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Background and Purpose The present study aimed to compare the efficacy and tolerability of different blood pressure (BP)-lowering strategies.Methods Randomized controlled trials that compared various antihypertensive treatments and stroke outcomes were included. Eligible trials were categorized into three scenarios: single or combination antihypertensive agents against placebos; single or combination agents against other agents; and different BP-lowering targets. The primary efficacy outcome was the risk reduction pertaining to strokes. The tolerability outcome was the withdrawal of drugs, owing to drug-related side effects (PROSPERO registration number CRD42018118454 [20/12/2018]).Results The present study included 93 trials (average follow-up duration, 3.3 years). In the pairwise analysis, angiotensin-converting enzyme inhibitors (ACEis) and beta-blockers (BBs) were inferior to calcium channel blockers (CCBs) (odds ratio [OR], 1.123; 95% confidence interval [CI], 1.008 to 1.252) (OR, 1.261; 95% CI, 1.116 to 1.425) for stroke prevention, BB was inferior to angiotensin II receptor blockers (ARB) (OR, 1.361; 95% CI, 1.142 to 1.622), and diuretics were superior to ACEi (OR, 0.871; 95% CI, 0.771 to 0.984). The combination of ACEi+CCB was superior to ACEi+diuretic (OR, 0.892; 95% CI, 0.823 to 0.966). The network meta-analysis confirmed that diuretics were superior to BB (OR, 1.34; 95% CI, 1.11 to 1.58), ACEi+diuretic (OR, 1.47; 95% CI, 1.02 to 2.08), BB+CCB (OR, 2.05; 95% CI, 1.05 to 3.79), and renin inhibitors (OR, 1.87; 95% CI, 1.25 to 2.75) for stroke prevention. Regarding the tolerability profile, the pairwise analysis revealed that ACEi was inferior to CCB and less tolerable, compared to the other treatments.Conclusions Monotherapy using diuretics, CCB, or ARB, and their combinations could be employed as first-line treatments for stroke prevention in terms of efficacy and tolerability.

To examine and compare fully-automated and manually measured corneal nerve fiber parameters in type 2 diabetes mellitus (T2DM) patients with and without diabetic peripheral neuropathy (DPN).A total of 128 T2DM subjects and 24 healthy controls underwent neuropathy assessment and bilateral corneal confocal microscopy (CCM). Five representative nerve fiber images were selected for each participant and analyzed manually and with fully-automated software. Corneal nerve fiber length (CNFL), branch density (CNBD), and fiber density (CNFD) were examined.Manual and full-automated methods for the whole cohort were significantly positive correlated for CNFL, CNBD and CNFD (r = 0.818, 0.845, 0.457, all P 0.001). Analysis of agreement between the two measurements using Bland-Altman method showed a bias of 2.05 mm/mmThis study demonstrated strong correlations between manual and fully-automated CNFL and CNBD, but not CNFD. Fully-automated corneal nerve fiber parameter quantification may be a fast, objective way to detect DPN.

Objective: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury. Data Sources: Key terms were “stroke”, “brain diseases”, “brain injuries”, “brain hemorrhage, traumatic”, “acute brain injury”, “dizocilpine maleate”, “dizocilpine”, “MK-801”, “MK801”, “rat”, “rats”, “rattus” and “murine”. PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform (VJIP) and SinoMed databases were searched from their inception dates to March 2018. Data Selection: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments. Outcome Measures: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury. Results: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume (34 studies, n = 966, MD = −58.31, 95% CI: −66.55 to −50.07; P < 0.00001) and degree of cerebral edema (5 studies, n = 75, MD = −1.21, 95% CI: −1.50 to −0.91; P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test (2 studies, n = 60, MD = −10.88, 95% CI: −20.75 to −1.00; P = 0.03) and neurological function 24 hours after brain injury (11 studies, n = 335, MD = −1.04, 95% CI: −1.47 to −0.60; P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models (34 studies, n = 966, MD = −58.31, 95% CI: −66.55 to −50.07; P = 0.004). Further network analysis showed that 0–1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model. Conclusion: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.

