Changes in cardiovascular disease risk predicted by the Framingham risk model in the Hong Kong population between 2003-2005 and 2014-2015: data from Population Health Surveys.

INTRODUCTION: The Framingham risk model estimates a person's 10-year cardiovascular disease (CVD) risk. This study used this model to calculate the changes in sex- and age-specific CVD risks in the Hong Kong Population Health Survey (PHS) 2014/15 compared with two previous surveys conducted during 2003 and 2005, namely, PHS 2003/2004 and Heart Health Survey (HHS) 2004/2005. METHODS: This study included individuals aged 30 to 74 years from PHS 2014/15 (n=1662; n=4 445 868 after population weighting) and PHS 2003/2004 and HHS 2004/2005 (n=818; n=3 495 074 after population weighting) with complete data for calculating the risk of CVD predicted by the Framingham model. Sex-specific CVD risks were calculated based on age, total cholesterol and high-density lipoprotein cholesterol levels, mean systolic blood pressure, smoking habit, diabetic status, and hypertension treatment. Mean sex- and age-specific CVD risks were calculated; differences in CVD risk between the two surveys were compared by independent t tests. RESULTS: The difference in 10-year CVD risk from 2003-2005 to 2014-2015 was not statistically significant (10.2% vs 10.6%; P=0.29). After age standardisation according to World Health Organization world standard population data, a small decrease in CVD risk was observed, from 9.4% in 2003-2005 to 8.8% in 2014-2015. Analysis according to age-group showed that more participants aged 65 to 74 years were considered high risk in 2003 to 2005 (2003-2005: 66.8% vs 2014-2015: 53.1%; P=0.028). This difference may be due to the decrease in smokers among men (2003-2005: 30.5% vs 2014-2015: 24.0%; P<0.001). CONCLUSION: From 2003-2005 to 2014-2015, there was a small decrease in age-standardised 10-year CVD risk. A holistic public health approach simultaneously targeting multiple risk factors is needed to achieve greater decreases in CVD risk.

Moving towards the ICOPE Approach: Evaluation of Community-Based Intervention Activities on Improving Intrinsic Capacity.

OBJECTIVES: Different types of community-based intervention activities may have differential effects in improving the intrinsic capacity (IC) of older people. This study aims to (i) identify subgroups of older people based on their IC impairments, (ii) examine the differential associations between different types of activity participations and change in IC across subgroups, and (iii) assess whether the activity participation patterns of older people align with the way that would benefit them the most. METHODS: Participants were community-dwelling older people aged 60 years or above. They were screened for IC impairments at baseline, and their participation records of different types (cognitive, physical, nutritional, mental, and social) of intervention activities were collected for one year. An aggregated IC score was created based on four IC domains including cognitive (self-rated memory), locomotor (self-rated difficulties in walking), vitality (self-rated weight loss), and psychological (subjective well-being). Cluster analysis was used to group homogenous participants. Mixed-effects regression was used to examine the associations between activity counts (i.e., number of sessions participated) and change in IC. Activity participation patterns were also compared across subgroups. RESULTS: Data were obtained from 7,357 participants (mean age = 74.72 years). Four clusters were identified, including those who were relatively robust (cluster 1, N = 4,380, 59.5%), those who had cognitive decline (cluster 2, N = 2,134, 29.0%), those who had impaired mobility and vitality (cluster 3, N = 319, 4.3%), and those with poor psychological well-being (cluster 4, N = 524, 7.1%). Overall, activity count was associated with IC improvement (ß = 0.073, 95% CI [0.037, 0.108]). However, as regards the cluster-specific results, different types of activities were associated with IC improvement for different specific clusters. For instance, cognitive activity count was associated with IC improvement only for cluster 2 (ß = 0.491, 95% CI [0.258, 0.732]). Notably, none of the activity types were associated with IC improvement for cluster 1. Regarding the activity participation patterns, there were no significant differences across the four clusters (Wilk's Λ = 0.997, F = 1.400, p = .138). CONCLUSIONS AND IMPLICATIONS: IC improvement depended on the activity types and IC status of older people. In view of this, a people-centred and targeted approach should be adopted to maximize the overall benefits of intervention activities.

