Effect of midazolam on delirium in critically ill patients: a propensity score analysis.

OBJECTIVE: To observe the association between exposure to midazolam within 24 hours prior to delirium assessment and the risk of delirium. METHODS: We performed a systematic cohort study with two sets of cohorts to estimate the relative risks of outcomes among patients administered midazolam within 24 hours prior to delirium assessment. Propensity score matching was performed to generate a balanced 1:1 matched cohort and identify potential prognostic factors. The outcomes included the odds of delirium, mortality, length of intensive care unit stay, length of hospitalization, and odds of being discharged home. RESULTS: A total of 78,364 patients were included in this study, of whom 22,159 (28.28%) had positive records. Propensity matching successfully balanced covariates for 9348 patients (4674 per group). Compared with no administration of midazolam, midazolam administration was associated with a significantly higher risk of delirium, higher mortality, and a longer intensive care unit stay. Patients treated with midazolam were relatively less likely to be discharged home. There was no significant difference in hospitalization duration. CONCLUSIONS: Midazolam may be an independent risk factor for delirium in critically ill patients.

Histone Methylation Related Therapeutic Challenge in Cardiovascular Diseases.

The epidemic of cardiovascular diseases (CVDs) is predicted to spread rapidly in advanced countries accompanied by the high prevalence of risk factors. In terms of pathogenesis, the pathophysiology of CVDs is featured by multiple disorders, including vascular inflammation accompanied by simultaneously perturbed pathways, such as cell death and acute/chronic inflammatory reactions. Epigenetic alteration is involved in the regulation of genome stabilization and cellular homeostasis. The association between CVD progression and histone modifications is widely known. Among the histone modifications, histone methylation is a reversible process involved in the development and homeostasis of the cardiovascular system. Abnormal methylation can promote CVD progression. This review discusses histone methylation and the enzymes involved in the cardiovascular system and determine the effects of histone methyltransferases and demethylases on the pathogenesis of CVDs. We will further demonstrate key proteins mediated by histone methylation in blood vessels and review histone methylation-mediated cardiomyocytes and cellular functions and pathways in CVDs. Finally, we will summarize the role of inhibitors of histone methylation and demethylation in CVDs and analyze their therapeutic potential, based on previous studies.

Structure and Function of Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) and Their Role in Cardiovascular Diseases.

Abnormal function of suborganelles such as mitochondria and endoplasmic reticulum often leads to abnormal function of cardiomyocytes or vascular endothelial cells and cardiovascular disease (CVD). Mitochondria-associated membrane (MAM) is involved in several important cellular functions. Increasing evidence shows that MAM is involved in the pathogenesis of CVD. MAM mediates multiple cellular processes, including calcium homeostasis regulation, lipid metabolism, unfolded protein response, ROS, mitochondrial dynamics, autophagy, apoptosis, and inflammation, which are key risk factors for CVD. In this review, we discuss the structure of MAM and MAM-associated proteins, their role in CVD progression, and the potential use of MAM as the therapeutic targets for CVD treatment.

Key Clinical Interest Outcomes of Pharmaceutical Administration for Veterans With Post-Traumatic Stress Disorder Based on Pooled Evidences of 36 Randomised Controlled Trials With 2,331 Adults.

