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The Cochrane Database of Systematic... Mar 2014This overview reports on interventions for pain relief and for subfertility in pre-menopausal women with clinically diagnosed endometriosis. (Review)
Review
BACKGROUND
This overview reports on interventions for pain relief and for subfertility in pre-menopausal women with clinically diagnosed endometriosis.
OBJECTIVES
The objective of this overview was to summarise the evidence from Cochrane systematic reviews on treatment options for women with pain or subfertility associated with endometriosis.
METHODS
Published Cochrane systematic reviews reporting pain or fertility outcomes in women with clinically diagnosed endometriosis were eligible for inclusion in the overview. We also identified Cochrane reviews in preparation (protocols and titles) for future inclusion. The reviews, protocols and titles were identified by searching the Cochrane Database of Systematic Reviews and Archie (the Cochrane information management system) in March 2014.Pain-related outcomes of the overview were pain relief, clinical improvement or resolution and pain recurrence. Fertility-related outcomes were live birth, clinical pregnancy, ongoing pregnancy, miscarriage and adverse events.Selection of systematic reviews, data extraction and quality assessment were undertaken in duplicate. Review quality was assessed using the AMSTAR tool. The quality of the evidence for each outcome was assessed using GRADE methods. Review findings were summarised in the text and the data for each outcome were reported in 'Additional tables'.
MAIN RESULTS
Seventeen systematic reviews published in The Cochrane Library were included. All the reviews were high quality. The quality of the evidence for specific comparisons ranged from very low to moderate. Limitations in the evidence included risk of bias in the primary studies, inconsistency between the studies, and imprecision in effect estimates. Pain relief (14 reviews) Gonadotrophin-releasing hormone (GnRH) analogues One systematic review reported low quality evidence of an overall benefit for GnRH analogues compared with placebo or no treatment. Ovulation suppression Five systematic reviews reported on medical treatment using ovulation suppression. There was moderate quality evidence that the levonorgestrel-releasing intrauterine system (LNG-IUD) was more effective than expectant management, and very low quality evidence that danazol was more effective than placebo. There was no consistent evidence of a difference in effectiveness between oral contraceptives and goserelin, estrogen plus progestogen and placebo, or progestogens and placebo, though in all cases the relevant evidence was of low or very low quality. Non-steroidal anti-inflammatory drugs (NSAIDS)A review of NSAIDs reported inconclusive evidence of a benefit in symptom relief compared with placebo. Surgical interventions There were two reviews of surgical interventions. One reported moderate quality evidence of a benefit in pain relief following laparoscopic surgery compared to diagnostic laparoscopy only. The other reported very low quality evidence that recurrence rates of endometriomata were lower after excisional surgery than after ablative surgery. Post-surgical medical interventions Two reviews reported on post-surgical medical interventions. Neither found evidence of an effect on pain outcomes, though in both cases the evidence was of low or very low quality. Alternative medicine There were two systematic reviews of alternative medicine. One reported evidence of a benefit from auricular acupuncture compared to Chinese herbal medicine, and the other reported no evidence of a difference between Chinese herbal medicine and danazol. In both cases the evidence was of low or very low quality. Anti-TNF-α drugs One review found no evidence of a difference in effectiveness between anti-TNF-α drugs and placebo. However, the evidence was of low quality. Reviews reporting fertility outcomes (8 reviews) Medical interventions Four reviews reported on medical interventions for improving fertility in women with endometriosis. One compared three months of GnRH agonists with a control in women undergoing assisted reproduction and found very low quality evidence of an increase in clinical pregnancies in the treatment group. There was no evidence of a difference in effectiveness between the interventions in the other three reviews, which compared GnRH agonists versus antagonists, ovulation suppression versus placebo or no treatment, and pre-surgical medical therapy versus surgery alone. In all cases the evidence was of low or very low quality. Surgical interventions Three reviews reported on surgical interventions. There was moderate quality evidence that both live births or ongoing