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International Journal of Molecular... Jul 2021Temporomandibular joint osteoarthritis (TMJ OA) is a low-inflammatory disorder with multifactorial etiology. The aim of this review was to present the current state of...
Mechanisms of Action and Efficacy of Hyaluronic Acid, Corticosteroids and Platelet-Rich Plasma in the Treatment of Temporomandibular Joint Osteoarthritis-A Systematic Review.
Temporomandibular joint osteoarthritis (TMJ OA) is a low-inflammatory disorder with multifactorial etiology. The aim of this review was to present the current state of knowledge regarding the mechanisms of action and the efficacy of hyaluronic acid (HA), corticosteroids (CS) and platelet-rich plasma (PRP) in the treatment of TMJ OA.: The PubMed database was analyzed with the keywords: "(temporomandibular joint) AND ((osteoarthritis) OR (dysfunction) OR (disorders) OR (pain)) AND ((treatment) OR (arthrocentesis) OR (arthroscopy) OR (injection)) AND ((hyaluronic acid) OR (corticosteroid) OR (platelet rich plasma))". After screening of 363 results, 16 studies were included in this review. Arthrocentesis alone effectively reduces pain and improves jaw function in patients diagnosed with TMJ OA. Additional injections of HA, either low-molecular-weight (LMW) HA or high-molecular-weight (HMW) HA, or CS at the end of the arthrocentesis do not improve the final clinical outcomes. CS present several negative effects on the articular cartilage. Results related to additional PRP injections are not consistent and are rather questionable. Further studies should be multicenter, based on a larger group of patients and should answer the question of whether other methods of TMJ OA treatment are more beneficial for the patients than simple arthrocentesis.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; Humans; Hyaluronic Acid; Injections, Intra-Articular; Osteoarthritis; Platelet-Rich Plasma; Signal Transduction; Temporomandibular Joint Disorders
PubMed: 34299024
DOI: 10.3390/ijms22147405 -
BMJ Evidence-based Medicine Jun 2021To evaluate association between biomarkers and outcomes in COVID-19 hospitalised patients. COVID-19 pandemic has been a challenge. Biomarkers have always played an... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate association between biomarkers and outcomes in COVID-19 hospitalised patients. COVID-19 pandemic has been a challenge. Biomarkers have always played an important role in clinical decision making in various infectious diseases. It is crucial to assess the role of biomarkers in evaluating severity of disease and appropriate allocation of resources.
DESIGN AND SETTING
Systematic review and meta-analysis. English full text observational studies describing the laboratory findings and outcomes of COVID-19 hospitalised patients were identified searching PubMed, Web of Science, Scopus, medRxiv using Medical Subject Headings (MeSH) terms COVID-19 OR coronavirus OR SARS-CoV-2 OR 2019-nCoV from 1 December 2019 to 15 August 2020 following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines.
PARTICIPANTS
Studies having biomarkers, including lymphocyte, platelets, D-dimer, lactate dehydrogenase (LDH), C reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, procalcitonin (PCT) and creatine kinase (CK), and describing outcomes were selected with the consensus of three independent reviewers.
MAIN OUTCOME MEASURES
Composite poor outcomes include intensive care unit admission, oxygen saturation <90%, invasive mechanical ventilation utilisation, severe disease, in-hospital admission and mortality. The OR and 95% CI were obtained and forest plots were created using random-effects models. Publication bias and heterogeneity were assessed by sensitivity analysis.
RESULTS
32 studies with 10 491 confirmed COVID-19 patients were included. We found that lymphopenia (pooled-OR: 3.33 (95% CI: 2.51-4.41); p<0.00001), thrombocytopenia (2.36 (1.64-3.40); p<0.00001), elevated D-dimer (3.39 (2.66-4.33); p<0.00001), elevated CRP (4.37 (3.37-5.68); p<0.00001), elevated PCT (6.33 (4.24-9.45); p<0.00001), elevated CK (2.42 (1.35-4.32); p=0.003), elevated AST (2.75 (2.30-3.29); p<0.00001), elevated ALT (1.71 (1.32-2.20); p<0.00001), elevated creatinine (2.84 (1.80-4.46); p<0.00001) and LDH (5.48 (3.89-7.71); p<0.00001) were independently associated with higher risk of poor outcomes.
