Nonselective Compared With Selective α-Blockade Is Associated With Less Intraoperative Hypertension in Patients With Pheochromocytomas and Paragangliomas: A Retrospective Cohort Study With Propensity Score Matching.

BACKGROUND: Both selective and nonselective α-blockade are used for preoperative preparation in patients with pheochromocytomas and paragangliomas (PPGLs). However, the effects of different types of α-blockade on perioperative outcomes remain inconclusive. This study was designed to assess the association between the choice of α-blockade and the amount of intraoperative hypertension in patients undergoing surgery for PPGLs. METHODS: In this propensity-matched retrospective cohort study, data of patients who received either selective or nonselective α-blockade preoperatively and underwent surgery for PPGLs were collected. The primary end point was the time-weighted average above the systolic blood pressure (SBP) of 160 mm Hg (TWA-SBP >160 mm Hg), which was calculated as the total area of the SBP-time curve above the SBP of 160 mm Hg and divided by anesthesia duration. RESULTS: A total of 286 patients were included in analysis; of them, 156 received selective α-blockade and 130 nonselective α-blockade. After propensity score matching, 89 patients remained in each group. Patients who received nonselective α-blockade had a lower TWA-SBP >160 (median 0.472 mm Hg, interquartile range [IQR], 0.081-1.300) versus those who received selective α-blockade (median 1.114 mm Hg, IQR, 0.162-2.853; median difference -0.391, 95% confidence interval [CI], -0.828 to -0.032; P = .016); they also had a lower highest SBP during surgery (193 ± 24 mm Hg versus 205 ± 34 mm Hg; mean difference -12, 95% CI, -20 to -3; P = .008). Postoperative outcomes did not differ significantly between the 2 groups. CONCLUSIONS: For patients undergoing surgery for PPGLs, preoperative nonselective α-blockade was associated with less intraoperative hypertension when compared with selective α-blockade.

The effect of probiotics supplementation on blood pressure: a systemic review and meta-analysis.

BACKGROUND: Fermented milk has over the last decade been intensively studied because of the putative antihypertensive effect. The aim of our study is to investigate the role of probiotics support therapy in blood pressure and, as a kind of convenient and economic drugs for prevention and auxiliary treatment of hypertension. MATERIALS AND METHODS: We performed a systemic review and meta-analysis to examine the effect of probiotics consumption on blood pressure. Databases including MEDLINE, EMBASE, Clinical trials, CNKI and the Cochrane library were searched. Also, the grey literature and references were searched. RESULTS: Twenty-three randomized controlled trials (RCTs) involving 2037 participants met the inclusion criteria and were included. Probiotic consumption significantly changed systolic blood pressure (SBP) by - 3.05 mmHg (95%CI: - 4.67, - 1.44; P < 0.001) and diastolic blood pressure (DBP) by - 1.51 mmHg (95%CI: - 2.38, - 0.65; P = 0.001). Subgroup analysis indicated that the benefit effect of probiotics supplementation in SBP was only observed in hypertension [weight mean difference (WMD) = - 3.31 mmHg, 95%CI: - 5.71, - 0.92; P = 0.007] or type 2 diabetes (WMD = -4.85 mmHg, 95%CI: - 9.28, - 0.42; P = 0.032) patients, and the decreased DBP level by probiotics supplementation was only observed in hypertension patients (WMD = -2.02 mmHg, 95%CI: - 3.68, - 0.36; P = 0.017).This effect could only last for a short-term time of 8 or 10 weeks, but not for a long-term time. CONCLUSION: This meta-analysis found a moderate and statistically significant reduction for either SBP or DBP with probiotics supplement compared with controls. Thus, probiotics is a potential for the dietary treatment of hypertension.

Exploring the drug-induced anemia signals in children using electronic medical records.