Obstructive sleep apnea (OSA) is associated with increased levels of systemic inflammatory markers, increased arterial stiffness, and endothelial dysfunction, which may lead to increased cardiovascular risk. We aimed to quantify the effects of continuous positive airway pressure (CPAP) on cardiovascular biomarkers and to establish predictors of response to CPAP. We searched PubMed and the Cochrane Library from inception to May 31, 2017. Randomized controlled trials (RCTs) assessing the efficacy of CPAP on high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor- alpha (TNF-α), augmentation index (AIx), pulse wave velocity (PWV), and flow-mediated dilatation (FMD) in patients with OSA were selected by consensus. We included 15 RCTs comprising 1090 patients in the meta-analysis. The pooled standard mean difference (SMD) of effect of CPAP on hs-CRP was − 0.64 (95% confidence interval (CI) − 1.19 to − 0.09; P = 0.02). CPAP was associated with a reduction in AIx of 1.53% (95% CI, 0.80 to 2.26%; P

To evaluate the efficacy of corneal confocal microscopy (CCM) as a non-invasive test to assess diabetic peripheral neuropathy in Chinese patients diagnosed with type 2 diabetes.Diabetic distal symmetric polyneuropathy (DSPN) and its severity degrees were assessed based on the modified Toronto diagnostic criteria in 128 patients with type 2 diabetes (No DSPN [n = 49], mild DSPN [n = 43], moderate-to-severe DSPN [n = 36]) and 24 age-matched controls. CCM was also examined in all enrolled subjects. Corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD) and corneal nerve fiber density (CNFD) were analyzed by Fiji imaging analysis software. The efficacy of CCM as a non-invasive test to assess diabetic peripheral neuropathy was determined.CNFL was 17.99 ± 0.66, 15.82 ± 0.64, 14.98 ± 0.63, and 12.49 ± 0.93 in healthy controls, T2DM patients with no, mild, and moderate-to-severe DPN, respectively. CNFL in type 2 diabetes patients with no, mild, and moderate-to-severe DSPN demonstrated a significant reduction than in healthy controls (P = .012, .003 and.001, respectively). CNFL in patients with moderate-to-severe DSPN was significantly shorter than in patients with no or mild DSPN (P .001 and .004, respectively). CNBD was 41.48 ± 3.35, 33.02 ± 2.50, 30.91 ± 2.33, and 18.00 ± 2.33 in healthy controls, T2DM patients with no, mild, and moderate-to-severe DPN, respectively. CNBD in healthy control was significantly higher than in type 2 diabetes patients with no, mild, and moderate-to-severe DSPN (P = .036, 0.016 and .001, respectively). CNBD in patients with moderate-to-severe DSPN was significantly lower than in patients with no or mild DSPN (P .001 for both). CNFD was 35.32 ± 1.18, 35.68 ± 1.10, 34.54 ± 1.12, and 32.28 ± 1.76 in healthy controls, T2DM patients with no, mild, and moderate-to-severe DPN, respectively. CNFD did not differ among the four groups. In an analysis that divided CNFL, CNFD and CNBD into quartiles, there were no significant differences in electromyography findings and vibration perception threshold among the 4 groups; however, significant differences were seen in the positive distribution of temperature perception measurements following CNFL and CNBD stratification (P = .001 and .001, respectively).CCM might be a non-invasive method for detecting DSPN and its severity degree in Chinese patients diagnosed with type 2 diabetes.

This article is the series of methodology of clinical prediction model construction (total 16 sections of this methodology series). The first section mainly introduces the concept, current application status, construction methods and processes, classification of clinical prediction models, and the necessary conditions for conducting such researches and the problems currently faced. The second episode of these series mainly concentrates on the screening method in multivariate regression analysis. The third section mainly introduces the construction method of prediction models based on Logistic regression and Nomogram drawing. The fourth episode mainly concentrates on Cox proportional hazards regression model and Nomogram drawing. The fifth Section of the series mainly introduces the calculation method of C-Statistics in the logistic regression model. The sixth section mainly introduces two common calculation methods for C-Index in Cox regression based on R. The seventh section focuses on the principle and calculation methods of Net Reclassification Index (NRI) using R. The eighth section focuses on the principle and calculation methods of IDI (Integrated Discrimination Index) using R. The ninth section continues to explore the evaluation method of clinical utility after predictive model construction: Decision Curve Analysis. The tenth section is a supplement to the previous section and mainly introduces the Decision Curve Analysis of survival outcome data. The eleventh section mainly discusses the external validation method of Logistic regression model. The twelfth mainly discusses the in-depth evaluation of Cox regression model based on R, including calculating the concordance index of discrimination (C-index) in the validation data set and drawing the calibration curve. The thirteenth section mainly introduces how to deal with the survival data outcome using competitive risk model with R. The fourteenth section mainly introduces how to draw the nomogram of the competitive risk model with R. The fifteenth section of the series mainly discusses the identification of outliers and the interpolation of missing values. The sixteenth section of the series mainly introduced the advanced variable selection methods in linear model, such as Ridge regression and LASSO regression.