Quantitative analysis of salivary and biofilm bacteria associated with cavitated and non-cavitated carious lesions in pre-school children.

OBJECTIVE: To quantify and compare Streptococcus mutans (S. mutans) and Lactobacillus fermentum (L. fermentum) in saliva and biofilm of caries-free children to those with cavitated and non-cavitated lesions. DESIGN: One hundred and thirty-five 3-4 years old children were grouped (n = 45 in each group) according to their caries status: Clinical examination was done by a calibrated examiner. Biofilm and saliva were collected to quantify the microorganisms using qRT-PCR. The decayed-missing-filled surfaces (dmfs) was calculated by adding the number of decayed (ICDAS-II score 3-6), filled (ICDAS-II score 7 and 8) and missing (ICDAS-II score 9) surfaces due to caries. The correlation between the bacterial amounts and the number of carious surfaces was evaluated using Spearman's correlation coefficient. The levels and proportions of the microorganisms were compared using the Kruskal-Wallis test at an α-level of 0.05. RESULTS: The quantity of S. mutans and L. fermentum was significantly higher in saliva and biofilm of children with cavitated lesions, followed by those with non-cavitated lesions and the lowest in caries-free children. Also, salivary and biofilm S. mutans, along with biofilm L. fermentum levels, significantly correlated with the number of non-cavitated surfaces; while salivary and biofilm S. mutans and L. fermentum levels significantly correlated with the number of cavitated surfaces. Additionally, dmfs scores significantly correlated with the salivary and biofilm S. mutans and L. fermentum levels. CONCLUSIONS: S. mutans and L. fermentum in saliva and biofilm samples are associated with caries lesion severity.

Case study of hypertriglyceridemia from COVID-19 Pfizer-BioNTech vaccination in a patient with familial hypercholesteremia.

The Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine is the first novel nucleoside-modified messenger ribonucleic acid (modRNA) vaccine to receive Emergency Use Authorization from the Food and Drug Administration in the United States. It is indicated to be used in patients ≥12 years-of-age as of May 25th, 2021, including populations with high atherosclerotic cardiovascular disease (ASCVD) burden. However, little is known about the potential impact this vaccine may have on serum lipoprotein levels in patients with familial hypercholesteremia (FH), who are predisposed to high ASCVD burden due to elevated low-density lipoprotein cholesterol (LDL-C). We present an interesting case where a patient with heterozygous FH (HeFH) and elevated triglycerides (TG)-controlled for years on medication and apheresis-experienced significantly elevated TG, one day after receiving his second Pfizer-BioNTech COVID-19 vaccine dose. It is not known whether this adverse event may be seen in other FH patients and may be worth assessing in such patients to determine the possibility of a rare adverse reaction from a COVID-19 vaccine.

Different mother and daughter manifestations due to very high cholesterol-containing lipoproteins.

OBJECTIVE: Familial hypercholesterolemia (FH) is an autosomal codominant genetic disorder associated with defective hepatic uptake of circulating low-density lipoproteins (LDL), which can lead to premature atherosclerotic cardiovascular disease (ASCVD). Evidence suggests elevated lipoprotein(a) (Lp(a)) levels in FH patients may also increase their ASCVD risk. We present a case series of 2 FH patients where a daughter has a higher ASCVD burden than her mother due to the daughter having elevated Lp(a). This underscores the importance of including Lp(a) in cascade lipid screening in FH patients and their first-degree relatives.

Fluconazole resistance in Candida albicans is induced by Pseudomonas aeruginosa quorum sensing.