Objectives: The objectives were to identify drugs related with anemia in children and evaluate the novelty of these correlations. Methods: The authors established a two-step method for detecting the relationship between drugs and anemia using electronic medical records (EMRs), which were obtained from 247,136 patients in Beijing Children's Hospital between 2007 and 2017. The authors extracted potential drugs by mining cases for hemoglobin abnormalities from the EMR and then performed a retrospective cohort study to correlate them with anemia by calculating the matched odds ratios and 95% confidence interval using unconditional logistic regression analysis. Results: In total, nine positive drug-anemia associations were identified. Among them, the correlations of drugs fluconazole (OR 3.95; 95%CI: 2.65-5.87) and cefathiamidine (OR 3.49; 95%CI: 2.94-4.15) with anemia were considered new signals in both children and adults. Three associations of drugs, vancomycin, cefoperazone-sulbactam and ibuprofen, with anemia were considered new signals in children. Conclusion: The authors detected nine signals of drug-induced anemia, including two new signals in children and adults and three new signals in children. This study could serve as a model for using EMR and automatic mining to monitor adverse drug reaction signals in the pediatric population.

Optimal management after paediatric lumbar puncture: a randomized controlled trial.

BACKGROUND: To evaluate whether a shorter time of lying supine without a pillow and fasting for solids and liquids (LSFSL) after a lumbar puncture (LP) is associated with a higher risk of post-lumbar puncture headache (PLPH) and post-lumbar puncture lower back pain (PLPBP) in a randomized, assessor-blinded, controlled trial. METHODS: Paediatric patients who underwent their first LP after hospital admission were randomly allocated to either the group with half an hour of LSFSL (0.5 h LSFSL) or 4 h of LSFSL (4 h LSFSL) immediately after LP. The primary outcome is PLPH after LP. The incidence of PLPH, PLPBP, and vomiting; vital signs (respiratory rate, heart rate, blood pressure); and other post-procedure conditions after LP were measured as the outcomes. The Non-inferiority test and Wilcoxon rank-sum test were used to analyse the outcome data. RESULTS: In total, 400 patients (201 in the 0.5-h LSFSL group and 199 in the 4-h LSFSL group) were included in this trial. Twelve (5.97%) of 201 patients experienced PLPH in the 0.5 h LSFSL group versus 13 (6.53%) of 199 patients in the 4 h LSFSL group (difference 0.56, 95% CI -4.18 to 5.31; p = 0·0108 for the non-inferiority test). Fourteen (6.97%) of 201 patients experienced PLPBP in the 0.5 h LSFSL group versus 17 (8.54%) of 199 patients in the 4 h LSFSL group (difference 1.57, 95% CI -3.66 to 6.82; p = 0.007 for the non-inferiority test). The changes in heart rate (HR), respiratory rate (RP) and systolic blood pressure (SBP) before and after the LP were not different between the 0.5-h LSFSL group and the 4-h LSFSL group. No other adverse events were reported. CONCLUSIONS: Compared with 4 h of LSFSL after LP, 0.5 h of LSFSL was not associated with a higher risk of PLPH, PLPBP or other adverse events. In conclusion, 0.5 h of LSFSL is sufficient for children undergoing LP. TRIAL REGISTRATION: Clinical trial NCT02590718 . The date of registration was 08/25/2015.

Pediatric drug safety signal detection of non-chemotherapy drug-induced neutropenia and agranulocytosis using electronic healthcare records.

Objectives: This study aimed to develop a procedure to explore the adverse drug reaction signals of drug-induced neutropenia (DIN) or drug-induced agranulocytosis (DIA) in children using an electronic health records (EHRs) database. Methods: A two-stage design was presented. First, the suspected drugs to induce DIN or DIA were selected. Second, the associations were evaluated by a retrospective cohort study. Results: Ten and five drugs were potentially identified to be associated with DIN and DIA, respectively. Finally, five (oseltamivir, chlorpheniramine, vancomycin, meropenem, and ganciclovir) and two (chlorpheniramine, and vancomycin) drugs were found to be associated with DIN and DIA, respectively. Of these, the association between oseltamivir and neutropenia (P = 9.83 × 10-9; OR, 2.10; 95% CI, 1.62-2.69) was considered as a new signal for both adults and children. Chlorpheniramine-induced neutropenia (P = 3.01 × 10-8; OR, 1.59; 95% CI, 1.35-1.87) and agranulocytosis (P = 3.16 × 10-7; OR, 3.76; 95% CI, 2.25-6.26) were considered as new signals in children. Other drugs associated with DIN or DIA were confirmed by previous studies. Conclusion: A method to detect signals for DIN and DIA has been described. Several pediatric drugs were found to be associated with DIN or DIA.

