Vagus nerve stimulation paired with rehabilitation for motor function, mental health and activities of daily living after stroke: a systematic review and meta-analysis.

OBJECTIVE: Vagus nerve stimulation (VNS) plus rehabilitation (Rehab) has shown a potential effect on recovery with a stroke. We systematically synthesised studies examining VNS+Rehab for improving motor function, mental health and activities of daily living (ADL) postintervention and at the end of follow-up in patients with a stroke. METHODS: The search was performed in electronic databases EMBASE, Medline, EBSCO, Cochrane Library, PubMed, PsycINFO, CINAHL, CNKI, and WANFANG and three clinical trial registries from inception to February 2022. Randomised controlled trials (RCTs) applied VNS+Rehab in stroke were included. RESULTS: Seven RCTs involving 263 (analysed) participants was included. The effect size of VNS+Rehab over Rehab for motor function was medium postintervention (g=0.432; 95% CI 0.186 to 0.678) and large at the end of follow-up (g=0.840; 95% CI 0.288 to 1.392). No difference was found in the effect of VNS+Rehab over traditional rehabilitation for ADL, mental health or safety outcomes. Subgroup analyses revealed larger effects for patients received taVNS (transcutaneous auricular VNS) devices (at acute/subacute phase of stroke, with lower VNS stimulation frequency or pluses per session, greater VNS on-off time or sessions, higher VNS intervention weekly frequency). CONCLUSION: The results suggest VNS+Rehab showed better motor function outcomes in patients after stroke, while no better than Rehab on mental health or ADL. Combinations of phase of stroke, specific parameters of VNS and VNS intervention frequency are key modulators of VNS effects. TRIAL REGISTRATION NUMBER: CRD42022310194.

Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis.

OBJECTIVE: Recently, several large randomised controlled trials about the treatments of cognitive impairment or dementia due to Parkinson's disease (CIND-PD or PDD) and dementia with Lewy bodies (DLB) were completed. Here, we systematically reviewed the studies (including the recent reports) to provide updated evidence for the treatments of CIND-PD, PDD and DLB. METHODS: We searched Cochrane Dementia and Cognitive Improvement Group Specialised Register, Pubmed, Embase, and other sources for eligible trials. We selected global impression and cognitive function as primary efficacy outcomes, and dropouts and adverse events as safety outcomes. Furthermore, Meta-analysis and trial sequential analysis (TSA) were used here. RESULTS: Ten trials were included in this study. Cholinesterase inhibitors and memantine produced small global efficacy on clinicians' global impression of change (CGIC), from a weighted mean difference of -0.40 (95% CI -0.77 to -0.03) to -0.65 (95% CI -1.28 to -0.01); however, cholinesterase inhibitors but not memantine significantly improved cognition on Mini-Mental State Examination (MMSE), from 1.04 (95% CI 0.43 to 1.65) to 2.57 (95% CI 0.90 to 4.23). Additionally, both of them had good safety outcomes, although rivastigmine showed an increased risk on adverse events than placebo (risk ratio, RR 1.19, TSA adjusted 95% CI 1.04 to 1.36), these events were usually mild or moderate, and the risk disappeared on serious adverse events. CONCLUSIONS: Cholinesterase inhibitors and memantine slightly improve global impression; however, only cholinesterase inhibitors enhance cognitive function. Besides, all the drugs have good safety outcomes. But the limited trials precluded the generalisation of these outcomes.

Lack of association between genetic polymorphisms of CYP3A4, CYP2C9 and CYP2C19 and antituberculosis drug-induced liver injury in a community-based Chinese population.

