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Leukemia Research Jan 2009A systematic review and meta-analysis was carried out to compare the frequency of clinically significant outcomes between JAK2 V617F positive and wild type patients with... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis was carried out to compare the frequency of clinically significant outcomes between JAK2 V617F positive and wild type patients with essential thrombocythemia (ET). JAK2 V617F positivity in patients with ET was associated with a clear increase in the odds of thrombosis [OR=1.83 (95% CI, 1.32-2.53), p<0.0001], and much higher odds of transformation to polycythemia vera [OR=7.67 (95% CI, 2.04-28.87), p=0.0009]. The mean difference of the white blood cell count between JAK2 positive and negative patients was associated with an increased odds ratio for thrombosis (p=0.02). The JAK2 V617F mutation in patients with ET is associated with an increased risk of adverse cardiovascular outcomes via an increase in the leukocyte count.
Topics: Cell Division; Hematopoietic Stem Cells; Humans; Janus Kinase 2; Mutation; Polycythemia Vera; Retrospective Studies; Thrombocythemia, Essential
PubMed: 18632151
DOI: 10.1016/j.leukres.2008.06.006 -
The Cochrane Database of Systematic... Apr 2008Polycythaemia vera and essential thrombocythaemia are chronic Philadelphia-negative myeloproliferative disorders, which increase the risk of arterial and venous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycythaemia vera and essential thrombocythaemia are chronic Philadelphia-negative myeloproliferative disorders, which increase the risk of arterial and venous thrombosis as well as bleeding. In addition to the different therapeutic strategies available, aspirin is often used to prevent platelet aggregation.
OBJECTIVES
To quantify the benefit and harm of antiplatelet drugs for long-term primary and secondary prophylaxis of arterial and venous thrombotic events in patients with polycythaemia vera or essential thrombocythaemia.
SEARCH STRATEGY
Our searched included the CENTRAL (The Cochrane Library, issue 1 2007), MEDLINE (1966 to 2007) and EMBASE (1980 to 2007) databases, online registers of ongoing trials and conference proceedings. The date of the last search was March 2007.
SELECTION CRITERIA
All randomised controlled trials (RCTs) comparing long-term (>6 months) use of an antiplatelet drug versus placebo or no treatment in patients with polycythaemia vera or essential thrombocythaemia, diagnosed by established international criteria, with data for at least one of the selected outcomes, were included.
DATA COLLECTION AND ANALYSIS
Using a predefined extraction form, we collected and analysed the following data where appropriate: mortality from arterial and venous thrombotic events, mortality from bleeding episodes, fatal and non-fatal arterial thrombotic events, fatal and non-fatal venous thrombotic events, micro-circulation events, transient neurological and ocular manifestations, major and minor bleeding episodes, all-cause mortality and any adverse events. We based quantitative analysis of outcome data on an intention-to-treat principle. The overall treatment effect was estimated by the pooled odds ratio (OR) with 95% confidence interval (CI) using a fixed-effect model (Mantel-Haenszel).
MAIN RESULTS
Two RCTs that investigated 630 patients with an established diagnosis of polycythaemia vera, with no clear indication or contraindication to aspirin therapy, were included in this review. The use of aspirin, compared with placebo, was associated with a lower risk of fatal thrombotic events (although this benefit was not statistically significant (OR 0.20, 95% CI 0.03 to 1.14)) and did not increase the risk of major bleeding (OR 0.99, 95% CI 0.23 to 4.36). No studies have been published in patients with essential thrombocythaemia or studying other antiplatelet drugs.
AUTHORS' CONCLUSIONS
The available evidence suggests that the use of aspirin is associated with a statistically non-significant reduction in the risk of fatal thrombotic events, without an increased risk of major bleeding, when compared with no treatment in patients polycythaemia vera who have no clear indication or contraindication to aspirin therapy.
