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BMC Pulmonary Medicine Apr 2020The prognostic value of elevated pretreatment platelet counts remains controversial in lung cancer patients. We performed the present meta-analysis to determine its... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prognostic value of elevated pretreatment platelet counts remains controversial in lung cancer patients. We performed the present meta-analysis to determine its precise role in these patients.
METHODS
We employed a multiple search strategy in the PubMed, EMBASE and Cochrane Library databases to identify eligible studies. Disease-free survival (DFS)/progression-free survival (PFS)/time to progression (TTP) and overall survival (OS) were used as outcomes with hazard ratios (HRs) and 95% confidence intervals (CIs). Heterogeneity among the studies and publication bias were also evaluated.
RESULTS
A total of 40 studies including 16,696 lung cancer patients were eligible for the analysis. Overall, the pooled analysis showed that compared with normal platelet counts, elevated pretreatment platelet counts were associated with poorer OS (HR = 1.54, 95% CI: 1.37-1.72, P < 0.001) and poorer DFS/PFS/TTP (HR = 1.62, 95% CI: 1.33-1.98, P < 0.001) in patients with lung cancer. In subgroup analyses, elevated pretreatment platelet counts were also associated with poorer OS and DFS/PFS/TTP in most subgroups. There was no evidence of publication bias.
CONCLUSIONS
This meta-analysis revealed that elevated pretreatment platelet counts were an independent predictor of OS and DFS/PFS/TTP in lung cancer patients. Large-scale prospective studies and a validation study are warranted.
Topics: Blood Platelets; Disease-Free Survival; Humans; Lung Neoplasms; Platelet Count; Predictive Value of Tests; Prognosis; Risk Factors
PubMed: 32312252
DOI: 10.1186/s12890-020-1139-5 -
Medicine Jun 2016Many studies have been reported that platelet-lymphocyte ratio (PLR) may be associated with the prognosis of colorectal cancer (CRC), but the results are inconsistent.... (Meta-Analysis)
Meta-Analysis Review
Many studies have been reported that platelet-lymphocyte ratio (PLR) may be associated with the prognosis of colorectal cancer (CRC), but the results are inconsistent. Current opinion on the prognostic role of the PLR in CRC is inconsistent and inconclusive. Therefore, we conduct a meta-analysis that combines these studies and to identify the prognostic value of PLR in patients with CRC. Data were retrieved from PubMed, EMBASE, Cochrane Library, and Web of Science databases that came from inception through January 2016. We extracted data from the characteristics of each study and analyzed the relationship between PLR and overall survival (OS), disease-free survival (DFS), or other prognosis in patients with CRC by using the hazard ratio (HR) and 95% confidence intervals (95% CIs). Of the 256 identified studies, 15 studies were included and a total of 3991 patients were included. In a meta-analysis, patients with an elevated PLR had a significantly lower OS (pooled HR, 1.53; 95% CI, 1.24-1.89; P ≤ 0.001), DFS (pooled HR, 1.68; 95% CI, 1.07-2.62; P = 0.023). Even after sensitivity analyses and trim and fill method, high PLR remains significantly predictive poorer OS, but not DFS. In addition, our meta-analysis indicated that increased PLR is also significantly associated with the poor tumor differentiation [odds ratio (OR) 2.12; 95% CI, 1.45-3.08, P < 0.001)], the propensity toward depth of infiltration (OR 1.69; 95% CI, 1.20-2.39, P = 0.003), and recurrence in patients with CRC (HR, 2.71; 95% CI, 1.31-5.60, P = 0.005). This meta-analysis suggested that a high peripheral blood PLR can be used as a predictor of OS connected with clinicopathological parameters in patients with CRC, not DFS. These ratios may thus contribute to inform more personalized treatment decisions and predict treatment outcomes.
Topics: Blood Platelets; Colorectal Neoplasms; Humans; Lymphocyte Count; Lymphocytes; Neoplasm Staging; Platelet Count; Prognosis
PubMed: 27310960
DOI: 10.1097/MD.0000000000003837 -
Medical Science Monitor Basic Research Mar 2017BACKGROUND This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of platelet cellular and functional... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of platelet cellular and functional characteristics including platelet count (PC), MPV, platelet distribution width (PDW), platelet factor 4, beta thromboglobulin (BTG), and p-selectin with the occurrence of atrial fibrillation (AF) and consequent stroke. MATERIAL AND METHODS We conducted a meta-analysis of observational studies evaluating platelet characteristics in patients with paroxysmal, persistent and permanent atrial fibrillations. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. RESULTS Literature search of all major databases retrieved 1,676 studies. After screening, a total of 73 studies were identified. Pooled analysis showed significant differences in PC (weighted mean difference (WMD)=-26.93 and p<0.001), MPV (WMD=0.61 and p<0.001), PDW (WMD=-0.22 and p=0.002), BTG (WMD=24.69 and p<0.001), PF4 (WMD=4.59 and p<0.001), and p-selectin (WMD=4.90 and p<0.001). CONCLUSIONS Platelets play a critical and precipitating role in the occurrence of AF. Whereas distribution width of platelets as well as factors of platelet activity was significantly greater in AF patients compared to SR patients, platelet count was significantly lower in AF patients.