Background: The effects of drug treatment on veterans, who have a high risk of post-traumatic stress disorder (PTSD), are not clear, and the guidelines are different from the recommendations of the recent meta-analysis. Our goal was to find the efficacy and frequencies of complications of drugs that can treat PTSD in veterans. Method: We searched Ovid MEDLINE, Ovid Embase, The Cochrane Library and Web of Science until January 1, 2020. The outcomes were designed as the change of PTSD total scale, subsymptom score, response rate, frequencies of complications outcomes, and acceptability. Results: We included a total of 36 randomised controlled trials with a total of 2,331 adults. In terms of overall effect, drug treatment is more effective than placebo in change in total PTSD symptoms scale (SMD = -0.24, 95% CI [-0.42, -0.06]) and response (RR = 1.66, 95% CI [1.01, 2.72]). However, in terms of frequencies of complications, drugs generally had a higher withdrawal rate (RR = 1.02, 95% CI [0.86, 1.20]) and a higher frequencies of complications (RR = 1.72, 95% CI [1.20, 2.47]) than placebo. Risperidone showed a good curative effect in change in total PTSD symptoms scale (SMD = -0.22, 95% CI [-0.43, 0.00]) and acceptability (RR = 1.31, 95% CI [0.82, 2.59]). The drugs acting on 5-HT receptors, our results showed that symptoms of hyper-arousal (SMD = -0.54, 95% CI [-0.86, -0.21]), symptoms of re-experiencing (SMD = -0.62, 95% CI [-0.86, -0.39]) and symptoms of avoidance (SMD = -0.53, 95% CI [- 0.77,-0.3]), The drugs acting on dopamine receptors, our results showed that symptoms of re-experiencing (SMD = -0.35, 95% CI [-0.55, -0.16]) and the drugs acting on α2 receptor has a significant effect on reducing total PTSD symptoms scale (SMD = -0.34, 95% CI [-0.62, -0.06]). Conclusion: Drug therapy can effectively treat PTSD, but its frequencies of complications should be considered. Different from the guidelines for adult PTSD, this study supports atypical antipsychotics, selective serotonin reuptake inhibitors and receptors that act on 5-HT and dopamine for the treatment of PTSD in veterans. Based on evidence among these drugs, the risperidone is the most effective for veterans, otherwise, sertraline is used as an alternative.

Poisson distribution and the development of probability theory: Siméon Denis Poisson / 中华疾病控制杂志

Siméon Denis Poisson (1781-1840) was a famous French mathematician, physicist and founder of statistical theory. He established the Poisson distribution model through the criminal trial cases and solved many random phenomena in natural science and social science. He also introduced birth statistics, Poisson's inference theory, Laplace's theorem and error theory, law of large numbers and judgment probability and other related theories. Poisson promoted the development of probability theory in the 19th century and opened up a new trend of physics from experimental research to theoretical research.

Effectiveness and Tolerability of Different Recommended Doses of PPIs and H2RAs in GERD: Network Meta-Analysis and GRADE system.

Proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) are used for gastro-esophageal reflux disease (GERD); however, the clinical evidence for treatment is poor. We evaluated the effectiveness and tolerability of different doses of PPIs, H2RAs and placebo in adults with GERD. Six online databases were searched through September 1, 2016. All related articles were included and combined with a Bayesian network meta-analysis from randomized controlled trials (RCTs). The GRADE systems were employed to assess the main outcome. Ninety-eight RCTs were identified, which included 45,964 participants. Our analysis indicated that the full/standard dose of esomeprazole at 40 mg per day was the most efficient in healing among nine different dosages of PPIs and H2RAs. The main efficacy outcome did not change after adjustments for the area, age, level of disease from endoscopy, year of publication, pharmaceutical industry sponsorship, Intention-to-treat (ITT)/per-protocol (PP), withdrawal rate, pre-set select design bias, single blinded and unblinded studies, study origination in China, study arms that included zero events, inconsistency node or discontinued drug were accounted for in the meta-regressions and sensitivity analyses. This research suggests that the full/standard doses (40 mg per day) of esomeprazole should be recommended as first-line treatments for GERD in adults for short-term therapy.

Sleep duration and risk of all-cause mortality: A flexible, non-linear, meta-regression of 40 prospective cohort studies.