pregnancy rates and clinical pregnancy rates were higher after laparoscopic surgery than after diagnostic laparoscopy alone. There was low quality evidence of no difference in effectiveness between surgery and expectant management for endometrioma. One review found low quality evidence that excisional surgery resulted in higher clinical pregnancy rates than drainage or ablation of endometriomata. Post-surgical interventions Two reviews reported on post-surgical medical interventions. They found no evidence of an effect on clinical pregnancy rates. The evidence was of low or very low quality. Alternative medicine A review of Chinese herbal medicine in comparison with gestrinone found no evidence of a difference between the groups in clinical pregnancy rates. However, the evidence was of low quality. Adverse events Reviews of GnRH analogues and of danazol reported that the interventions were associated with higher rates of adverse effects than placebo; and depot progestagens were associated with higher rates of adverse events than other treatments. Chinese herbal medicine was associated with fewer side effects than gestrinone or danazol.Three reviews reported miscarriage as an outcome. No difference was found between surgical and diagnostic laparoscopy, between GnRH agonists and antagonists, or between aspiration of endometrioma and expectant management. However, in all cases the quality of the evidence was of low quality.
AUTHORS' CONCLUSIONS
For women with pain and endometriosis, suppression of menstrual cycles with gonadotrophin-releasing hormone (GnRH) analogues, the levonorgestrel-releasing intrauterine system (LNG-IUD) and danazol were beneficial interventions. Laparoscopic treatment of endometriosis and excision of endometriomata were also associated with improvements in pain. The evidence on NSAIDs was inconclusive. There was no evidence of benefit with post-surgical medical treatment.In women with endometriosis undergoing assisted reproduction, three months of treatment with GnRH agonist improved pregnancy rates. Excisional surgery improved spontaneous pregnancy rates in the nine to 12 months after surgery compared to ablative surgery. Laparoscopic surgery improved live birth and pregnancy rates compared to diagnostic laparoscopy alone. There was no evidence that medical treatment improved clinical pregnancy rates.Evidence on harms was scanty, but GnRH analogues, danazol and depot progestagens were associated with higher rates than other interventions.
Topics: Acupuncture, Ear; Anti-Inflammatory Agents, Non-Steroidal; Drugs, Chinese Herbal; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; NM23 Nucleoside Diphosphate Kinases; Ovulation Inhibition; Pelvic Pain; Review Literature as Topic
PubMed: 24610050
DOI: 10.1002/14651858.CD009590.pub2 -
Pharmacology & Therapeutics Jan 2014UDP-glucuronosyltransferases (UGT) catalyze the biotransformation of many endobiotics and xenobiotics, and are coded by polymorphic genes. However, knowledge about the... (Meta-Analysis)
Meta-Analysis Review
UDP-glucuronosyltransferases (UGT) catalyze the biotransformation of many endobiotics and xenobiotics, and are coded by polymorphic genes. However, knowledge about the effects of these polymorphisms is rarely used for the individualization of drug therapy. Here, we present a quantitative systematic review of clinical studies on the impact of UGT variants on drug metabolism to clarify the potential for genotype-adjusted therapy recommendations. Data on UGT polymorphisms and dose-related pharmacokinetic parameters in man were retrieved by a systematic search in public databases. Mean estimates of pharmacokinetic parameters were extracted for each group of carriers of UGT variants to assess their effect size. Pooled estimates and relative confidence bounds were computed with a random-effects meta-analytic approach whenever multiple studies on the same variant, ethnic group, and substrate were available. Information was retrieved on 30 polymorphic metabolic pathways involving 10 UGT enzymes. For irinotecan and mycophenolic acid a wealth of data was available for assessing the impact of genetic polymorphisms on pharmacokinetics under different dosages, between ethnicities, under comedication, and under toxicity. Evidence for effects of potential clinical relevance exists for 19 drugs, but the data are not sufficient to assess effect size with the precision required to issue dose recommendations. In conclusion, compared to other drug metabolizing enzymes much less systematic research has been conducted on the polymorphisms of UGT enzymes. However, there is evidence of the existence of large monogenetic functional polymorphisms affecting pharmacokinetics and suggesting a potential use of UGT polymorphisms for the individualization of drug therapy.