CONCLUSION
Our study found a significant association between lymphopenia, thrombocytopenia and elevated levels of CRP, PCT, LDH, D-dimer and COVID-19 severity. The results have the potential to be used as an early biomarker to improve the management of COVID-19 patients, by identification of high-risk patients and appropriate allocation of healthcare resources in the pandemic.
Topics: Biomarkers; COVID-19; Clinical Decision-Making; Critical Care; Hospital Mortality; Hospitalization; Humans; Outcome Assessment, Health Care; Pandemics; Respiration, Artificial; Risk Assessment; SARS-CoV-2; Severity of Illness Index
PubMed: 32934000
DOI: 10.1136/bmjebm-2020-111536 -
American Journal of Hematology Jul 2021The effectiveness and safety of non-heparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT) are not fully established, and the optimal... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
The effectiveness and safety of non-heparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT) are not fully established, and the optimal treatment strategy is unknown. In a systematic review and meta-analysis, we aimed to determine precise rates of platelet recovery, new or progressive thromboembolism (TE), major bleeding, and death for all non-heparin anticoagulants and to study potential sources of variability.
METHODS
Following a detailed protocol (PROSPERO: CRD42020219027), EMBASE and Medline were searched for all studies reporting clinical outcomes of patients treated with non-heparin anticoagulants (argatroban, danaparoid, fondaparinux, direct oral anticoagulants [DOAC], bivalirudin, and other hirudins) for acute HIT. Proportions of patients with the outcomes of interest were pooled using a random-effects model for each drug. The influence of the patient population, the diagnostic test used, the study design, and the type of article was assessed.
RESULTS
Out of 3194 articles screened, 92 studies with 119 treatment groups describing 4698 patients were included. The pooled rates of platelet recovery ranged from 74% (bivalirudin) to 99% (fondaparinux), TE from 1% (fondaparinux) to 7% (danaparoid), major bleeding from 1% (DOAC) to 14% (bivalirudin), and death from 7% (fondaparinux) to 19% (bivalirudin). Confidence intervals were mostly overlapping, and results were not influenced by patient population, diagnostic test used, study design, or type of article.
DISCUSSION
Effectiveness and safety outcomes were similar among various anticoagulants, and significant factors affecting these outcomes were not identified. These findings support fondaparinux and DOACs as viable alternatives to conventional anticoagulants for treatment of acute HIT in clinical practice.
Topics: Anticoagulants; Blood Platelets; Hemorrhage; Heparin; Humans; Thrombocytopenia; Thromboembolism; Treatment Outcome
PubMed: 33857342
DOI: 10.1002/ajh.26194 -
Reviews in Medical Virology Mar 2023Severe acute respiratory syndrome coronavirus 2 may inflict a post-viral condition known as post-COVID-19 syndrome (PCS) or long-COVID. Studies measuring levels of... (Meta-Analysis)
Meta-Analysis Review
Severe acute respiratory syndrome coronavirus 2 may inflict a post-viral condition known as post-COVID-19 syndrome (PCS) or long-COVID. Studies measuring levels of inflammatory and vascular biomarkers in blood, serum, or plasma of COVID-19 survivors with PCS versus non-PCS controls have produced mixed findings. Our review sought to meta-analyse those studies. A systematic literature search was performed across five databases until 25 June 2022, with an updated search on 1 November 2022. Data analyses were performed with Review Manager and R Studio statistical software. Twenty-four biomarkers from 23 studies were meta-analysed. Higher levels of C-reactive protein (Standardized mean difference (SMD) = 0.20; 95% CI: 0.02-0.39), D-dimer (SMD = 0.27; 95% CI: 0.09-0.46), lactate dehydrogenase (SMD = 0.30; 95% CI: 0.05-0.54), and leukocytes (SMD = 0.34; 95% CI: 0.02-0.66) were found in COVID-19 survivors with PCS than in those without PCS. After sensitivity analyses, lymphocytes (SMD = 0.30; 95% CI: 0.12-0.48) and interleukin-6 (SMD = 0.30; 95% CI: 0.12-0.49) were also significantly higher in PCS than non-PCS cases. No significant differences were noted in the remaining biomarkers investigated (e.g., ferritin, platelets, troponin, and fibrinogen). Subgroup analyses suggested the biomarker changes were mainly driven by PCS cases diagnosed via manifestation of organ abnormalities rather than symptomatic persistence, as well as PCS cases with duration of <6 than ≥6 months. In conclusion, our review pinpointed certain inflammatory and vascular biomarkers associated with PCS, which may shed light on potential new approaches to understanding, diagnosing, and treating PCS.