Topics: Atrial Fibrillation; Blood Coagulation; Blood Platelets; Humans; Platelet Activation; Platelet Count; Stroke
PubMed: 28302997
DOI: 10.12659/msmbr.902557 -
Tropical Diseases, Travel Medicine and... Nov 2023The American Society of Haematology defines immune thrombocytopenic purpura (ITP) as a common hematologic disorder characterized by a transient or long-term decrease in... (Review)
Review
BACKGROUND
The American Society of Haematology defines immune thrombocytopenic purpura (ITP) as a common hematologic disorder characterized by a transient or long-term decrease in platelet counts (< 100 × 109/L.), purpura, and haemorrhagic episodes caused by antiplatelet autoantibodies, with the exclusion of other clinical conditions. We aimed to systematically determine the incidence of ITP in adults and children following influenza vaccination, the duration between vaccination and the occurrence of ITP, and to identify predictors of ITP after the vaccine.
METHODS
We searched PubMed, Cochrane Library, Google Scholar, Web of Science, Scopus, and Science Direct. We included primary studies that assessed the occurrence of immune thrombocytopenia in individuals who had received any influenza vaccine (primary or booster dose), regardless of the dosage, preparation, time of administration, or age of the participants. We excluded studies that were (a) Narrative, scoping, and umbrella reviews ;(b) studies with no accessible full text, abstract-only studies, or (c) Overlapping or unreliable data. The risk of bias in the included studies was assessed using the Joanna Briggs Institute (JBI) tool. We categorized studies for qualitative analysis based on study design. Descriptive statistics were used to summarize quantitative data, including the incidence of ITP after influenza vaccination.
RESULTS
Out of 729 articles retrieved from the database search, we included 24 studies. All patients identified and included in this systematic review presented with immune thrombocytopenia, determined by their platelet count. The period between vaccination and the occurrence of ITP ranged from (2:35 days). The mean duration was 13.5 days. The analysis revealed a statistically significant incidence rate ratio (IRR) = 1.85,95% CI [1.03-3.32] of ITP occurrence after 42 days.
CONCLUSIONS
Influenza-associated ITP is uncommon, self-limiting, non-life-threatening, and curable. None of the patients reported having severe adverse events or death. Further studies are required to confirm the exact incidence of the ITP to better understand the pathophysiology of ITP development post-influenza vaccination.
PubMed: 38001495
DOI: 10.1186/s40794-023-00206-9 -
International Angiology : a Journal of... Feb 2018Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported to predict prognosis of acute pulmonary embolism (PE). However, the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported to predict prognosis of acute pulmonary embolism (PE). However, the prognostic value of NLR and PLR remained inconsistent between studies. The aim of this meta-analysis was to assess the prognostic role of NLR and PLR in acute PE.
EVIDENCE ACQUISITION
We systematically searched Pubmed, Embase, Web of Science and CNKI for relative literature up to March 2017. The pooled statistics for all outcomes were expressed as odds ratio (OR) and 95% confidence intervals (95% CI). The statistical analyses were performed using Review Manager 5.3.5 analysis software and Stata software.
EVIDENCE SYNTHESIS
Totally 7 eligible studies consisting of 2323 patients were enrolled in our meta-analysis. Elevated NLR was significantly associated with overall (short-term and long-term) mortality (OR 10.13, 95% CI 6.57-15.64, P<0.001) and short-term (in-hospital and 30 days) mortality (OR 8.43, 95% CI 5.23-13.61, P<0.001). And elevated PLR was significantly associated with overall mortality (OR 6.32, 95% CI 4.52-8.84, P<0.001), short-term mortality (OR 6.69, 95% CI 2.86-15.66, P<0.001) and long-term mortality (OR 6.11, 95% CI 3.90-9.55, P<0.001).