Microorganisms employ quorum sensing (QS) mechanisms to communicate with each other within microbial ecosystems. Emerging evidence suggests that intraspecies and interspecies QS plays an important role in antimicrobial resistance in microbial communities. However, the relationship between interkingdom QS and antimicrobial resistance is largely unknown. Here, we demonstrate that interkingdom QS interactions between a bacterium, Pseudomonas aeruginosa and a yeast, Candida albicans, induce the resistance of the latter to a widely used antifungal fluconazole. Phenotypic, transcriptomic, and proteomic analyses reveal that P. aeruginosa's main QS molecule, N-(3-Oxododecanoyl)-L-homoserine lactone, induces candidal resistance to fluconazole by reversing the antifungal's effect on the ergosterol biosynthesis pathway. Accessory resistance mechanisms including upregulation of C. albicans drug-efflux, regulation of oxidative stress response, and maintenance of cell membrane integrity, further confirm this phenomenon. These findings demonstrate that P. aeruginosa QS molecules may confer protection to neighboring yeasts against azoles, in turn strengthening their co-existence in hostile polymicrobial infection sites.

The influence of substrate surface conditioning and biofilm age on the composition of Enterococcus faecalis biofilms.

AIM: To investigate the null hypothesis that neither the surface conditioning (collagen, serum, saliva) of hydroxyapatite (HA) discs, nor the biofilm age (3 days vs. 21 days) has a significant effect on the cellular and matrix composition of biofilms, using Enterococcus faecalis as the model organism. METHODOLOGY: Sterile HA discs were conditioned with collagen, saliva or serum, and inoculated with E. faecalis to form 3-day and 21-day-old biofilms. Unconditioned discs served as controls. The biofilms were analysed using culture-dependent and independent (confocal microscopy and biochemical analysis) methods, to determine the colony-forming units and the biofilm matrix composition (polysaccharides and proteins), respectively. Statistical analyses were performed using appropriate parametric and nonparametric tests (P = 0.05). RESULTS: Collagen conditioning significantly increased the number of CFUs in the 21-day biofilms, compared to the 3-day biofilms (P < 0.05). Although the biochemical analysis revealed that surface conditioning had no significant effect on the total carbohydrate content in the 21-day biofilms, confocal microscopic analysis revealed that collagen and saliva conditioning selectively increased the polysaccharide content of 21-day biofilms, compared to the 3-day biofilms (P < 0.05). CONCLUSIONS: The results of this study raise an important methodological concern that the substrate conditioning substances and biofilm age differentially influence the cellular and extracellular matrix components of E. faecalis biofilms.

Matrix stiffness induces epithelial-mesenchymal transition and promotes chemoresistance in pancreatic cancer cells.

Increased matrix rigidity associated with the fibrotic reaction is documented to stimulate intracellular signalling pathways that promote cancer cell survival and tumour growth. Pancreatic cancer is one of the stiffest of all human solid carcinomas and is characterised by a remarkable desmoplastic reaction. Here we use mouse models, genetically engineered to recapitulate human pancreatic cancer, and several pancreatic cancer cell lines as a model to investigate the effect of matrix stiffness in epithelial-mesenchymal transition (EMT) and resistance to chemotherapeutics. We found that recapitulation of the fibrotic rigidities found in pancreatic cancer tissues promote elements of EMT, including increases in vimentin expression, decreases in E-cadherin expression, nuclear localisation of ß-catenin, YAP and TAZ and changes in cell shape towards a mesenchymal phenotype. We also report that stiffness induces chemoresistance to paclitaxel, but not to gemcitabine, both commonly used therapeutics, suggesting that environmental rigidity underlies an aspect of chemoresistance.

2016 Consensus statement on prevention of atherosclerotic cardiovascular disease in the Hong Kong population.

INTRODUCTION: In Hong Kong, the prevalence of atherosclerotic cardiovascular disease has increased markedly over the past few decades, and further increases are expected. In 2008, the Hong Kong Cardiovascular Task Force released a consensus statement on preventing cardiovascular disease in the Hong Kong population. The present article provides an update on these recommendations. PARTICIPANTS: A multidisciplinary group of clinicians comprising the Hong Kong Cardiovascular Task Force-10 cardiologists, an endocrinologist, and a family physician-met in September 2014 and June 2015 in Hong Kong. EVIDENCE: Guidelines from the American College of Cardiology/American Heart Association, the European Society of Hypertension/European Society of Cardiology, and the Eighth Joint National Committee for the Management of High Blood Pressure were reviewed. CONSENSUS PROCESS: Group members reviewed the 2008 Consensus Statement and relevant international guidelines. At the meetings, each topical recommendation of the 2008 Statement was assessed against the pooled recommendations on that topic from the international guidelines. A final recommendation on each topic was generated by consensus after discussion. CONCLUSIONS: It is recommended that a formal risk scoring system should be used for risk assessment of all adults aged 40 years or older who have at least one cardiovascular risk factor. Individuals can be classified as having a low, moderate, or high risk of developing atherosclerotic cardiovascular disease, and appropriate interventions selected accordingly. Recommended lifestyle modifications include adopting a healthy eating pattern; maintaining a low body mass index; quitting smoking; and undertaking regular, moderate-intensity physical activity. Pharmacological interventions should be selected as appropriate after lifestyle modification.

