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American Journal of Hematology Mar 2018Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of... (Meta-Analysis)
Meta-Analysis
Ruxolitinib exerts immunosuppressive activity that may increase the risk of infectious complications. We performed a systematic review of the literature with the aim of estimating the risk of infections in patients treated with ruxolitinib. Studies were identified by electronic search of MEDLINE and EMBASE database. Differences in the incidence of infectious events between ruxolitinib and comparison groups were expressed as odds ratios (ORs) and 95% confidence intervals (95% CI). Five phase III randomized clinical trials (RCTs) (3 phase IIIa with their extended phase and 2 phase IIIb), 6 phase IV studies and 28 case reports were included in this systematic review. Ruxolitinib was associated with a statistically significant increased risk of herpes zoster infection compared to control group in 3 RCTs including patients with polycythemia vera (OR 7.39 [1.33, 41.07]) and in a pooled analysis of the extended phase IIIa RCTs (OR 5.20 [95%CI 1.27, 21.18]). In the larger phase IV post-marketing study, the incidence of the most frequent infections was 8% for herpes zoster, 6.1% for bronchitis and 6% for urinary tract infections. In the published case reports, the most frequent infections were tuberculosis (N = 10), hepatitis B reactivation (N = 5) and pneumocystis jeroveci infection (N = 2). Evidence is not solid enough to accurately estimate the risk of infection in ruxolitinib-treated patients. However, published data clearly suggest that the infection risk may be clinically relevant. Well-designed studies are warranted to evaluate the risk of ruxolitinib-associated infection, in order to identify the most appropriate antimicrobial prophylactic strategy.
Topics: Antibiotic Prophylaxis; Bacterial Infections; Clinical Trials, Phase III as Topic; Confidence Intervals; Disease Susceptibility; Herpes Zoster; Humans; Immunocompromised Host; Immunosuppressive Agents; Incidence; Infections; Janus Kinase 1; Janus Kinase 2; Mycoses; Nitriles; Odds Ratio; Product Surveillance, Postmarketing; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; Risk
PubMed: 29150886
DOI: 10.1002/ajh.24976 -
Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis.American Journal of Obstetrics and... Jan 2018The effects of delayed cord clamping of the umbilical cord in preterm infants are unclear. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The effects of delayed cord clamping of the umbilical cord in preterm infants are unclear.
OBJECTIVE
We sought to compare the effects of delayed vs early cord clamping on hospital mortality (primary outcome) and morbidity in preterm infants using Cochrane Collaboration neonatal review group methodology.
STUDY DESIGN
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Chinese articles, cross-referencing citations, expert informants, and trial registries to July 31, 2017, for randomized controlled trials of delayed (≥30 seconds) vs early (<30 seconds) clamping in infants born <37 weeks' gestation. Before searching the literature, we specified that trials estimated to have cord milking in >20% of infants in any arm would be ineligible. Two reviewers independently selected studies, assessed bias, and extracted data. Relative risk (ie, risk ratio), risk difference, and mean difference with 95% confidence intervals were assessed by fixed effects models, heterogeneity by I statistics, and the quality of evidence by Grading of Recommendations, Assessment, Development, and Evaluations.
RESULTS
Eighteen randomized controlled trials compared delayed vs early clamping in 2834 infants. Most infants allocated to have delayed clamping were assigned a delay of ≥60 seconds. Delayed clamping reduced hospital mortality (risk ratio, 0.68; 95% confidence interval, 0.52-0.90; risk difference, -0.03; 95% confidence interval, -0.05 to -0.01; P = .005; number needed to benefit, 33; 95% confidence interval, 20-100; Grading of Recommendations, Assessment, Development, and Evaluations = high, with I = 0 indicating no heterogeneity). In 3 trials in 996 infants ≤28 weeks' gestation, delayed clamping reduced hospital mortality (risk ratio, 0.70; 95% confidence interval, 0.51-0.95; risk difference, -0.05; 95% confidence interval, -0.09 to -0.01; P = .02, number needed to benefit, 20; 95% confidence interval, 11-100; I = 0). In subgroup analyses, delayed clamping reduced the incidence of low Apgar score at 1 minute, but not at 5 minutes, and did not reduce the incidence of intubation for resuscitation, admission temperature, mechanical ventilation, intraventricular hemorrhage, brain injury, chronic lung disease, patent ductus arteriosus, necrotizing enterocolitis, late onset sepsis or retinopathy of prematurity. Delayed clamping increased peak hematocrit by 2.73 percentage points (95% confidence interval, 1.94-3.52; P < .00001) and reduced the proportion of infants having blood transfusion by 10% (95% confidence interval, 6-13%; P < .00001). Potential harms of delayed clamping included polycythemia and hyperbilirubinemia.
