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Prenatal Diagnosis Mar 2014To estimate incidence and risk factors of severe cerebral injury in survivors from monochorionic pregnancies with selective intrauterine growth restriction (sIUGR)... (Review)
Review
OBJECTIVE
To estimate incidence and risk factors of severe cerebral injury in survivors from monochorionic pregnancies with selective intrauterine growth restriction (sIUGR) and/or birth weight discordance (BWD).
METHODS
Electronic databases were searched for studies describing perinatal and neurologic outcome in monochorionic twins with sIUGR and/or BWD. Exclusion criteria were twin-twin transfusion syndrome, twin anemia-polycythemia sequence, selective feticide or laser treatment.
RESULTS
Eleven articles were included in the systematic review. Analysis was hampered by different methodology and definitions of cerebral injury. The incidence of severe cerebral injury varied from 0% to 33% (average 8%, 52/661), and was higher in studies including single intrauterine demise [odds ratio (OR) 2.92; 95% confidence interval (CI) 0.89-9.56] and studies with a median gestational age at birth of ≤32 weeks (OR 1.56; 95% CI 1.06-2.27). The risk of severe cerebral injury was higher in pregnancies with abnormal umbilical artery Doppler (13.5% vs 2.5%; OR 7.69; 95% CI 2.56-25.00) and in larger twins (9% vs 5%; OR 1.93; 95% CI 0.95-3.92).
CONCLUSIONS
The incidence of severe cerebral injury in monochorionic twins with sIUGR and/or BWD is approximately 8% and is associated with abnormal umbilical artery Doppler, larger twins, intrauterine fetal demise and low gestational age at birth.
Topics: Birth Weight; Brain Injuries; Female; Fetal Growth Retardation; Humans; Incidence; Infant, Newborn; Pregnancy; Risk Factors; Twins, Monozygotic
PubMed: 24338685
DOI: 10.1002/pd.4298 -
The Cochrane Database of Systematic... Apr 2013Polycythaemia vera and essential thrombocythaemia are chronic Philadelphia-negative myeloproliferative neoplasms that increase the risk of arterial and venous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Polycythaemia vera and essential thrombocythaemia are chronic Philadelphia-negative myeloproliferative neoplasms that increase the risk of arterial and venous thrombosis, as well as bleeding. In addition to the different therapeutic strategies available, an antiplatelet drug is often used to reduce thrombotic risk.
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 METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library (Issue 1 2012), MEDLINE (1966 to 2012), and EMBASE (1980 to 2012), as well as online registers of ongoing trials and conference proceedings. The date of the last search was October 2012.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) comparing long-term (>6 months) use of an antiplatelet drug versus placebo or no treatment in participants with polycythaemia vera or essential thrombocythaemia, as diagnosed by established international criteria, with data for at least one of the selected outcomes.
DATA COLLECTION AND ANALYSIS
Using a pre-defined extraction form, two review authors independently screened results, extracted data, and assessed quality. We planned to analyse the following outcomes: mortality from arterial and venous thrombotic events (primary efficacy outcome), mortality from bleeding episodes (primary safety outcome), 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, and all-cause mortality and any adverse events. We based quantitative analysis of outcome data on an intention-to-treat principle. We used the pooled odds ratio (OR) with 95% confidence interval (CI) with a fixed-effect model (Mantel-Haenszel) to estimate the overall treatment effect.
MAIN RESULTS
We identified no new studies from the updated searches. We included in this review two RCTs for a total of 630 participants. Both RCTs included participants with an established diagnosis of polycythaemia vera and with no clear indication or contraindication to aspirin therapy. We judged both studies to be of moderate quality. Published data from both studies were insufficient for a time-to-event data analysis and for some of the primary and secondary outcomes that we planned. The use of low-dose 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; P = 0.07). No data on mortality from bleeding episodes were available. A non-significant benefit of aspirin was shown for all-cause mortality (OR 0.46, 95% CI 0.21 to 1.01; P = 0.05). No increase in the risk of major bleeding was reported in participants taking aspirin compared with those given placebo (OR 0.99, 95% CI 0.23 to 4.36; P = 0.99), and a non-significant increase with aspirin treatment was shown for minor bleeding (OR 1.85, 95% CI 0.90 to 3.79; P = 0.09). No published studies have reported findings in participants with essential thrombocythaemia or in the study of other antiplatelet drugs.