Topics: Anticoagulants; Aspirin; Humans; Platelet Aggregation Inhibitors; Polycythemia Vera; Randomized Controlled Trials as Topic; Thrombocythemia, Essential; Thrombosis
PubMed: 18425953
DOI: 10.1002/14651858.CD006503.pub2 -
Blood Reviews Mar 2008While there is good evidence for a protective effect of aspirin against occlusive vascular events in individuals with arterial disease, its role in preventing venous... (Review)
Review
While there is good evidence for a protective effect of aspirin against occlusive vascular events in individuals with arterial disease, its role in preventing venous thromboembolism (VTE) is unclear. In this article we review the role of aspirin and other antiplatelet drugs in prevention of venous thromboembolism in surgical patients, high risk medical patients requiring aspirin for other reasons, patients with myeloproliferative disorders, long distance travellers and patients receiving treatment with the IMiD class of drugs. Overall, data from the PEP study and Anti-Platelet Trialists' systematic review show that aspirin reduces the risk of VTE by around 25% in high risk surgical patients. Data from retrospective and before/after studies also suggest efficacy in reducing VTE in myeloma patients on IMiD drugs in combination with dexamethasone or chemotherapy. However, there has been no direct comparison with coumarins or heparin to indicate that aspirin is the optimal form of thromboprophylaxis. In patients who require aspirin because of high risk of arterial vascular occlusion (including patients with polycythaemia vera and essential thrombocythaemia), the additional small reduction in VTE risk is an added benefit with no additional risk associated. There is no evidence for a role of aspirin in prevention of travel-related thrombosis. At present there is no clear evidence that aspirin is the drug of choice for the prevention of VTE in any patient group.
Topics: Aspirin; Clinical Trials as Topic; Humans; Platelet Aggregation Inhibitors; Venous Thromboembolism; Venous Thrombosis
PubMed: 18226435
DOI: 10.1016/j.blre.2007.11.001 -
JAMA Mar 2007With few exceptions, the umbilical cord of every newborn is clamped and cut at birth, yet the optimal timing for this intervention remains controversial. (Meta-Analysis)
Meta-Analysis Review
CONTEXT
With few exceptions, the umbilical cord of every newborn is clamped and cut at birth, yet the optimal timing for this intervention remains controversial.
OBJECTIVE
To compare the potential benefits and harms of late vs early cord clamping in term infants.
DATA SOURCES
Search of 6 electronic databases (on November 15, 2006, starting from the beginning of each): the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Neonatal Group trials register, the Cochrane library, MEDLINE, EMBASE, and CINHAL; hand search of secondary references in relevant studies; and contact of investigators about relevant published research.
STUDY SELECTION
Controlled trials comparing late vs early cord clamping following birth in infants born at 37 or more weeks' gestation.
DATA EXTRACTION
Two reviewers independently assessed eligibility and quality of trials and extracted data for outcomes of interest: infant hematologic status; iron status; and risk of adverse events such as jaundice, polycythemia, and respiratory distress.
DATA SYNTHESIS
The meta-analysis included 15 controlled trials (1912 newborns). Late cord clamping was delayed for at least 2 minutes (n = 1001 newborns), while early clamping in most trials (n = 911 newborns) was performed immediately after birth. Benefits over ages 2 to 6 months associated with late cord clamping include improved hematologic status measured as hematocrit (weighted mean difference [WMD], 3.70%; 95% confidence interval [CI], 2.00%-5.40%); iron status as measured by ferritin concentration (WMD, 17.89; 95% CI, 16.58-19.21) and stored iron (WMD, 19.90; 95% CI, 7.67-32.13); and a clinically important reduction in the risk of anemia (relative risk (RR), 0.53; 95% CI, 0.40-0.70). Neonates with late clamping were at increased risk of experiencing asymptomatic polycythemia (7 studies [403 neonates]: RR, 3.82; 95% CI, 1.11-13.21; 2 high-quality studies only [281 infants]: RR, 3.91; 95% CI, 1.00-15.36).
CONCLUSIONS
Delaying clamping of the umbilical cord in full-term neonates for a minimum of 2 minutes following birth is beneficial to the newborn, extending into infancy. Although there was an increase in polycythemia among infants in whom cord clamping was delayed, this condition appeared to be benign.
