Rivastigmine in Chinese patients with subcortical vascular dementia

Vincent Mok1, Adrian Wong1, Simon Ho2, Thomas Leung1, Wynnie WM Lam2, Ka Sing Wong11Department of Medicine and Therapeutics; 2Department of Radiology and Organ Imaging, The Chinese University of Hong Kong, Shatin, Hong Kong, ChinaBackground: We explored the efficacy and tolerability of rivastigmine among Chinese patients with subcortical vascular dementia.Methods: Forty subjects were randomized to either placebo (n = 20) or rivastigmine (n = 20) in a double-blind 26-week trial. Outcome measures were cognition (mini-mental state examination, frontal assessment battery), neuropsychiatric inventory (NPI), instrumental activities of daily living, clinical dementia rating scale, and adverse events.Results: No statistical significant benefit could be observed in the active group in any of the efficacy measures. A trend favoring active group was observed only in the NPI subscore of irritability (p = 0.066) and aberrant motor behavior (p = 0.068). Withdrawal rate was 30% and 15% in the active and placebo group, respectively.Conclusion: Among Chinese subcortical vascular dementia patients, there was no apparent cognitive benefit associated with use of rivastigmine over the 6 months period. A trend favoring rivastigmine was observed in certain behavioral measures. Rivastigmine was associated with more withdrawals relative to placebo.Keywords: rivastigmine, subcortical vascular dementia, Chines

Factors associated with grade 1 hypertension: implications for hypertension care based on the Dietary Approaches to Stop Hypertension (DASH) in primary care settings

Background: A Reference Framework for Hypertension Care was recently developed by Hong Kong government to emphasise the importance of primary care for subjects with high blood pressure (BP). The Dietary Approaches to Stop Hypertension (DASH) interventional regime was recommended for patients aged 40–70 years with grade 1 hypertension (having systolic BP of 140-159 mmHg and/or diastolic BP of 90-99 mmHg). This study explored factors associated with grade 1 hypertension among subjects screened in primary care settings. Methods: The study sample consisted of community dwellers (N = 10,693) enrolled in a primary care programme in which participants overall had similar characteristics when compared to the Hong Kong population census. Invitation phone calls were given by trained researchers to a randomly selected subjects (N = 2,673, [50% of total subjects aged 40–70 years]) between January and June 2013. BP and body mass index (BMI) were measured by trained clinical professionals according to a standard protocol. Interviewer-administered survey questionnaires were used to collect self-report information on socio-demographics, family history, and lifestyle characteristics. Multiple logistic regression analysis was performed to explore factors associated with grade 1 hypertension. Adjusted odds ratios (aORs) were estimated with 95% confidence intervals (CI). Results A total of 679 out of 2,673 subjects agreed to participate in the screening and completed the baseline assessment (100% completion rate), among which, 320 subjects (47.1%, [320/679]) were grade 1 hypertensive. Unhealthy diet (aOR = 2.19, 95%CI 1.04-4.62), irregular meals (aOR = 1.47, 95%CI 1.11-1.95), BMI >27.5 kg/m2 (aOR = 1.87, 95%CI 1.53-2.27), duration of cigarette smoking (aOR = 1.83 per year), increased daily cigarette consumption (aOR = 1.59 per pack [20 cigarettes per pack]), duration of alcohol drinking (aOR = 1.65 per year), and higher frequency of weekly binge drinking (aOR = 1.87 per occasion) were independently associated with grade 1 hypertension. The increase in the number of risk factors combined significantly correlated with higher predicted probability of grade 1 hypertension. Conclusions: Dietary-intake factors were significantly associated with grade 1 hypertension, echoing the recommendation in the Reference Framework on incorporating dietary-related intervention based on the DASH approach for hypertension care in primary care settings. The association between aggregate risk factors and grade 1 hypertension should also be taken into consideration in long-term preventive strategy