Topics: Analgesics; Anti-HIV Agents; Antihypertensive Agents; Antineoplastic Agents; Glucuronosyltransferase; Humans; Pharmaceutical Preparations; Pharmacokinetics; Polymorphism, Genetic; Psychotropic Drugs; Uridine Diphosphate
PubMed: 24076267
DOI: 10.1016/j.pharmthera.2013.09.002 -
Restorative Neurology and Neuroscience 2013Surgical repair alone does not lead to satisfactory recovery after nerve laceration injury, yet no adjuvant clinical treatments are available. The goal of this review is... (Review)
Review
Surgical repair alone does not lead to satisfactory recovery after nerve laceration injury, yet no adjuvant clinical treatments are available. The goal of this review is to systematically survey all adjuvant treatments after surgery investigated in rat and mouse models. Both PubMed and Embase were explored with a systematic bibliographic search algorithm. Inclusion criteria consisted of treatments applied to rats or mice after complete transection and microsurgical repair of lower-limb motor or mixed nerves. Effect size statistics enabled numerical comparison between outcomes of treated and untreated animals and ranked the best treatments. 1,553 articles were found according to our search strategies, and 22 of them corresponded to our pre-defined inclusion criteria. After data extraction and analysis, the top 3 adjuvant strategies in terms of combined average effect size were citicoline, neurotrophin-4, and nitric oxide synthesis inhibitor, with values of 5.52, 5.14 and 4.08, respectively. Definitive treatment comparison was difficult due to the lack of uniformity in outcome evaluation in the experiments performed. Animal studies, comparing treatments administered within the same experimental protocol, are needed to truly assess efficiency and to provide solid recommendations for future clinical investigation.
Topics: Animals; Cytidine Diphosphate Choline; Disease Models, Animal; Humans; Lacerations; Nerve Growth Factors; Nitric Oxide Synthase; Peripheral Nerves; Rodentia; Treatment Outcome
PubMed: 23478341
DOI: 10.3233/RNN-120253 -
Clinical Cardiology Apr 2013There is considerable debate about whether concomitant use of proton pump inhibitors (PPIs) should be recommended for patients who are prescribed clopidogrel after acute... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is considerable debate about whether concomitant use of proton pump inhibitors (PPIs) should be recommended for patients who are prescribed clopidogrel after acute coronary syndrome. Most pharmacokinetic and pharmacodynamic studies in vivo were conducted using small sample sizes and were single centered, resulting in conflicting data.
HYPOTHESIS
PPIs may attenuate the antiplatelet effect of clopidogrel in vivo and lead to an increased risk of cardiovascular events.
METHODS
PubMed, the Cochrane Library, Embase, Web of Science, and China Biology Medicine Disc were searched. Randomized controlled trials that compared pharmacodynamic impacts of a PPI on the efficacy of clopidogrel in vivo were included. Two independent reviewers evaluated study quality and extracted data for meta-analysis.
RESULTS
We identified 8 eligible studies. Compared to clopidogrel treatment alone, patients who received both a PPI and clopidogrel had less of a decrease in the platelet reactivity index (weighted mean difference [WMD]: 8.18; 95% confidence interval [CI]: 6.81-9.56; P<0.00001), less adenosine 5'-diphosphate-induced platelet aggregation inhibition (WMD: 7.28; 95% CI: 2.44-12.11; P=0.003), higher P2Y12 reaction units (WMD: 40.58; 95% CI: 19.31-61.86; P=0.0002), and higher risks of clopidogrel resistance (odds ratio [OR]: 2.49; 95% CI: 1.49-4.14; P=0.0005). There were no significant differences, however, for the incidences of major adverse cardiovascular events between the 2 groups (OR: 1.07; 95% CI: 0.44-2.59; P=0.88), and treatment with a PPI and clopidogrel significantly reduced the risk of adverse gastrointestinal events (OR: 0.16; 95% CI: 0.04-0.62; P=0.008).
