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Thrombosis and Haemostasis Feb 2014Antibodies to prothrombin are detected by directly coating prothrombin on irradiated ELISA plates (aPT) or by using the phosphatidylserine/prothrombin complex as antigen... (Review)
Review
Antibodies to prothrombin are detected by directly coating prothrombin on irradiated ELISA plates (aPT) or by using the phosphatidylserine/prothrombin complex as antigen (aPS/PT). Although these antibodies have both been associated with antiphospholipid syndrome (APS) and a correlation between the two assays have been reported, it seems that aPT and aPS/PT belong to different populations of autoantibodies. It was our objective to systematically review the available evidence on aPT and aPS/PT antibodies and the risk of thrombosis in APS. Medline-reports published between 1988 and 2013 investigating aPT and aPS/PT as a risk factor for thrombosis were included. Whenever possible, antibody isotype(s) and site of thrombosis were analysed. This systematic review is based on available data from more than 7,000 patients and controls from 38 studies analysing aPT and 10 aPS/PT. Antibodies to prothrombin (both aPT and aPS/PT) increased the risk of thrombosis (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.72-3.5). aPS/PT seemed to represent a stronger risk factor for thrombosis, both arterial and/or venous than aPT (OR 5.11; 95%CI 4.2-6.3 and OR 1.82; 95%CI 1.44-2.75, respectively). In conclusion, routine measurement of aPS/PT (but not aPT) might be useful in establishing the thrombotic risk of patients with previous thrombosis and/or systemic lupus erythematosus. Their inclusion as laboratory criteria for the APS should be indisputably further explored.
Topics: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Biomarkers; Humans; Odds Ratio; Phosphatidylserines; Predictive Value of Tests; Prothrombin; Risk Assessment; Risk Factors; Thrombosis
PubMed: 24172938
DOI: 10.1160/TH13-06-0509 -
Current Medical Research and Opinion Nov 2013Allergic rhinitis is a complex inflammatory disease whose pathophysiology involves local and systemic mechanisms. Rupatadine, a molecule with intense antihistaminic... (Review)
Review
BACKGROUND
Allergic rhinitis is a complex inflammatory disease whose pathophysiology involves local and systemic mechanisms. Rupatadine, a molecule with intense antihistaminic activity and with antagonist PAF effects through its interaction with specific receptors, is indicated for the treatment of intermittent or persistent allergic rhinitis and urticaria.
SCOPE
This systematic review was aimed at identifying in the most important databases, up to January 2013, the double-blind placebo-controlled randomized trials administering rupatadine in allergic rhinitis. No restriction was introduced for treatment duration and dose, study design, population age, allergen exposition and disease classification. The methodological quality of included studies and risk of bias were systematically assessed. Meta-analysis was performed when possible to summarize information.
FINDINGS
Seventeen of 413 initially identified records were fully assessed for eligibility. Ten trials involving 2573 patients overall met the inclusion criteria and entered the analysis. Their internal validity was satisfactory. Data synthesis showed that rupatadine is superior to placebo in relieving the overall allergy symptoms on reflective (SMD: -0.37, 95% CI -0.46 to -0.27; p < 0.00001) and instantaneous (SMD: -0.41, 95% CI -0.71 to -0.11; p = 0.007) assessment, the nasal symptoms considered together (reflective SMD: -0.36, 95% CI -0.48 to -0.25; p < 0.00001; instantaneous SMD: -0.39, 95% CI -0.61 to -0.17; p = 0.0004) or individually and ocular symptoms. Inter-study heterogeneity was low for the main outcomes and the risk of publication bias was judged as unlikely. A number of secondary endpoints were favorably affected by rupatadine. No difference was observed in the incidence of total adverse reactions between rupatadine and placebo (OR 1.23, 95% CI 0.95 to 1.59; p = 0.12).
CONCLUSION
Randomized double-blind controlled trials show a favorable risk-benefit ratio in rupatadine for the treatment of allergic rhino-conjunctivitis. This evidence is strengthened when data are pooled in the form of meta-analysis, where accurate and robust effect estimations are derived from a large population.
