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British Journal of Anaesthesia Jan 2021Adverse cardiovascular events are a leading cause of perioperative morbidity and mortality. The definitions of perioperative cardiovascular adverse events are...
BACKGROUND
Adverse cardiovascular events are a leading cause of perioperative morbidity and mortality. The definitions of perioperative cardiovascular adverse events are heterogeneous. As part of the international Standardized Endpoints in Perioperative Medicine initiative, this study aimed to find consensus amongst clinical trialists on a set of standardised and valid cardiovascular outcomes for use in future perioperative clinical trials.
METHODS
We identified currently used perioperative cardiovascular outcomes by a systematic review of the anaesthesia and perioperative medicine literature (PubMed/Ovid, Embase, and Cochrane Library). We performed a three-stage Delphi consensus-gaining process that involved 55 clinician researchers worldwide. Cardiovascular outcomes were first shortlisted and the most suitable definitions determined. These cardiovascular outcomes were then assessed for validity, reliability, feasibility, and clarity.
RESULTS
We identified 18 cardiovascular outcomes. Participation in the three Delphi rounds was 100% (n=19), 71% (n=55), and 89% (n=17), respectively. A final list of nine cardiovascular outcomes was elicited from the consensus: myocardial infarction, myocardial injury, cardiovascular death, non-fatal cardiac arrest, coronary revascularisation, major adverse cardiac events, pulmonary embolism, deep vein thrombosis, and atrial fibrillation. These nine cardiovascular outcomes were rated by the majority of experts as valid, reliable, feasible, and clearly defined.
CONCLUSIONS
These nine consensus cardiovascular outcomes can be confidently used as endpoints in clinical trials designed to evaluate perioperative interventions with the goal of improving perioperative outcomes.
Topics: Cardiovascular Diseases; Clinical Trials as Topic; Consensus; Delphi Technique; Endpoint Determination; Humans; Perioperative Care; Perioperative Medicine; Postoperative Complications; Research Design
PubMed: 33092804
DOI: 10.1016/j.bja.2020.09.023 -
HSS Journal : the Musculoskeletal... Oct 2020Hip hemiarthroplasty is a well-established treatment of displaced femoral neck fracture, although debate exists over whether cemented or uncemented fixation is superior.... (Review)
Review
BACKGROUND
Hip hemiarthroplasty is a well-established treatment of displaced femoral neck fracture, although debate exists over whether cemented or uncemented fixation is superior. Uncemented prostheses have typically been used in younger, healthier patients and cemented prostheses in older patients with less-stable bone. Also, earlier research has suggested that bone cement has cytotoxic effects and may trigger cardiovascular and respiratory adverse events.
QUESTIONS/PURPOSES
The aim of this systematic review and meta-analysis was to compare morbidity and mortality rates after cemented and uncemented hemiarthroplasty for the treatment of displaced femoral neck fractures in elderly patients.
METHODS
Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched seven medical databases for randomized clinical trials and observational studies. We compared cemented and uncemented hemiarthroplasty using the Harris Hip Score (HHS), as well as measures of postoperative pain, mortality, and complications. Data were extracted and pooled as risk ratios or standardized mean difference with their corresponding 95% confidence intervals in a meta-analysis model.
RESULTS
The meta-analysis included 34 studies (12 randomized trials and 22 observational studies), with a total of 42,411 patients. In the pooled estimate, cemented hemiarthroplasty was associated with less risk of postoperative pain than uncemented hemiarthroplasty. There were no significant differences between groups regarding HHS or rates of postoperative mortality, pulmonary embolism, cardiac arrest, myocardial infarction, acute cardiac arrhythmia, or deep venous thrombosis.
CONCLUSIONS
While we found that cemented hemiarthroplasty results in less postoperative pain than uncemented hemiarthroplasty in older patients with femoral neck fracture, the lack of significant differences in functional hip scores, mortality, and complications was surprising. Further high-level research is needed.
