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.     

Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE‐LY trial

Background

Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF.

Objectives

To compare the performance of contemporary clinical bleeding risk scores in 18 113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE‐LY trial.

Methods

HAS‐BLED, ORBIT, ATRIA and HEMORR₂HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated.

Results

There were 1182 (6.5%) major bleeding events during a median follow‐up of 2.0 years. For all the four schemes, high‐risk subgroups had higher risk of major bleeding (all P  < 0.001). The ORBIT score showed the best discrimination with c‐indices of 0.66, 0.66 and 0.62, respectively, for major, life‐threatening and intracranial bleeding, which were significantly better than for the HAS‐BLED score (difference in c‐indices: 0.050, 0.053 and 0.048, respectively, all P  < 0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P  = 0.0019), ATRIA (P  < 0.001) and HEMORR₂HAGES (P  < 0.001) scores. HAS‐BLED score showed a nonsignificant trend for interaction (P  = 0.0607).

Conclusions

Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin.

     

Placental genomic risk scores and early neurodevelopmental outcomes

Tracing the early paths leading to developmental disorders is critical for prevention. In previous work, we detected an interaction between genomic risk scores for schizophrenia (GRSs) and early-life complications (ELCs), so that the liability of the disorder explained by genomic risk was higher in the presence of a history of ELCs, compared with its absence. This interaction was specifically driven by loci harboring genes highly expressed in placentae from normal and complicated pregnancies [G. Ursini et al., Nat. Med. 24, 792–801 (2018)]. Here, we analyze whether fractionated genomic risk scores for schizophrenia and other developmental disorders and traits, based on placental gene-expression loci (PlacGRSs), are linked with early neurodevelopmental outcomes in individuals with a history of ELCs. We found that schizophrenia’s PlacGRSs are negatively associated with neonatal brain volume in singletons and offspring of multiple pregnancies and, in singletons, with cognitive development at 1 y and, less strongly, at 2 y, when cognitive scores become more sensitive to other factors. These negative associations are stronger in males, found only with GRSs fractionated by placental gene expression, and not found in PlacGRSs for other developmental disorders and traits. The relationship of PlacGRSs with brain volume persists as an anlage of placenta biology in adults with schizophrenia, again selectively in males. Higher placental genomic risk for schizophrenia, in the presence of ELCs and particularly in males, alters early brain growth and function, defining a potentially reversible neurodevelopmental path of risk that may be unique to schizophrenia.

Understanding the deviations from normal trajectories of brain development may be crucial for predicting illness and for prevention. Epidemiological studies have consistently identified early antecedents, including complications during pregnancy (1–4) and delays in developmental milestones (5–8). The incidence of many developmental disorders tends to be higher in males (9), and risk is typically highly heritable (10). While rare and moderately penetrant genetic variations account for a minority of cases, genome-wide association studies (GWASs) show that most risk is attributable to common variants across the genome (11, 12). Genomic risk scores (GRSs) from GWASs allow a much greater prediction of liability of the disorder than single common variant genotypes, but GRSs per se are not useful in predicting individual risk (13).We previously identified an environmental context in early life in which genomic risk for schizophrenia may enhance disease susceptibility (14). We found that the liability of schizophrenia explained by genomic risk (that is, schizophrenia GRS, also referred to as polygenic risk score; PRS) was more than five times higher in individuals with a history of obstetrical complications (here, early-life complications; ELCs; i.e., during pregnancy, at labor/delivery, and early in neonatal life) compared with its absence (14). Such interaction was exclusive of the GRSs constructed from the loci with the most significant associations with schizophrenia (GRS1: GWAS P < 5 × 10⁻⁸; GRS2: GWAS P < 1 × 10⁻⁶). Genes in the GRS1 and GRS2 loci were more highly expressed in placental tissue compared with genes in GWAS loci not interacting with ELCs (GRS3 to 10); they were up-regulated in placentae from complicated pregnancies and strongly correlated within placenta with expression of immune response genes (14), consistent with previous evidence linking placenta, inflammation, and brain development (15, 16).To investigate the role of placenta biology in the interaction between schizophrenia GRSs and ELCs, we derived sets of GRSs based on single-nucleotide polymorphisms (SNPs) marking schizophrenia-GWAS loci containing genes highly expressed in placenta and differentially expressed in placentae from complicated compared with normal pregnancies (PlacGRSs; placental genomic risk scores) and also from the remaining GWAS loci (NonPlacGRSs; nonplacental genomic risk scores). We found that only PlacGRSs interacted with ELCs on schizophrenia-case control status, while NonPlacGRSs did not, implicating genes involved in placenta stress as driving the interaction between genomic risk and ELCs. These interactions were specifically related to placental gene expression, in that they were not detected when calculating GRSs based on SNPs marking loci highly expressed or epigenetically regulated in other tissues, including various adult and fetal tissues/embryonic cells, and fetal brain. Finally, we detected a much stronger enrichment of expression of the schizophrenia-risk genes in placentae from male compared with female offspring, suggesting a role of placenta in the higher incidence of schizophrenia in males (14).We here investigate whether placental genomic risk for schizophrenia as well as several other developmental disorders and traits is linked with early neurodevelopmental outcomes in individuals with a history of ELCs associated with placenta pathophysiology. Abundant evidence shows that ELCs have implications for early developmental trajectories, including brain size, intellectual development, and neuromotor function as well as for schizophrenia later in life (3, 5, 17–19). Based on these prior observations and our earlier findings (14), we hypothesized that schizophrenia PlacGRSs, in contrast to NonPlacGRSs, have a negative effect on early developmental outcomes, especially in males. Further consistent with our earlier findings, we hypothesized that this negative relationship is characteristic of the PlacGRSs constructed from the placental schizophrenia-GWAS loci with the strongest association with the disorder (PlacGRS1: GWAS P < 5 × 10⁻⁸; PlacGRS2: GWAS P < 1 × 10⁻⁶). We studied the relationship of PlacGRSs and NonPlacGRSs with brain volume in a unique sample of neonates who underwent MRI scanning shortly after birth, and analyzed the relationship with neurocognitive development at 1 and 2 y of age in the same subjects. Finally, we analyzed the relationship of PlacGRSs and NonPlacGRSs with brain volume in a sample of adult controls and patients with schizophrenia.     