AUTHORS' CONCLUSIONS
For patients with polycythaemia vera who have no clear indication or contraindication to aspirin therapy, available evidence suggests that the use of low-dose aspirin, when compared with no treatment, is associated with a statistically non-significant reduction in the risk of fatal thrombotic events and all-cause mortality, without an increased risk of major bleeding.
Topics: Anticoagulants; Aspirin; Humans; Platelet Aggregation Inhibitors; Polycythemia Vera; Randomized Controlled Trials as Topic; Thrombocythemia, Essential; Thrombosis
PubMed: 23633335
DOI: 10.1002/14651858.CD006503.pub3 -
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 -
Thrombosis and Haemostasis May 2013In Western countries, thrombotic risk factors for Budd-Chiari syndrome (BCS) are very common, including factor V Leiden mutation, prothrombin G20210A mutation,... (Review)
Review
In Western countries, thrombotic risk factors for Budd-Chiari syndrome (BCS) are very common, including factor V Leiden mutation, prothrombin G20210A mutation, myeloproliferative neoplasms, paroxysmal nocturnal haemoglobinuria, etc. However, the data regarding thrombotic risk factors in Chinese BCS patients are extremely limited. An observational study was conducted to examine this issue. A total of 246 BCS patients who were consecutively admitted to our department between July 1999 and December 2011 were invited to be examined for thrombotic risk factors. Of these, 169 patients were enrolled. Neither factor V Leiden mutation nor prothrombin G20210A mutation was found in any of 136 patients tested. JAK2 V617F mutation was positive in four of 169 patients tested. Neither MPL W515L/K mutation nor JAK2 exon 12 mutation was found in any of 135 patients tested. Overt myeloproliferative neoplasms were diagnosed in five patients (polycythemia vera, n=3; essential thrombocythemia, n=1; idiopathic myelofibrosis, n=1). Two of them had positive JAK2 V617F mutation. Both CD55 and CD59 deficiencies were found in one of 166 patients tested. This patient had a previous history of paroxysmal nocturnal haemo-globinuria before BCS. Anticardiolipin IgG antibodies were positive or weakly positive in six of 166 patients tested. Hyperhomocysteinaemia was found in 64 of 128 patients tested. 5,10-methylenetetrahydrofolate reductase C677T mutation was found in 96 of 135 patients tested. In conclusion, factor V Leiden mutation, prothrombin G20210A mutation, myeloproliferative neoplasms, and paroxysmal nocturnal haemoglobinuria are very rare in Chinese BCS patients, suggesting that the etiological distribution of BCS might be different between Western countries and China.
Topics: Adult; Antibodies, Anticardiolipin; Asian People; Biomarkers; Budd-Chiari Syndrome; CD55 Antigens; CD59 Antigens; Chi-Square Distribution; China; DNA Mutational Analysis; Factor V; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Hyperhomocysteinemia; Janus Kinase 2; Male; Methylenetetrahydrofolate Reductase (NADPH2); Mutation; Myeloproliferative Disorders; Prothrombin; Risk Factors
PubMed: 23447059
DOI: 10.1160/TH12-10-0784 -
Clinical Genetics Feb 2013This systematic review investigated the inheritance of the classical chronic myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential... (Review)
Review
This systematic review investigated the inheritance of the classical chronic myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and chronic myelogenous leukemia (CML). Sixty-one articles were included and provided 135 families with a total of 341 participants distributed to various subtypes of MPN: 50% PV, 23% ET, 14% PMF, 10% CML and 3% non-MPN hematological disorder. Women developed the disease earlier than men (43.1 years vs 47.3 years; p = 0.074), while the general average age of onset was 46 years, notably younger than sporadic cases. The clinical phenotype of the families showed a homogenous (67%) and a heterogeneous (33%) pattern, with the majority being PV-PV pairs (36%) and PV-PMF pairs (17%), respectively. This observation suggests that the susceptibility gene (or genes) is not restricted to one subtype supporting the hypothesis of a mutation in an early multipotent stem cell. Furthermore, a major subgroup of families provided evidence of an autosomal dominant (AD) inheritance with reduced penetrance. This study suggests that the origin of MPNs may occur in at least three different settings: (i) a sporadic, (ii) genetic heterogeneity with polygenetic and environmental impact and (iii) a familial phenotype following an AD inheritance.