PubMed: 33082721
DOI: 10.1007/s11420-020-09769-1 -
Medical Science Monitor : International... Jul 2020BACKGROUND Left ventricular decompression is the primary method for solving VA-ECMO-induced LV afterload increase, but the effect of specific methods on patient outcomes... (Meta-Analysis)
Meta-Analysis
Outcomes of VA-ECMO with and without Left Centricular (LV) Decompression Using Intra-Aortic Balloon Pumping (IABP) versus Other LV Decompression Techniques: A Systematic Review and Meta-Analysis.
BACKGROUND Left ventricular decompression is the primary method for solving VA-ECMO-induced LV afterload increase, but the effect of specific methods on patient outcomes and complications is unknown. MATERIAL AND METHODS We searched for all published reports conducted in patients undergoing ECMO combined with LVD. Statistical analyses were performed using Stata 12.0. RESULTS The results showed that the risk of death with ECMO combined with LVD was 29% lower than that with ECMO alone (OR=0.71, 95% CI: 0.56-0.89, I²=59.5%, P<0.001). Although the risk of death with ECMO combined other LV decompression techniques was higher than that with ECMO combined with IABP, the difference was not statistically significant (OR=1.27, 95% CI: 0.86-1.87, I²=44.0%, P=0.057). In addition, the ORs values of hemorrhage, stroke/acute episodes, lower-limb ischemia, and hemolysis for ECMO combined with LVD were 0.69 (0.66-0.71), 0.82 (0.78-0.89), 0.71 (0.30-1.66), and 0.48 (0.16-1.39), respectively. The risk of complications, such as stroke/TIA, limb ischemia, and hemolysis, of ECMO combined with IABP was lower than that of ECMO combined other LV decompression techniques, and the risk of bleeding was higher for ECMO combined with IABP. CONCLUSIONS ECMO combined with LVD is more beneficial than using ECMO alone and helps to lower patient mortality.
Topics: Extracorporeal Membrane Oxygenation; Heart Ventricles; Heart-Assist Devices; Humans; Intra-Aortic Balloon Pumping; Models, Statistical; Myocardial Infarction; Risk Factors; Shock, Cardiogenic; Treatment Outcome; Ventricular Dysfunction, Left
PubMed: 32729556
DOI: 10.12659/MSM.924009 -
Cureus Jun 2020Chronic myeloid leukemia (CML) represents a common condition in the spectrum of myeloproliferative disorders (MPD). It classically exhibits leukocytosis, but rarely... (Review)
Review
Chronic myeloid leukemia (CML) represents a common condition in the spectrum of myeloproliferative disorders (MPD). It classically exhibits leukocytosis, but rarely presents with isolated thrombocytosis. This paper is designed to review the clinicopathologic features, treatment, and outcomes of patients with CML who present with isolated thrombocytosis. We searched PubMed, MEDLINE®, ScienceDirect, and Scopus for English-language articles about case series and case reports for the period 2000-2020 with the terms "chronic myeloid leukemia" and "thrombocytosis" and pooled them with a case from our institution. Cases were also incorporated from the reference list and screened for inclusion. A total of 20 cases were included in the final cohort. The male-to-female ratio was 1:1.86. The mean age of the patients at the time of initial diagnosis was 40.5 years (range: 9-77 years). Out of 17 cases with available data, seven (41%) were asymptomatic and found to have thrombocytosis incidentally upon routine blood work. Five cases (29.4%) either had a history of thrombotic events or presented with severe thrombotic complications, including ischemic cerebrovascular accidents (CVA), myocardial infarction (MI), pulmonary embolism (PE), and/or miscarriages. Four cases (23.5%) had more than one symptom at presentation, including headache, syncope, and bruising. The average platelet count was 1,923 × 10/L (range: 584-8,688 × 10/L), and one case (5%) had anemia. The bone marrow (BM) examination showed normal cellularity and normal myeloid to erythroid (M/E) ratio in seven (50%) and 11 (84.6%) out of the 14 and 13 cases with reported data, respectively. Moreover, megakaryocytes in the BM were small in 10 cases (71.4%), pleomorphic in three cases (21.4%), and dysplastic in one case (7.1%). Accurate differentiation among MPD subtypes and the exclusion of CML is critical in reaching a proper diagnosis to decide on proper therapy and eventually modify outcomes. Prompt evaluation for the precise diagnosis of patients presenting with isolated marked thrombocytosis will help expedite their diagnosis and initiation of a specific tyrosine kinase inhibitor (TKI) therapy, thereby promptly inducing remission, preventing thrombotic complications, and avoiding adverse drug events, which would eventually improve outcomes.