Topics: Conjunctivitis, Allergic; Cyproheptadine; Histamine Antagonists; Humans; Platelet Activating Factor; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome; Urticaria
PubMed: 23826741
DOI: 10.1185/03007995.2013.822855 -
Intensive Care Medicine Oct 2013Parenteral lipid emulsions (LEs) are commonly rich in long-chain triglycerides derived from soybean oil (SO). SO-containing emulsions may promote systemic inflammation... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Parenteral lipid emulsions (LEs) are commonly rich in long-chain triglycerides derived from soybean oil (SO). SO-containing emulsions may promote systemic inflammation and therefore may adversely affect clinical outcomes. We hypothesized that alternative oil-based LEs (SO-sparing strategies) may improve clinical outcomes in critically ill adult patients compared to products containing SO emulsion only. The purpose of this systematic review was to evaluate the effect of parenteral SO-sparing strategies on clinical outcomes in intensive care unit (ICU) patients.
METHODS
We searched computerized databases from 1980 to 2013. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated SO-sparing strategies versus SO-based LEs in the context of parenteral nutrition.
RESULTS
A total of 12 RCTs met the inclusion criteria. When the results of these RCTs were statistically aggregated, SO-sparing strategies were associated with clinically important reductions in mortality (risk ratio, RR 0.83; 95 % confidence intervals, CI 0.62, 1.11; P = 0.20), in duration of ventilation (weighted mean difference, WMD -2.57; 95 % CI -5.51, 0.37; P = 0.09), and in ICU length of stay (LOS) (WMD -2.31; 95 % CI -5.28, 0.66; P = 0.13) but none of these differences were statistically significant. SO-sparing strategies had no effect on infectious complications (RR 1.13; 95 % CI 0.87, 1.46; P = 0.35).
CONCLUSION
Alternative oil-based LEs may be associated with clinically important reductions in mortality, duration of ventilation, and ICU LOS but lack of statistical precision precludes any clinical recommendations at this time. Further research is warranted to confirm these potential positive treatment effects.
Topics: Adult; Critical Illness; Databases, Bibliographic; Emulsions; Fat Emulsions, Intravenous; Fish Oils; Humans; Immune System; Inflammation; Intensive Care Units; Lecithins; Oxidative Stress; Parenteral Nutrition; Phospholipids; Plant Oils; Randomized Controlled Trials as Topic; Safflower Oil; Soybean Oil; Treatment Outcome; Triglycerides
PubMed: 23812404
DOI: 10.1007/s00134-013-2999-4 -
Expert Opinion on Pharmacotherapy Sep 2013Rupatadine fumarate is a second-generation antihistamine provided with a potent, long-lasting and balanced in vivo dual platelet-activating factor (PAF) and histamine... (Review)
Review
INTRODUCTION
Rupatadine fumarate is a second-generation antihistamine provided with a potent, long-lasting and balanced in vivo dual platelet-activating factor (PAF) and histamine antagonist activity and it uniquely combines both activities at a high level of potency. Rupatadine has a rapid onset of action and a long-lasting effect, so a once-daily dosing is permitted, moreover is well tolerated by young adults and the elders. Rupatadine does not present the side effects of first-generation H1-antihistamines, such as somnolence, fatigue, headache, impaired memory and learning, sedation, increased appetite, dry mouth, dry eyes, visual disturbances, constipation, urinary retention and erectile dysfunction.
AREAS COVERED
This study evaluates the effectiveness and safety of rupatadine in chronic urticaria (CU) and acquired cold urticaria (ACU), through a systematic review of the literature.
EXPERT OPINION
Patients affected by urticaria are often discouraged because frequently their disease does not recognize a cause and it is unresponsive to treatments. Patients can control their symptoms assuming second-generation H1-antihistamines, such as rupatadine. Several randomized, double-blind, placebo-controlled trials testify effectiveness and safety of rupatadine in CU and ACU. However, further clinical trials to evaluate the efficacy of rupatadine in different urticaria subtypes and to test the safety of doses higher than 20 mg are encouraged.