Relationship between autoantibody clustering and clinical subsets in SLE: cluster and association analyses in Hong Kong Chinese

OBJECTIVE: This study aims to identify the existence of, and relationship between autoantibody clusters and clinical subsets in Chinese SLE patients. METHODS: Data from 1928 SLE patients from Hong Kong were analysed. Using cluster analysis, patients were grouped by autoantibodies into clusters. The frequencies of various clinical manifestations were then compared between each cluster. Separate association analyses between individual autoantibodies and clinical manifestations as well as between clinical manifestations were also performed without any prior clustering. RESULTS: Three separate autoantibody clusters were identified, each with significantly different clinical manifestations. Cluster 1 was characterized by anti-dsDNA and the greatest prevalence of renal disorder but the lowest frequencies of other clinical manifestations. Cluster 2 was represented by the predominance of anti-Smith, anti-RNP and aPL, with greater prevalence of malar rash, oral ulcers, arthritis and serositis. Cluster 3 was characterized by anti-Ro and anti-La with greater prevalence of discoid rash, photosensitivity and haematological involvement. Individual association analysis also revealed similar findings. Patients of clusters 2 and 3 were more closely related, while cluster 1 was more distinct, associated with renal disorder only and negatively associated or not associated with other manifestations. CONCLUSION: We conclude that autoantibody clustering and clinical subsets exist in SLE patients of our locality. These clusters may be viewed as a bipolar spectrum of related autoantibody and clinical manifestations. At one end are patients with over-representation of anti-dsDNA and renal disorder, while at the other end are two distinct autoantibody clusters (anti-Sm/anti-RNP/aPL and anti-Ro/anti-La) with overlapping of other clinical manifestations.postprin

Frameless stereotactic radiosurgery for brain metastases: a review of outcomes and prognostic scores evaluation

Introduction: Stereotactic brain radiosurgery provides good local control in patients with limited brain metastases. A newly developed frameless system allows pain-free treatment. We reviewed the effectiveness of this frameless stereotactic brain radiosurgery and identified prognostic factors that may aid better patient selection. Methods: Medical records of patients with brain metastases treated with linear accelerator–based frameless stereotactic brain radiosurgery between January 2010 and July 2015 in a university affiliated hospital in Hong Kong were reviewed. Outcomes including local and distant brain control rate, progression-free survival, and overall survival were analysed. Prognostic factors were identified by univariable and multivariable analyses. Association of outcomes with four common prognostic scores was performed. Results: In this study, 64 patients with 94 lesions were treated with a median dose of 18 Gy (range, 12-22 Gy) in a single fraction. The median follow-up was 11.5 months. One-year actuarial local and distant brain control rates were 72% and 71%, respectively. The median overall survival was 13.0 months. On multivariable analysis, Karnofsky performance status score (>50 vs ≤50) and number of lesions (1-2 vs ≥3) were found to associate significantly with distinct brain progression-free survival (P=0.022, hazard ratio=0.20, 95% confidence interval 0.05-0.80 and P=0.003, hazard ratio=0.31, 95% confidence interval 0.14-0.68, respectively). Overall survival was associated significantly with Basic Score for Brain Metastases (P=0.031), Score Index for Radiosurgery in Brain Metastases (P=0.007), and Graded Prognostic Assessment (P=0.003). Improvement in overall survival was observed in all groups of different prognostic scores. Conclusion: Frameless stereotactic brain radiosurgery is effective in patients with oligometastases of brain and should be increasingly considered in patients with favourable prognostic scoring.published_or_final_versio

Meta-analysis of two Chinese populations identifies an autoimmune disease risk allele in 22q11.21 as associated with systemic lupus erythematosus