CONCLUSIONS
Concomitant use of a PPI with clopidogrel attenuated the antiplatelet effect of clopidogrel, but may be clinically unimportant because there were no clinical differences in the risk for major adverse cardiovascular events.
Topics: Adenosine Diphosphate; Blood Platelets; Cardiovascular Diseases; Clopidogrel; Drug Interactions; Drug Resistance; Gastrointestinal Diseases; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Receptors, Purinergic P2Y12; Ticlopidine
PubMed: 23450832
DOI: 10.1002/clc.22094 -
PharmacoEconomics Mar 2013Metastatic colorectal cancer (mCRC) imposes a substantial health burden on individual patients and society. Furthermore, rising costs in oncology cause a growing concern... (Review)
Review
BACKGROUND
Metastatic colorectal cancer (mCRC) imposes a substantial health burden on individual patients and society. Furthermore, rising costs in oncology cause a growing concern about reimbursement for innovations in this sector. The promise of pharmacogenomic profiling and related stratified therapies in mCRC is to improve treatment efficacy and potentially save costs. Among other examples, the commonly used epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab are only effective in patients with kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type cancers. Hence, the adaptation of predictive biomarker testing might be a valid strategy for healthcare systems worldwide.
OBJECTIVE
This study aims to review the clinical and economic evidence supporting pharmacogenomic profiling prior to the administration of pharmaceutical treatment in mCRC. Moreover, key drivers and areas of uncertainty in cost-effectiveness evaluations are analysed.
METHODS
A systematic literature review was conducted to identify studies evaluating the cost effectiveness of predictive biomarkers and the result dependent usage of pharmaceutical agents in mCRC.
RESULTS
The application of predictive biomarkers to detect KRAS mutations prior to the administration of EGFR antibodies saved treatment costs and was cost effective in all identified evaluations. However, because of the lack of data regarding cost-effectiveness analyses for predictive biomarker testing, e.g. for first-line treatment, definitive conclusions cannot be stated. Key drivers and areas of uncertainty in current cost-effectiveness analyses are, among others, the consideration of predictive biomarker costs, the characteristics of single predictive biomarkers and the availability of clinical data for the respective pharmaceutical intervention. Especially the cost effectiveness of uridine diphosphate-glucuronyl transferase 1A1 (UGT1A1) mutation analysis prior to irinotecan-based chemotherapy remains unclear.
CONCLUSION
Pharmacogenomic profiling has the potential to improve the cost effectiveness of pharmaceutical treatment in mCRC. Hence, quantification of the economic impact of stratified medicine as well as cost-effectiveness analyses of pharmacogenomic profiling are becoming more important. Nevertheless, the methods applied in cost-effectiveness evaluations for the usage of predictive biomarkers for patient selection as well as the level of evidence required to determine clinical effectiveness are areas for further research. However, mCRC is one of the first indications in which stratified therapies are used in clinical practice. Thus, clinical and economic experiences could be helpful when adopting pharmacogenomic profiling into clinical practice for other indications.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Cost-Benefit Analysis; ErbB Receptors; Genetic Markers; Genetic Testing; Health Care Costs; Humans; Mutation; Neoplasm Metastasis; Pharmacogenetics; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); Treatment Outcome; ras Proteins
PubMed: 23338963
DOI: 10.1007/s40273-012-0017-2 -
The Cochrane Database of Systematic... Nov 2012Cardiovascular disease (CVD) is the most prevalent complication of type 2 diabetes with an estimated 65% of people with type 2 diabetes dying from a cause related to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cardiovascular disease (CVD) is the most prevalent complication of type 2 diabetes with an estimated 65% of people with type 2 diabetes dying from a cause related to atherosclerosis. Adenosine-diphosphate (ADP) receptor antagonists like clopidogrel, ticlopidine, prasugrel and ticagrelor impair platelet aggregation and fibrinogen-mediated platelet cross-linking and may be effective in preventing CVD.