Approximately 27-37% of the general population experience prolonged sleep duration and 12-16% report shortened sleep duration. However, prolonged or shortened sleep duration may be associated with serious health problems. A comprehensive, flexible, non-linear meta-regression with restricted cubic spline (RCS) was used to investigate the dose-response relationship between sleep duration and all-cause mortality in adults. Medline (Ovid), Embase, EBSCOhost-PsycINFO, and EBSCOhost-CINAHL Plus databases, reference lists of relevant review articles, and included studies were searched up to Nov. 29, 2015. Prospective cohort studies investigating the association between sleep duration and all-cause mortality in adults with at least three categories of sleep duration were eligible for inclusion. We eventually included in our study 40 cohort studies enrolling 2,200,425 participants with 271,507 deaths. A J-shaped association between sleep duration and all-cause mortality was present: compared with 7 h of sleep (reference for 24-h sleep duration), both shortened and prolonged sleep durations were associated with increased risk of all-cause mortality (4 h: relative risk [RR] = 1.05; 95% confidence interval [CI] = 1.02-1.07; 5 h: RR = 1.06; 95% CI = 1.03-1.09; 6 h: RR = 1.04; 95% CI = 1.03-1.06; 8 h: RR = 1.03; 95% CI = 1.02-1.05; 9 h: RR = 1.13; 95% CI = 1.10-1.16; 10 h: RR = 1.25; 95% CI = 1.22-1.28; 11 h: RR = 1.38; 95% CI = 1.33-1.44; n = 29; P < 0.01 for non-linear test). With regard to the night-sleep duration, prolonged night-sleep duration was associated with increased all-cause mortality (8 h: RR = 1.01; 95% CI = 0.99-1.02; 9 h: RR = 1.08; 95% CI = 1.05-1.11; 10 h: RR = 1.24; 95% CI = 1.21-1.28; n = 13; P < 0.01 for non-linear test). Subgroup analysis showed females with short sleep duration a day (<7 h) were at high risk of all-cause mortality (4 h: RR = 1.07; 95% CI = 1.02-1.13; 5 h: RR = 1.08; 95% CI = 1.03-1.14; 6 h: RR = 1.05; 95% CI = 1.02-1.09), but males were not (4 h: RR = 1.01; 95% CI = 0.96-1.06; 5 h: RR = 1.02; 95% CI = 0.97-1.08; 6 h: RR = 1.02; 95% CI = 0.98-1.06). The current evidence suggests that insufficient or prolonged sleep may increase all-cause mortality. Women may be more susceptible to short sleep duration on all-cause mortality.

Association between Estrogen Receptor-α Gene XbaI and PvuII Polymorphisms and Periodontitis Susceptibility: A Meta-Analysis.

BACKGROUND: Certain studies have previously explored the association between the estrogen receptor-α (ER-α) gene polymorphisms and periodontitis susceptibility, although the current results are controversial. The present study, using meta-analysis, aimed to investigate the nature of the genetic susceptibility of the ER-α for developing periodontitis. METHODS: A comprehensive literature search of PubMed, Embase, CNKI, and Wanfang databases was conducted up to January 8, 2015. Statistical manipulation was performed using Stata version 13.0 software. Odds ratios (ORs) and corresponding 95% confident intervals (CIs) were calculated to estimate the association in five genetic models. RESULTS: A total of 17 eligible case-control studies from seven identified publications consisting of nine studies for the XbaI polymorphism and eight studies for the PvuII polymorphism were included in the meta-analysis. We found elevated risk of periodontitis in XbaI XX genotype carriers. Moreover, subgroup analyses demonstrated increased risk for chronic periodontitis of XbaI XX genotype carriers, specifically in the Chinese Han female population. No significant association was observed between PvuII polymorphism and periodontitis. CONCLUSION: Current evidence indicated that the homozygote (XX) genotype of ER-α gene XbaI polymorphism, but not PvuII mutation, may increase the risk of chronic periodontitis, specifically in the Chinese Han female population.

Increased risks between Interleukin-10 gene polymorphisms and haplotype and head and neck cancer: a meta-analysis.