INTRODUCTION: Systemic lupus erythematosus (SLE) is a heterogeneous disease with a diverse spectrum of clinical symptoms from skin rash to end-organ damage. 22q11.21 has been identified as a susceptibility region for several autoimmune diseases, including SLE. However, the detailed information for SLE association and the underlying functional mechanism(s) are still lacking. METHODS: Through meta-analysis of two genome-wide association studies (GWAS) on Chinese Han populations with a total of 1659 cases and 3398 controls matched geographically, we closely examined this region, especially on the reported single nucleotide polymorphisms (SNPs) associated with different autoimmune diseases and their relationships. We further replicated the most significant association SNP with SLE using 2612 cases and 2323 controls of Asian ancestry. RESULTS: All reported SNPs in this region with different autoimmune diseases were examined in the two GWAS data and meta- analysis result, and supportive evidence of association with SLE was found (meta-analysis P_meta ≤ 7.27E-05), which might require further investigation. SNP rs2298428 was identified as the most significant SNP associated with SLE in this region (P_meta = 2.70E-09). It showed independent effect through both stepwise and conditional logistic regression, and there is no evidence of other independent association signals for SLE in this region. The association of rs2298428 was further replicated in three cohorts from Hong Kong, Anhui and Thailand with a total of 2612 cases and 2323 controls (joint analysis of GWAS and replication result P_all = 1.31E-11, OR = 1.23). SNP rs2298428 was shown to be an eQTL for UBE2L3 gene in different cell types, with the risk allele (T) being correlated with higher expression of UBE2L3. This is consistent with earlier reports on higher expression of UBE2L3 in SLE cases. CONCLUSIONS: Association to distinct autoimmune diseases highlights the significance of this region in autoreactive responses and potentially shared functional mechanisms by these diseases.published_or_final_versio

Gene-Based Meta-Analysis of Genome-Wide Association Study Data Identifies Independent Single-Nucleotide Polymorphisms in ANXA6 as Being Associated With Systemic Lupus Erythematosus in Asian Populations

Objective Previous genome-wide association studies (GWAS), which were mainly based on single-variant analysis, have identified many systemic lupus erythematosus (SLE) susceptibility loci. However, the genetic architecture of this complex disease is far from being understood. The aim of this study was to investigate whether using a gene-based analysis may help to identify novel loci, by considering global evidence of association from a gene or a genomic region rather than focusing on evidence for individual variants. Methods Based on the results of a meta-analysis of 2 GWAS of SLE conducted in 2 Asian cohorts, we performed an in-depth gene-based analysis followed by replication in a total of 4,626 patients and 7,466 control subjects of Asian ancestry. Differential allelic expression was measured by pyrosequencing. Results More than one-half of the reported SLE susceptibility loci showed evidence of independent effects, and this finding is important for understanding the mechanisms of association and explaining disease heritability. ANXA6 was detected as a novel SLE susceptibility gene, with several single-nucleotide polymorphisms (SNPs) contributing independently to the association with disease. The risk allele of rs11960458 correlated significantly with increased expression of ANXA6 in peripheral blood mononuclear cells from heterozygous healthy control subjects. Several other associated SNPs may also regulate ANXA6 expression, according to data obtained from public databases. Higher expression of ANXA6 in patients with SLE was also reported previously. Conclusion Our study demonstrated the merit of using gene-based analysis to identify novel susceptibility loci, especially those with independent effects, and also demonstrated the widespread presence of loci with independent effects in SLE susceptibility genes. © 2015, American College of Rheumatology.postprin