CONCLUSIONS
Our meta-analysis revealed that NLR and PLR are promising biomarkers in predicting prognosis in acute PE patients. We suggest NLR and PLR be used routinely in the PE prognostic assessment.
Topics: Biomarkers; Blood Platelets; Humans; Lymphocyte Count; Lymphocytes; Neutrophils; Platelet Count; Prognosis; Pulmonary Embolism
PubMed: 28541022
DOI: 10.23736/S0392-9590.17.03848-2 -
The Cochrane Database of Systematic... Nov 2015Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although... (Meta-Analysis)
Meta-Analysis Review
Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation.
BACKGROUND
Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding.This is an update of a Cochrane review first published in 2004, and previously updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews looking at these questions individually; this review compares prophylactic platelet transfusion thresholds.
OBJECTIVES
To determine whether different platelet transfusion thresholds for administration of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect the efficacy and safety of prophylactic platelet transfusions in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy or haematopoietic stem cell transplantation (HSCT).
SEARCH METHODS
We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6, 23 July 2015), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015.
SELECTION CRITERIA
We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with haematological disorders (receiving myelosuppressive chemotherapy or undergoing HSCT) that compared different thresholds for administration of prophylactic platelet transfusions (low trigger (5 x 10(9)/L); standard trigger (10 x 10(9)/L); higher trigger (20 x 10(9)/L, 30 x 10(9)/L, 50 x 10(9)/L); or alternative platelet trigger (for example platelet mass)).
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane.
MAIN RESULTS
Three trials met our predefined inclusion criteria and were included for analysis in the review (499 participants). All three trials compared a standard trigger (10 x 10(9)/L) versus a higher trigger (20 x 10(9)/L or 30 x 10(9)/L). None of the trials compared a low trigger versus a standard trigger or an alternative platelet trigger. The trials were conducted between 1991 and 2001 and enrolled participants from fairly comparable patient populations.The original review contained four trials (658 participants); in the previous update of this review we excluded one trial (159 participants) because fewer than 80% of participants had a haematological disorder. We identified no new trials in this update of the review.Overall, the methodological quality of the studies was low across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity.Three studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no evidence of a difference in the number of participants with a clinically significant bleeding episode between the standard and higher trigger groups (three studies; 499 participants; risk ratio (RR) 1.35, 95% confidence interval (CI) 0.95 to 1.90; low-quality evidence).One study reported the number of days with a clinically significant bleeding event (adjusted for repeated measures). There was no evidence of a difference in the number of days of bleeding per participant between the standard and higher trigger groups (one study; 255 participants; relative proportion of days with World Health Organization Grade 2 or worse bleeding (RR 1.71, 95% CI 0.84 to 3.48, P = 0.162; authors' own results; low-quality evidence).Two studies reported the number of participants with severe or life-threatening bleeding. There was no evidence of any difference in the number of participants with severe or life-threatening bleeding between a standard trigger level and a higher trigger level (two studies; 421 participants; RR 0.99, 95% CI 0.52 to 1.88; low-quality evidence).Only one study reported the time to first bleeding episode. There was no evidence of any difference in the time to the first bleeding episode between a standard trigger level and a higher trigger level (one study; 255 participants; hazard ratio 1.11, 95% CI 0.64 to 1.91; low-quality evidence).Only one study reported on all-cause mortality within 30 days from the start of the study. There was no evidence of any difference in all-cause mortality between standard and higher trigger groups (one study; 255 participants; RR 1.78, 95% CI 0.83 to 3.81; low-quality evidence).Three studies reported on the number of platelet transfusions per participant. Two studies reported on the mean number of platelet transfusions per participant. There was a significant reduction in the number of platelet transfusions per participant in the standard trigger group (two studies, mean difference -2.09, 95% CI -3.20 to -0.99; low-quality evidence).One study reported on the number of transfusion reactions. There was no evidence to demonstrate any difference in transfusion reactions between the standard and higher trigger groups (one study; 79 participants; RR 0.07, 95% CI 0.00 to 1.09).None of the studies reported on quality of life.
AUTHORS' CONCLUSIONS
In people with haematological disorders who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found low-quality evidence that a standard trigger level (10 x 10(9)/L) is associated with no increase in the risk of bleeding when compared to a higher trigger level (20 x 10(9)/L or 30 x 10(9)/L). There was low-quality evidence that a standard trigger level is associated with a decreased number of transfusion episodes when compared to a higher trigger level (20 x 10(9)/L or 30 x 10(9)/L).Findings from this review were based on three studies and 499 participants. Without further evidence, it is reasonable to continue with the current practice of administering prophylactic platelet transfusions using the standard trigger level (10 x 10(9)/L) in the absence of other risk factors for bleeding.