PubMed: 32596094
DOI: 10.7759/cureus.8788 -
The Cochrane Database of Systematic... Jun 2020Cardiogenic shock (CS) is a state of critical end-organ hypoperfusion due to a primary cardiac disorder. For people with refractory CS despite maximal vasopressors,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiogenic shock (CS) is a state of critical end-organ hypoperfusion due to a primary cardiac disorder. For people with refractory CS despite maximal vasopressors, inotropic support and intra-aortic balloon pump, mortality approaches 100%. Mechanical assist devices provide mechanical circulatory support (MCS) which has the ability to maintain vital organ perfusion, to unload the failing ventricle thus reduce intracardiac filling pressures which reduces pulmonary congestion, myocardial wall stress and myocardial oxygen consumption. This has been hypothesised to allow time for myocardial recovery (bridge to recovery) or allow time to come to a decision as to whether the person is a candidate for a longer-term ventricular assist device (VAD) either as a bridge to heart transplantation or as a destination therapy with a long-term VAD.
OBJECTIVES
To assess whether mechanical assist devices improve survival in people with acute cardiogenic shock.
SEARCH METHODS
We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid) and Web of Science Core Collection in November 2019. In addition, we searched three trials registers in August 2019. We scanned reference lists and contacted experts in the field to obtain further information. There were no language restrictions.
SELECTION CRITERIA
Randomised controlled trials on people with acute CS comparing mechanical assist devices with best current intensive care management, including intra-aortic balloon pump and inotropic support.
DATA COLLECTION AND ANALYSIS
We performed data collection and analysis according to the published protocol. Primary outcomes were survival to discharge, 30 days, 1 year and secondary outcomes included, quality of life, major adverse cardiovascular events (30 days/end of follow-up), dialysis-dependent (30 days/end of follow-up), length of hospital stay and length of intensive care unit stay and major adverse events. We used the five GRADE considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of a body of evidence as it relates to the studies which contribute data to the meta-analyses for the prespecified outcomes Summary statistics for the primary endpoints were risk ratios (RR), hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs).
MAIN RESULTS
The search identified five studies from 4534 original citations reviewed. Two studies included acute CS of all causes randomised to treatment using TandemHeart percutaneous VAD and three studies included people with CS secondary to acute myocardial infarction who were randomised to Impella CP or best medical management. Meta-analysis was performed only to assess the 30-day survival as there were insufficient data to perform any further meta-analyses. The results from the five studies with 162 participants showed mechanical assist devices may have little or no effect on 30-day survival (RR of 1.01 95% CI 0.76 to 1.35) but the evidence is very uncertain. Complications such as sepsis, thromboembolic phenomena, bleeding and major adverse cardiovascular events were not infrequent in both the MAD and control group across the studies, but these could not be pooled due to inconsistencies in adverse event definitions and reporting. We identified four randomised control trials assessing mechanical assist devices in acute CS that are currently ongoing.
AUTHORS' CONCLUSIONS
There is no evidence from this review of a benefit from MCS in improving survival for people with acute CS. Further use of the technology, risk stratification and optimising the use protocols have been highlighted as potential reasons for lack of benefit and are being addressed in the current ongoing clinical trials.
Topics: Acute Disease; Coronary Care Units; Heart-Assist Devices; Humans; Length of Stay; Quality of Life; Renal Dialysis; Shock, Cardiogenic
PubMed: 32496607
DOI: 10.1002/14651858.CD013002.pub2 -
Journal of Cardiothoracic Surgery May 2020Does the manipulation of the off-pump CABG (OPCAB) in patient with depressed left ventricular function is better than on-pump CABG (ONCAB) approach in in-hospital... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVES
Does the manipulation of the off-pump CABG (OPCAB) in patient with depressed left ventricular function is better than on-pump CABG (ONCAB) approach in in-hospital mortality and morbidities? Here we undertook a meta-analysis of the best evidence available on the comparison of primary and second clinical outcomes of the off-pump and on-pump CABG.