Topics: Animals; Cyproheptadine; Histamine Antagonists; Humans; Platelet Activating Factor; Urticaria
PubMed: 23806068
DOI: 10.1517/14656566.2013.813481 -
European Journal of Obstetrics,... Jul 2013To determine and compare the diagnostic accuracy of the lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC) in the prediction of neonatal respiratory... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine and compare the diagnostic accuracy of the lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC) in the prediction of neonatal respiratory distress syndrome (RDS).
STUDY DESIGN
A systematic review was performed to identify studies comparing either the L/S ratio or the LBC with the occurrence of RDS published between January 1999 and February 2009. Two independent reviewers performed study selection and data extraction. For each study sensitivity and specificity were calculated. Summary receiver-operating characteristics (ROC) curves, assessing the diagnostic performance of both tests, were constructed. A subgroup analysis was performed to estimate the sensitivity and specificity of the various cut-off values.
RESULTS
13 studies were included. The ROC curves of the collected data illustrate that the LBC and L/S ratio perform equally well in the prediction of RDS. Comparison of the two summary ROC curves of each test indicates that the diagnostic performance of LBC might even have a slight advantage over L/S ratio. Due to the wide cut-off range it was not possible to define specific cut-off values with the best accuracy.
CONCLUSION
We recommend replacing the L/S ratio as gold standard with the lamellar body count since the LBC is easy to perform, rapid, inexpensive, and available to all hospitals 24h per day.
Topics: Amniotic Fluid; Female; Fetal Organ Maturity; Humans; Lecithins; Lung; Predictive Value of Tests; Pregnancy; Respiratory Distress Syndrome, Newborn; Sphingomyelins
PubMed: 23481577
DOI: 10.1016/j.ejogrb.2013.02.013 -
Annals of Nutrition & Metabolism 2013Sex hormones may influence the activity of enzymes which are involved in the synthesis of long-chain polyunsaturated fatty acids. The objective of this review was to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
Sex hormones may influence the activity of enzymes which are involved in the synthesis of long-chain polyunsaturated fatty acids. The objective of this review was to assess the role of gender in determining the fatty acid composition of human samples, like plasma and erythrocyte membrane lipids, and adipose tissue.
METHODS
The method included a structured search strategy on MEDLINE, Scopus and the Cochrane databases, with formal inclusion/exclusion criteria, data extraction procedure and meta-analysis.
RESULTS
We evaluated 51 publications, dated from 1975 to 2011. Meta-analysis showed significantly lower values of both arachidonic acid (AA) and docosahexaenoic acid (DHA) in total plasma lipids (32 and 33 studies) and in plasma phospholipids (PL; 21 and 23 studies) in men than in women. Primary analysis of the phospholipid fraction showed the mean difference in AA to be 0.42% weight/weight (95% CI: 0.18-0.65, n = 7,769) and in DHA 0.37% weight/weight (95% CI: 0.24-0.51, n = 8,541), while there was no gender difference in the values of linoleic acid and α-linolenic acid.
CONCLUSIONS
This systematic review based on 51 publications showed significantly lower contribution of AA and DHA to plasma total lipids and plasma PL in men than in women. Gender distribution should be regarded as a significant potential confounding factor in every study assessing data on fatty acid composition.