Topics: Antineoplastic Agents; Bone Marrow Diseases; Hematologic Diseases; Hemorrhage; Humans; Platelet Count; Platelet Transfusion; Randomized Controlled Trials as Topic; Stem Cell Transplantation; Thrombocytopenia
PubMed: 26576687
DOI: 10.1002/14651858.CD010983.pub2 -
The Cochrane Database of Systematic... Sep 2010Pre-eclampsia is a relatively common complication of pregnancy. HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome is a severe manifestation of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pre-eclampsia is a relatively common complication of pregnancy. HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome is a severe manifestation of pre-eclampsia with significant morbidity and mortality for pregnant women and their children. Corticosteroids are commonly used in the treatment of HELLP syndrome in the belief that they improve outcomes.
OBJECTIVES
To determine the effects of corticosteroids on women with HELLP syndrome and their children.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2010).
SELECTION CRITERIA
Randomized controlled trials comparing any corticosteroid with placebo, no treatment, or other drug; or comparing one corticosteroid with another corticosteroid or dosage in women with HELLP syndrome.
DATA COLLECTION AND ANALYSIS
Two review authors assessed trial quality and extracted data independently.
MAIN RESULTS
Eleven trials (550 women) compared corticosteroids with placebo or no treatment. There was no difference in the risk of maternal death (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.28 to 3.21), maternal death or severe maternal morbidity (RR 0.27, 95% CI 0.03 to 2.12), or perinatal/infant death (RR 0.64, 95% CI 0.21 to 1.97). The only clear effect of treatment on individual outcomes was improved platelet count (standardized mean difference (SMD) 0.67, 95% CI 0.24 to 1.10). The effect on platelet count was strongest for women who commenced treatment antenatally (SMD 0.80, 95% CI 0.25 to 1.35).Two trials (76 women) compared dexamethasone with betamethasone. There was no clear evidence of a difference between groups in respect to perinatal/infant death (RR 0.95, 95% CI 0.15 to 6.17) or severe perinatal/infant morbidity or death (RR 0.64, 95% CI 0.27 to 1.48). Maternal death and severe maternal morbidity were not reported. In respect to platelet count, dexamethasone was superior to betamethasone (MD 6.02, 95% CI 1.71 to 10.33), both when treatment was commenced antenatally (MD 8.10, 95% CI 6.23 to 9.97) and postnatally (MD 3.70, 95% CI 0.96 to 6.44).
AUTHORS' CONCLUSIONS
There was no clear evidence of any effect of corticosteroids on substantive clinical outcomes. Those receiving steroids showed significantly greater improvement in platelet counts which was greater for those receiving dexamethasone than those receiving betamethasone. There is to date insufficient evidence of benefits in terms of substantive clinical outcomes to support the routine use of steroids for the management of HELLP. The use of corticosteroids may be justified in clinical situations in which increased rate of recovery in platelet count is considered clinically worthwhile.
Topics: Adrenal Cortex Hormones; Betamethasone; Dexamethasone; Female; HELLP Syndrome; Humans; Maternal Mortality; Perinatal Mortality; Platelet Count; Prednisolone; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 20824872
DOI: 10.1002/14651858.CD008148.pub2 -
Blood Nov 2004Splenectomy has been a standard treatment for adult patients with idiopathic thrombocytopenic purpura (ITP) for more than 50 years. However, the durability of responses,... (Meta-Analysis)
Meta-Analysis Review
Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications.
Splenectomy has been a standard treatment for adult patients with idiopathic thrombocytopenic purpura (ITP) for more than 50 years. However, the durability of responses, the ability to predict who will respond, and the frequency of surgical complications with splenectomy all remain uncertain. To better interpret current knowledge we systematically identified and reviewed all 135 case series, 1966 to 2004, that described 15 or more consecutive patients who had splenectomy for ITP and that had data for 1 of these 3 outcomes. Complete response was defined as a normal platelet count following splenectomy and for the duration of follow-up with no additional treatment. Forty-seven case series reported complete response in 1731 (66%) of 2623 adult patients with follow-up for 1 to 153 months; complete response rates did not correlate with duration of follow-up (r = -0.103, P = .49). None of 12 preoperative characteristics that have been reported consistently predicted response to splenectomy. Mortality was 1.0% (48 of 4955 patients) with laparotomy and 0.2% (3 of 1301 patients) with laparoscopy. Complication rates were 12.9% (318 of 2465) with laparotomy and 9.6% (88 of 921 patients) with laparoscopic splenectomy. Although the risk of surgery is an important consideration, splenectomy provides a high frequency of durable responses for adult patients with ITP.