Topics: Humans; COVID-19; Post-Acute COVID-19 Syndrome; Biomarkers; SARS-CoV-2; C-Reactive Protein
PubMed: 36708022
DOI: 10.1002/rmv.2424 -
The Lancet. Haematology Oct 2016Whether high-dose dexamethasone has long-term efficacy and safety in previously untreated patients with immune thrombocytopenia is unclear. We did a systematic review... (Comparative Study)
Comparative Study Review
BACKGROUND
Whether high-dose dexamethasone has long-term efficacy and safety in previously untreated patients with immune thrombocytopenia is unclear. We did a systematic review and a meta-analysis of randomised trials to establish the effect of high-dose dexamethasone compared with prednisone for long-term platelet count response.
METHODS
We searched MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Library Database for papers published from 1970 to July, 2016, and abstracts from American Society of Hematology annual meetings published from 2004 to 2015 for randomised trials comparing different corticosteroid regimens for patients with previously untreated immune thrombocytopenia who achieved a platelet count response. Trials that compared corticosteroids exclusively with other interventions were excluded. The primary endpoint was overall (platelets >30 × 10/L) and complete (platelets >100 × 10/L) platelet count response at 6 months with high-dose dexamethasone compared with standard-dose prednisone. Children and adults were analysed separately. Estimates of effect were pooled with a random-effects model.
FINDINGS
Nine randomised trials (n=1138) were included. Of those, five (n=533) compared one to three cycles of dexamethasone (40 mg per day for 4 days) with prednisone (1 mg per kg) for 14-28 days followed by dose tapering in adults. We found no difference in overall platelet count response at 6 months (pooled proportions 54% vs 43%, relative risk [RR] 1·16, 95% CI 0·79-1·71; p=0·44). At 14 days, overall platelet count response was higher with dexamethasone (79% vs 59%, RR 1·22, 95% CI 1·00-1·49; p=0·048). The dexamethasone group had fewer reported toxicities. Long-term response rates were similar when the data were analysed by cumulative corticosteroid dose over the course of treatment. No difference in initial platelet count response was observed with different high-dose corticosteroid regimens in children.
INTERPRETATION
In adults with previously untreated immune thrombocytopenia, high-dose dexamethasone did not improve durable platelet count responses compared with standard-dose prednisone. High-dose dexamethasone might be preferred over prednisone for patients with severe immune thrombocytopenia who require a rapid rise in platelet count.
FUNDING
Canadian Institutes of Health Research, and Canadian Blood Services, and Health Canada.
Topics: Adult; Aged; Anti-Inflammatory Agents; Child; Dexamethasone; Dose-Response Relationship, Drug; Female; Humans; Male; Meta-Analysis as Topic; Middle Aged; Platelet Count; Prednisone; Purpura, Thrombocytopenic, Idiopathic; Randomized Controlled Trials as Topic; Young Adult
PubMed: 27658982
DOI: 10.1016/S2352-3026(16)30109-0 -
Shock (Augusta, Ga.) Dec 2021Trauma-induced coagulopathy is associated with very high mortality, and hemorrhage remains the leading preventable cause of death after injury. Directed methods to...