Single nucleotide polymorphisms (SNPs) in the interleukin-17 (IL-17) gene have been shown to be correlated with susceptibility to cancer. However, various studies report different results of this association. The aim of the present work was to clarify the effects of IL-17A G197A (rs2275913) and IL-17F T7488C (rs763780) polymorphisms on cancer risk. We performed systematic searches of the PubMed and CNKI databases to obtain relevant publications. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association of rs2275913 and rs763780 polymorphisms with cancer risk. Data were extracted from the selected studies and statistical analysis was conducted using the STATA software. Our results indicated that rs2275913 and rs763780 polymorphisms significantly increase cancer risk, especially in gastric cancers. Subgroup analysis suggested the existence of a significant correlation between rs763780 polymorphism and cancer susceptibility in Caucasian populations. This updated meta-analysis confirms that rs2275913 and rs763780 polymorphisms are highly associated with increased risk for multiple forms of cancer.

Background Short-course preoperative radiation (SCRT) with delayed surgery was found to increase pathologic complete response (pCR) rates in several trials. However, there was no clear answer on whether SCRT or long-course chemo-radiotherapy (LCRT) is more effective. Therefore we conducted this meta-analysis to evaluate the safety and efficacy of SCRT versus LCRT, both with delayed surgery, for treatment of rectal cancer. Materials and methods The literature was searched from PubMed, EMBASE, Web of Science, Cochrane Library and clinicaltrials.gov up to November, 2014. Quality of the randomized controlled trials (RCTs) was evaluated according to the Cochrane's risk of bias tool of RCT. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to rate the level of evidence. Review Manager 5.3 was employed for statistical analysis. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. Results Three RCTs, with a total of 357 rectal cancer patients, were included in this systematic review. Meta- analysis results demonstrated there were no significantly differences in sphincter preservation rate, local recurrence rate, grade 3~4 acute toxicity, R0 resection rate and downstaging rate. Compared with SCRT, LCRT was associated with significant increase in the pCR rate [RR=0.49, 95%CI (0.31, 0.78), P=0.003]. Conclusions In terms of sphincter preservation rate, local recurrence rate, grade 3~4 acute toxicity, R0 resection rate and downstaging rate, SCRT with delayed surgery is as effective as LCRT with delayed surgery for management of rectal cancer. LCRT significantly increased pCR rate compared with SCRT. Due to risk of bias and imprecision, further multi-center large sample RCTs were needed to confirm this conclusion.

Introduction Although most prostate cancers initially respond to castration with luteinizing hormone- releasing analogues or bilateral orchiectomy, progression eventually occurs. Based on the exciting results of several randomized controlled trials (RCTs), it seems that patients with metastatic castration-resistant prostate cancer (mCRPC) might benefit more from treatment withabiraterone. Therefore we conducted a systematic review to evaluate the efficacy and toxicity of abiraterone in the treatment of mCRPC. Methods Literature was searched from Embase, PubMed, Web of Science, and Cochrane Library up to July, 2013. Quality of the study was evaluated according to the Cochrane's risk of bias of randomized controlled trial (RCT) tool, then the Grading of Recommendations Assessment, Development and Evaluation (GRADE) System was used to rate the level of evidence. Stata 12.0 was used for statistical analysis. Summary data from RCTs comparing abiraterone plus prednisone versus placebo plus prednisone for mCRPC were meta-analyzed. Pooled hazard ratios (HRs) for overall survival (OS), radiographic progression-free survival (RPFS) and time to PSA progression (TTPP); Pooled risk ratios (RR) for PSA response rate, objective response rate and adverse event were calculated. Results Ten trials were included in the systematic review; Data of 2,283 patients (1,343 abiraterone; 940 placebo) from two phase 3 trials: COU-AA-301 and COU-AA-302 were meta-analyzed. Compared with placebo, abiraterone significantly prolonged OS (HR, 0.74; 95% confidence interval [CI], 0.66 to 0.84), RPFS (HR, 0.59; 95% CI, 0.48 to 0.74) and time to PSA progression (HR, 0.55; 95% CI, 0.43 to 0.70); it also significantly increased PSA response rate (RR, 3.63; 95% CI, 1.72 to 7.65) and objective response rate (RR, 3.05; 95% CI, 1.51 to 6.15). This meta-analysis suggested that the adverse events caused by abiraterone are acceptable and can be controlled. CONCLUTIOS: Abiraterone significantly prolonged OS, RPFS and time to progression patients with mCRPC, regardless of prior chemotherapy or whether chemotherapy-naive, and no unexpected toxicity was evident. Abiraterone can serve as a new standard therapy for mCRPC.

