Cryotherapy alone or with another therapy aiming to reduce pain and swelling.
Comparison
No treatment; other treatments aiming to reduce pain and swelling (e.g., compression bandaging, regional nerve block or continuous passive motion).
Outcome
Blood loss was 264 mL less with cryotherapy at up to 13 days after surgery. 11% more people had a blood transfusion with cryotherapy, or 11 more out of 100, at up to 13 days after surgery. Pain was better by 1.6 points on a 0‐ to 10‐point scale with cryotherapy at 2 days after surgery. For knee range of motion: flexion was 8.3 degrees greater with cryotherapy when people left hospital. Knee function was 13.2 points better on a 0- to 100-point scale with cryotherapy at 2 weeks after surgery. For total adverse events: 2.7 out of 100 people reported adverse events with cryotherapy, and 2.1 out of 100 people reported adverse events without cryotherapy. The certainty of evidence was low for blood loss, pain and range of motion, and very low for transfusion rate, function, total adverse events and withdrawals from adverse events. The authors are uncertain whether cryotherapy improves transfusion rate, function, total adverse events or withdrawals from adverse events. The authors downgraded evidence for bias, indirectness, imprecision and inconsistency.
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COVID-19 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-analysis of Individual Participant Data From Five Randomized Trials
Levine AC, Fukuta Y, Huaman MA, Ou J, Meisenberg BR, Patel B, Paxton JH, Hanley DF, Rijnders BJ, Gharbharan A, et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023
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Editor's Choice
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.
PICO Summary
Population
Adult COVID-19 outpatients (5 studies, n= 2,620).
Intervention
Intravenous COVID-19 convalescent plasma (CCP) transfusion (n= 1,305).
Comparison
Non-convalescent plasma or normal saline (n= 1,315).
Outcome
The virus neutralizing antibody dilutional titre levels ranged from 8 to 14,580 in diverse assays. 160 (12.2%) of 1,315 control patients were hospitalized, versus 111 (8.5%) of 1,305 COVID-19 convalescent plasma treated patients, yielding a 3.7% (95% CI: 1.3% - 6.0%) 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 titre with a 7.6% absolute risk reduction (95% CI: 4.0% - 11.1%) 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 titres below the median titre.
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Evaluation of the Safety and Effectiveness of Topical Intrapleural Application of Tranexamic Acid in Thoracic Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Alzahrani, A., Alkofide, H., Joharji, H., Korayem, G. B., Aljohani, S., Alshareef, H., AlFaifi, M., Alalawi, H., Sulaiman, K. A.
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2023;29:10760296231218215
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Abstract
OBJECTIVES Bleeding remains a common complication post-thoracic surgery. Although intravenous tranexamic acid (TXA) has been shown to decrease blood loss, its use has been associated with adverse effects. Accordingly, topical TXA has been proposed as an alternative to reduce bleeding with fewer systemic complications. METHODS We searched Medline, Embase, and Cochrane Central databases for randomized controlled trials (RCTs) comparing topical TXA versus control (i.e., placebo) in patients undergoing thoracic procedures. The primary outcome was total postoperative blood loss at 24 hours. Secondary outcomes included were the number of red blood cell (RBC) transfusions, and hospital length of stay (LOS). Meta-analyses were pooled using mean difference with inverse-variance weighting and random-effects. RESULTS Out of the 575 unique studies that were screened, we identified three randomized controlled trials (RCTs) involving 399 patients. Out of the three RCTs analyzed, two studies, accounting for 67% of the total, were found to have a low risk of bias. The primary outcome of 24-h post-operative blood loss was significantly lower in patients who received TXA (mean difference [MD] -93.6 ml, 95% CI -121.8 to -65.4 ml, I(2 )= 45%). In addition, the need for RBC transfusion was significantly lower in the topical TXA group compared to control (MD -0.5 units, 95% CI -0.8 to -0.3 units, I(2 )= 60%). However, there was no significant difference in the hospital length of stay (LOS) (MD -0.3 days, 95% CI -0.9 to 0.4 days, I(2 )= 0%). These results remained consistent after several sensitivity analyses. The use of topical intrapleural tranexamic acid has also been found to be safe without any significant safety concerns. CONCLUSION Topical intrapleural TXA reduces blood loss and the need for blood transfusions during thoracic surgery. In addition, there is no evidence of the increased safety concerns associated with its use. Larger trials are necessary to validate these findings and evaluate the safety and efficacy of different dosages.
PICO Summary
Population
Patients undergoing thoracic surgery procedures (3 randomised controlled trials, n= 399).
Intervention
Topical intrapleural tranexamic acid (TXA).
Comparison
Placebo.
Outcome
The primary outcome of postoperative blood loss at 24 hours was significantly lower in patients who received TXA (mean difference [MD] -93.6 ml; 95% CI [-121.8, -65.4 ml], I(2)= 45%). The need for red blood cell transfusion was significantly lower in the topical TXA group compared to control (MD -0.5 units; 95% CI [-0.8, -0.3 units], I(2)= 60%). There was no significant difference in the hospital length of stay, (MD -0.3 days; 95% CI [-0.9, 0.4 days], I(2)= 0%). These results remained consistent after several sensitivity analyses.