Topics: Anemia; Constriction; Delivery, Obstetric; Fetal Blood; Humans; Infant, Newborn; Jaundice, Neonatal; Ligation; Polycythemia; Risk; Term Birth; Time Factors; Umbilical Cord
PubMed: 17374818
DOI: 10.1001/jama.297.11.1241 -
Circulation Mar 2007More than 140 million people worldwide live >2500 m above sea level. Of them, 80 million live in Asia, and 35 million live in the Andean mountains. This latter region... (Review)
Review
More than 140 million people worldwide live >2500 m above sea level. Of them, 80 million live in Asia, and 35 million live in the Andean mountains. This latter region has its major population density living above 3500 m. The primary objective of the present study is to review the physiology, pathology, pathogenesis, and clinical features of the heart and pulmonary circulation in healthy highlanders and patients with chronic mountain sickness. A systematic review of worldwide literature was undertaken, beginning with the pioneering work done in the Andes several decades ago. Original articles were analyzed in most cases and English abstracts or translations of articles written in Chinese were reviewed. Pulmonary hypertension in healthy highlanders is related to a delayed postnatal remodeling of the distal pulmonary arterial branches. The magnitude of pulmonary hypertension increases with the altitude level and the degree of exercise. There is reversal of pulmonary hypertension after prolonged residence at sea level. Chronic mountain sickness develops when the capacity for altitude adaptation is lost. These patients have moderate to severe pulmonary hypertension with accentuated hypoxemia and exaggerated polycythemia. The clinical picture of chronic mountain sickness differs from subacute mountain sickness and resembles other chronic altitude diseases described in China and Kyrgyzstan. The heart and pulmonary circulation in healthy highlanders have distinct features in comparison with residents at sea level. Chronic mountain sickness is a public health problem in the Andean mountains and other mountainous regions around the world. Therefore, dissemination of preventive and therapeutic measures is essential.
Topics: Adaptation, Physiological; Adolescent; Adult; Aged; Aged, 80 and over; Altitude; Altitude Sickness; Animals; Cardiac Catheterization; Cardiac Output; Cattle; Cattle Diseases; Child; Child, Preschool; China; Chronic Disease; Diagnosis, Differential; Exercise; Female; Heart Ventricles; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Infant; Infant, Newborn; Latin America; Male; Middle Aged; Muscle, Smooth, Vascular; Polycythemia; Pulmonary Artery; Pulmonary Circulation; Pulmonary Heart Disease; Vasodilator Agents; Ventricular Function
PubMed: 17339571
DOI: 10.1161/CIRCULATIONAHA.106.624544 -
Archives of Disease in Childhood. Fetal... Jan 2006Several studies have shown the efficacy of dilutional exchange transfusion (DET) in reducing haematocrit (Ht) and relieving clinical symptoms in neonatal polycythaemia.... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Several studies have shown the efficacy of dilutional exchange transfusion (DET) in reducing haematocrit (Ht) and relieving clinical symptoms in neonatal polycythaemia. We conducted a systematic review to determine the efficacy of crystalloid versus colloid solutions used in DET in an effort to identify the best solution to replace red blood cells.
METHODS
The Cochrane Library, MEDLINE, and EMBASE were searched for relevant randomised controlled trials. Quality assessment and data analysis were performed using the methods and software of the Cochrane Collaboration. Relative risk (RR) and weighted mean difference (WMD) were calculated as measures of effect for categorical and continuous outcome data, respectively. Ninety five percent confidence intervals (95% CI) were calculated and a fixed effect model was used for meta-analysis.
RESULTS
Six studies with a total of 235 newborns matched our inclusion criteria. When comparing crystalloid and colloid replacement solutions for DET, there was a clinically unimportant difference in Ht at 2-6 h and at 24 h in favour of colloidal solutions (WMD 2.29% (95% CI 1.28 to 3.31) and 1.74% (95% CI 0.80 to 2.68), respectively). This difference in post DET Ht was more evident when normal saline was compared to plasma but absent when normal saline was compared to 5% albumin.
CONCLUSION
There is little difference in effectiveness between plasma, 5% albumin, and crystalloid solutions. Since normal saline is cheap, readily available, and does not carry the potential risk of transfusion associated infection, normal saline is the optimal dilutional fluid for exchange transfusion in polycythaemic neonates.
Topics: Crystalloid Solutions; Exchange Transfusion, Whole Blood; Hematocrit; Humans; Infant, Newborn; Isotonic Solutions; Plasma Substitutes; Polycythemia; Randomized Controlled Trials as Topic; Rehydration Solutions
PubMed: 16371393
DOI: 10.1136/adc.2004.063925 -
Acta Paediatrica (Oslo, Norway : 1992) Nov 2005To determine whether crystalloid solutions are as effective as colloid solutions when a partial exchange transfusion is performed in newborns with polycythemia. (Meta-Analysis)
Meta-Analysis Review
AIMS
To determine whether crystalloid solutions are as effective as colloid solutions when a partial exchange transfusion is performed in newborns with polycythemia.