Molecular epidemiological research suggests that interleukin-10 (IL-10) polymorphisms may be associated with an increased risk of head and neck cancer (HNC), but results remain controversial. To derive a more precise evaluation, we performed a meta-analysis focused on genetic polymorphisms of IL-10. PubMed, Embase, CNKI and Wanfang databases were searched for studies that examined the relationship between IL-10 polymorphisms or haplotypes and HNC risk. The odds ratio (OR) and 95% confidence interval (CI) were applied to assess the relationship strength. Publication bias, sensitivity and cumulative analyses were conducted to measure the robustness of our findings. Overall, nine related studies involving 2,258 patients and 2,887 control samples were analyzed. Significant associations between the IL-10-1082A > G polymorphism and HNC risk were observed (G vs. A: OR = 1.56, 95% CI = 1.27-1.92, P < 0.01, I(2) = 69.4%; AG vs. AA: OR = 1.64, 95% CI = 1.32-2.05, P < 0.01, I(2) = 55.6%; GG vs. AA: OR = 2.24, 95% CI = 1.69-2.97, P < 0.01, I(2) = 38.5%; AG + GG vs. AA: OR = 1.70, 95% CI = 1.36-2.14, P = 0.02, I(2) = 61.8%; GG vs. AA + AG: OR = 1.89, 95% CI = 1.23-2.90, P = 0.01, I(2) = 46.3%) in the total population, as well as in subgroup analysis. Moreover, increased HNC risks were also associated with the IL-10 -819T > C polymorphism and the GCC haplotype. In conclusion, our meta-analyses suggest that IL-10 polymorphisms, specifically the -1082A > G polymorphism, may be associated with increased risk of HNC development.

Systematic Review by Multivariate Meta-analyses on the Possible Role of Tumor Necrosis Factor-α Gene Polymorphisms in Association with Ischemic Stroke.

A number of studies have investigated the association between tumor necrosis factor (TNF)-α gene polymorphisms and ischemic stroke susceptibility. However, results of different individual studies are often inconsistent. To provide a more robust evaluation of the association between polymorphisms of the TNF-α gene and ischemic stroke risk, we performed a systematic review with multivariate meta-analyses. PubMed, Embase, CNKI, and WanFang databases were searched up to December 20, 2014. Two reviewers independently extracted information and assessed quality of included studies after all the eligible studies were identified. Afterward, multivariate meta-analyses were performed using Stata 13. The estimation of polymorphisms and disease risk was presented by odds ratios (ORs) and corresponding 95 % confidence intervals (CIs). Forty-nine eligible case-control studies from 25 articles that explored the association between 10 TNF-α polymorphisms and ischemic stroke were indentified from aforementioned databases. The results of multivariate meta-analysis showed a significant association between -238G/A polymorphism (4760 patients and 4389 controls) and ischemic stroke risk in heterozygotes compared with wild genotype (AG vs. GG: OR 1.44, 95 % CI 1.11-1.87; AA vs. GG: OR 1.98, 95 % CI 0.73-5.40). No significant association of -308G/A, -857C/T, and -1031T/C polymorphisms was observed. The results of stratification analyses of -238G/A polymorphism showed that the AG genotype only increased the risk of ischemic stroke in Asians compared to GG genotype. No additional significant association was observed in this study. In conclusion, the present systematic review and meta-analysis support a prominent role of the TNF-α -238G/A polymorphism in the risk of ischemic stroke in Asian adults only, but do not support the role of -308G/A, -857C/T, -1031T/C, -244G/A, -367G/A, -646G/A, -806C/T, -863C/A, and +448G/A in the risk of ischemic stroke. The current evidence warrants further studies with high quality and large sample size to confirm.

Association between Interleukin-1ß Gene -511C>T/+3954C>T Polymorphisms and Aggressive Periodontitis Susceptibility: Evidence from a Meta-Analysis.