肋间神经阻滞在胸腔镜自发性气胸术后镇痛的应用

目的 探讨肋间神经阻滞在电视辅助胸腔镜(VATS)自发性气胸术后镇痛的应用价值.方法 120例自发性气胸患者均接受择期患侧单操作孔VATS探查和肺大疱切除术,随机分为3组:A组为单纯肋间神经阻滞组,采用0.375％罗哌卡因5 ml在切口所在肋间及其上下各1个肋间的椎旁阻滞肋间神经;B组为肋间神经阻滞+经静脉患者自控镇痛(patient controlled intravenous analgesia,PCIA)组,方案为氟比洛芬酯注射液200 mg+芬太尼20 μg/kg+盐酸昂丹司琼注射液16 mg;C组为单纯PCIA,方案同B组.观察并记录3组患者术后2、6、24、48 h(T1～T4)在静息状态和活动状态下的视觉模拟评分(VAS评分);记录B组和C组术后各时段静脉镇痛泵用量,及额外要求注射盐酸哌替啶的患者例数及用量.结果 除A组T3时点静息状态外,A组和B组患者在术后T1～T3时点静息及活动状态的VAS评分明显低于C组(P＜0.05),尤以T1和T2时点为明显;T4时点B组和C组的VAS评分低于A组(P＜0.05),但B、C组间的差异无统计学意义.结论 肋间神经阻滞+PCIA是胸腔镜自发性气胸手术后比较满意的镇痛方案,肋间神经阻滞对胸腔镜自发性气胸手术后24 h内的急性疼痛的镇痛效果明显优于单纯PCIA.     

不同分娩时间产妇的一般情况及母婴并发症发生情况的调查

目的调查不同分娩时间产妇的一般情况及母婴并发症发生情况,以期为制定针对性措施提供临床依据。方法回顾性分析2014年1月至12月在上海交通大学医学院附属国际和平妇幼保健院妊娠28周以上、单胎头位、阴道分娩的产妇8931例的病史资料。根据分娩时间分为白班组(8:00-17:00)和中夜班组(17:00至次日8:00),比较两组产妇的一般情况、母婴分娩并发症的发生情况等。结果白班组与中夜班组分娩量以及产妇的一般情况的差异无统计学意义(P0.05)。中夜班时,急产的发生率为6.43%,明显高于白班;白班组,人工破膜、镇痛分娩、产钳助产、阴道切开、宫腔探查等助产操作比例明显高于中夜班组。两组产妇阴道血肿以及产后出血发生率的差异无统计学意义(P0.05),但中夜班分娩产妇产后2h发生产后出血比率明显高于白班(P0.05)。两组新生儿娩出5min Apgar评分差异无统计学意义(P0.05)。结论产房白班与中夜班的工作量相当,白班时产科助产操作比例更高,中夜班存在母婴安全的潜在危险因素。     

Risk stratification for ST segment elevation myocardial infarction in the era of primary percutaneous coronary intervention

Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction(NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention(PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed.     

Bleeding risk stratification in an era of aggressive management of acute coronary syndromes

Major bleeding is currently one of the most common non-cardiac complications observed in the treatment of patients with acute coronary syndrome (ACS). Hemorrhagic complications occur with a frequency of 1% to 10% during treatment for ACS. In fact, bleeding events are the most common extrinsic complication associated with ACS therapy. The identification of clinical characteristics and particularities of the antithrombin therapy associated with an increased risk of hemorrhagic complications would make it possible to adopt prevention strategies, especially among those exposed to greater risk. The international societies of cardiology renewed emphasis on bleeding risk stratification in order to decide strategy and therapy for patients with ACS. With this review, we performed an update about the ACS bleeding risk scores most frequently used in daily clinical practice.