METHODS
We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register of the Cochrane Library (1966-2004). Keywords used were: polycythemia, partial exchange transfusion, hyperviscosity, and limited to newborn. Randomized studies in newborns with polycythemia were selected for evaluation. Outcomes examined were: long-term neurodevelopment; short-term physiological effects; improvement in clinical symptoms; reduction in haematocrit at 4-6 h; haematocrit at 24 h; and frequency of serious complications.
RESULTS
Four randomized controlled clinical trials, including 200 patients in total, with evaluable data, which satisfied our criteria, were found. There were no data on long-term outcomes. There is no reported important difference in short-term physiologic effects. Use of crystalloid was as effective as colloid in both correction of haematological values and reduction of clinical symptoms following partial exchange transfusion.
CONCLUSION
Crystalloid solutions are as effective as colloid solutions for partial exchange transfusion. When crystalloid solutions are used for this purpose, there is no risk of transmission of blood-borne diseases, there is no risk of anaphylaxis, they are rapidly and easily available, and are less expensive. The use of crystalloid should become the standard for partial exchange transfusion.
Topics: Colloids; Crystalloid Solutions; Exchange Transfusion, Whole Blood; Humans; Infant, Newborn; Isotonic Solutions; Polycythemia; Treatment Outcome
PubMed: 16303705
DOI: 10.1080/08035250500192748 -
The Cochrane Database of Systematic... Oct 2005Umbilical venous catheters are often used in unwell neonates. Infection related to the use of these catheters may cause significant morbidity and mortality. The use of... (Review)
Review
BACKGROUND
Umbilical venous catheters are often used in unwell neonates. Infection related to the use of these catheters may cause significant morbidity and mortality. The use of prophylactic antibiotics has been advocated for newborns with umbilical venous catheters in order to reduce the risk of colonisation and acquired infection. Countering this is the possibility that harm may outweigh benefit. Prophylactic antibiotics may be effective in preventing catheter-related blood stream infection, but may have the undesirable effect of promoting the emergence of resistant strains of micro-organisms. A policy of prophylactic antibiotic use should take into account this possibility, and has been used as a basis for arguing against its implementation.
OBJECTIVES
The primary objective was to assess whether prophylactic antibiotics, in neonates with umbilical venous catheters, reduce mortality and morbidity. In separate comparisons, we planned to review two different policies regarding the prophylactic use of antibiotics in neonates with umbilical venous catheters: 1) Among neonates with umbilical venous catheters, a policy of prophylactic antibiotics for the duration of catheterisation (or other fixed duration of antibiotic treatment) versus placebo or no treatment; 2) Among neonates with umbilical venous catheters who had been started on antibiotics at the time of catheterisation, but whose initial cultures to rule out sepsis are negative, a policy of continuing versus discontinuing prophylactic antibiotics.
SEARCH STRATEGY
We searched MEDLINE (January 1966 to April 2005), CINAHL (1982 to April 2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005).
SELECTION CRITERIA
Randomised controlled trials or quasi-randomised trials in which newborn infants with umbilical venous catheters are randomised to receive prophylactic antibiotics versus placebo or no treatment.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial quality.
MAIN RESULTS
One study, of poor quality, met the criteria for inclusion in this review. Twenty-nine term infants, who had umbilical venous catheters inserted specifically for transfusion procedures for hyperbilirubinaemia or polycythaemia, allocated non-randomly (quasi-randomised - alternate allocation) to treatment (n = 15) or control (n = 14) groups. Those in the treatment group received penicillin and gentamicin for three days. 5/15 infants given antibiotics and 5/14 control infants having positive blood cultures three days after catheter insertion. All positive blood cultures were considered contaminated, due to lack of corroborating clinical and haematological evidence of infection. Therefore, no infants were identified with evidence of septicaemia.
AUTHORS' CONCLUSIONS
There is insufficient evidence from randomised trials to support or refute the use of prophylactic antibiotics when umbilical venous catheters are inserted in newborn infants. There is no evidence to support or refute continuing antibiotics once initial cultures rule out infection in newborn infants with umbilical venous catheters.
Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Catheterization, Peripheral; Catheters, Indwelling; Cross Infection; Humans; Infant Mortality; Infant, Newborn; Randomized Controlled Trials as Topic; Umbilical Veins
PubMed: 16235397
DOI: 10.1002/14651858.CD005251.pub2 -
Archives of Disease in Childhood. Fetal... Jan 2006Severe polycythaemia in the neonate may produce symptoms due to hyperviscosity and may be associated with serious complications. Partial exchange transfusion will reduce... (Review)
Review
BACKGROUND
Severe polycythaemia in the neonate may produce symptoms due to hyperviscosity and may be associated with serious complications. Partial exchange transfusion will reduce the packed cell volume.
OBJECTIVE
To determine whether partial exchange transfusion in term infants with polycythaemia (symptomatic and asymptomatic) is associated with improved short and long term outcomes.
SEARCH STRATEGY
Medline, EMBASE, and the Cochrane Controlled Trials Register of the Cochrane Library were searched. The following keywords were used: polycythaemia, partial exchange transfusion, hyperviscosity, and limited to the newborn. This covered years 1966-2004. Abstracts of the Pediatric Academic Societies and personal files were also searched.
SELECTION CRITERIA
Randomised or quasi-randomised trials in term infants with polycythaemia and/or documented hyperviscosity were considered. Clinically relevant outcomes included were short term (resolution of symptoms, neurobehavioural scores, major complications) and long term neurodevelopmental outcome.
DATA COLLECTION AND ANALYSIS
All data for each study were extracted, assessed, and coded separately. Any disagreements were resolved by discussion.
MAIN RESULTS
Six studies were identified; five had data that could be evaluated for analysis. There is no evidence of an improvement in long term neurological outcome (mental developmental index, incidence of mental delay, and incidence of neurological diagnoses) after partial exchange transfusion in symptomatic or asymptomatic infants. There is no evidence of improvement in early neurobehavioural assessment scores (Brazelton neonatal behavioural assessment scale). Partial exchange transfusion may be associated with an earlier improvement in symptoms, but there are insufficient data to calculate the size of the effect. Necrotising enterocolitis is probably increased by partial exchange transfusion (relative risk 8.68, 95% confidence interval 1.06 to 71.1).
CONCLUSION
There is no evidence of long term benefit from partial exchange in polycythaemic infants, and the incidence of gastrointestinal injury is increased. The long term outcome is more likely to be related to the underlying cause of polycythaemia.
Topics: Blood Viscosity; Exchange Transfusion, Whole Blood; Humans; Infant, Newborn; Intellectual Disability; Polycythemia; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 16174666
DOI: 10.1136/adc.2004.071431 -
Annals of Tropical Paediatrics Mar 2004This review evaluates the potential of delayed cord-clamping for improving iron status and reducing anaemia in term infants and for increasing the risk of polycythaemia... (Meta-Analysis)
Meta-Analysis Review
This review evaluates the potential of delayed cord-clamping for improving iron status and reducing anaemia in term infants and for increasing the risk of polycythaemia and hyperbilirubinaemia. We applied a strict search protocol to identify controlled trials of early vs late cord-clamping. Four trials from developing and four from industrialised countries were finally assessed. Two of the four studies from developing countries found a significant difference in infant haemoglobin levels at 2-3 months of age in favour of delayed cord-clamping. This difference was more marked when mothers were anaemic. Three of four studies from industrialised countries showed a significant difference in haematocrit levels in favour of delayed clamping. Although meta-analysis showed an increased risk for hyperbilirubinaemia of 12%, no studies reported the need to apply phototherapy or perform exchange transfusion. We conclude that delayed cord-clamping in term infants, especially those with anaemic mothers, increases haemoglobin concentration in infants at 2-3 months of age and reduces the risk of anaemia, without an associated increased risk of perinatal complications. In developing countries where fetal anaemia is common, the advantages of delayed cord-clamping might be especially beneficial.
Topics: Anemia, Iron-Deficiency; Anemia, Neonatal; Constriction; Developed Countries; Developing Countries; Humans; Infant, Newborn; Polycythemia; Randomized Controlled Trials as Topic; Reproducibility of Results; Time Factors; Umbilical Cord
PubMed: 15005961
DOI: 10.1179/027249304225013286