OBJECTIVES
To assess the effects of adenosine-diphosphate (ADP) receptor antagonists for the prevention of cardiovascular disease in type 2 diabetes mellitus.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (issue 2, 2011), MEDLINE (until April 2011) and EMBASE (until May 2011). We also performed a manual search, checking references of original articles and pertinent reviews to identify additional studies.
SELECTION CRITERIA
Randomised controlled trials comparing an ADP receptor antagonist with another antiplatelet agent or placebo for a minimum of 12 months in patients with diabetes. In particular, we looked for trials assessing clinical cardiovascular outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data for studies which fulfilled the inclusion criteria, using standard data extraction templates. We sought additional unpublished information and data from the principal investigators of all included studies.
MAIN RESULTS
Eight studies with a total of 21,379 patients with diabetes were included. Three included studies investigated ticlopidine compared to aspirin or placebo. Five included studies investigated clopidogrel compared to aspirin or a combination of aspirin and dipyridamole, or compared clopidogrel in combination with aspirin to aspirin alone. All trials included patients with previous CVD except the CHARISMA trial which included patients with multiple risk factors for coronary artery disease. Overall the risk of bias of the trials was low. The mean duration of follow-up ranged from 365 days to 913 days.Data for diabetes patients on all-cause mortality, vascular mortality and myocardial infarction were only available for one trial (355 patients). This trial compared ticlopidine to placebo and did not demonstrate any statistically significant differences for all-cause mortality, vascular mortality or myocardial infarction. Diabetes outcome data for stroke were available in three trials (31% of total diabetes participants). Overall pooling of two (statistically heterogeneous) studies showed no statistically significant reduction in the combination of fatal and non-fatal stroke (359/3194 (11.2%) versus 356/3146 (11.3%), random effects odds ratio (OR) 0.81; 95% confidence interval (CI) 0.44 to 1.49) for ADP receptor antagonists versus other antiplatelet drugs. There were no data available from any of the trials on peripheral vascular disease, health-related quality of life, adverse events specifically for patients with diabetes, or costs.
AUTHORS' CONCLUSIONS
The available evidence for ADP receptor antagonists in patients with diabetes mellitus is limited and most trials do not report outcomes for patients with diabetes separately. Therefore, recommendations for the use of ADP receptor antagonists for the prevention of CVD in patients with diabetes are based on available evidence from trials including patients with and without diabetes. Trials with diabetes patients and subgroup analyses of patients with diabetes in trials with combined populations are needed to provide a more robust evidence base to guide clinical management in patients with diabetes.
Topics: Aspirin; Cardiovascular Diseases; Clopidogrel; Diabetes Mellitus, Type 2; Dipyridamole; Drug Therapy, Combination; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Ticlopidine
PubMed: 23152231
DOI: 10.1002/14651858.CD005449.pub2 -
Journal of Neurochemistry Oct 2012The neuroprotective actions of citicoline have been documented for experimental stroke therapy. We used a systematic review and meta-analysis to assess this evidence.... (Meta-Analysis)
Meta-Analysis Review
Citicoline in pre-clinical animal models of stroke: a meta-analysis shows the optimal neuroprotective profile and the missing steps for jumping into a stroke clinical trial.