Trauma-induced coagulopathy is associated with very high mortality, and hemorrhage remains the leading preventable cause of death after injury. Directed methods to combat coagulopathy and attain hemostasis are needed. The available literature regarding viscoelastic testing, including thrombelastography (TEG) and rotational thromboelastometry (ROTEM), was reviewed to provide clinically relevant guidance for emergency resuscitation. These tests predict massive transfusion and developing coagulopathy earlier than conventional coagulation testing, within 15 min using rapid testing. They can guide resuscitation after trauma, as well. TEG and ROTEM direct early transfusion of fresh frozen plasma when clinical gestalt has not activated a massive transfusion protocol. Reaction time and clotting time via these tests can also detect clinically significant levels of direct oral anticoagulants. Slowed clot kinetics suggest the need for transfusion of fibrinogen via concentrates or cryoprecipitate. Lowered clot strength can be corrected with platelets and fibrinogen. Finally, viscoelastic tests identify fibrinolysis, a finding associated with significantly increased mortality yet one that no conventional coagulation test can reliably detect. Using these parameters, guided resuscitation begins within minutes of a patient's arrival. A growing body of evidence suggests this approach may improve survival while reducing volumes of blood products transfused.
Topics: Disseminated Intravascular Coagulation; Hemorrhage; Hemostasis; Humans; Resuscitation; Thrombelastography; Wounds and Injuries
PubMed: 33769424
DOI: 10.1097/SHK.0000000000001686 -
Critical Care (London, England) Jul 2023Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this... (Review)
Review
BACKGROUND
Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this first systematic review, we aimed to identify all MT definitions used in randomised controlled trials (RCTs) to date to inform the development of consensus definitions for MT.
METHODS
We systematically searched the following databases for RCTs from inception until 11 August 2022: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Cumulative Index to Nursing and Allied Health Literature, and Transfusion Evidence Library. Ongoing trials were sought from CENTRAL, ClinicalTrials.gov, and World Health Organisation International Clinical Trials Registry Platform. To be eligible for inclusion, studies had to fulfil all the following three criteria: (1) be an RCT; (2) include an adult patient population with major bleeding who had received, or were anticipated to receive, an MT in any clinical setting; and (3) specify a definition for MT as an inclusion criterion or outcome measure.
RESULTS
Of the 8,458 distinct references identified, 30 trials were included for analysis (19 published, 11 ongoing). Trauma was the most common clinical setting in published trials, while for ongoing trials, it was obstetrics. A total of 15 different definitions of MT were identified across published and ongoing trials, varying greatly in cut-offs for volume transfused and time period. Almost all definitions specified the number of red blood cells (RBCs) within a set time period, with none including plasma, platelets or other haemostatic agents that are part of contemporary transfusion resuscitation. For completed trials, the most commonly used definition was transfusion of ≥ 10 RBC units in 24 h (9/19, all in trauma), while for ongoing trials it was 3-5 RBC units (n = 7), with the timing for transfusion being poorly defined, or in some trials not provided at all (n = 5).
CONCLUSIONS
Transfusion of ≥ 10 RBC units within 24 h was the most commonly used definition in published RCTs, while lower RBC volumes are being used in ongoing RCTs. Any consensus definitions should reflect the need to incorporate different blood components/products for MT and agree on whether a 'one-size-fits-all' approach should be used across different clinical settings.
Topics: Adult; Humans; Hemorrhage; Hemostatics; Blood Transfusion; Blood Platelets; Erythrocyte Transfusion
PubMed: 37407998
DOI: 10.1186/s13054-023-04537-z -
The Journal of Infection May 2019To assess the utility of the neutrophil:lymphocyte (NLR), lymphocyte:monocyte (LMR) and platelet:lymphocyte ratios (PLR) as infection biomarkers. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the utility of the neutrophil:lymphocyte (NLR), lymphocyte:monocyte (LMR) and platelet:lymphocyte ratios (PLR) as infection biomarkers.