Modeling birds on wires.

In this paper we introduce a mathematical model to study the group dynamics of birds resting on wires. The model is agent-based and postulates attraction-repulsion forces between the interacting birds: the interactions are "topological", in the sense that they involve a given number of neighbors irrespective of their distance. The model is first mathematically analyzed and then simulated to study its main properties: we observe that the model predicts birds to be more widely spaced near the borders of each group. We compare the results from the model with experimental data, derived from the analysis of pictures of pigeons and starlings taken in New Jersey: two different image elaboration protocols allow us to establish a good agreement with the model and to quantify its main parameters. We also discuss the potential handedness of the birds, by analyzing the group organization features and the group dynamics at the arrival of new birds. Finally, we propose a more refined mathematical model that describes landing and departing birds by suitable stochastic processes.

Optimal Cut-Offs of Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) to Identify Dysglycemia and Type 2 Diabetes Mellitus: A 15-Year Prospective Study in Chinese.

BACKGROUND: The optimal reference range of homeostasis model assessment of insulin resistance (HOMA-IR) in normal Chinese population has not been clearly defined. Here we address this issue using the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS), a prospective population-based cohort study with long-term follow-up. MATERIAL & METHODS: In this study, normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) were defined according to the 1998 World Health Organization criteria. Dysglycemia referred to IFG, IGT or T2DM. This study comprised two parts. Part one was a cross-sectional study involving 2,649 Hong Kong Chinese subjects, aged 25-74 years, at baseline CRISPS-1 (1995-1996). The optimal HOMA-IR cut-offs for dysglycemia and T2DM were determined by the receiver-operating characteristic (ROC) curve. Part two was a prospective study involving 872 subjects who had persistent NGT at CRISPS-4 (2010-2012) after 15 years of follow-up. RESULTS: At baseline, the optimal HOMA-IR cut-offs to identify dysglyceia and T2DM were 1.37 (AUC = 0.735; 95% confidence interval [CI] = 0.713-0.758; Sensitivity [Se] = 65.6%, Specificity [Sp] = 71.3%] and 1.97 (AUC = 0.807; 95% CI = 0.777-0.886; Se = 65.5%, Sp = 82.9%) respectively. These cut-offs, derived from the cross-sectional study at baseline, corresponded closely to the 75th (1.44) and 90th (2.03) percentiles, respectively, of the HOMA-IR reference range derived from the prospective study of subjects with persistent NGT. CONCLUSIONS: HOMA-IR cut-offs, of 1.4 and 2.0, which discriminated dysglycemia and T2DM respectively from NGT in Southern Chinese, can be usefully employed as references in clinical research involving the assessment of insulin resistance.

HLA-B*38:02:01 predicts carbimazole/methimazole-induced agranulocytosis.

Thioamides antithyroid-drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD-induced agranulocytosis is important for clinical management. We performed a genome-wide association study (GWAS) involving 20 patients with ATD-induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single-nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD-induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8-103.7; P = 1.3 × 10(-24)) and replication (OR = 37; 95% CI = 3.7-367.4; P = 9.6 × 10(-7)). HLA-B*38:02:01 was in complete linkage disequilibrium with rs185386680. High-resolution HLA typing confirmed that HLA-B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)-induced agranulocytosis (OR = 265.5; 95% CI = 27.9-2528.0; P = 2.5 × 10(-14)), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA-B*38:02:01 in predicting CMZ/MMI-induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.

