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Background: Previous studies have implicated childhood trauma and abnormal brain-derived neurotrophic factor in the pathogenesis of schizophrenia. Here, we explored whether brain-derived neurotrophic factor levels mediated the relationship between childhood trauma and psychopathological symptoms in patients with first-episode schizophrenia. Methods: Patients with first-episode schizophrenia (n = 192) and healthy controls (n = 136) were enrolled. Childhood traumatic experiences and psychopathology were assessed by Childhood Trauma Questionnaire and Positive and Negative Syndrome Scale, respectively. Enzyme-linked immunosorbent assay was used to quantify brain-derived neurotrophic factor levels. Results: The patients with first-episode schizophrenia experienced more severe childhood trauma and had lower serum brain-derived neurotrophic factor levels than healthy controls. Emotional abuse and Childhood Trauma Questionnaire total score showed positive correlation with Positive and Negative Syndrome Scale positive, general psychopathological subscore and total score. Emotional neglect showed positive correlation with Positive and Negative Syndrome Scale positive subscore. Physical neglect was positively associated with Positive and Negative Syndrome Scale negative subscore. Emotional neglect and Childhood Trauma Questionnaire total score were negatively correlated with serum brain-derived neurotrophic factor levels. The serum brain-derived neurotrophic factor levels mediated the relationship between both Childhood Trauma Questionnaire total score and Positive and Negative Syndrome Scale total score and negative symptoms in the patients. The brain-derived neurotrophic factor levels also mediated the relationship between emotional neglect and Positive and Negative Syndrome Scale total score in the patients. Conclusion: Childhood trauma might contribute to the clinical symptoms of schizophrenia by affecting brain-derived neurotrophic factor levels. Perhaps we can prevent schizophrenia by reducing childhood traumatic experiences. [ABSTRACT FROM AUTHOR]

Purpose: Low-dose rivaroxaban is often given to patients with atrial fibrillation (AF) around the world, but the rationale for its use remains unclear. We aimed to compare the efficacy and safety of standard- or low-dose rivaroxaban in patients with AF through systematic review of literature with meta-analysis. Methods: We searched PubMed, Web of Science, EMBASE, Clinical Trials.gov, the Cochrane Library, and Bayer trial website from inception of each database until June 2020. Randomized controlled trials (RCTs) and cohort studies were included in the meta-analysis. A random-effects model was employed to calculate the pooled effect estimates. Results: Two RCTs and 17 cohort studies were included in the qualitative analysis. Indirect comparison of RCTs showed no significant difference between the two rivaroxaban dosages in risk of efficacy or safety outcomes (p > 0.05). Indirect comparison of cohort studies showed a lower risk of MACE among Caucasians in standard-dose group (HR 0.779; 95% CI 0.687–0.884; p < 0.001). Bleeding outcomes did not differ significantly between the two dosage regimens in Asian or Caucasian populations, except that the standard dose was associated with higher risk of major bleeding among elderly Caucasian patients (HR 1.329; 95% CI 1.141–1.547; p < 0.001). The quality of evidence was rated ranging from very low to low for all the efficacy and safety outcomes. Conclusion: In Caucasians with AF, standard-dose rivaroxaban may prevent MACE significantly better than low-dose treatment. Further studies in Asians are needed to verify the advantages of the standard dose. [ABSTRACT FROM AUTHOR]