BackgroundRebleeding is a serious complication of aneurysmal subarachnoid hemorrhaging. To date, there are conflicting data regarding the factors contributing to rebleeding and their significance.MethodsA systematic review of PubMed and Embase databases was conducted for studies pertaining to aneurysmal subarachnoid hemorrhage (aSAH) and rebleeding in order to assess the associated risk factors. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated from fourteen studies comprised of a total of 5693 patients that met the inclusion criteria.ResultsHigher rebleeding rates were observed < 6 h after the initial aSAH (OR = 3.22, 95% CI = 1.46-7.12), and were associated with high systolic blood pressure (OR = 1.93, 95% CI = 1.31-2.83), poor Hunt-Hess grade (III-IV) (OR = 3.43, 95% CI = 2.33-5.05), intracerebral or intraventricular hematomas (OR = 1.65, 95% CI = 1.33-2.05), posterior circulation aneurysms (OR = 2.15, 95% CI = 1.32-3.49), and aneurysms >10 mm in size (OR = 1.70, 95% CI = 1.35-2.14).ConclusionsAneurysmal rebleeding occurs more frequently within the first 6 hours after the initial aSAH. Risk factors associated with rebleeding include high systolic pressure, the presence of an intracerebral or intraventricular hematoma, poor Hunt-Hess grade (III-IV), aneurysms in the posterior circulation, and an aneurysm >10 mm in size.

Chemotherapy plays a critical and venturous role against the co-morbidity of nonsmall cell lung cancer and interstitial lung disease (NSCLC-ILD).We performed a Bayesian meta-analysis and systematic review to evaluate the safety and efficacy of the chemotherapy in NSCLC-ILD patients.EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov (up to January 2015).We included all study designs except case reports, all studies with NSCLC-ILD patients and all the possible chemotherapy regimens.Quality was assessed by a components approach. We derived summary estimates using Bayesian method through WinBUGS (version 1.4.3, MRC Biostatistics Unit, Cambridge, UK).Seven studies involving 251 patients with NSCLC-ILD were included in the meta-analysis. The treatment response (complete remission, 0; [partial remission, 39.1%; 95% credible interval [CrI], 32.6-45.7]; [stable disease, 36%; 95% CrI, 29.6-42.2]; [PD, 15.4%; 95% CrI, 11.3-19.8]; [nonevaluable, 6.4%; 95% CrI, 2.7-10.1]; [overall response rate, 41.3%; 95% CrI, 35.3-47.4]; [disease control rate, 77.7%; 95% CrI, 72.2-82.7]) were comparable to that of patients with NSCLC alone; the survival outcomes (median overall survival, median progression-free survival, and 1-year survival rate) were slightly worse, especially the lower 1-year survival rate. Platinum-based doublets as first-line chemotherapy may be related to higher incidence of acute exacerbation-ILD in first line chemotherapy (AE, 8.47%; 95% CrI, 5.04-12.6).The data selection bias and small patient number make the meta-analysis of treatment response and conclusions generated from these data inaccurate.The present meta-analysis suggests that chemotherapy might be an effective therapy for patients with NSCLC-ILD, but it might be associated with higher incidence of acute exacerbation.