Serum calcium and incident diabetes: an observational study and meta-analysis.

UNLABELLED: The study aimed to prospectively evaluate if serum calcium is related to diabetes incidence in Hong Kong Chinese. The results showed that serum calcium has a significant association with increased risk of diabetes. The result of meta-analysis reinforced our findings. INTRODUCTION: This study aimed to evaluate the association of serum calcium, including serum total calcium and albumin-corrected calcium, with incident diabetes in Hong Kong Chinese. METHODS: We conducted a retrospective cohort study in 6096 participants aged 20 or above and free of diabetes at baseline. Serum calcium was measured at baseline. Incident diabetes was determined from several electronic databases. We also searched relevant databases for studies on serum calcium and incident diabetes and conducted a meta-analysis using fixed-effect modeling. RESULTS: During 59,130.9 person-years of follow-up, 631 participants developed diabetes. Serum total calcium and albumin-corrected calcium were associated with incident diabetes in the unadjusted model. After adjusting for demographic and clinical variables, the association remained significant only for serum total calcium (hazard ratio (HR), 1.32 (95 % confidence interval (CI), 1.02-1.70), highest vs. lowest quartile). In a meta-analysis of four studies including the current study, both serum total calcium (pooled risk ratio (RR), 1.38 (95 % CI, 1.15-1.65); I (2) = 5 %, comparing extreme quantiles) and albumin-corrected calcium (pooled RR, 1.29 (95 % CI, 1.03-1.61); I (2) = 0 %, comparing extreme quantiles) were associated with incident diabetes. Penalized regression splines showed that the association of incident diabetes with serum total calcium and albumin-correlated calcium was non-linear and linear, respectively. CONCLUSIONS: Elevated serum calcium concentration is associated with incident diabetes. The mechanism underlying this association warrants further investigation.

Cardiometabolic risk profile of participants with prediabetes diagnosed by HbA1c criteria in an urban Hong Kong Chinese population over 40 years of age.

AIMS: To investigate the usefulness of the additional measurement of HbA1c , compared with performing only the oral glucose tolerance test (OGTT), in identifying participants at increased cardiometabolic risk, in an urban Chinese population. METHODS: All participants from the fourth visit of the population-based Hong Kong Cardiovascular Risk Factors Prevalence Study, without known diabetes, were included. All had their glycaemic status assessed by OGTT and HbA1c , according to American Diabetic Association 2010 criteria. RESULTS: Based on OGTT criteria alone, 3.5% of the study cohort (N = 1300) had diabetes and 19.2% had prediabetes. Based on HbA1c criteria only, 6.2% had diabetes and 61.2% had prediabetes. The measurement of HbA1c , in addition to the OGTT, increased the proportion of participants with diabetes to 7.8% and with prediabetes to 65.3%. Subjects with prediabetes having raised HbA1c but normal glycaemia (N = 600) had waist circumference, systolic blood pressure, fasting glucose, insulin resistance index (HOMA-IR), Gutt Index and Framingham 10-year cardiovascular risk scores intermediate between those with both normal HbA1c and glycaemia (N = 350), and those with impaired fasting glucose and/or impaired glucose tolerance (N = 249; all P < 0.01). CONCLUSION: The measurement of HbA1c in our population, in addition to the OGTT, results in the detection of a large number of participants with prediabetes having raised HbA1c but normal glycaemia who have a cardiometabolic risk profile intermediate between impaired fasting glucose and/or impaired glucose tolerance and normal participants, and would benefit from early lifestyle intervention.

Human serum potentiates the expression of genes associated with antifungal drug resistance in C. albicans biofilms on central venous catheters.