CONCLUSION
This systematic review provides high-quality evidence that delayed clamping reduced hospital mortality, which supports current guidelines recommending delayed clamping in preterm infants. This review does not evaluate cord milking, which may also be of benefit. Analyses of individual patient data in these and other randomized controlled trials will be critically important in reliably evaluating important secondary outcomes.
Topics: Apgar Score; Blood Transfusion; Constriction; Female; Hematocrit; Hospital Mortality; Humans; Hyperbilirubinemia; Infant, Newborn; Infant, Premature; Polycythemia; Pregnancy; Randomized Controlled Trials as Topic; Time Factors; Umbilical Cord
PubMed: 29097178
DOI: 10.1016/j.ajog.2017.10.231 -
The Journal of Allergy and Clinical... 2018The idiopathic systemic capillary leak syndrome is a rare disease characterized by unexplained recurrent shock caused by capillary hyperpermeability. Because of the...
BACKGROUND
The idiopathic systemic capillary leak syndrome is a rare disease characterized by unexplained recurrent shock caused by capillary hyperpermeability. Because of the rarity of the disease, this disease has easily been misdiagnosed and evidence of efficacious agents used empirically is lacking.
OBJECTIVE
To analyze the clinical and laboratory data, treatment modalities, and mortality rate of patients and to find contributing factors leading to mortality.
METHODS
We searched MEDLINE (inception to December 2016) and reviewed reference lists of previous systematic reviews. A total of 133 case reports (161 patients) and 5 case series (102 patients) of idiopathic systemic capillary leak syndrome were included.
RESULTS
Patients had hypotension (81.4%), edema (64.6%), and previous flu-like illness (34.2%). This disease was misdiagnosed as hypovolemic shock, septic shock, polycythemia vera, or angioedema. Thirty-seven patients died (23%) mainly because of systemic capillary leak syndrome itself (78.4%). There were significant differences in the survival rates between patients who were treated with prophylactic β2 agonists, methylxanthines, and intravenous immunoglobulins and those who were not. The estimated 1-, 5-, and 10-year survival rate of patients treated with intravenous immunoglobulins was 100%, 94%, and 94%, respectively.
CONCLUSIONS
We systematically analyzed in detail clinical presentations of all reported patients and identified various factors associated with mortality and effects of prophylactic treatment in idiopathic systemic capillary leak syndrome. The findings of this review will facilitate diagnostic approaches of idiopathic systemic capillary leak syndrome and aid in the selection of treatment.
Topics: Capillary Leak Syndrome; Humans; Prognosis
PubMed: 28939140
DOI: 10.1016/j.jaip.2017.07.021 -
Revue Neurologique Apr 2017High altitude may be a factor associated with cerebral venous thrombosis (CVT). As our knowledge of CVT at high altitude is limited, it was decided to pool such... (Review)
Review
BACKGROUND AND OBJECTIVE
High altitude may be a factor associated with cerebral venous thrombosis (CVT). As our knowledge of CVT at high altitude is limited, it was decided to pool such information from the available case studies to determine whether high altitude can predispose to CVT.
METHODS
A systematic review of the literature was performed for cases reporting CVT at high altitude. Searches of the PubMed database (up to July 2016) were performed for publications, using 'cerebral venous thrombosis' and 'high altitude' as keywords. Cross-referencing was also done to complete the search.
RESULTS
Ultimately, 13 articles were included in our systematic review. The population consisted of 17 patients, predominately male (14/17), with a mean age of 32 (range: 19-47) years. Altitude range was 3000-8200m. Nine patients stayed at high altitude for>2 weeks; the duration of high altitude stay was unknown for the remainder. A hypercoagulable state was found in nine patients: secondary polycythemia in five; protein C deficiency in one; protein S deficiency in one; and factor V Leiden mutations in two. No comorbidities were found in any of these patients.