DESIGN
Systematic literature reviewer and meta-analysis.
DATA SOURCES
PubMed, EMBASE, Web of science and Cochrane Center Registry of Controlled Trials were searched the studies which comparing the use of the off-pump CABG(OPCAB) and on-pump CABG (ONCAB) for patients with LVD during January 1990.1 to January 2018.
ELIGIBILITY CRITERIA
All observation studies and randomized controlled trials comparing on-pump and off-pump as main technique for multi-vessel coronary artery disease (defined as severe stenosis (>70%) in at least 2 major diseased coronary arteries) with left ventricular dysfunction(defined as ejection fraction (EF) 40% or less) were included.
DATA EXTRACTION AND SYNTHESIS
Authors will screen and select the studies extract the following data, first author, year of publication, trial characters, study design, inclusion and exclusion criteria, graft type, clinical outcome, assess the risk of bias and heterogeneity. Study-specific estimates will pool through the modification of the Newcastle-Ottawa scale for the quality of study and while leave-one-out analysis will be used to detect the impact of individual studies on the robustness of outcomes.
RESULTS
Among the 987 screened articles, a total of 16 studies (32,354 patients) were included. A significant relationship between patient risk profile and benefits from OPCAB was found in terms of the 30-day mortality (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.73-0.97; P = 0.02), stroke (OR, 0.69; 95% CI, 0.55-0.86; P = 0.00), myocardial infarction (MI) (OR, 0.71; 95% CI, 0.53-0.96; P = 0.02), renal failure (OR, 0.71; 95% CI, 0.55-0.93; P = 0.01), pulmonary complication (OR, 0.68; 95% CI, 0.52-0.90; P = 0.01), infection (OR, 0.67; 95% CI, 0.49-0.91; P = 0.00),postoperative transfusion (OR, 0.25; 95% CI, 0.08-0.84; P = 0.02) and reoperation for bleeding (OR, 0.56; 95% CI, 0.41-0.75; P = 0.00). There was no significant difference in atrial fibrillation (AF) (OR, 0.96;95%; CI, 0.78-1.41; P = 0.56) and neurological dysfunction (OR, 0.88; 95% CI, 0.49-1.57; P = 0.65).
CONCLUSIONS
Compared with the on-pump CABG with LVD, using the off-pump CABG is a better choice for patients with lower mortality, stroke, MI, RF, pulmonary complication, infection, postoperative transfusion and reoperation for bleeding. Further randomized studies are warranted to corroborate these observational data.
Topics: Atrial Fibrillation; Coronary Artery Bypass; Coronary Artery Bypass, Off-Pump; Coronary Artery Disease; Hospital Mortality; Humans; Myocardial Infarction; Odds Ratio; Reoperation; Stroke; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left
PubMed: 32393284
DOI: 10.1186/s13019-020-01115-0 -
Journal of Thoracic Disease Mar 2020Patients with achondroplasia and other causes of dwarfism suffer from increased rates of cardiovascular disease relative to the remainder of the population. Few studies... (Review)
Review
Patients with achondroplasia and other causes of dwarfism suffer from increased rates of cardiovascular disease relative to the remainder of the population. Few studies have examined these patients when undergoing cardiac surgery or percutaneous intervention. This systematic review examines the literature to determine outcomes following cardiac intervention in this unique population. An electronic search was performed in the English literature to identify all reports of achondroplasia, dwarfism, and cardiac intervention. Of the 5,274 articles identified, 14 articles with 14 cases met inclusion criteria. Patient-level data was extracted and analyzed. Median patient age was 55.5 [interquartile ranges (IQR), 43.8, 59.8] years, median height 102.0 [98.8, 112.5] cm, median BMI 32.1 [27.0, 45.9], and 57.1% (8/14) were male. Of these 14 patients, nine had the following documented skeletal abnormalities: 66.7% (6/9) had scoliosis, 66.7% (6/9) had kyphosis, 11.1% (1/9) had lordosis, 11.1% (1/9) pectus carinatum and 11.1% (1/9) spinal stenosis. Coronary artery disease was present in 53.8% (7/13), and 30.8% (4/13) patients previously suffered a myocardial infarction. Of the eight patients who underwent cardiac surgery, 37.5% (3/8) underwent multivessel coronary artery bypass grafting, 37.5% (3/8) underwent aortic valve replacement, 25.0% (2/8) underwent type A aortic dissection repair, and the remaining 12.5% (1/8) underwent pulmonary thromboendarterectomy. Six patients underwent percutaneous intervention. Median cardiopulmonary bypass time was 136.5 [110.0, 178.8] minutes. Median arterial cannula size was 20.0 [20.0, 24.0] Fr. Bicaval cannulation was performed in all cases describing cannulation strategy (5/5). Median superior vena cava cannula size was 28.0 [28.0, 28.0] Fr, and inferior vena cava cannula size was 28.0 [28.0, 28.0] Fr. No mortality was reported with a median follow up time of 6.0 [6.0, 10.5] months. In conclusion, Common cardiac procedures can be performed with reasonable safety in this patient population. Operative adjustments may need to be made with respect to equipment to accommodate patient-specific needs.