METHODS
PubMed/MEDLINE, Embase and Cochrane databases were searched to identify eligible articles. Studies of diagnosis, severity or outcome were included. PROSPERO systematic review registration CRD42017075032.
RESULTS
Forty studies were included, reporting on bacterial and viral infections, malaria, and critical illness due to sepsis. Ten studies reported an association of higher NLR with bacteraemia, supported by meta-analysis of patient-level data (five studies, n = 3320; AUC 0.72, p<0.0001) identifying a cut-off of >12.65. Two studies reported an association with lower LMR and diagnosis of influenza virus infection in patients with respiratory tract infection. Meta-analysis of patient-level data (n = 85; AUC 0.66, p = 0.01) identified a cut-off of ≤2.06. The directionality of associations between NLR and outcomes in heterogeneous cohorts of critically ill adults with sepsis varied. Potential clinical utility was also demonstrated in pneumonia (NLR), pertussis (NLR), urinary tract infection (NLR), diabetic foot infections (NLR) and Crimean Congo Haemorrhagic Fever (PLR). Longitudinal measurement of LMR during respiratory virus infection reflected symptoms and NLR during sepsis and bacteraemia predicted mortality.
CONCLUSIONS
Peripheral blood leucocyte ratios are useful infection biomarkers, with the most evidence related to diagnosis of bacteraemia and influenza virus infection. In critical illness due to sepsis, a signal towards an association with NLR and outcomes exists, and NLR should be evaluated in future stratification models. Longitudinal measurement of ratios during infection could be informative. Overall, these biomarkers warrant further recognition and study in infectious diseases.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Child; Child, Preschool; Communicable Diseases; Female; Humans; Infant; Infant, Newborn; Leukocyte Count; Male; Middle Aged; Young Adult
PubMed: 30802469
DOI: 10.1016/j.jinf.2019.02.006 -
American Journal of Obstetrics and... Feb 2022This study aimed to review pregnancy hypertension clinical practice guidelines to inform international clinical practice and research priorities.
OBJECTIVE
This study aimed to review pregnancy hypertension clinical practice guidelines to inform international clinical practice and research priorities.
STUDY ELIGIBILITY CRITERIA
Relevant national and international clinical practice guidelines, 2009-19, published in English, French, Dutch or German.
STUDY APPRAISAL AND SYNTHESIS METHODS
Following published methods and prospective registration (CRD42019123787), a literature search was updated. CPGs were identified by 2 authors independently who scored quality and usefulness for practice (Appraisal of Guidelines for Research and Evaluation II instrument), abstracted data, and resolved any disagreement by consensus.
RESULTS
Of note, 15 of 17 identified clinical practice guidelines (4 international) were deemed "clinically useful" and had recommendations abstracted. The highest Appraisal of Guidelines for Research and Evaluation II scores were from government organizations, and scores have improved over time. The following were consistently recommended: (1) automated blood pressure measurement with devices validated for pregnancy and preeclampsia, reflecting increasing recognition of the prevalence of white-coat hypertension and the potential usefulness of home blood pressure monitoring; (2) use of dipstick proteinuria testing for screening followed by quantitative testing by urinary protein-to-creatinine ratio or 24-hour urine collection; (3) key definitions and most aspects of classification, including a broad definition of preeclampsia (which includes proteinuria and maternal end-organ dysfunction, including headache and visual symptoms and laboratory abnormalities of platelets, creatinine, or liver enzymes) and a recognition that it can worsen after delivery; (4) preeclampsia prevention with aspirin; (5) treatment of severe hypertension, most commonly with intravenous labetalol, oral nifedipine, or intravenous hydralazine; (6) treatment for nonsevere hypertension when undertaken, with oral labetalol (in particular), methyldopa, or nifedipine, with recommendations against the use of renin-angiotensin-aldosterone inhibitors; (7) magnesium sulfate for eclampsia treatment and prevention among