Perioperative Management May Improve Long-term Survival in Patients After Lung Cancer Surgery: A Retrospective Cohort Study.

BACKGROUND: Surgical resection is the main treatment for patients with non-small-cell lung cancer (NSCLC), but patients' long-term outcome is still challenging. The purpose of this study was to identify predictors of long-term survival in patients after lung cancer surgery. METHODS: Patients who underwent surgery for NSCLC from January 1, 2006, to December 31, 2009, were enrolled into this retrospective cohort study. The primary outcome was the survival length after surgery. Predictors of long-term survival were screened with the multivariable Cox proportional hazard model. RESULTS: Postoperative follow-up was completed in 588 patients with a median follow-up duration of 5.2 years (interquartile range, 2.0-6.8). Two hundred ninety-one patients (49.5%) survived at the end of follow-up with median survival duration of 64.3 months (interquartile range, 28.5-81.6). The overall survival rates were 90.8%, 70.0%, and 57.1% at the end of the first, third, and fifth year after surgery, respectively. Limited resection (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.08-1.98; P = .013) and large tumor size (HR, 1.29; 95% CI, 1.17-1.42; P < .001) were associated with short survival; whereas high body mass index grade (HR, 0.82; 95% CI, 0.69-0.97; P = .021), highly differentiated tumor (HR, 0.59; 95% CI, 0.37-0.93; P = .024), dissection of mediastinal lymph node during surgery (HR, 0.45; 95% CI, 0.30-0.67; P < .001), and perioperative use of dexamethasone (HR, 0.70; 95% CI, 0.54-0.90; P = .006) were associated with long survival. No association was found between perioperative use of flurbiprofen axetil and long survival (HR, 0.80; 95% CI, 0.62-1.03; P = .086). However, combined administration of dexamethasone and flurbiprofen axetil was associated with longer survival (compared to no use of both: adjusted HR, 0.57; 95% CI, 0.38-0.84; P = .005). CONCLUSIONS: Certain factors in particular perioperative dexamethasone and flurbiprofen axetil therapy may improve patients' long-term survival after surgery for NSCLC. Given the small sample size, these findings should be interpreted with caution, and randomized clinical trials are needed for further clarification.

Vitamin D and hypertension: Prospective study and meta-analysis.

OBJECTIVES: The study sought to determine the link between vitamin D concentrations and incident hypertension in prospective study and meta-analysis. METHODS: The study was embedded in the Kailuan Study, a population-based cohort of adults that contains underground miners. In 2012, we studied 2,456 men and women free of prevalent hypertension, age 21 to 67 at baseline. Serum 25-hydroxyvitamin D was measured from previously frozen baseline samples using ELISA (Enzyme-Linked ImmunoadSorbent Assay). We use the logistic regression analysis to estimate the odd radio (ORs) 95% confidence intervals (CIs) for 25-hydroxyvitamin D [25(OH)D] concentrations with incident hypertension. To help place our new data in context, we conducted a systemic review and meta-analysis of previous prospective reports of vitamin D and hypertension. RESULTS: During a median follow-up of 2 years, 42.6% of the cohort (n = 1047) developed hypertension. Compared with the 25-hydroxyvitamin D >30ng/ml, 25-hydroxyvitamin D <20 ng/ml was associated with a greater hypertension risk (OR: 1.225 [95% CI: 1.010 to 1.485] p = 0.04), although the association was attenuated and not statistically significant after adjusting for potential confounders (OR: 1.092 [95% CI: 0.866 to 1.377] p = 0.456). This meta-analysis included seven prospective studies for 53,375 participants using adjusted HR founded a significant association between vitamin D deficiencies and incident hypertension (HRs = 1.235 (95% CI: 1.083 to 1.409, p = 0.002)). CONCLUSION: Lower serum 25-hydroxyvitamin D concentrations were not associated with a greater risk of incident hypertension. More research is needed to further determine the role of 25-hydroxyvitamin D in hypertension prevention and therapy.

Impact of dexmedetomidine on the incidence of delirium in elderly patients after cardiac surgery: A randomized controlled trial.

