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Medicine and Science in Sports and... Sep 2013Altitude acclimatization is associated with a rapid increase in hematocrit. The time course and the contribution of the red cell volume expansion are not clear. The... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Altitude acclimatization is associated with a rapid increase in hematocrit. The time course and the contribution of the red cell volume expansion are not clear. The purpose of the present meta-analysis was to explore how much altitude exposure is required to induce polycythemia in healthy lowlanders.
METHODS
A systematic review was performed of 66 published articles (including 447 volunteers) identified through literature search. We performed a mixed-model random-effects meta-analysis and a Monte Carlo simulation on the extracted data.
RESULTS
The following results were obtained in this study: 1) the red cell volume expansion for a given duration of exposure is dependent on altitude (P < 0.0001), that is, that the increase in red cell volume was accelerated at higher altitudes; and 2) the extent of the erythropoietic response depends on the initial red cell volume (P < 0.0001). It seems that exposure time must exceed 2 wk at an altitude of more than 4000 m to exert a statistically significant effect. At lower altitudes, longer exposure times are needed with altitudes lower than 3000 m not yielding an increase within 4 wk.
CONCLUSIONS
Red cell volume response to hypoxia is generally slow, although it accelerates with increasing altitude. This, in combination with a dependency on initial red cell volume, suggests that, for example, athletes may need to spend more time at altitude to see an effect on red cell volume than commonly recommended.
Topics: Acclimatization; Altitude; Erythrocyte Volume; Erythrocytes; Hypoxia; Monte Carlo Method; Polycythemia; Time Factors
PubMed: 23502972
DOI: 10.1249/MSS.0b013e31829047e5 -
The Cochrane Database of Systematic... Nov 2011Active management of the third stage of labour involves giving a prophylactic uterotonic, early cord clamping and controlled cord traction to deliver the placenta. With... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Active management of the third stage of labour involves giving a prophylactic uterotonic, early cord clamping and controlled cord traction to deliver the placenta. With expectant management, signs of placental separation are awaited and the placenta is delivered spontaneously. Active management was introduced to try to reduce haemorrhage, a major contributor to maternal mortality in low-income countries.
OBJECTIVES
To compare the effectiveness of active versus expectant management of the third stage of labour.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group Trials Register (15 February 2011).
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials comparing active versus expectant management of the third stage of labour.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction.
MAIN RESULTS
We included seven studies (involving 8247 women), all undertaken in hospitals, six in high-income countries and one in a low-income country. Four studies compared active versus expectant management, and three compared active versus a mixture of managements. We used random-effects in the analyses because of clinical heterogeneity. There was an absence of high quality evidence for our primary outcomes. The evidence suggested that for women at mixed levels of risk of bleeding, active management showed a reduction in the average risk of maternal primary haemorrhage at time of birth (more than 1000 mL) (average risk ratio (RR) 0.34, 95% confidence interval (CI) 0.14 to 0.87, three studies, 4636 women) and of maternal haemoglobin (Hb) less than 9 g/dL following birth (average RR 0.50, 95% CI 0.30 to 0.83, two studies, 1572 women). We also found no difference in the incidence in admission of infants to neonatal units (average RR 0.81, 95% CI 0.60 to 1.11, two studies, 3207 women) nor in the incidence of infant jaundice requiring treatment (0.96, 95% CI 0.55 to 1.68, two studies, 3142 women). There were no data on our other primary outcomes of very severe postpartum haemorrhage (PPH) at the time of birth (more than 2500 mL), maternal mortality, or neonatal polycythaemia needing treatment.Active management also showed a significant decrease in primary blood loss greater than 500 mL, and mean maternal blood loss at birth, maternal blood transfusion and therapeutic uterotonics during the third stage or within the first 24 hours, or both and significant increases in maternal diastolic blood pressure, vomiting after birth, after-pains, use of analgesia from birth up to discharge from the labour ward and more women returning to hospital with bleeding (outcome not pre-specified). There was also a decrease in the baby's birthweight with active management, reflecting the lower blood volume from interference with placental transfusion.In the subgroup of women at low risk of excessive bleeding, there were similar findings, except there was no significant difference identified between groups for severe haemorrhage or maternal Hb less than 9 g/dL (at 24 to 72 hours).Hypertension and interference with placental transfusion might be avoided by using modifications to the active management package, e.g. omitting ergot and deferring cord clamping, but we have no direct evidence of this here.
AUTHORS' CONCLUSIONS
Although there is a lack of high quality evidence, active management of the third stage reduced the risk of haemorrhage greater than 1000 mL at the time of birth in a population of women at mixed risk of excessive bleeding, but adverse effects were identified. Women should be given information on the benefits and harms of both methods to support informed choice. Given the concerns about early cord clamping and the potential adverse effects of some uterotonics, it is critical now to look at the individual components of third-stage management. Data are also required from low-income countries.
Topics: Birth Weight; Constriction; Delivery, Obstetric; Female; Humans; Labor Stage, Third; Oxytocics; Placenta; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic; Watchful Waiting
PubMed: 22071837
DOI: 10.1002/14651858.CD007412.pub3 -
Annals of Hematology Aug 2009Polycythemia vera (PV) in children and adolescents is very rare. Data on clinical and laboratory evaluations as well as on treatment modalities are sparse. Here, we... (Review)
Review
Polycythemia vera (PV) in children and adolescents is very rare. Data on clinical and laboratory evaluations as well as on treatment modalities are sparse. Here, we report the long-term clinical course of a PV patient first diagnosed more than 40 years ago at age 12. In addition, after a systematic review of the scientific medical literature, clinical and hematological data of 35 patients (19 female and 17 male) from 25 previous reports are summarized. Three patients developed PV following antecedent hematological malignancies. Budd-Chiari syndrome was diagnosed in seven patients indicating a particular risk of young patients of developing this disorder. One patient presented with ischemic stroke, one patient with gangrene, and three patients with severe hemorrhage. Three patients died from disease-related complications. Hematocrit levels and platelet counts were not correlated with disease severity. Leukocytosis >15 x 10(9)/L was present in 9/35 patients and associated with a thromboembolic or hemorrhagic complication in seven patients. The few available data on molecular genetics and endogenous erythroid colony growth indicate changes comparable to those detectable in adult patients. Treatment varied enormously. It included aspirin, phlebotomy, hydroxycarbamide, busulfan, melphalan, pyrimethamine, and interferon-alpha. Two patients successfully underwent stem cell transplantation. Currently, it is impossible to treat an individual pediatric PV patient with an evidence-based regimen.
Topics: Adolescent; Budd-Chiari Syndrome; Child; Erythropoiesis; Hematologic Neoplasms; Hematologic Tests; Humans; Middle Aged; Polycythemia; Polycythemia Vera
PubMed: 19468728
DOI: 10.1007/s00277-009-0758-y -
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 -
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 -
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