The precise pathogenic mechanism of antituberculosis (anti-TB) drug-induced liver injury (ATLI) is poorly understood. It may be associated with drug-metabolizing enzymes, such as cytochrome P450 (CYP) 3A4, CYP2C9 and CYP2C19. The aim of the present study was to explore the role of tagging single nucleotide polymorphisms (tSNPs) of CYP3A4, CYP2C9 and CYP2C19 in the risk of ATLI in a population-based anti-TB treatment cohort. A nested case-control study was designed. Each ATLI case was matched 1 : 4 with controls on the basis of age, gender, treatment history, disease severity and drug dosage. The tSNPs were selected using Haploview 4.2 based on the HapMap database of Han Chinese in Beijing and genotyped by TaqMan allelic discrimination technology. Eighty-nine patients with ATLI and 356 controls were included in the study. One tSNP in CYP3A4 (rs12333983), two in CYP2C9 (rs4918758, rs9332098) and two in CYP2C19 (rs11568732, rs4986894) were selected and genotyped. The minor allele frequencies of rs12333983, rs4918758, rs9332098, rs11568732 and rs4986894 were 36.0%, 41.4%, 1.1%, 5.7% and 35.7%, respectively, in the patients, compared with 31.7%, 42.9%, 3.4%, 8.9% and 35.1%, respectively, in the controls. No significant differences were observed in genotypes or allele frequencies of the five tSNPs between the two groups and none of the CYP2C9 or CYP2C19 haplotypes was significantly associated with the development of ATLI. Based on the Chinese anti-TB treatment cohort, we did not find a significant association between the risk of ATLI and genetic polymorphisms of CYP3A4, CYP2C9 and CYP2C19. None of the haplotypes exhibited a significant association with the development of ATLI in a Chinese tuberculosis population.

Development Trend of Infectious Disease Hospitals in China 2002-2018: A Longitudinal Analysis of National Survey Data.

BACKGROUND: Infectious disease hospitals (IDHs) play very important roles in the battle against the infectious disease. The present study aims to systematically analyze the development trends and possible problems of IDHs in China. METHODS: Most of the data came from the China Health Statistics Yearbook 2003-2019. Joinpoint Regression Model was used to analyze the development trends of IDHs between 2002 and 2018. RESULTS: From 2002 to 2018, the number of IDHs in China increased from 126 to 167, with an average annual percent change (AAPC) of 1.82%. The ratio of nurses to beds increased from 0.38 to 0.46 with the AAPC of 0.88%, and average business housing area per bed increased with an AAPC of 1.97%. The percentage of liabilities to total assets increased year by year and the percentage of medical business costs to total expenditure decreased. The segmented trend of daily visits per physician from 2014 to 2018 was stable, and the segmented trend of daily inpatients per physician from 2012 to 2018 decreased significantly. In 2017, the rates of surgical inpatients leaving the hospital without the doctor's advice and surgical inpatients mortality were higher than 2016. CONCLUSION: Although the development of IDHs was generally good in China, the scale of IDHs was generally small, the ability to respond to major emergencies was weak, the problem of irrational resource allocation was still prominent, and the operation of IDHs was facing a dilemma.

Clinical Significance of 4L Lymph Node Dissection in Left Lung Cancer.

PURPOSE: To investigate the prognostic impact of 4L lymph node (LN) dissection in left lung cancer and to analyze the relative risk factors for 4L LN metastasis. PATIENTS AND METHODS: We retrospectively collected data from 657 patients with primary left lung cancer who underwent surgical pulmonary resection from January 2005 to December 2009. One hundred thirty-nine patients underwent 4L LN dissection (4LD+ group); the other 518 patients did not receive 4L LN dissection (4LD- group). Propensity score weighting was applied to reduce the effects of observed confounding between the two groups. Study end points were disease-free survival (DFS) and overall survival (OS). RESULTS: The metastasis rate of station 4L was 20.9%, which was significantly higher than those of station 7 (14.0%; P = .048) and station 9 (9.8%; P < .001). Station 4L metastasis was associated with most other LN station metastases in univariate analysis, but only station 10 LN metastasis was an independent risk factor for 4L LN metastasis (odds ratio, 0.253; 95% CI, 0.109 to 0.588; P = .001) in multivariate logistic analysis. The 4LD+ group had a significantly better survival than the 4LD- group (5-year DFS, 54.8% v 42.7%; P = .0376; 5-year OS, 58.9% v 47.2%; P = .0200). After allowing potential confounders in multivariate survival analysis, dissection of 4L LN retained its independent favorable effect on DFS (hazard ratio, 1.502; 95% CI, 1.159 to 1.947; P = .002) and OS (hazard ratio, 1.585; 95% CI, 1.222 to 2.057; P = .001). Propensity score weighting further confirmed that the 4LD+ group had a more favorable DFS ( P = .0014) and OS ( P < .001) than the 4LD- group. CONCLUSION: Station 4L LN involvement is not rare in left lung cancer, and dissection of the 4L LN station seems to be associated with a more favorable prognosis as compared with those who did not undergo this dissection.