BACKGROUND: Delirium is a frequent complication after cardiac surgery and its occurrence is associated with poor outcomes. The purpose of this study was to investigate the impact of perioperative dexmedetomidine administration on the incidence of delirium in elderly patients after cardiac surgery. METHODS: This randomized, double-blinded, and placebo-controlled trial was conducted in two tertiary hospitals in Beijing between December 1, 2014 and July 19, 2015. Eligible patients were randomized into two groups. Dexmedetomidine (DEX) was administered during anesthesia and early postoperative period for patients in the DEX group, whereas normal saline was administered in the same rate for the same duration for patients in the control (CTRL) group. The primary endpoint was the incidence of delirium during the first five days after surgery. Secondary endpoints included the cognitive function assessed on postoperative days 6 and 30, the overall incidence of non-delirium complications within 30 days after surgery, and the all-cause 30-day mortality. RESULTS: Two hundred eighty-five patients were enrolled and randomized. Dexmedetomidine did not decrease the incidence of delirium (4.9% [7/142] in the DEX group vs 7.7% [11/143] in the CTRL group; OR 0.62, 95% CI 0.23 to 1.65, p = 0.341). Secondary endpoints were similar between the two groups; however, the incidence of pulmonary complications was slightly decreased (OR 0.51, 95% CI 0.26 to 1.00, p = 0.050) and the percentage of early extubation was significantly increased (OR 3.32, 95% CI 1.36 to 8.08, p = 0.008) in the DEX group. Dexmedetomidine decreased the required treatment for intraoperative tachycardia (21.1% [30/142] in the DEX group vs 33.6% [48/143] in the CTRL group, p = 0.019), but increased the required treatment for postoperative hypotension (84.5% [120/142] in the DEX group vs 69.9% [100/143] in the CTRL group, p = 0.003). CONCLUSIONS: Dexmedetomidine administered during anesthesia and early postoperative period did not decrease the incidence of postoperative delirium in elderly patients undergoing elective cardiac surgery. However, considering the low delirium incidence, the trial might have been underpowered. TRIAL REGISTRATION: ClinicalTrials.gov NCT02267538.

The Content of Statistical Requirements for Authors in Biomedical Research Journals.

BACKGROUND: Robust statistical designing, sound statistical analysis, and standardized presentation are important to enhance the quality and transparency of biomedical research. This systematic review was conducted to summarize the statistical reporting requirements introduced by biomedical research journals with an impact factor of 10 or above so that researchers are able to give statistical issues' serious considerations not only at the stage of data analysis but also at the stage of methodological design. METHODS: Detailed statistical instructions for authors were downloaded from the homepage of each of the included journals or obtained from the editors directly via email. Then, we described the types and numbers of statistical guidelines introduced by different press groups. Items of statistical reporting guideline as well as particular requirements were summarized in frequency, which were grouped into design, method of analysis, and presentation, respectively. Finally, updated statistical guidelines and particular requirements for improvement were summed up. RESULTS: Totally, 21 of 23 press groups introduced at least one statistical guideline. More than half of press groups can update their statistical instruction for authors gradually relative to issues of new statistical reporting guidelines. In addition, 16 press groups, covering 44 journals, address particular statistical requirements. The most of the particular requirements focused on the performance of statistical analysis and transparency in statistical reporting, including "address issues relevant to research design, including participant flow diagram, eligibility criteria, and sample size estimation," and "statistical methods and the reasons." CONCLUSIONS: Statistical requirements for authors are becoming increasingly perfected. Statistical requirements for authors remind researchers that they should make sufficient consideration not only in regards to statistical methods during the research design, but also standardized statistical reporting, which would be beneficial in providing stronger evidence and making a greater critical appraisal of evidence more accessible.

Expression and functional characterization of NOD2 in decidual stromal cells isolated during the first trimester of pregnancy.