Topics: Adult; Humans; MEDLINE; Platelet Count; Postoperative Complications; Prognosis; Purpura, Thrombocytopenic, Idiopathic; Splenectomy
PubMed: 15217831
DOI: 10.1182/blood-2004-03-1168 -
PloS One 2012Rituximab has been widely used off-label as a second line treatment for children with immune thrombocytopenia (ITP). However, its role in the management of pediatric ITP... (Review)
Review
BACKGROUND
Rituximab has been widely used off-label as a second line treatment for children with immune thrombocytopenia (ITP). However, its role in the management of pediatric ITP requires clarification. To understand and interpret the available evidence, we conducted a systematic review to assess the efficacy and safety of rituximab for children with ITP.
METHODOLOGY/PRINCIPAL FINDINGS
We searched MEDLINE, EMBASE, Cochrane Library, CBM, CNKI, abstract databases of American Society of Hematology, American Society of Clinical Oncology and Pediatric Academic Society. Clinical studies published in full text or abstract only in any language that met predefined inclusion criteria were eligible. Efficacy analysis was restricted to studies enrolling 5 or more patients. Safety was evaluated from all studies that reported data of toxicity. 14 studies (323 patients) were included for efficacy assessment in children with primary ITP. The pooled complete response (platelet count ≥ 100 × 10(9)/L) and response (platelet count ≥ 30 × 10(9)/L) rate after rituximab treatment were 39% (95% CI, 30% to 49%) and 68% (95%CI, 58% to 77%), respectively, with median response duration of 12.8 month. 4 studies (29 patients) were included for efficacy assessment in children with secondary ITP. 11 (64.7%) of 17 patients associated with Evans syndrome achieved response. All 6 patients with systemic lupus erythematosus associated ITP and all 6 patients with autoimmune lymphoproliferative syndrome associated ITP achieved response. 91 patients experienced 108 adverse events associated with rituximab, among that, 91 (84.3%) were mild to moderate, and no death was reported.
CONCLUSIONS/SIGNIFICANCE
Randomized controlled studies on effect of rituximab for children with ITP are urgently needed, although a series of uncontrolled studies found that rituximab resulted in a good platelet count response both in children with primary and children secondary ITP. Most adverse events associated with rituximab were mild to moderate, and no death was reported.
Topics: Antibodies, Monoclonal, Murine-Derived; Child; Drug Administration Schedule; Humans; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Rituximab; Treatment Outcome
PubMed: 22666325
DOI: 10.1371/journal.pone.0036698 -
Qatar Medical Journal 2022Thrombolysis is an established therapeutic modality for patients with high-risk (and some selected intermediate-risk) pulmonary embolism (PE) with hemodynamic...
Thrombolysis is an established therapeutic modality for patients with high-risk (and some selected intermediate-risk) pulmonary embolism (PE) with hemodynamic instability. Physicians sometimes experience cases where both a high-risk PE and thrombocytopenia coexist. Although thrombocytopenia of < 100 × 10/mm is considered a contraindication in patients with ischemic stroke, the safety and outcomes of thrombolysis in patients with acute PE and thrombocytopenia are unknown. This systemic review aimed to pool data on the safety and outcomes of thrombolysis use in patients with PE and platelet count less than 150 × 10/mm. Patients' demographics, clinical characteristics, management, type of thrombolytic therapy, and outcomes were extracted and analyzed. Of 283 articles identified through the systematic search, 11 case reports fulfilled the inclusion criteria. The mean age of the patients was 52.27 years, and 54.5% were women. The median platelet level before thrombolysis was 65.50 × 10/mm. Before thrombolysis was initiated, the lowest and highest platelet levels were 29 × 10/mm and 105 × 10/mm, respectively. Alteplase was used in 10 patients and urokinase in one patient. One patient who had a massive PE died of aspiration pneumonia. Interestingly, no thrombocytopenia-related complications were reported. This systematic review highlights the potential benefits and safety of thrombolysis in patients with acute PE in the context of thrombocytopenia. Nevertheless, data available in the literature concerning this topic are scarce and limited to case reports. More extensive studies on the use of thrombolysis in patients with PE and thrombocytopenia are desperately needed. Systematic review registration: The protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42021286415.
PubMed: 35974889
DOI: 10.5339/qmj.2022.33