Topics: Chronic Disease; Female; Genetic Predisposition to Disease; Humans; Inheritance Patterns; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential
PubMed: 23094849
DOI: 10.1111/cge.12044 -
The Journal of Sexual Medicine Jan 2013Testosterone (T) deficiency (TD) may significantly affect sexual function and multiple organ systems. (Review)
Review
INTRODUCTION
Testosterone (T) deficiency (TD) may significantly affect sexual function and multiple organ systems.
AIM
To provide recommendations and Standard Operating Procedures (SOPs) based on best evidence for diagnosis and treatment of TD in men.
METHODS
Medical literature was reviewed by the Endocrine subcommittee of the ISSM Standards Committee, followed by extensive internal discussion over two years, then public presentation and discussion with other experts.
MAIN OUTCOME MEASURE
Recommendations and SOPs based on grading of evidence-based medical literature and interactive discussion.
RESULTS
TD is the association of a low serum T with consistent symptoms or signs. T level tends to decline with age. T modulates sexual motivation and erection. It also plays a broader role in men's health. Recent studies have established associations between low T, male sexual dysfunctions and metabolic risk factors. Though association does not mean causation, low T is associated with reduced longevity, risk of fatal cardiovascular events, obesity, sarcopenia, mobility limitations, osteoporosis, frailty, cognitive impairment, depression, Sleep Apnea Syndrome, and other chronic diseases. The paper proposes a standardized process for diagnosis and treatment of TD, and updates the knowledge on T therapy (Tth) and prostate and cardiovascular safety. There is no compelling evidence that Tth causes prostate cancer or its progression in men without severe TD. Polycythemia is presently the only cardiovascular-related adverse-event significantly associated with Tth. But follow-up of controlled T trials is limited to 3 years.
CONCLUSIONS
Men with sexual dysfunctions, and/or with visceral obesity and metabolic diseases should be screened for TD and treated. Young men with TD should also be treated. Benefits and risks of Tth should be carefully assessed in older men. Prospective, long-term, placebo-controlled, interventional studies are required before screening for TD in more conditions, including cardiovascular diseases, and considering correction of TD as preventive medicine.
Topics: Cardiovascular Diseases; Clinical Laboratory Techniques; Clinical Protocols; Humans; Male; Practice Guidelines as Topic; Testosterone
PubMed: 22971200
DOI: 10.1111/j.1743-6109.2012.02783.x -
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 -
The Journal of Clinical Endocrinology... Jun 2010The risks of testosterone therapy in men remain poorly understood. (Meta-Analysis)
Meta-Analysis Review
CONTEXT
The risks of testosterone therapy in men remain poorly understood.
OBJECTIVE
The aim of this study was to conduct a systematic review and meta-analyses of testosterone trials to evaluate the adverse effects of testosterone treatment in men.
DATA SOURCES
We searched MEDLINE, EMBASE, and Cochrane CENTRAL from 2003 through August 2008. Review of reference lists and contact with experts further identified candidate studies.
STUDY SELECTION
Eligible studies were comparative, randomized, and nonrandomized and reported the effects of testosterone on outcomes of interest (death, cardiovascular events and risk factors, prostate outcomes, and erythrocytosis). Reviewers, working independently and in duplicate, determined study eligibility.
DATA EXTRACTION
Reviewers working independently and in duplicate determined the methodological quality of studies and collected descriptive, quality, and outcome data.