PubMed: 32274169
DOI: 10.21037/jtd.2020.02.05 -
BMC Neurology Apr 2020This systematic review and meta-analysis aimed to synthesize the latest evidence on the efficacy and safety of tranexamic acid (TXA) on traumatic brain injury (TBI). (Meta-Analysis)
Meta-Analysis
Tranexamic acid is associated with reduced mortality, hemorrhagic expansion, and vascular occlusive events in traumatic brain injury - meta-analysis of randomized controlled trials.
BACKGROUND
This systematic review and meta-analysis aimed to synthesize the latest evidence on the efficacy and safety of tranexamic acid (TXA) on traumatic brain injury (TBI).
METHODS
We performed a systematic literature search on topics that compared intravenous TXA to placebo in patients with TBI up until January 2020 from several electronic databases.
RESULTS
There were 30.522 patients from 7 studies. Meta-analysis showed that TXA was associated with reduced mortality (RR 0.92 [0.88, 0.97], p = 0.002; I: 0%) and hemorrhagic expansion (RR 0.79 [0.64, 0.97], p = 0.03; I: 0%). Both TXA and control group has a similar need for neurosurgical intervention (p = 0.87) and unfavourable Glasgow Outcome Scale (GOS) (p = 0.59). The rate for vascular occlusive events (p = 0.09), and its deep vein thrombosis subgroup (p = 0.23), pulmonary embolism subgroup (p = 1), stroke subgroup (p = 0.38), and myocardial infarction subgroup (p = 0.15) were similar in both groups. Subgroup analysis on RCTs with low risk of bias showed that TXA was associated with reduced mortality and hemorrhagic expansion. TXA was associated with reduced vascular occlusive events (RR 0.85 [0.73, 0.99], p = 0.04; I: 4%). GRADE was performed for the RCT with low risk of bias subgroup, it showed a high certainty of evidence for lower mortality, less hemorrhage expansion, and similar need for neurosurgical intervention in TXA group compared to placebo group.
CONCLUSION
TXA was associated with reduced mortality and hemorrhagic expansion but similar need for neurosurgical intervention and unfavorable GOS. Vascular occlusive events were slightly lower in TXA group on subgroup analysis of RCTs with low risk of bias.
Topics: Antifibrinolytic Agents; Brain Injuries, Traumatic; Hemorrhage; Humans; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 32252661
DOI: 10.1186/s12883-020-01694-4 -
The Cochrane Database of Systematic... Apr 2020Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Silent cerebral infarcts are the commonest neurological complication in children and probably adults with SCD. Silent cerebral infarcts also affect academic performance, increase cognitive deficits and may lower intelligence quotient.
OBJECTIVES
To assess the effectiveness of interventions to reduce or prevent silent cerebral infarcts in people with SCD.
SEARCH METHODS
We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 14 November 2019. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register: 07 October 2019.
