Lactulose improves cognition, quality of life, and gut microbiota in minimal hepatic encephalopathy: A multicenter, randomized controlled trial.

OBJECTIVE: Lactulose is effective in the treatment and prevention of overt hepatic encephalopathy (OHE), but there are limited data on its use on microbiota in relations to minimal hepatic encephalopathy (MHE) recovery. The present study aimed to assess the efficacy of lactulose in recovery of MHE in aspects of cognitive function, quality of life, and impact on intestinal microbiota. METHODS: This multicenter, open-label randomized controlled trial was conducted in 11 teaching hospitals in China. Participants were randomly allocated on a 2:1 basis to receive lactulose (Gp-L) or no therapy as control (Gp-NL) for 60 days. The primary endpoint was the MHE reversal rate. Gut microbiota were compared between MHE patients and healthy volunteers, as well as lactulose-responders and non-responders. RESULTS: A total of 98 cirrhotic patients were included in the study, with 31 patients in the Gp-NL group and 67 patients in the Gp-L group. At day 60, the MHE reversal rate in Gp-L (64.18%) was significantly higher than that in Gp-NL (22.58%) (P = .0002) with a relative risk of 0.46 (95% confidence interval 0.32-0.67). Number needed to treat was 2.4. Further, there was significantly more improvement in physical functioning in Gp-L (4.62 ± 6.16) than in Gp-NL (1.50 ± 5.34) (P = .0212). Proteobacteria was significantly higher in MHE patients compared with healthy volunteers (12.27% vs 4.65%, P < .05). Significant differences were found between lactulose responders and non-responders in Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. CONCLUSIONS: Treatment with lactulose significantly improves MHE recovery rate, and gut microbiota change in MHE patients can modulate the effectiveness of this therapy. Chinese Clinical Trial Register (ChiCTR) (ID: ChiCTR-TRC-12002342).

Elderly population have a decreased aneurysmal subarachnoid hemorrhage incidence rate than Middle aged population: a descriptive analysis of 8,144 cases in mainland China.

PURPOSE: Rupture of an intracranial aneurysm is a life-threatening acute cerebrovascular event. The purpose of this study was to investigate whether aneurysmal subarachnoid haemorrhage (SAH) incidence rate is higher or lower in elderly population than in middle aged population. MATERIALS AND METHODS: Aneurysmal SAH cases were collected retrospectively from the archives of 21 hospitals in Mainland China. All the cases were collected from September 2016 and backward consecutively for a period of time up to 8 years. SAH was initially diagnosed by brain computed tomography (CT). CT angiography (CTA) or digital subtraction angiography (DSA) was followed and SAH was confirmed to be due to cerebral aneurysm rupture. For cases when multiple bleeding occurred, the age of the first SAH was used in this study. The total incidence from all hospitals at each age group were summed together for females and males respectively; then adjusted by the total population number at each age group for females and males which was from the 2010 population census of the People's Republic of China. RESULTS: In total there were 8,144 cases of intracranial aneurysmal SAH, with 4,861 females and 3,283 males. For females the relative aneurysmal SAH incidence rate started to decrease after around 65 years old, while for males the relative aneurysmal SAH incidence rate started to decrease after around 53 years old. CONCLUSION: Our data tentatively suggest elderly patients may be at a reduced risk of rupture compared with patients who are younger while have similar other risk factors.

Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial.

BACKGROUND: Increased oxidative stress and inflammation has a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Drugs with antioxidant and anti-inflammatory properties, such as N-acetylcysteine, might provide a useful therapeutic approach for COPD. We aimed to assess whether N-acetylcysteine could reduce the rate of exacerbations in patients with COPD. METHODS: In our prospective, randomised, double-blind, placebo-controlled, parallel-group study, we enrolled patients aged 40-80 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <0·7 and FEV1 of 30-70% of predicted) at 34 hospitals in China. We stratified patients according to use of inhaled corticosteroids (regular use or not) at baseline and randomly allocated them to receive N-acetylcysteine (one 600 mg tablet, twice daily) or matched placebo for 1 year. The primary endpoint was the annual exacerbation rate in patients who received at least one dose of study drug and had at least one assessment visit after randomisation. This study is registered with the Chinese Clinical Trials Registry, ChiCTR-TRC-09000460. FINDINGS: Between June 25, 2009, and Dec 29, 2010, we screened 1297 patients, of whom 1006 were eligible for randomisation (504 to N-acetylcysteine and 502 to placebo). After 1 year, we noted 497 acute exacerbations in 482 patients in the N-acetylcysteine group who received at least one dose and had at least one assessment visit (1·16 exacerbations per patient-year) and 641 acute exacerbations in 482 patients in the placebo group (1·49 exacerbations per patient-year; risk ratio 0·78, 95% CI 0·67-0·90; p=0·0011). N-acetylcysteine was well tolerated: 146 (29%) of 495 patients who received at least one dose of N-acetylcysteine had adverse events (48 serious), as did 130 (26%) of 495 patients who received at least one dose of placebo (46 serious). The most common serious adverse event was acute exacerbation of COPD, occurring in 32 (6%) of 495 patients in the N-acetylcysteine group and 36 (7%) of 495 patients in the placebo group. INTERPRETATION: Our findings show that in Chinese patients with moderate-to-severe COPD, long-term use of N-acetylcysteine 600 mg twice daily can prevent exacerbations, especially in disease of moderate severity. Future studies are needed to explore efficacy in patients with mild COPD (GOLD I). FUNDING: Hainan Zambon Pharmaceutical.

