Systematic review on the prevalence,frequency and comparative value of adverse events data in social media

Aim

The aim of this review was to summarize the prevalence, frequency and comparative value of information on the adverse events of healthcare interventions from user comments and videos in social media.

Methods

A systematic review of assessments of the prevalence or type of information on adverse events in social media was undertaken. Sixteen databases and two internet search engines were searched in addition to handsearching, reference checking and contacting experts. The results were sifted independently by two researchers. Data extraction and quality assessment were carried out by one researcher and checked by a second. The quality assessment tool was devised in-house and a narrative synthesis of the results followed.

Results

From 3064 records, 51 studies met the inclusion criteria. The studies assessed over 174 social media sites with discussion forums (71%) being the most popular. The overall prevalence of adverse events reports in social media varied from 0.2% to 8% of posts.Twenty-nine studies compared the results from searching social media with using other data sources to identify adverse events. There was general agreement that a higher frequency of adverse events was found in social media and that this was particularly true for ‘symptom’ related and ‘mild’ adverse events.Those adverse events that were under-represented in social media were laboratory-based and serious adverse events.

Conclusions

Reports of adverse events are identifiable within social media. However, there is considerable heterogeneity in the frequency and type of events reported, and the reliability or validity of the data has not been thoroughly evaluated.     

Impaired nitric oxide modulation of myocardial oxygen consumption in genetically cardiomyopathic hamsters

We investigated the role of kinin and nitric oxide (NO) in the modulation of cardiac O(2)consumption in Syrian hamsters with overt heart failure (HF) and age-matched normal hamsters. Using echocardiography, the hamsters with heart failure had reduced ejection fraction [31(+/-8) v 76(+/-5)%] and LV dilation [4.9(+/-0. 2) v 5.7(+/-0.3) mm, both P<0.05 from normal]. O(2)consumption in the left ventricular free wall was measured using a Clark-type O(2)electrode in an air-tight chamber, containing Krebs solution buffered with Hepes (37 degrees C, pH 7.4). Concentration response curves to bradykinin (BK), ramiprilat (RAM), amlodipine (AMLO) and the NO donor, S -nitroso- N -acetyl-penicillamine (SNAP) were performed. Basal myocardial O(2)consumption was lower in the HF group compared to normal [316(+/-21) v 404(+/-36) nmol O(2)/min/g, respectively, P<0.05]. In the hearts from normal hamsters BK (10(-4)mol/l), RAM (10(-4)mol/l), and AMLO (10(-5)mol/l) all significantly reduced myocardial O(2)consumption by 42(+/-6)%, 29(+/-7)% and 27(+/-5)% respectively. This reduction was attenuated in the presence of N -nitro- l -arginine methyl ester (l -NAME) [BK: 3.3(+/-1.5)%, RAM: 3.3(+/-1.2)%, AMLO: 2.3(+/-1.2)%, P<0.05]. Interestingly in the hearts from HF group, BK, RAM and AMLO caused a significantly smaller reduction in myocardial O(2)consumption [10(+/-2)%, 2.5(+/-1.3)%, 6.3(+/-2.3)%, P<0.05]. In contrast, the NO donor SNAP reduced myocardial O(2)consumption in both groups and all those responses were not affected by l -NAME. These data indicate that endogenous NO production through the kinin-dependent mechanism is impaired at end-stage heart failure. The loss of kinin and NO control of mitochondrial respiration may contribute to the pathogenesis of heart failure.     

Myocardial glucose uptake is regulated by nitric oxide via endothelial nitric oxide synthase in Langendorff mouse heart

Although the role of nitric oxide (NO) in the modulation of vascular tone has been studied and well understood, its potential role in the control of myocardial metabolism is only recently evident. Several lines of evidence indicate that NO regulates myocardial glucose metabolism; however, the details and mechanisms responsible are still unknown. The aim of this study was to further define the role of NO in the control of myocardial glucose metabolism and the nitric oxide synthase (NOS) isoform responsible using transgenic animals lacking endothelial NOS (ecNOS). In the present study, we examined the regulation of myocardial glucose uptake using isometrically contracting Langendorff-perfused hearts from normal mice (C57BL/6J), mice with defects in the expression of ecNOS [ecNOS (-/-)], and its heterozygote [ecNOS (+/-)], and wild-type mice [ecNOS (+/+)] (n=6, respectively). In hearts from normal mice, little myocardial glucose uptake was observed. This myocardial glucose uptake increased significantly in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME). Similarly, in the hearts from ecNOS (-/-), glucose uptake was much greater than in normal mice, whereas myocardial glucose uptake of ecNOS (+/-) and ecNOS (+/+) mice was not different from normal mice. In addition, myocardial glucose uptake of ecNOS (+/-) and ecNOS (+/+) mice increased significantly in the presence of L-NAME. At a workload of 800 g. beats/min, L-NAME increased glucose uptake from 0.1+/-0.1 to 3+/-0.4 microg/min x mg in ecNOS (+/-) mice and from 0.2+/-0.1 to 2.7+/-0.7 microg/min x mg in ecNOS (+/+) mice. Furthermore, in the hearts from ecNOS (-/-) mice, 8-bromoguanosine 3':5'-cyclic monophosphate (8-Br-cGMP), a cGMP analog or S-nitroso-N-acetylpenicillamine (SNAP), a NO donor essentially shut off glucose uptake, and in hearts from ecNOS (+/-) mice, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ), an inhibitor of cGMP, increased the glucose uptake significantly. These results indicate clearly that cardiac NO production regulates myocardial glucose uptake via a cGMP-dependent mechanism and strongly suggest that ecNOS plays a pivotal role in this regulation. These findings may be important in the understanding of the pathogenesis of the diseases such as ischemic heart disease, heart failure, diabetes mellitus, hypertension, and hypercholesterolemia, in which NO synthesis is altered and substrate utilization by the heart changes.     