DATA SYNTHESIS
The methodological quality of the 51 included studies varied from low to medium, and follow-up duration ranged from 3 months to 3 yr. Testosterone treatment was associated with a significant increase in hemoglobin [weighted mean difference (WMD), 0.80 g/dl; 95% confidence interval (CI), 0.45 to 1.14] and hematocrit (WMD, 3.18%; 95% CI, 1.35 to 5.01), and a decrease in high-density lipoprotein cholesterol (WMD, -0.49 mg/dl; 95% CI, -0.85 to -0.13). There was no significant effect on mortality, prostate, or cardiovascular outcomes.
CONCLUSIONS
The adverse effects of testosterone therapy include an increase in hemoglobin and hematocrit and a small decrease in high-density lipoprotein cholesterol. These findings are of unknown clinical significance. Current evidence about the safety of testosterone treatment in men in terms of patient-important outcomes is of low quality and is hampered by the brief study follow-up.
Topics: Adult; Cardiovascular Diseases; Data Interpretation, Statistical; Humans; Male; Mortality; Polycythemia; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Research Design; Risk Factors; Testosterone; Treatment Outcome; Urologic Diseases
PubMed: 20525906
DOI: 10.1210/jc.2009-2575 -
The Cochrane Database of Systematic... Jan 2010Hyperviscosity of blood results in increased resistance to blood flow and decreased oxygen delivery. In the neonate, hyperviscosity can cause abnormalities of central... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hyperviscosity of blood results in increased resistance to blood flow and decreased oxygen delivery. In the neonate, hyperviscosity can cause abnormalities of central nervous system function, hypoglycemia, decreased renal function, cardiorespiratory distress, and coagulation disorders. Hyperviscosity has been reported to be associated with long-term motor and cognitive neurodevelopmental disorders. Blood viscosity exponentially increases when an infant has polycythemia (hematocrit >/= 65%). Partial exchange transfusion (PET) is traditionally used as the method to lower the hematocrit and treat hyperviscosity.
OBJECTIVES
To evaluate the effect of PET on mortality and neurodevelopmental outcome in infants with neonatal polycythemia.
SEARCH STRATEGY
Electronic databases searched included: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (1966 to October 2009), EMBASE (1980 to October 2009) and CINAHL (1982 to October 2009).
SELECTION CRITERIA
Randomized controlled clinical trials or quasi-randomized trials comparing partial exchange transfusion to control (non-treatment) in infants with neonatal polycythemia
DATA COLLECTION AND ANALYSIS
Data collection and analysis was performed according to the standards of the Cochrane Neonatal Review Group.
MAIN RESULTS
One study (Kumar 2004) reported no demonstrable effect on the risk of neonatal mortality (RR 5.23, 95% CI 0.66, 41.26).Four studies reported on neurodevelopmental assessment at 18 months or older. The completeness of follow-up differed widely between the studies. Overall, no difference was seen in developmental delay when all trials are analysed based on available cases (typical RR 1.45, 95% CI 0.83 to 2.54) and when only the randomized controlled trials are analysed (typical RR 1.35, 95% CI 0.68 to 2.69). A best case/worst case analysis of developmental delay is consistent with large benefit or harm from PET.Two studies reported on necrotizing enterocolitis (Van der Elst 1980; Black 1985). An increase in the risk of NEC was noted in infants receiving PET (typical RR 11.18, 95% CI 1.49, 83.64; typical RD 0.14, 95% CI 0.05, 0.22). No differences in short-term complications including hypoglycemia (two studies) and thrombocytopenia (one study) were noted.
AUTHORS' CONCLUSIONS
There are no proven clinically significant short or long-term benefits of PET in polycythemic newborn infants who are clinically well or who have minor symptoms related to hyperviscosity. PET may lead to an increase in the risk of NEC. The data regarding developmental follow-up is extremely imprecise due to the large number of surviving infants who were not assessed and, therefore, the true risks and benefits of PET are unclear.
Topics: Blood Viscosity; Blood Volume; Developmental Disabilities; Hematocrit; Humans; Infant; Infant, Newborn; Plasma Substitutes; Polycythemia; Randomized Controlled Trials as Topic
PubMed: 20091569
DOI: 10.1002/14651858.CD005089.pub2 -
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