Topics: Adipose Tissue; Arachidonic Acid; Biomarkers; Cholesterol Esters; Databases, Factual; Docosahexaenoic Acids; Erythrocyte Membrane; Female; Humans; Linoleic Acid; Male; Nutritional Status; Phosphatidylcholines; Phosphatidylethanolamines; Sex Factors; Triglycerides; alpha-Linolenic Acid
PubMed: 23327902
DOI: 10.1159/000345599 -
International Journal of Molecular... Nov 2012The present paper aims at a systematic review of the current knowledge on phosphatidylethanol (PEth) in blood as a direct marker of chronic alcohol use and abuse. In... (Meta-Analysis)
Meta-Analysis Review
The present paper aims at a systematic review of the current knowledge on phosphatidylethanol (PEth) in blood as a direct marker of chronic alcohol use and abuse. In March 2012, the search through "MeSH" and "free-text" protocols in the databases Medline/PubMed, SCOPUS, Web of Science, and Ovid/Embase, combining the terms phosphatidylethanol and alcohol, provided 444 records, 58 of which fulfilled the inclusion criteria and were used to summarize the current evidence on the formation, distribution and degradation of PEth in human blood: (1), the presence and distribution of different PEth molecular species (2), the most diffused analytical methods devoted to PEth identification and quantization (3), the clinical efficiency of total PEth quantification as a marker of chronic excessive drinking (4), and the potential utility of this marker for identifying binge drinking behaviors (5). Twelve papers were included in the meta-analysis and the mean (M) and 95% confidence interval (CI) of total PEth concentrations in social drinkers (DAI ≤ 60 g/die; M = 0.288 μM; CI 0.208-0.367 μM) and heavy drinkers (DAI > 60 g/die; M = 3.897 μM; CI 2.404-5.391 μM) were calculated. The present analysis demonstrates a good clinical efficiency of PEth for detecting chronic heavy drinking.
Topics: Alcohol Drinking; Alcoholism; Binge Drinking; Biomarkers; Glycerophospholipids; Humans; Time Factors
PubMed: 23203094
DOI: 10.3390/ijms131114788 -
Neonatology 2012Lung lavage with diluted surfactant has emerged as an innovative treatment for meconium aspiration syndrome (MAS). However, the treatment effect has not yet been fully... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lung lavage with diluted surfactant has emerged as an innovative treatment for meconium aspiration syndrome (MAS). However, the treatment effect has not yet been fully established.
OBJECTIVE
To investigate the effects of surfactant lavage therapy for MAS by a systematic meta-analysis.
METHODS
Relevant studies were identified by database searches in MEDLINE (from 1950), EMBASE (from 1980), and CENTRAL, up to June 2010, and by additional hand searches. Meta-analyses were separately conducted for randomized controlled trials (RCTs) and non-randomized controlled studies (NRSs). Risk of bias was assessed and clinical as well as statistical heterogeneities were also investigated in explaining the potential bias.
RESULTS
Two RCTs (87 patients) and eight NRSs (178 patients) were identified. From the results of the meta-analysis of RCTs, surfactant lavage significantly decreased death or the need for extracorporeal membrane oxygenation (RR 0.34, 95% CI 0.11, 0.99). An interventional benefit was indicated for other outcomes, although it was not statistically significant based only on the two RCTs. Results from the analysis of outcomes from NRSs are consistent with those from RCTs and demonstrated a beneficial effect, which could be considered as supporting evidence.
CONCLUSIONS
Lung lavage with diluted surfactant appeared to improve the clinical outcome in infants with MAS. Given that less than 100 infants were included in the two RCTs, the findings of this study may still be regarded as insufficient evidence. Further research will be needed to confirm the benefit as well as to refine the lavage technique.
Topics: Biological Products; Bronchoalveolar Lavage; Drug Combinations; Fatty Alcohols; Humans; Infant, Newborn; Meconium Aspiration Syndrome; Phosphatidylglycerols; Proteins; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome
PubMed: 22067375
DOI: 10.1159/000329822 -
Brain Injury Jul 2008There has been increasing interest in the role of cholinomimetic agents in the long-term management of cognitive impairment following traumatic brain injury. This paper... (Review)
Review
PRIMARY OBJECTIVE
There has been increasing interest in the role of cholinomimetic agents in the long-term management of cognitive impairment following traumatic brain injury. This paper aims to assess the evidence accumulated thus far.
METHODS
Studies are identified by searching MEDLINE, EMBASE and PsychINFO, contacting experts and pharmaceutical companies and hand searching bibliographies. All study designs are included.
MAIN OUTCOME AND RESULTS
This study identified 25 papers that studied cholinesterase inhibitors, physostigmine and choline in mild-to-severe traumatic brain injury. The outcome with cholinesterase inhibitors and choline is suggestive but not conclusive while physostigmine appears of little benefit. A lack of rigorous studies and a plethora of outcome measures preclude drawing definitive conclusions. Further randomized controlled trials are urgently required.