Genetic associations in peripheral joint osteoarthritis and spinal degenerative disease: a systematic review

We conducted a systematic review of genetic association studies for osteoarthritis of the peripheral joints (OA) and spinal degenerative disease (SDD). Electronic searches were carried out for any English language article reporting on a gene association study for either OA or SDD published up until the end of 2006. A team of seven reviewers used a standardised template to extract data in duplicate. In all, 90 studies fulfilled our inclusion criteria, reporting a total of 94 significant associations from 83 different genes. We found relatively few instances in which a specific gene-disease association had been analysed by more than one study, and there were 14 cases in which significant associations were replicated in independent studies (at joints associated with the AGC1, ASPN, COL9A2, COL9A3, COL11A2, ESR1, FZRB, HFE, IL1A, IL1RN, PTGS2 and VDR genes). METHOD: logical and reporting problems were widespread, including failure to report full results, missing population details, multiple testing, and over-reliance on subgroup analysis. In summary, the complex phenotypes of OA and SDD may have made it difficult for researchers to focus their efforts. The field is dominated by isolated analyses of disparate potential associations, a problem that is amplified by the frequent analysis of different polymorphisms within individual genes. Flaws in study methodology and interpretation undoubtedly increase the risk of publication bias. Closer adherence to published recommendations (in particular those produced by HuGENet) will help to ensure that future studies are well-designed and build on current understanding, rather than simply adding to the growing bank of potential associations.     

LC-MS/MS测定人血浆中对乙酰氨基酚及其人体药动学和生物等效性研究

目的 建立一种快速、灵敏的高效液相色谱-串联质谱（HPLC-MS/MS）方法以测定人血浆中对乙酰氨基酚浓度,并应用于两种对乙酰氨基酚制剂的人体药代动力学和生物等效性研究。方法 以替硝唑为内标,200μL血浆样品经5倍于其体积的乙酸乙酯液液萃取,再经Waters XBridge? C18柱等度洗脱分离后导入串联质谱,以正离子多反应监测模式进行定量分析,对乙酰氨基酚和内标的选择性反应离子对分别是m/z 152→110和248→121。方法经验证后应用于19名健康受试者单剂量空腹口服两种对乙酰氨基酚制剂500mg后药代动力学和生物等效性的研究。结果 血浆中对乙酰氨基酚在0.1～8.0 μg·mL-1范围内线性良好（r2 > 0.99）,最低检测限为 0.1 μg·mL-1,提取回收率为91.0%～98.7%,日内和日间准确度分别为98.8%～111.3% （精密度：CV ? 9.03%）和94.9%～102.6% （精密度：CV ? 10.68%）。生物等效性试验中,受试制剂与参比制剂的主要药代动力学参数Cmax、AUC0-t和AUC0-∞ 几何均值比的90%置信区间分别为83.50%～105.79%,94.25%～101.54%和93.24%～101.02%,均落在生物等效可接受标准80.00%～125.00%范围内。结论 所建立测定人血浆中对乙酰氨基酚浓度的HPLC-MS/MS法具有快速灵敏、回收率高、选择性好的特点,适用于对乙酰氨基酚片人体药代动力学和生物等效性研究。受试制剂与参比制剂在人体内吸收速度和程度相似,两种制剂生物等效。     

Prognostic Tools for Early Mortality in Hemorrhagic Stroke: Systematic Review and Meta-Analysis

Background and Purpose

Several risk scores have been developed to predict mortality in intracerebral hemorrhage (ICH). We aimed to systematically determine the performance of published prognostic tools.

Methods

We searched MEDLINE and EMBASE for prognostic models (published between 2004 and April 2014) used in predicting early mortality (<6 months) after ICH. We evaluated the discrimination performance of the tools through a random-effects meta-analysis of the area under the receiver operating characteristic curve (AUC) or c-statistic. We evaluated the following components of the study validity: study design, collection of prognostic variables, treatment pathways, and missing data.

Results

We identified 11 articles (involving 41,555 patients) reporting on the accuracy of 12 different tools for predicting mortality in ICH. Most studies were either retrospective or post-hoc analyses of prospectively collected data; all but one produced validation data. The Hemphill-ICH score had the largest number of validation cohorts (9 studies involving 3,819 patients) within our systematic review and showed good performance in 4 countries, with a pooled AUC of 0.80 [95% confidence interval (CI)=0.77-0.85]. We identified several modified versions of the Hemphill-ICH score, with the ICH-Grading Scale (GS) score appearing to be the most promising variant, with a pooled AUC across four studies of 0.87 (95% CI=0.84-0.90). Subgroup testing found statistically significant differences between the AUCs obtained in studies involving Hemphill-ICH and ICH-GS scores (p=0.01).

Conclusions

Our meta-analysis evaluated the performance of 12 ICH prognostic tools and found greater supporting evidence for 2 models (Hemphill-ICH and ICH-GS), with generally good performance overall.