CONCLUSION
Long-term stays at high altitude in association with a hypercoagulable state - in particular, congenital or acquired thrombophilia - appears to predispose to CVT. The association of CVT with a single exposure to high altitude seems low, but the risk cannot as yet be specifically estimated.
Topics: Adult; Altitude; Blood Coagulation Disorders; Female; Humans; Intracranial Thrombosis; Male; Middle Aged; Neuroimaging; Venous Thrombosis; Young Adult
PubMed: 28038774
DOI: 10.1016/j.neurol.2016.11.004 -
Journal of Bone and Mineral Research :... Apr 2017Blood cell production and bone homeostasis are physically interlinked systems that exhibit active cross-talk. We examined how bone health is affected in patients with... (Meta-Analysis)
Meta-Analysis Review
Blood cell production and bone homeostasis are physically interlinked systems that exhibit active cross-talk. We examined how bone health is affected in patients with hematopoietic disorders due to abnormal proliferation of bone marrow cells. The electronic databases Medline, Embase, PubMed, BIOSIS Previews, Web of Science, and Cochrane were searched for studies presenting numerical values for trabecular bone volume or bone mineral density in control and patients with hematopoietic disorders. We identified 5 studies for beta-thalassemia, 6 for sickle cell anemia, 2 for polycythemia vera and essential thrombocythemia, 3 for chronic myelogenous leukemia, 6 for myelofibrosis, 5 for multiple myeloma, and 4 studies each for systemic mastocytosis, lymphocytic leukemia, and hemochromatosis. The effect of the disease state on bone density was significant and negative for beta-thalassemia (r = -2.00; 95% confidence interval [CI] -3.41, -0.58; p < 0.005), sickle cell anemia (-0.91; -1.36, -0.47; p < 0.00005), chronic myelogenous leukemia (-0.55; -0.88, -0.22; p < 0005), mastocytosis (-0.99; -1.16, -0.82; p < 0.00001), lymphoblastic leukemia (-0.69; -0.98, -0.40; p < 0.00001), multiple myeloma (-0.67; -0.99, -0.35; p < 0.00005), and hemochromatosis (-1.15; -1.64, -0.66; p < 0.00001). The changes were negative but not significant for polycythemia vera (-0.16; -0.38, 0.05; p = 0.069) and essential thrombocythemia (-0.33; -0.92, 0.26; p = 0.14). In myelofibrosis, disease state was associated with increased bone density (0.74; 0.12, 1.36; p < 0.05). Bone density change significantly and negatively correlated with the level of ferritin and bone marrow cellularity but not with hemoglobin or erythropoietin. Thus, independent of hematopoietic lineage, abnormal proliferation of bone marrow cells appears to be associated with bone loss. Iron metabolism may independently contribute to bone homeostasis. © 2016 American Society for Bone and Mineral Research.
Topics: Bone Density; Bone Marrow; Bone Marrow Cells; Bone Marrow Diseases; Cell Proliferation; Female; Ferritins; Homeostasis; Humans; Male
PubMed: 27787922
DOI: 10.1002/jbmr.3026 -
The Cochrane Database of Systematic... Mar 2015Active 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 (30 September 2014) and reference lists of retrieved studies.
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 according to GRADE assessments 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, GRADE:very low quality) 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, GRADE:low quality). 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 infants, GRADE:low quality) nor in the incidence of infant jaundice requiring treatment (0.96, 95% CI 0.55 to 1.68, two studies, 3142 infants, GRADE:very low quality). 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: 25730178
DOI: 10.1002/14651858.CD007412.pub4 -
Ultrasound in Obstetrics & Gynecology :... Nov 2015To compare the Solomon and selective techniques for fetoscopic laser ablation (FLA) for the treatment of twin-twin transfusion syndrome (TTTS) in... (Comparative Study)
Comparative Study Review
OBJECTIVE
To compare the Solomon and selective techniques for fetoscopic laser ablation (FLA) for the treatment of twin-twin transfusion syndrome (TTTS) in monochorionic-diamniotic twin pregnancies.