women with "severe" preeclampsia; (8) antenatal corticosteroids for preterm birth but not hemolysis, elevated liver enzymes, and low platelet count syndrome; (9) delivery at term for preeclampsia; (10) a focus on usual labor and delivery care but avoidance of ergometrine; and (11) an appreciation that long-term health complications are increased in incidence, mandating lifestyle change and risk factor modification. Lack of uniformity was seen in the following areas: (1) the components of a broad preeclampsia definition (specifically respiratory and gastrointestinal symptoms, fetal manifestations, and biomarkers), what constitutes severe preeclampsia, and whether the definition has utility because at present what constitutes severe preeclampsia by some guidelines that mandate proteinuria now defines any preeclampsia for most other clinical practice guidelines; (2) how preeclampsia risk should be identified early in pregnancy, and aspirin administered for preeclampsia prevention, because multivariable models (with biomarkers and ultrasonography added to clinical risk markers) used in this way to guide aspirin therapy can substantially reduce the incidence of preterm preeclampsia; (3) the value of calcium added to aspirin for preeclampsia prevention, particularly for women with low intake and at increased risk of preeclampsia; (4) emerging recommendations to normalize blood pressure with antihypertensive agents even in the absence of comorbidities; (5) fetal neuroprotection as an indication for magnesium sulfate in the absence of "severe" preeclampsia; and (6) timing of birth for chronic and gestational hypertension and preterm preeclampsia.
CONCLUSION
Consistent recommendations should be implemented and audited. Inconsistencies should be the focus of research.
Topics: Anticonvulsants; Antihypertensive Agents; Aspirin; Calcium; Delivery, Obstetric; Female; Glucocorticoids; Humans; Hypertension, Pregnancy-Induced; Magnesium Sulfate; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Pre-Eclampsia; Pregnancy; Proteinuria; Risk Assessment
PubMed: 32828743
DOI: 10.1016/j.ajog.2020.08.018 -
Transfusion Medicine Reviews Jan 2018Optimal dose, timing and ratio to red blood cells (RBC) of blood component therapy (fresh frozen plasma [FFP], platelets, cryoprecipitate or fibrinogen concentrate) to... (Meta-Analysis)
Meta-Analysis Review
Optimal dose, timing and ratio to red blood cells (RBC) of blood component therapy (fresh frozen plasma [FFP], platelets, cryoprecipitate or fibrinogen concentrate) to reduce morbidity and mortality in critically bleeding patients requiring massive transfusion is unknown. We performed a systematic review for randomized controlled trials (RCT) in MEDLINE, The Cochrane Library, Embase, CINAHL, PubMed the Transfusion Evidence Library and using multiple clinical trials registries to 21 February 2017. Sixteen RCTs were identified: six completed (five in adult trauma patients, one pediatric burn patients) and ten ongoing trials. Of the completed trials: three were feasibility trials, comparing a FFP, platelets and RBC ratio of 1:1:1 to laboratory-guided transfusion practice [n=69], early cryoprecipitate compared to standard practice [n=41], and early fibrinogen concentrate compared to placebo [n=45]; one trial compared the effect of FFP, platelets and RBC ratio of 1:1:1 with 1:1:2 on 24-hour and 30-day mortality [n=680]; one compared whole blood to blood component therapy on 24-hour blood use [n=107]; one compared a FFP to RBC ratio of 1:1 with 1:4 [n=16]. Data from two trials were pooled in a meta-analysis for 28-day mortality because the transfusion ratios achieved were similar. Results from these two trials suggest higher transfusion ratios were associated with transfusion of more FFP and platelets without evidence of significant difference with respect to mortality or morbidity. On the limited evidence available, there is insufficient basis to recommend a 1:1:1 over a 1:1:2 ratio or standard care for adult patients with critical bleeding requiring massive transfusion.
Topics: Adult; Blood Component Transfusion; Blood Transfusion; Child; Erythrocyte Transfusion; Hemorrhage; Hemostatics; Humans; Plasma; Platelet Transfusion; Randomized Controlled Trials as Topic; Time Factors; Transfusion Reaction
PubMed: 28803752
DOI: 10.1016/j.tmrv.2017.06.003