The neuroprotective actions of citicoline have been documented for experimental stroke therapy. We used a systematic review and meta-analysis to assess this evidence. From 64 identified studies using citicoline in stroke animal models, only those describing ischemic occlusive stroke and reporting data on infarct volume and/or neurological outcome were included (14 studies, 522 animals). Overall, the quality of the studies was modest (5, 4-6), while the absence of studies involving animals with co-morbidities, females, old animals or strain differences indicated that studies did not fulfill the STAIR recommendations. Weighted mean difference meta-analysis showed citicoline to reduce infarct volume by 27.8% [(19.9%, 35.6%); p < 0.001]. In the stratified analysis, citicoline effect on reducing infarct volume was higher in proximal occlusive models of middle cerebral artery (MCA) compared with distal occlusion. Moreover, the efficacy was superior using multiple doses than single dose and when a co-treatment was administered compared with citicoline monotherapy, the only independent factor identified in the meta-regression. Citicoline improved neurological deficit by 20.2% [(6.8%, 33.7%); p = 0.015], but only four studies including 176 animals reported these data. In conclusion, this meta-analysis provides evidence of citicoline efficacy in stroke animal models and shows the optimal neuroprotective profile and the missing experimental requirements before jumping into clinical trials.
Topics: Animals; Clinical Trials as Topic; Cytidine Diphosphate Choline; Disease Models, Animal; Humans; Neuroprotective Agents; Nootropic Agents; Stroke
PubMed: 22845688
DOI: 10.1111/j.1471-4159.2012.07891.x -
Platelets 2013The VerifyNow P2Y12 test is a whole-blood, light transmission-based optical detection assay that measures adenosine diphosphate-induced platelet aggregation in a... (Meta-Analysis)
Meta-Analysis Review
The VerifyNow P2Y12 test is a whole-blood, light transmission-based optical detection assay that measures adenosine diphosphate-induced platelet aggregation in a cartridge containing fibrinogen-coated beads. The usefulness of this device to assess the effect of clopidogrel on platelet function was recently highlighted for predicting cardiovascular (CV) events. We therefore performed a meta-analysis to analyze whether adverse clinical outcomes of patients with CV disease increase in association with high on-treatment platelet reactivity (HPR) using the VerifyNow P2Y12 test. We also investigated the effect of the CYP2C19*2 polymorphism on the occurrence of CV events among clopidogrel-treated patients. Relevant studies were searched for in the PubMed database and Cochrane Central Register of Controlled Trials database, and selected if they included data about platelet function assessed using the VerifyNow P2Y12 test or CYP2C19*2 polymorphism in clopidogrel-treated patients with CV disease, and the occurrence of CV events within 6-12 months. In our meta-analysis, 4817 subjects from eight studies and 5307 subjects from seven studies were included for review of platelet function and CYP2C19*2 polymorphism, respectively. Overall, 2237 (46.4%) patients had HPR and these patients had significantly higher odds of CV events compared to patients without HPR (odds ratio(OR) = 3.05, 95% confidence interval: 2.33-3.98, p < 0.001). Heterogeneity among studies was not significant (Cochran's Q-test, p = 0.80 and I(2) = 0%). In the secondary investigation, 1926 (36.3%) patients had at least one CYP2C19*2 allele. Heterogeneity in the OR of the CV events between the CYP2C19*2 allele carriers and non-carriers was observed among the seven studies (Cochran's Q-test, p = 0.01 and I(2) = 56.5%), and the range of the ORs among the seven studies was 0.58-16.6. In conclusion, HPR assessed by VerifyNow P2Y12 test was associated with increased adverse clinical outcomes of clopidogrel-treated patients with CV disease.
Topics: Alleles; Aryl Hydrocarbon Hydroxylases; Cardiovascular Diseases; Cytochrome P-450 CYP2C19; Genotype; Humans; Odds Ratio; Patient Outcome Assessment; Platelet Function Tests; Prognosis; Receptors, Purinergic P2Y12
PubMed: 22757746
DOI: 10.3109/09537104.2012.700969 -
Pharmacotherapy May 2011To determine the effect of standardized Ginkgo biloba leaf extracts (GBE) on outcome parameters of hemostasis associated with risk of bleeding. (Meta-Analysis)
Meta-Analysis Review
STUDY OBJECTIVE
To determine the effect of standardized Ginkgo biloba leaf extracts (GBE) on outcome parameters of hemostasis associated with risk of bleeding.