METHODS
This was a systematic review conducted in accordance with the PRISMA statement. Electronic searches were performed for relevant citations published from inception to September 2014. Selected studies included pregnancies undergoing FLA for TTTS that reported on recurrence of TTTS, occurrence of twin anemia-polycythemia sequence (TAPS) or survival.
RESULTS
From 270 possible citations, three studies were included, two cohort studies and one randomized controlled trial (RCT), which directly compared the Solomon and selective techniques for FLA. The odds ratios (OR) of recurrent TTTS when using the Solomon vs the selective technique in the two cohort studies (n = 249) were 0.30 (95% CI, 0.00-4.46) and 0.45 (95% CI, 0.07-2.20). The RCT (n = 274) demonstrated a statistically significant reduction in risk of recurrent TTTS with the Solomon technique (OR, 0.21 (95% CI, 0.04-0.98); P = 0.03). The ORs for the development of TAPS following the Solomon and the selective techniques were 0.20 (95% CI, 0.00-2.46) and 0.61 (95% CI, 0.05-5.53) in the cohort studies and 0.16 (95% CI, 0.05-0.49) in the RCT, with statistically significant differences for the RCT only (P < 0.001). Observational evidence suggested overall better survival with the Solomon technique, which was statistically significant for survival of at least one twin. The RCT did not demonstrate a significant difference in survival between the two techniques, most probably owing to the small sample size and lack of power.
CONCLUSION
This systematic review of observational, comparative cohort and RCT data suggests a trend towards a reduction in TAPS and recurrent TTTS and an increase in twin survival, with no increase in the occurrence of complications or adverse events, when using the Solomon compared to the selective technique for the treatment of TTTS. These findings need to be confirmed by an appropriately-powered RCT with long-term neurological follow-up.
Topics: Arteriovenous Anastomosis; Female; Fetofetal Transfusion; Fetoscopy; Humans; Laser Coagulation; Observational Studies as Topic; Placenta; Pregnancy; Randomized Controlled Trials as Topic; Twins
PubMed: 25677883
DOI: 10.1002/uog.14813 -
European Journal of Gastroenterology &... Jan 2015Until now, no data on the routine screening for thrombotic risk factors in Chinese nonmalignant and noncirrhotic patients with portal vein thrombosis (PVT) have been... (Observational Study)
Observational Study Review
BACKGROUND
Until now, no data on the routine screening for thrombotic risk factors in Chinese nonmalignant and noncirrhotic patients with portal vein thrombosis (PVT) have been reported.
METHODS
A total of 141 nonmalignant and noncirrhotic patients with PVT who underwent screening tests for thrombotic risk factors between September 2009 and August 2012 were included in this study.
RESULTS
The JAK2 V617F mutation was found in 35 of the 141 patients tested. Neither the JAK2 exon 12 mutation nor the MPL W515 L/K mutation was found in any of the 50 patients tested. Overt myeloproliferative neoplasms (MPNs) were diagnosed in 13 patients (polycythemia vera, n=1; essential thrombocythemia, n=9; idiopathic myelofibrosis, n=3). Latent MPNs were considered in 23 patients with the JAK2 V617F mutation but without any significant abnormalities, as determined through regular blood tests. Anticardiolipin IgG antibodies were positive in none of the 136 patients tested. Paroxysmal nocturnal hemoglobinuria was not found in any of the 141 patients tested. Neither the factor V G1691A mutation nor the factor II G20210A mutation was found in any of the 72 patients tested. The C677T mutation in 5,10-methylenetetrahydrofolate reductase (MTHFR) was found in 29 of the 38 patients tested. Hyperhomocysteinemia was detected in eight of the 39 patients tested.
CONCLUSION
MPNs are an important thrombotic risk factor in Chinese patients with PVT. However, the extreme rarity of paroxysmal nocturnal hemoglobinuria, anticardiolipin IgG antibodies, and factor V G1691A and factor II G20210A mutations has precluded any support for the implementation of routine screening for these thrombotic factors in such patients. Additional case-control studies should confirm the role of the MTHFR C677T mutation and hyperhomocysteinemia in the pathogenesis of PVT.