Background: Due to the high risk of ischemic and arterial or venous bleeding events in atrial fibrillation (AF) or venous thromboembolism (VTE) patients with renal impairment (RI), selection of appropriate anticoagulant regimen is important. Therefore, we systematically reviewed and compared the safety and effects of oral anticoagulants in AF and VTE patients with RI. Methods: Eligible articles were identified through a literature search in PubMed, Embase, ClinicalTrials.gov, and the Cochrane Library for studies published between January 2008 and November 2020. Network meta-analysis was conducted with STATA 14.0 to analyze the effects and safety of each drug with regard to different levels of renal function. Results: 15 studies including 82,931 patients (76,957 with AF and 5974 with VTE) were analyzed. Compared with those of warfarin, the risk ratios of effect and safety outcomes of apixaban were 0.70 (95% confidence interval [CI] 0.60–0.82) and 0.56 (95% CI 0.42–0.76) in AF patients and 0.33 (95% CI 0.19–0.59) and 0.95 (95% CI 0.68–1.34) in VTE patients. Apixaban had the first or second highest probability of being ranked first with respect to surface under the cumulative ranking curve (SUCRA) scores in the prevention of major bleeding events, while in the prevention of ischemic events, rivaroxaban showed a higher SUCRA score (0.78–0.92) in mild RI patients and dabigatran showed a higher SUCRA value (0.90–0.99) in moderate RI patients. Conclusions and Relevance: In the systematic review and meta-analysis, for AF or VTE patients with RI, direct oral anticoagulants performed comparably to or better than warfarin with regard to safety and effects. The network meta-analysis indicated that for patients with mild RI, apixaban might be safer for patients with a lower risk of ischemic events, while rivaroxaban might be suitable for patients with a lower risk of bleeding events. For patients with moderate RI, apixaban could reduce the risk of ischemic events without increasing the risk of bleeding events. For AF patients with severe RI, apixaban, rivaroxaban, and warfarin showed a similar effect. These results might provide suggestions for clinical arterial and venous thrombosis prevention. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to detail the characteristics of chemotherapy-related acute kidney injury (CR-AKI) and investigate its effect on patient outcomes. Methods: This is a multicenter cross-sectional study of cancer patients with CR-AKI screened from hospital-acquired adult AKI patients based on a nationwide AKI survey in China. Results: Of the 3468 patients with hospital-acquired AKI, 258 cases of CR-AKI were identified. Of the patients, 20.1% (52/258) were ≥ 70 years old. Among the 258 CR-AKI cases, 61 (23.6%) reached AKI stage 3, and 75 (29.1%) reached AKI stage 2. The remaining 122 (47.3%) remained at AKI stage 1. A total of 413 chemotherapeutic agents were related to AKI, of which platinum compounds (24.5%, 101/413) were the most common. In-hospital mortality was 14.7% (38/258), and the rate of AKI non-recovery was 48.3% (100/207). AKI stage 3 (OR 2.930, 95% CI 1.156–7.427) and age ≥ 70 years (OR 3.138, 95% CI 1.309–7.519) were independent risk factors for in-hospital death. Compared to stage 2 or 3 AKI cases, a higher proportion of patients with stage 1 AKI did not recover their renal function (57.1% vs. 41.4% vs. 36.4%, P = 0.032). More AKI episodes were not recognized in patients with stage 1 AKI compared with the other two groups (82.8% vs. 60.0% vs. 36.1%, P < 0.001). Conclusions: CR-AKI accounted for a noteworthy proportion of hospital-acquired AKI, and severe CR-AKI increased in-hospital mortality. Mild CR-AKI was more likely to be overlooked, and sustained kidney injury was common in this situation. Recognizing CR-AKI at an early stage and personalizing treatment should be emphasized in those undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: The association between plasma magnesium and risk of incident cancer remains inconclusive in previous studies. We aimed to investigate the prospective relationship of baseline plasma magnesium concentrations with the risk of incident cancer and to examine possible effect modifiers. Methods: A nested case-control study with 228 incident cancer cases and 228 matched controls was conducted using data from the China Stroke Primary Prevention Trial (CSPPT), a randomized, double-blind, controlled trial, conducted from May 2008 to August 2013. Study outcomes included incident cancer and its subtypes. Results: When plasma magnesium concentrations were assessed as quartiles, a significantly higher incident risk of total cancer was found in participants in quartile 1 (<0.76 mmol/L; odds ratio [OR] = 2.70; 95% CI: 1.33–5.49) and quartile 4 (≥0.89 mmol/L; OR = 2.05; 95% CI: 1.12–3.76), compared with those in quartile 3 (0.83 to <0.89 mmol/L). In cancer site-specific analyses, similar trends were found for gastrointestinal cancer, esophageal cancer, gastric cancer, breast cancer, lung cancer, and other cancers. Furthermore, none of the variables, including age, sex, current smoking status, current alcohol intake, BMI, systolic blood pressure, and total cholesterol levels at baseline significantly modified the association between plasma magnesium and cancer risk. Conclusions: Both low and high plasma magnesium concentrations were significantly associated with an increased incident risk of cancer, compared with the reference concentrations of 0.83 to <0.89 mmol/L among hypertensive adults. [ABSTRACT FROM AUTHOR]

Background: Acromegaly is a rare, chronic and severe disease. Drug therapy including somatostatin analogues (SAs), dopamine receptor agonists and growth hormone receptor antagonists (pegvisomant, PEG) are commonly used to treat patients who do not respond to surgery. The use of combination therapy with PEG and SAs has become more common over the last decade. We performed this study to accurately evaluate the effect of combination therapy of SAs with PEG on acromegalic patients. Methods: PubMed, EMBASE, The Cochrane Library, ClinicalTrials.gov, Scopus, Web of Science, Chinese Biomedical Literature Database and Trip database were searched for relevant studies. Prospective clinical trials treating acromegaly with the co-administration of SAs and PEG were included. We performed a meta-analysis by using Stata 12.1. Sensitivity analysis was conducted to explore heterogeneity. Results: Nine studies were included in this meta-analysis. The overall rate of serum insulin-like growth factor 1 (IGF-1) normalization was 66% (95% CI: 52–78%; I2 = 62.59%). The combination therapy did not significantly change patients' fasting plasma glucose (ES: 0.011 mmol*L− 1; 95% CI: − 0.374 to 0.397 mmol*L− 1; P = 0.954) or glycosylated haemoglobin (ES: − 0.074%; 95% CI: − 0.166 to 0.315%; P = 0.544) while decreasing the fasting plasma insulin (ES: − 21.487 pmol*L-1; 95% CI: − 35.713 to − 7.260 pmol*L-1; P = 0.003). Elevation of liver enzyme levels was found in 14% (95% CI: 8 to 21%) of the patients. There was no significant difference for serious adverse events and treatment discontinuation due to adverse event between SAs monotherapy group and combination therapy group. Conclusions: Combined therapy of SAs and PEG effectively normalized IGF-1 levels in most of the patients whose IGF-1 level was greater than the upper limit of normal after high dose SAs monotherapy. The therapy also decreased significantly FPI levels with a neutral effect on glucose parameters in acromegaly patients. Moreover, elevated liver enzyme levels were observed in a small number of patients, which suggests a need for liver function monitoring. Trial registration: We have our protocol registered in PROSPERO. (Registration number: CRD42019115549). [ABSTRACT FROM AUTHOR]