Effectiveness of vasectomy using cautery

BACKGROUND: Little evidence supports the use of any one vas occlusion method. Data from a number of studies now suggest that there are differences in effectiveness among different occlusion methods. The main objectives of this study were to estimate the effectiveness of vasectomy by cautery and to describe the trends in sperm counts after cautery vasectomy. Other objectives were to estimate time and number of ejaculations to success and to determine the predictive value of success at 12 weeks for final status at 24 weeks. METHODS: A prospective, non-comparative observational study was conducted between November 2001 and June 2002 at 4 centers in Brazil, Canada, the UK, and the US. Four hundred men who chose vasectomy were enrolled and followed for 6 months. Sites used their usual cautery vasectomy technique. Earlier and more frequent than normal semen analyses (2, 5, 8, 12, 16, 20, and 24 weeks after vasectomy) were performed. Planned outcomes included effectiveness (early failure based on semen analysis), trends in sperm counts, time and number of ejaculations to success, predictive value of success at 12 weeks for the outcome at 24 weeks, and safety evaluation. RESULTS: A total of 364 (91%) participants completed follow-up. The overall failure rate based on semen analysis was 0.8% (95% confidence interval 0.2, 2.3). By 12 weeks 96.4% of participants showed azoospermia or severe oligozoospermia (< 100,000 sperm/mL). The predictive value of a single severely oligozoospermia sample at 12 weeks for vasectomy success at the end of the study was 99.7%. One serious unrelated adverse event and no pregnancies were reported. CONCLUSION: Cautery is a very effective method for occluding the vas. Failure based on semen analysis is rare. In settings where semen analysis is not practical, using 12 weeks as a guideline for when men can rely on their vasectomy should lessen the risk of failure compared to using a guideline of 20 ejaculations after vasectomy

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Oral health of Chinese people with systemic sclerosis

The aim was to study oral health status, salivary function, and oral features of Chinese people with Systemic Sclerosis (SSc). Chinese people with SSc attending a university specialist clinic were invited for a questionnaire survey and a clinical examination. Ethics approval was sought (UW 08-305). Gender- and age-matched individuals without SSc who attended a university dental hospital were recruited for comparison. Forty-two SSc patients with a mean age of 54.0 ± 12.2 were examined. This study found no Chinese people with systemic sclerosis were periodontally healthy and many (76%) had periodontal pockets despite most of them (93%) practiced daily tooth-brushing. They all had caries experience (DMFT = 10.5) and many (65%) had untreated decay. Mucosal telangiectasia was a common oral feature (80%). They had lower resting salivary flow rates (0.18 ± 0.17 ml/min vs. 0.31 ± 0.21 ml/min; p = 0.003) and pH values (6.90 ± 0.40 vs. 7.28 ± 0.31; p < 0.001) and reduced maximal mouth opening (40.1 ± 6.5 mm vs. 43.6 ± 7.0 mm) than people without SSc

Identification of Novel Pax8 Targets in FRTL-5 Thyroid Cells by Gene Silencing and Expression Microarray Analysis

The differentiation program of thyroid follicular cells (TFCs), by far the most abundant cell population of the thyroid gland, relies on the interplay between sequence-specific transcription factors and transcriptional coregulators with the basal transcriptional machinery of the cell. However, the molecular mechanisms leading to the fully differentiated thyrocyte are still the object of intense study. The transcription factor Pax8, a member of the Paired-box gene family, has been demonstrated to be a critical regulator required for proper development and differentiation of thyroid follicular cells. Despite being Pax8 well-characterized with respect to its role in regulating genes involved in thyroid differentiation, genomics approaches aiming at the identification of additional Pax8 targets are lacking and the biological pathways controlled by this transcription factor are largely unknown.To identify unique downstream targets of Pax8, we investigated the genome-wide effect of Pax8 silencing comparing the transcriptome of silenced versus normal differentiated FRTL-5 thyroid cells. In total, 2815 genes were found modulated 72 h after Pax8 RNAi, induced or repressed. Genes previously reported to be regulated by Pax8 in FRTL-5 cells were confirmed. In addition, novel targets genes involved in functional processes such as DNA replication, anion transport, kinase activity, apoptosis and cellular processes were newly identified. Transcriptome analysis highlighted that Pax8 is a key molecule for thyroid morphogenesis and differentiation.This is the first large-scale study aimed at the identification of new genes regulated by Pax8, a master regulator of thyroid development and differentiation. The biological pathways and target genes controlled by Pax8 will have considerable importance to understand thyroid disease progression as well as to set up novel therapeutic strategies