BACKGROUND: Interleukin-1ß (IL-1ß) is an important inflammatory cytokine. The associations between IL-1ß gene -511C>T/+3954C>T polymorphisms and aggressive periodontitis (AgP) susceptibility have been conflicting. We therefore conducted a meta-analysis to investigate the association of IL-1ß genetic polymorphisms with susceptibility to AgP. MATERIAL AND METHODS: PubMed and Embase electronic databases were searched for relevant studies. Odds ratios (ORs) with 95% confidence interval (CIs) were used to assess the association between IL-1ß polymorphisms and AgP risk. Heterogeneity, publication bias, and sensitivity analysis were performed to guarantee the statistical power. RESULTS: Twenty published studies involving 965 patients and 1234 control subjects were included. No significant association between IL-1ß polymorphisms and AgP was found. For -511C>T (T vs. C: OR=0.966, 95%CI=0.696-1.341, P=0.869; CT vs. CC: OR=0.936, 95%CI=0.761-1.151; TT vs. CC: OR=0.892, 95%CI=0.464-1.715, P=0.719; CT+TT vs. CC: OR=1.026, 95%CI=0.795-1.323; TT vs. CC+CT: OR=0.864, 95%CI=0.436-1.713). For +3954C>T (T vs. C: OR=1.069, 95%CI=0.901-1.268; CT vs. CC: OR=0.921, 95%CI=0.699-1.212; TT vs. CC: OR=1.064, 95%CI=0.747-1.515; CT+TT vs. CC: OR=0.990, 95%CI=0.764-1.283; TT vs. CC+CT: OR=1.229, 95%CI=0.919-1.643). Subgroup analyses were conducted with HWE, ethnicity, and study design, and no significant association was detected. CONCLUSIONS: These results demonstrate that IL-1ß -511C>T and +3954C>T polymorphisms are not the risk factors for developing AgP.

Significance of ST-segment deviation in patients with acute pulmonary embolism and negative T waves.

BACKGROUND: Common electrocardiogram (ECG) manifestations in acute pulmonary em-bolism (APE) include ST-segment deviation (STDV) along with negative T-waves (NTW). STDV could occur in 3 typical ischemic patterns: (i) the left ventricular (LV) subendocardial ischemic pattern; (ii) the right ventricular (RV) transmural ischemic pattern; and (iii) the LV subendocardial plus RV transmural ischemic pattern. The purpose of this study was to evalu-ate the relationship of STDV and adverse clinical outcomes and to identify the relationship of relatively normal ECG and favorable clinical outcomes. METHODS: Retrospective analysis of electronic charts in APE patients was performed in a tertiary hospital. ECGs on admission were obtained and classified as with or without STDV. Adverse clinical outcomes were defined as need to intensify therapy and 30-day mortality. Relatively normal ECG was defined as without any STDV, abnormal QRS morphology in lead V1 and S1Q3T3. RESULTS: From a total of 210 patients with NTW, 131 had STDV ≥ 0.1 mV, while 79 did not. Patients with STDV had worse evolution: higher incidence of dyspnea, hypotension, cardiogen-ic shock, intensification of therapy, and death compared to patients without STDV (p = 0.001 for each variable). The majority (89%) of the patients with STDV presented with 1 of the 3 typical ischemic ECG patterns. LV subendocardial ischemic pattern (OR = 4.963, p = 0.004), RV transmural ischemic pattern (OR = 3.128, p = 0.021) and LV subendocardial plus RV transmural ischemic pattern (OR = 3.036, p = 0.017) independently predicted the need to intensify therapy. RV transmural ischemic pattern (OR = 4.227, p = 0.031) and LV subendocardial plus RV transmural ischemic pattern (OR = 4.022, p = 0.032) independently predicted 30-day mortality. Compared to the patients with abnormal ECG, the patients with relatively normal ECG had a significant lower incidence of death (0% vs. 16%; p = 0.001) and need to intensify therapy during hospitalization (6% vs. 30%; p = 0.002). CONCLUSIONS: Ischemic ECG patterns are common ECG manifestations of APE and predict worse evolution and 30-day mortality. Additionally, relatively normal ECGs may associate with favorable clinical outcomes.