NOD2, one of the cytosolic proteins that contain a nuclear oligomerization domain (NOD), is a pattern recognition receptor (PRR) involved in innate immune responses to intracellular pathogens. Little is known, however, about the effect of NOD2 expression on the maternal-fetal relationship. Our aim was to elucidate the functions of NOD2 in normal decidual stromal cells (DSCs) from the first trimester. Tissues and DSCs were isolated from 26 patients with normal pregnancies that required abortion. The expression of NOD2 in deciduas/decidual stromal cells (DSCs) was examined by real-time PCR, immunohistochemistry, and In-cell western. DSCs containing NOD2 were stimulated by its ligand, muramyl dipeptide (MDP). The secretion of various cytokines and chemokines were measured by ELISA and the apoptotic rate was determined by flow cytometry. Treatment with MDP significantly elevated the expression of both NOD2 mRNA and protein levels in DSCs. In addition, MDP activation of NOD2 significantly increased IL-1ß and MCP-1 cytokine expression in a dose dependent manner but had no effect on IL-12 expression. IL-1ß and TNF-α also significantly increased the expression of NOD2 in DSCs, suggesting a positive feedback loop mechanism. Moreover, MDP stimulation augmented DSC apoptosis. In summary, the results suggest that NOD2 expression in DSCs plays an important role in protecting the embryo and preventing infection in the maternal-fetal interface.

Leptin and coronary heart disease: a systematic review and meta-analysis.

INTRODUCTION: Leptin, an adipose tissue-derived hormone, plays a central role in regulating human energy homeostasis. The role of leptin in regulating blood pressure, activating the sympathetic nervous system, insulin resistance, platelet aggregation, arterial thrombosis, angiogenesis, and inflammatory vascular responses suggests that leptin may have a close relationship with the development of coronary heart disease (CHD). However, no conclusive data are available to determine the association between leptin and CHD. METHODS: The PubMed, EMBASE and Cochrane databases were surveyed for original studies describing the association between leptin and CHD outcome from the date of publication of each database through March 2013. The data were extracted by two investigators independently. RESULTS: The meta-analysis reported here was comprised of eight original articles with a total of 21,064 participants (10,842 men, 10,222 women) and 2053 CHD events. The odds ratio for the sociodemographic-adjusted study reported here was 1.57 (95% confidence interval, 1.14-2.16) and 1.72 (95% confidence internal, 1.03-2.87) in males and females, respectively. Further adjustment for additional cardiovascular risk factors resulted in an odds ratio of 1.36 (95% confidence interval, 0.98-1.88) in males and 1.50 (95% confidence interval, 0.93-2.42) in females. Sensitivity analysis restricted to sociodemographics-adjusted studies with high methodological quality indicated an estimate of 1.47 (95% confidence internal, 1.06-2.04) in males and 1.85 (95% confidence internal, 0.61-5.63) in females. Sensitivity analysis restricted to cardiovascular risk factor-adjusted studies showed no significant differences in both males and females. CONCLUSION: The results of the meta-analysis represents the most precise and accurate estimate of the relationship between leptin and CHD. Although the associations of leptin and CHD were not statistically significant both in male and female overall, males with high levels of leptin should be paid more attention to. Our findings highlight the need for additional well-designed and gender-specific prospective studies to evaluate the role of leptin on the development of CHD.

Ketoconazole associated hepatotoxicity: a systematic review and meta- analysis.

OBJECTIVE: To evaluate the incidence of Ketoconazole associated hepatotoxicity and related factor. METHODS: Literature retrieval was conducted by using multi-databases for meta-analysis on Ketoconazole associated hepatotoxicity. The data were collected with a standardized form. Overall estimation of incidence of hepatotoxicity for specific study type was calculated by using a DerSimonian-Laird random-effects model owing to the substantial differences among the studies. RESULTS: Totally 204 eligible studies were included in the analysis. The incidence of Ketoconazole associated hepatotoxicity was 3.6%-4.2%. The dosage and duration specific subgroup analyses did not show any significant difference among groups, while the age specific subgroup analysis showed the incidence in children and people aged >60 years was 1.4% (95% CI: 0.5%-4.2%) and 3.2% (95% CI: 1.1%-8.7%) respectively. Additionally, the incidence of the hepatotoxicity was higher in people who had oral administration of ketoconazole beyond the provisions of the usage instructions, and the incidence was 5.7% (95% CI: 4.5%-7.2%). CONCLUSION: Ketoconazole associated hepatotoxicity was common. Off-label use might increase the risk of liver damage. Well-designed large sample studies are needed to identify the risk factors in future.

[Meta-analysis of Dengzhanxixin injection treatment for unstable angina pectoris].