Association Between the MUC5B Promoter Polymorphism rs35705950 and Idiopathic Pulmonary Fibrosis: A Meta-analysis and Trial Sequential Analysis in Caucasian and Asian Populations.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. A number of studies reported the association between MUC5B promoter polymorphism rs35705950 and IPF, but substantial inconsistent findings were observed and the strength of association remains unclear.The aim of the study was to investigate the association between rs35705950 and IPF in different ethnic populations.PubMed, EMBASE, Web of Science, and CENTRAL were searched from their inception to April 15, 2015. Allelic and phenotypic comparisons were conducted separately, as were comparisons in Caucasian and Asian populations. A meta-analysis with trial sequential analysis was conducted.Nine studies presented in 7 full-text articles were included, encompassing 2733 IPF patients and 5044 controls. Six studies were carried out in the Caucasian population, and 3 in the Asian population. Minor T allele was associated with an increased risk of IPF compared with G allele (odds ratio [OR] 4.85, 95% confidence interval [CI] 3.79-6.21, P = 5.88 × 10), as were TG and TT genotypes compared with GG genotype (TG vs GG: OR 6.20, 95% CI 5.14-7.48, P = 1.70 × 10; TT vs GG: OR 11.29, 95% CI 5.69-22.40, P = 4.22 × 10), in an allele dose-dependent manner. These observations were confirmed in trial sequential analysis in both populations. The strength of association was more remarkable in the Caucasian population than in the Asian population, and no homozygous TT genotype was detected in the Asian population in our study.Our study revealed strong association between the MUC5B promoter rs35705950 polymorphism and the risk of IPF. The strength of association between rs35705950 minor T allele and IPF susceptibility was particularly evident in the Caucasian population, and milder but still significant in the Asian population.

Anti-inflammatory drugs and risk of Alzheimer's disease: an updated systematic review and meta-analysis.

BACKGROUND: In the past 20 years, substantial evidence from laboratory and epidemiologic studies have suggested that anti-inflammatory medications could defer or prevent the occurrence of Alzheimer's disease (AD). However, several studies do not corroborate these findings. OBJECTIVE: To evaluate the association of anti-inflammatory drug use on the incidence of AD. METHODS: Pubmed, Embase, and Cochrane Library databases were searched up to March 2014. Studies evaluating the association between use of anti-inflammatory drugs and AD risk were included. Relative risks (RRs) with 95% confidence intervals (CIs) were meta-analyzed using random effects models and were grouped by anti-inflammatory type and duration of drug use. RESULTS: In observational studies, use of non-steroidal anti-inflammatory drugs (NSAIDs) was significantly associated with a reduced risk of AD (RR, 0.72; 95%CI, 0.62-0.84) compared to no use of NSAIDs, especially in long term users (RR, 0.36; 95%CI, 0.17-0.74); the risks of AD were also lower in both aspirin (RR, 0.77; 95%CI, 0.63-0.95) and non-aspirin NSAID users (RR, 0.65; 95%CI, 0.47-0.88) compared with nonusers; whereas the use of corticosteroids showed no significant association (RR, 0.62; 95%CI, 0.26-1.46). In the single randomized controlled trial (RCT), NSAID use showed no significant effect on AD risk among dementia-free individuals (p > 0.05). CONCLUSION: Observational studies support the use of NSAIDs for prevention of AD, but RCT do not. Well-designed studies and innovative approaches are required to illuminate the exact relationship between NSAID use and AD risk. The appropriate dosage and duration of use to benefit and the safety are also needed to determine.