Candida albicans is a major agent of fungaemias and frequently causes systemic disease through seeded, blood stream dissemination. These infections, particularly common in hospitalized patients with central venous catheters (CVCs), appear to persevere due to biofilm reservoirs of the yeast that tend to develop on the device. Although it is known that candidal biofilms are intrinsically resistant to antifungals compared with their planktonic counterparts, there is a paucity of data on the expression of antifungal drug resistance genes (DRGs) in candidal biofilms in CVC reservoirs. Furthermore, notwithstanding the fact that CVCs are constantly bathed in human serum, there are no studies on the effect of the latter on the DRG expression in candidal biofilms. Hence, we developed in vitro biofilms of three different C. albicans strains on silicone CVC discs immersed in human serum and evaluated the temporal expression of nine antifungal DRGs. In an attempt to evaluate the effect of hyphal elements on DRG expression, we incorporated a hyphal mutant (HM) and its wild-type (WT) counterpart, as well as a fresh clinical isolate in the studies. Human serum significantly up-regulated DRG transcripts in Candida biofilms on CVCs, at different stages of biofilm growth, while the WT strain over-expressed more DRGs than the HM strain. Here, we report, for the first time, that both human serum and the hyphal elements of the yeast have a profound modulatory effect on DRG expression in C. albicans biofilms on CVCs.

Implementing a bar-code assisted medication administration system: effects on the dispensing process and user perceptions.

PURPOSE: We assessed the effects of a bar-code assisted medication administration system used without the support of computerised prescribing (stand-alone BCMA), on the dispensing process and its users. METHODS: The stand-alone BCMA system was implemented in one ward of a teaching hospital. The number of dispensing steps, dispensing time and potential dispensing errors (PDEs) were directly observed one month before and eight months after the intervention. Attitudes of pharmacy and nursing staff were assessed using a questionnaire (Likert scale) and interviews. RESULTS: Among 1291 and 471 drug items observed before and after the introduction of the technology respectively, the number of dispensing steps increased from five to eight and time (standard deviation) to dispense one drug item by one staff personnel increased from 0.8 (0.09) to 1.5 (0.12) min. Among 2828 and 471 drug items observed before and after the intervention respectively, the number of PDEs increased significantly (P<0.001). 'Procedural errors' and 'missing drug items' were the frequently observed PDEs in the after study. 'Perceived usefulness' and 'job relevance' of the technology decreased significantly (P=0.003 and P=0.004 respectively) among users who participated in the before (N=16) and after (N=16) questionnaires surveys. Among the interviewees, pharmacy staff felt that the system offered less benefit to the dispensing process (9/16). Nursing staff perceived the system as useful in improving the accuracy of drug administration (7/10). CONCLUSION: Implementing a stand-alone BCMA system may slow down and complicate the dispensing process. Nursing staff believe the stand-alone BCMA system could improve the drug administration process but pharmacy staff believes the technology would be more helpful if supported by computerised prescribing. However, periodical assessments are needed to identify weaknesses in the process after implementation, and all users should be educated on the benefits of using this technology.

Enteric Gram-negative bacilli suppress Candida biofilms on Foley urinary catheters.

Mixed Candida-bacterial biofilms in urinary catheters are common in hospitalized patients. (i) The aims of this study were to evaluate, quantitatively and qualitatively, the in vitro development of mono- and dual-species biofilms (MSBs and DSBs) of Candida albicans and two enteric gram-negative bacilli (EGNB; Pseudomonas aeruginosa or Escherichia coli) on Foley catheter (FC) discs, (ii) to determine the biofilm growth in tryptic soy broth or glucose supplemented artificial urine (AU) and (iii) to assess the inhibitory effects of EGNB and their lipopolysaccharides (LPS) on Candida biofilm growth. The growth of MSBs and DSBs on FC discs was monitored by cell counts and SEM. The metabolic activity of LPS-treated Candida biofilms was determined by the XTT reduction assay. Candida albicans and EGNB demonstrated significant inter- and intra-species differences in biofilm growth on FC discs (p < 0.01). Pseudomonas aeruginosa suppressed Candida albicans significantly (p < 0.001) in DSBs. Compared with MSBs, DSB of EGNB in glucose supplemented AU demonstrated robust growth. Escherichia coli and its LPS, significantly suppressed Candida biofilm growth, compared with Pseudomonas aeruginosa and its LPS (p < 0.001). Candida albicans and EGNB colonization in FC is significantly increased in AU with glucose, and variably modified by Escherichia coli, Pseudomonas aeruginosa and their corresponding LPS.