OBJECTIVE: To assess the efficacy and safety of Dengzhanxixin injection for unstable angina pectoris. METHOD: All clinical studies of Dengzhanxixin injection for unstable angina pectoris (UAP) were searched from Cochrane library, Medline, EM-base, CBM, CNKI, Wanfang and VIP. Quality assessment and information extraction were done by two independent screening . The quality of the included documents was evaluated by the Cochrane Collaboration's tool for assessing risk of bias and allocation concealment. Revman 5.1.4 software was used for data analysis. RESULT: A total of 17 randomized controlled trials were included (1 644 patients), in which, only 2 studies were true RCT, 1 study used single blind method, while other studies did not mention allocation concealment, blind and loss-up information. Meta-analysis showed that the Dengzhanxixin injection group was better than the conventional treatment group in efficiency (OR = 3.54, 95% CI [2.60-4.82]) and ECG (OR = 2.36, 95% CI[1.88-2.96]). Researches with ADR/AE information of Dengzhanxixin injection showed that the symptoms of ADR/AE were slight. This study may exist publication bias. CONCLUSION: Dengzhanxixin injection on the basis of conventional treatment can improve the efficacy of the treatment of unstable angina pectoris. However, due to the sample size of included studies were small and of lower quality, conclusions above still need high-qualitied randomized, double-blind, controlled trials be confirmed.

[Meta-analysis of Shenmai injection treatment for acute myocardial infarction].

OBJECTIVE: To assess the efficacy and safety of Shenmai injection for acute myocardial infarction (AMI). METHOD: All clinical studies of Shenmai for AMI were searched from Cochrane library, Medline, EMbase, CBM, CNKI, Wanfang and VIP. For efficacy analysis of Shenmai, randomized controlled trials (RCTs) and quasi-RCTs were included and the Cochrane Collaboration's RevMan 5.1 was used for data analysis. RESULT: 1) Fifty studies were included for efficacy analysis, in which, only 1 study was true RCT, all of studies did not mention allocation concealment, blind and information of loss to follow-up. The fatality rate during hospitalization (OR 0.43, 95% CI [0.31-0.60]), incidence of heart failure (OR 0.49, 95% CI [0.34-0.70]), incidence of shock (OR 0.53, 95% CI[0.30-0.93]) and incidence of re-infarction (OR 0.16, 95% CI [0.03-0.77]) in Shenmai injection plus conventional treatment group was lower than that in the conventional treatment group, while the rate of recanalization (OR 1.24, 95% CI [0.90-1.71]) was similar between the two groups. 2) For safety analysis, we did not found serious adverse drug reaction/adverse events (ADR/AE) of Shenmai injection for AMI. CONCLUSION: The currently available evidence showed that Shenmai injection plus conventional treatment group may decrease the fatality rate during hospitalization, the incidence of cardiac failure, shock and re-infarction. However, these findings should be carefully interpreted due to the low methodological quality and small sample size of trials. Although serious ADR/AE was did not report of Shenmai injection, the post-marketing safety evaluation is need to be performed.

[Systematic review of Shuxuetong injection for progressive ischaemic stroke].

OBJECTIVE: To assess the clinical efficacy and safety of Shuxuetong injection against progressive ischaemic stroke. METHOD: Randomized controlled trials (RCTs) and quasi randomized controlled trials (quasi-RCTs), which focused on treating patients with progressive ischaemic stroke using Shuxuetong injection were identified from Cochrane library, Medline, EMbase, CBM database, CNKI database, VIP database and Wanfang database. Data was extracted and evaluated with designed form. RevMan 5.1 software was used for data analysis. RESULT: Eleven RCTs with 972 patients were included in this review. Only one research reported the mortality rate. None of the trials mentioned dependency of the patients during the follow-up period. The results of Meta analysis were listed as follows. Compared with normal treatment measures, total effective rate of 11 RCTs suggested that Shuxuetong were more effective with OR 4.46, 95% CI [3.02-6.59]. A greater difference in patients using Shuxuetong injection was found in 7 RCTs about the NDS with MD 5.86, 95% CI [4.80-6.93], compared with normal treatment measures. Researches with ADR/AE information of Shuxuetong injection showed that the symptoms of ADR/AE were moderate. CONCLUSION: Conclusions from this review may have a high risk of bias because of the low quality of the researches, hence it was not adequate to draw any reliable conclusions about the efficacy of Shuxuetong injection in progressive ischaemic stroke. More trials with high quality are required in the following researches.