Meta-analysis of associations of IL1 receptor antagonist and estrogen receptor gene polymorphisms with systemic lupus erythematosus susceptibility.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects a number of different organs and tissues. Interleukin-1 (IL1) and estrogen are considered potential elements in the pathology of SLE. Recently, the variable number of tandem repeats (VNTR) polymorphism in the IL1 receptor antagonist gene (IL1-RN) and PvuII (rs2234693) and XbaI (rs9340799) polymorphisms in the estrogen receptor 1 gene (ESR1) have been associated with a predisposition to SLE. However, the evidence for these associations is inconclusive. We therefore conducted a meta-analysis to validate the roles of these polymorphisms in SLE susceptibility. We searched four databases and identified a total of 17 eligible articles comprising 24 studies. The Newcastle-Ottawa quality assessment scale was used to assess the qualities of the selected studies. We assessed the strengths of the associations using odds ratios (ORs) with 95% confidence intervals (95% CIs). Regarding the IL-1RN VNTR, the 2 allele significantly increased SLE susceptibility (2 vs. L: OR = 1.34, 95% CI = 1.03-1.73, P = 0.03). The ESR1 PvuII CC/CT genotype was also associated with SLE susceptibility (CC/CT vs. TT: OR = 1.25, 95% CI = 1.06-1.47, P = 0.01), and the difference was especially pronounced among Asians (CC/CT vs. TT: OR = 1.33, 95% CI = 1.04-1.69, P = 0.02). No significant association between the ESR1 XbaI polymorphism and SLE susceptibility was observed in the overall analysis. However, a marginally significant association between the GG/GA genotype was found in individuals of Asian descent (GG/GA vs. AA: OR = 1.30, 95% CI = 1.01-1.67, P = 0.04). These results indicate that the IL1-RN VNTR 2 allele, ESR1 PvuII CC/CT genotype and ESR1 XbaI GG/GA genotype may increase SLE susceptibility, especially in Asian individuals.

[Application of gene-based logistic kernel-machine regression model on studies related to the genome-wide association].

To explore the gene-based logistic kernel-machine regression model and its application in genome-wide association study(GWAS). Using the simulated genome-wide single-nucleotide polymorphism(SNPs)genotypes data, we proposed a practical statistical analysis strategy-named 'the logistic kernel-machine regression model', based on the gene levels to assess the association between genetic variations and complex diseases. The results from simulation showed that the P value of genes in related diseases was the smallest among all the genes. The results of simulation indicated that not only it could borrow information from different SNPs that were grouped in genes and reducing the degree of freedom through hypothesis testing, but could also incorporate the covariate effects and the complex SNPs interactions. The gene-based logistic kernel-machine regression model seemed to have certain statistical power for testing the association between genetic genes and diseases in GWAS.

[Logistic analysis on risk factors related to smear positive pulmonary tuberculosis].

OBJECTIVE: To explore the risk factors on relapsing tuberculosis related to smear positive pulmonary tuberculosis which had been cured for five years. METHODS: Patients with smear positive pulmonary tuberculosis registered in 1995 from ten countries in Hubei province were studied and logistic regression was used for data analysis. RESULTS: The 5-year relapse rate of smear positive pulmonary tuberculosis was 3.85 percent. Risk factors related to relapse would include being non-modeled county, negative smear after treated for three months, the class of retreatment, management of non-DOTS, method of chemotherapy and patients that did not get treated by the tuberculosis institute, with odds ratios of 0.15, 4.62, 3.68, 5.88 and 6.47, respectively. CONCLUSION: Effect standard, regulation DOTS and the centralized management measure might have had effects on decreasing the relapse rate.