Topics: Adult; Antibodies, Anticardiolipin; China; Exons; Factor V; Female; Hemoglobinuria, Paroxysmal; Humans; Hyperhomocysteinemia; Janus Kinase 2; Male; Methylenetetrahydrofolate Reductase (NADPH2); Mutation; Myeloproliferative Disorders; Portal Vein; Prothrombin; Risk Factors; Venous Thrombosis
PubMed: 25426980
DOI: 10.1097/MEG.0000000000000221 -
Journal of Obstetrics and Gynaecology... Aug 2014To analyze outcomes of monochorionic twins with twin anemia-polycythemia sequence (TAPS). (Review)
Review
OBJECTIVE
To analyze outcomes of monochorionic twins with twin anemia-polycythemia sequence (TAPS).
DATA SOURCES
PubMed, EMBASE, Medline, and reference list.
STUDY SELECTION
We included reports of TAPS defined prenatally with abnormal Doppler studies of middle cerebral artery and normal amniotic fluid volume which reported data as proportional rates.
DATA EXTRACTION
Abstracted outcomes were postnatal hemoglobin levels, postnatal procedures, and survival rates. Outcomes were analyzed for gestational age at diagnosis of TAPS (15 to 23 weeks, 24 to 29 weeks, > 29 weeks), in utero therapy, and nature of onset (isolated TAPS, or following twin-to-twin transfusion syndrome). The review was performed using MOOSE guidelines. Differences were significant if P < 0.05.
DATA SYNTHESIS
We assessed data on 28 pregnancies with TAPS. Diagnosis at 15 to 23 weeks' gestation and in utero therapy were associated with the highest mean levels of hemoglobin in anemic twins (P = 0.021), the lowest levels in polycythemic twins (P = 0.025), and the lowest frequency of postnatal procedures (P < 0.001). Survival rate was independent of gestational age at diagnosis and in utero therapy. In cases of TAPS following twin-to-twin transfusion, the mean hemoglobin level was higher in donors than in anemic twins with isolated TAPS (P = 0.029) and similar between recipients and polycythemic twins with isolated TAPS (P = 0.135). Twins with TAPS following twin-to-twin transfusion received in utero therapy more frequently than isolated TAPS twins (P = 0.030) and required a postnatal procedure less often (P < 0.001). Survival rates were similar in each group.
CONCLUSION
Diagnosis of TAPS at an early gestational age is associated with more favourable outcomes than later diagnosis. In utero therapy improves neonatal hemoglobin levels but does not change survival rates. Previous twin-to-twin transfusion syndrome does not worsen outcomes.
Topics: Female; Fetofetal Transfusion; Gestational Age; Hemoglobins; Humans; Pregnancy; Pregnancy Outcome; Prenatal Diagnosis
PubMed: 25222165
DOI: 10.1016/S1701-2163(15)30512-0 -
American Journal of Hematology Jun 2014Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases including polycythemia vera (PV), essential thrombocythemia (ET), and primary(idiopathic)... (Meta-Analysis)
Meta-Analysis Review
Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases including polycythemia vera (PV), essential thrombocythemia (ET), and primary(idiopathic) myelofibrosis (PMF). In this systematic review, we provide a comprehensive report on the incidence and prevalence of MPNs across the globe. Electronic databases (PubMed, EMBASE, MEDLINE, and Web of Science) were searched from their inception to August 2012 for articles reporting MPN incidence or prevalence rates. A random effects meta-analysis was undertaken to produce combined incidence rates for PV, ET, and PMF. Both heterogeneity and small study bias were assessed. Thirty-four studies were included. Reported annual incidence rates ranged from 0.01 to 2.61, 0.21 to 2.27, and 0.22 to 0.99 per 100,000 for PV, ET, and PMF, respectively. The combined annual incidence rates for PV, ET, and PMF were 0.84, 1.03, and 0.47 per 100,000. There was high heterogeneity across disease entities (I(2) 97.1-99.8%) and evidence of publication bias for ET and PMF (Egger test, P = 50.007 and P ≤ 0.001, respectively).The pooled incidence reflects the rarity of MPNs. The calculated pooled incidence rates do not reflect MPN incidence across the globe due to the high unexplained heterogeneity. Improved, widespread registration of MPNs would provide better information for global comparison of the incidence and prevalence of MPNs.
Topics: Humans; Incidence; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential
PubMed: 24971434
DOI: 10.1002/ajh.23690