SELECTION CRITERIA
Randomised controlled trials comparing interventions to prevent silent cerebral infarcts in people with SCD. There were no restrictions by outcomes examined, language or publication status.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
We included five trials (660 children or adolescents) published between 1998 and 2016. Four of the five trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of SCD. One trial focused on preventing silent cerebral infarcts or stroke; three trials were for primary stroke prevention and one trial dealt with secondary stroke prevention. Three trials compared the use of regular long-term red blood cell transfusions to standard care. Two of these trials included children with no previous long-term transfusions: one in children with normal transcranial doppler (TCD) velocities; and one in children with abnormal TCD velocities. The third trial included children and adolescents on long-term transfusion. Two trials compared the drug hydroxyurea and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children), and one in secondary prevention (children and adolescents). The quality of the evidence was moderate to very low across different outcomes according to GRADE methodology. This was due to trials being at high risk of bias because they were unblinded; indirectness (available evidence was only for children with HbSS); and imprecise outcome estimates. Long-term red blood cell transfusions versus standard care Children with no previous long-term transfusions and higher risk of stroke (abnormal TCD velocities or previous history of silent cerebral infarcts) Long-term red blood cell transfusions may reduce the incidence of silent cerebral infarcts in children with abnormal TCD velocities, risk ratio (RR) 0.11 (95% confidence interval (CI) 0.02 to 0.86) (one trial, 124 participants, low-quality evidence); but make little or no difference to the incidence of silent cerebral infarcts in children with previous silent cerebral infarcts on magnetic resonance imaging and normal or conditional TCDs, RR 0.70 (95% CI 0.23 to 2.13) (one trial, 196 participants, low-quality evidence). No deaths were reported in either trial. Long-term red blood cell transfusions may reduce the incidence of: acute chest syndrome, RR 0.24 (95% CI 0.12 to 0.49) (two trials, 326 participants, low-quality evidence); and painful crisis, RR 0.63 (95% CI 0.42 to 0.95) (two trials, 326 participants, low-quality evidence); and probably reduces the incidence of clinical stroke, RR 0.12 (95% CI 0.03 to 0.49) (two trials, 326 participants, moderate-quality evidence). Long-term red blood cell transfusions may improve quality of life in children with previous silent cerebral infarcts (difference estimate -0.54; 95% confidence interval -0.92 to -0.17; one trial; 166 participants), but may have no effect on cognitive function (least squares means: 1.7, 95% CI -1.1 to 4.4) (one trial, 166 participants, low-quality evidence). Transfusions continued versus transfusions halted: children and adolescents with normalised TCD velocities (79 participants; one trial) Continuing red blood cell transfusions may reduce the incidence of silent cerebral infarcts, RR 0.29 (95% CI 0.09 to 0.97 (low-quality evidence). We are very uncertain whether continuing red blood cell transfusions has any effect on all-cause mortality, Peto odds ratio (OR) 8.00 (95% CI 0.16 to 404.12); or clinical stroke, RR 0.22 (95% CI 0.01 to 4.35) (very low-quality evidence). The trial did not report: comparative numbers for SCD-related adverse events; quality of life; or cognitive function. Hydroxyurea and phlebotomy versus transfusions and chelation Primary prevention, children (121 participants; one trial) We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: silent cerebral infarcts (no infarcts); all-cause mortality (no deaths); risk of stroke (no strokes); or SCD-related complications, RR 1.52 (95% CI 0.58 to 4.02) (very low-quality evidence). Secondary prevention, children and adolescents with a history of stroke (133 participants; one trial) We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: silent cerebral infarcts, Peto OR 7.28 (95% CI 0.14 to 366.91); all-cause mortality, Peto OR 1.02 (95%CI 0.06 to 16.41); or clinical stroke, RR 14.78 (95% CI 0.86 to 253.66) (very low-quality evidence). Switching to hydroxyurea and phlebotomy may increase the risk of SCD-related complications, RR 3.10 (95% CI 1.42 to 6.75) (low-quality evidence). Neither trial reported on quality of life or cognitive function.