The efficacy and safety of arsenic trioxide with or without all-trans retinoic acid for the treatment of acute promyelocytic leukemia: a meta-analysis.

Arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) could induce apoptosis and differentiation in acute promyelocytic leukemia (APL) cells, respectively, thus the possibility of synergism between them was raised. This meta-analysis assessed the effectiveness and safety of ATO combined with ATRA in the treatment of APL. Compared with ATO alone, induction therapy with ATO/ATRA significantly increased the complete remission (CR) rate (RR: 1.08, 95% CI: 1.00-1.17, P=0.04), shortened the time to achieve CR (WMD: -6.51, 95% CI: -11.32 to -1.70, P=0.008), and improved the molecular remission rate after consolidation therapy (RR: 1.74, 95% CI: 1.14-2.66, P=0.01) and the 1-year disease-free survival rate (RR: 1.22, 95% CI: 1.00-1.50, P=0.05). There were no statistically significant differences between two treatments in terms of early death and main adverse events. These results suggested that ATO/ATRA could synergistically improve the overall outcome of newly diagnosed and relapsed APL patients, supporting the use of ATO/ATRA as an effective treatment for all APL patients previously untreated with ATO.

Atropine in ameliorating the progression of myopia in children with mild to moderate myopia: a meta-analysis of controlled clinical trials.

OBJECTIVES: Myopia is the most common ocular disorder associated with increasing risk for chorioretinal degeneration, retinal detachment, and other vision-threatening abnormalities worldwide. Recently, atropine has been becoming a focus of attention due to its role in ameliorating the myopia progression in children. This meta-analysis was conducted to address the efficacy and safety of atropine on myopia in children and the dose-response relationship between atropine and annual rate of myopia progression. METHODS: Controlled clinical trials were retrospectively analyzed to compare atropine and placebo for the treatment of myopia. The primary outcome measure was annual rate of myopia progression after daily atropine application over 1 year. Data were extracted from 6 randomized clinical trials and analyzed using standard meta-analysis and meta-regression methods. RESULTS: Comparing with placebo, the effect size of atropine for retarding myopia progression was 0.773 diopters (D)/year [95% confidence interval (CI): 0.699-0.848]. Regression model, -0.728+1.281log (dose+1), revealed the dose-response relationship between atropine and myopia progression. The estimate of effect for 0.05%, 0.1%, and 0.25% atropine was -0.665 (95% CI: -1.070 to -0.260), -0.606 (95% CI: -0.967 to -0.245), and -0.442 (95% CI: -0.701 to -0.183) D/year respectively, whereas that for 0.5% and 1% was -0.208 (95% CI: -0.435-0.018) and 0.160 (95% CI: -0.293-0.613), respectively, suggesting that myopia might deteriorate at low dose of atropine but not at 0.5% atropine and 1% atropine within the duration of 6-24 months. No serious adverse event was reported during the period of treatment. The major adverse reactions associated with 0.5% and 1% atropine were photophobia, glare, and recurrent allergic blepharitis. Photochromatic lenses or sunglasses with ultraviolet protection could be used to minimize the glare and photophobia. CONCLUSION: In summary, 0.5% and 1% atropine was demonstrated to be effective and safe to ameliorate myopia progression in childhood with low-to-moderate myopia.

Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis.

The objective of this study was to provide an updated meta-analysis of the efficacy and safety of huperzine A (HupA) in Alzheimer's disease (AD). We searched for randomized trials comparing HupA with placebo in the treatment of AD. The primary outcome measures were mini-mental state examination (MMSE) and activities of daily living scale (ADL). Data were extracted from four randomized clinical trials and analyzed using standard meta-analysis and meta-regression methods. Oral administration of HupA for 8-24 weeks (300-500 microg daily) led to significant improvements in MMSE and ADL. The results of meta-regression showed that the estimated effect size of MMSE and ADL was increased over the treatment time. Most adverse events were cholinergic in nature and no serious adverse events occurred. Huperzine A is a well-tolerated drug that could significantly improve cognitive performance and ADL in patients with AD.

Is acupuncture beneficial in depression: a meta-analysis of 8 randomized controlled trials?

BACKGROUND: Depression is one of the most common mental health disorders. Acupuncture is a popular complementary and alternative medicine intervention suggested in the treatment of depression, but its effectiveness is uncertain. This updated meta-analysis was conducted to more precisely assess the beneficial effect of acupuncture in depression therapy. METHODS: The following databases were searched: MEDLINE, EMBASE, BIOSIS, Cochrane Central Register of Controlled Trials, and Chinese Scientific Journal Database. The following terms were used: acupuncture, acupressure, depression, depressive disorder, clinical trial, and randomized controlled trial. RESULTS: Eight small-randomized controlled trials comparing 477 subjects were included in the meta-analysis. Our results confirmed that acupuncture could significantly reduce the severity of depression, which was indicated by decreased scores of Hamilton rating scale for depression (HAMD) or Beck Depression Inventory (BDI). The pooled standardized mean difference of the 'Improvement of depression' was -0.65 (95% CI -1.18, -0.11; P=0.02) by random effect model. However, no significant effect of active acupuncture was found on the response rate (RR 1.32, 95% CI 0.83 to 2.10; P=0.25) and remission rate (RR 1.30, 95% CI 0.57 to 2.95; P=0.53). CONCLUSION: Although this meta-analysis might be discounted due to the low quality of individual trials, it supported that acupuncture was an effective treatment that could significantly reduce the severity of disease in the patients with depression. More full-scale randomized clinical trials with reliable designs are recommended to further warrant the effectiveness of acupuncture.