DESIGN
Meta-analysis of 18 randomized controlled trials.
SUBJECTS
A total of 1985 adults were enrolled to receive either GBE or placebo; 87% were patients with dementia, peripheral artery disease, or diabetes mellitus; 13% were healthy volunteers.
MEASUREMENTS AND MAIN RESULTS
The MEDLINE, EMBASE, Cochrane Library, and SciSearch databases were searched from inception through 2009. The following outcome parameters of hemostasis were assessed: blood flow, blood viscosity, adenosine 5'-diphosphate (ADP)-induced platelet aggregation, fibrinogen concentration, activated partial thromboplastin time (aPTT), and prothrombin time (PT). Reference parameter values were taken into account when assessing clinical relevance of statistically significant treatment effects. The quality and risk of bias of each study were evaluated by using the Jadad score and Cochrane Collaboration tool, respectively. According to the continuous data, the following statistical methods were used: weighted mean difference (WMD), standardized mean difference (SMD), and generic inverse variance (GIV), with 95% confidence intervals (CIs). Random-effects models of effects on baseline change or mean difference showed a positive effect of GBE on blood perfusion, as shown by a significant reduction in blood viscosity (WMD -1.03 mPa•sec, 95% CI -1.29 to -0.78 mPa•sec), but no evidence of any significant effect on ADP-induced platelet aggregation (WMD -0.35%, 95% CI -15.16-14.46%), fibrinogen concentration (GIV -2.45 mg/dl, 95% CI -11.59-6.70 mg/dl), aPTT (GIV -0.42 sec, 95% CI -0.97-0.12 sec), and PT (SMD 0.00, 95% CI -0.09-0.09). Subgroup analyses revealed a statistically significant reduction in aPTT for subgroups receiving high-dose GBE of 240 mg/day or more (GIV -0.47 sec, 95% CI -0.88 to -0.05 sec) and for studies including only patients, not healthy volunteers (GIV -0.61 sec, 95% CI -0.95 to -0.27 sec); however, both findings were not clinically relevant.
CONCLUSION
Based on meta-analysis of hemostasis outcomes, comparison of mean difference or baseline change between treatment and placebo groups did not indicate a higher bleeding risk associated with standardized GBE. This finding ultimately contributes to an informed evaluation of GBE use, including patient self-medication.
Topics: Adult; Aged; Female; Ginkgo biloba; Hemorrhage; Hemostasis; Humans; Male; Middle Aged; Plant Extracts; Plant Leaves; Randomized Controlled Trials as Topic; Risk
PubMed: 21923430
DOI: 10.1592/phco.31.5.490 -
Clinical Pharmacology and Therapeutics May 2011Currently, there are very few guidelines linking the results of pharmacogenetic tests to specific therapeutic recommendations. Therefore, the Royal Dutch Association for... (Review)
Review
Currently, there are very few guidelines linking the results of pharmacogenetic tests to specific therapeutic recommendations. Therefore, the Royal Dutch Association for the Advancement of Pharmacy established the Pharmacogenetics Working Group with the objective of developing pharmacogenetics-based therapeutic (dose) recommendations. After systematic review of the literature, recommendations were developed for 53 drugs associated with genes coding for CYP2D6, CYP2C19, CYP2C9, thiopurine-S-methyltransferase (TPMT), dihydropyrimidine dehydrogenase (DPD), vitamin K epoxide reductase (VKORC1), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), HLA-B44, HLA-B*5701, CYP3A5, and factor V Leiden (FVL).
Topics: Animals; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C9; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmaceutical Preparations; Pharmacogenetics; Practice Guidelines as Topic
PubMed: 21412232
DOI: 10.1038/clpt.2011.34