Topics: Brain Injuries; Cholinesterase Inhibitors; Cognition Disorders; Cytidine Diphosphate Choline; Humans; Lecithins; Neuropsychological Tests; Nootropic Agents; Physostigmine; Surface-Active Agents; Time Factors
PubMed: 18568705
DOI: 10.1080/02699050802132495 -
The Cochrane Database of Systematic... Oct 2007Respiratory distress syndrome (RDS) is a significant cause of morbidity and mortality in preterm infants. RDS is caused by a deficiency, dysfunction, or inactivation of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Respiratory distress syndrome (RDS) is a significant cause of morbidity and mortality in preterm infants. RDS is caused by a deficiency, dysfunction, or inactivation of pulmonary surfactant. Numerous surfactants of either animal extract or synthetic design have been shown to improve outcomes. New surfactant preparations that include peptides or whole proteins that mimic endogenous surfactant protein have recently been developed and tested.
OBJECTIVES
To assess the effect of administration of synthetic surfactant containing surfactant protein mimics compared to animal derived surfactant extract on the risk of mortality, chronic lung disease, and other morbidities associated with prematurity in preterm infants at risk for or having RDS.
SEARCH STRATEGY
Standard search methods of the Cochrane Neonatal Review Group were used. The search included MEDLINE (1966 - May 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) in all languages. In addition, published abstracts of the Society of Pediatric Research were searched electronically. For abstract books that did not include key words, the search was limited to the relevant sections on pulmonary and neonatology. The bibliography cited in each publication was obtained and searched in order to identify additional relevant articles.
SELECTION CRITERIA
Randomized and quasi-randomized controlled clinical trials were considered for this review. Studies that enrolled preterm infants or low birth weight infants at risk for or having RDS who were treated with either a synthetic surfactant containing surfactant protein mimics or an animal-derived surfactant preparation were included for this review. Studies that either attempted to treat or prevent respiratory distress syndrome were included.
DATA COLLECTION AND ANALYSIS
Primary outcome measures, including mortality, chronic lung disease and multiple secondary outcome measures were abstracted by the reviewers. Statistical analysis was performed using Review Manager software. Categorical data was analyzed using relative risk, risk difference, and number needed to treat. 95% confidence intervals reported. A fixed effects model was used for the meta-analysis. Heterogeneity was assessed using the I-squared statistic.
MAIN RESULTS
Two studies were identified that compared protein containing synthetic surfactants to animal derived surfactant preparations. In a meta-analysis of these two studies, infants who received protein containing synthetic surfactant compared to animal derived surfactant extract did not demonstrate significantly different risks of prespecified primary outcomes: mortality at 36 weeks [typical RR 0.81 (95% CI 0.64, 1.03)], chronic lung disease at 36 weeks [typical RR 0.99 (95% CI 0.84, 1.18)], or the combined outcome of mortality or chronic lung disease at 36 weeks [typical RR 0.96 (95% CI 0.82, 1.12)]. There were also no differences in any of the secondary outcomes regarding complications of prematurity between the two surfactant groups with the exception of necrotizing enterocolitis. A decrease in the risk of necrotizing enterocolitis was noted in infants who received protein containing synthetic surfactants compared to animal derived surfactant extract [typical RR 0.60 (95% CI 0.42, 0.86)]. However, this was a secondary outcome in both of the primary studies and there was moderate heterogeneity between the studies.
AUTHORS' CONCLUSIONS
In two trials of protein containing synthetic surfactants compared to animal derived surfactant extract, no statistically different clinical differences in death and chronic lung disease were noted. In general, clinical outcomes between the two groups were similar. Further well designed studies of adequate size and power will help confirm and refine these findings.
Topics: 1,2-Dipalmitoylphosphatidylcholine; Animals; Biological Products; Drug Combinations; Fatty Alcohols; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Phosphatidylglycerols; Phospholipids; Proteins; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn
PubMed: 17943881
DOI: 10.1002/14651858.CD006069.pub3