AUTHORS' CONCLUSIONS
We identified no trials for preventing silent cerebral infarcts in adults, or in children who do not have HbSS SCD. Long-term red blood cell transfusions may reduce the incidence of silent cerebral infarcts in children with abnormal TCD velocities, but may have little or no effect on children with normal TCD velocities. In children who are at higher risk of stroke and have not had previous long-term transfusions, long-term red blood cell transfusions probably reduce the risk of stroke, and other SCD-related complications (acute chest syndrome and painful crises). In children and adolescents at high risk of stroke whose TCD velocities have normalised, continuing red blood cell transfusions may reduce the risk of silent cerebral infarcts. No treatment duration threshold has been established for stopping transfusions. Switching to hydroxyurea with phlebotomy may increase the risk of silent cerebral infarcts and SCD-related serious adverse events in secondary stroke prevention. All other evidence in this review is of very low-quality.
Topics: Adolescent; Anemia, Sickle Cell; Antisickling Agents; Brain Infarction; Cause of Death; Child; Cognition; Erythrocyte Transfusion; Humans; Hydroxyurea; Phlebotomy; Primary Prevention; Quality of Life; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke
PubMed: 32250453
DOI: 10.1002/14651858.CD012389.pub3 -
JAMA Network Open Aug 2019Cardiovascular adverse events (CVAEs) after treatment with BRAF and MEK inhibitors in patients with melanoma remain incompletely characterized. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Cardiovascular adverse events (CVAEs) after treatment with BRAF and MEK inhibitors in patients with melanoma remain incompletely characterized.
OBJECTIVE
To determine the association of BRAF and MEK inhibitor treatment with CVAEs in patients with melanoma compared with BRAF inhibitor monotherapy.
DATA SOURCES
PubMed, Cochrane, and Web of Science were systematically searched for keywords vemurafenib, dabrafenib, encorafenib, trametinib, binimetinib, and cobinimetinib from database inception through November 30, 2018.
STUDY SELECTION
Randomized clinical trials reporting on CVAEs in patients with melanoma being treated with BRAF and MEK inhibitors compared with patients with melanoma being treated with BRAF inhibitor monotherapy were selected.
DATA EXTRACTION AND SYNTHESIS
Data assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Pooled relative risks (RRs) and 95% CIs were determined using random-effects and fixed-effects analyses. Subgroup analyses were conducted to assess study-level characteristics associated with CVAEs.
MAIN OUTCOMES AND MEASURES
The selected end points were pulmonary embolism, a decrease in left ventricular ejection fraction, arterial hypertension, myocardial infarction, atrial fibrillation, and QTc interval prolongation. All-grade and high-grade (≥3) CVAEs were recorded.
RESULTS
Overall, 5 randomized clinical trials including 2317 patients with melanoma were selected. Treatment with BRAF and MEK inhibitors was associated with an increased risk of pulmonary embolism (RR, 4.36; 95% CI, 1.23-15.44; P = .02), a decrease in left ventricular ejection fraction (RR, 3.72; 95% CI, 1.74-7.94; P < .001), and arterial hypertension (RR, 1.49; 95% CI, 1.12-1.97; P = .005) compared with BRAF inhibitor monotherapy. The RRs for myocardial infarction, atrial fibrillation, and QTc prolongation were similar between the groups. These results were consistent when assessing high-grade CVAEs (left ventricular ejection fraction: RR, 2.79; 95% CI, 1.36-5.73; P = .005; I2 = 29%; high-grade arterial hypertension: RR, 1.54; 95% CI, 1.14-2.08; P = .005; I2 = 0%), but RRs for high-grade pulmonary embolism were similar between groups. A higher risk of a decrease in left ventricular ejection fraction was associated with patients with a mean age younger than 55 years (RR, 26.50; 95% CI, 3.58-196.10; P = .001), and the associated risk of pulmonary embolism was higher for patients with a mean follow-up time longer than 15 months (RR, 7.70; 95% CI, 1.40-42.12; P = .02).
CONCLUSIONS AND RELEVANCE
Therapy with BRAF and MEK inhibitors was associated with a higher risk of CVAEs compared with BRAF inhibitor monotherapy. The findings may help to balance between beneficial melanoma treatment and cardiovascular morbidity and mortality.
Topics: Acrylonitrile; Adult; Aged; Aged, 80 and over; Aniline Compounds; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Diseases; Female; Humans; Male; Melanoma; Middle Aged; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Randomized Controlled Trials as Topic; Skin Neoplasms; Young Adult
PubMed: 31397860
DOI: 10.1001/jamanetworkopen.2019.8890