SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron.

We address whether T cell responses induced by different vaccine platforms (mRNA-1273, BNT162b2, Ad26.COV2.S, and NVX-CoV2373) cross-recognize early SARS-CoV-2 variants. T cell responses to early variants were preserved across vaccine platforms. By contrast, significant overall decreases were observed for memory B cells and neutralizing antibodies. In subjects ∼6 months post-vaccination, 90% (CD4+) and 87% (CD8+) of memory T cell responses were preserved against variants on average by AIM assay, and 84% (CD4+) and 85% (CD8+) preserved against Omicron. Omicron RBD memory B cell recognition was substantially reduced to 42% compared with other variants. T cell epitope repertoire analysis revealed a median of 11 and 10 spike epitopes recognized by CD4+ and CD8+ T cells, with average preservation > 80% for Omicron. Functional preservation of the majority of T cell responses may play an important role as a second-level defense against diverse variants.

Evaluating different low-density lipoprotein cholesterol thresholds to initiate statin for prevention of cardiovascular diseases in patients with type 2 diabetes mellitus: A target trial emulation study.

AIM: The present study aimed to evaluate the effect of statin therapy for primary prevention of cardiovascular diseases (CVDs) when initiating therapy at different baseline low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Using territory-wide public electronic medical records in Hong Kong, we emulated a sequence of trials on patients with T2DM with elevated LDL-C levels in every calendar month from January 2008 to December 2014. Pooled logistic regression was applied to obtain the hazard ratios for the major CVDs (stroke, myocardial infarction, heart failure), all-cause mortality and major adverse events (myopathies and liver dysfunction) of statin therapy. RESULTS: The estimated hazard ratios (95% confidence intervals) of CVD incidence for statin initiation were 0.78 (0.72, 0.84) in patients with baseline LDL-C of 1.8-2.5 mmol/L (i.e., 70-99 mg/dL) and 0.90 (0.88, 0.92) in patients with baseline LDL-C ≥2.6 mmol/L (i.e., ≥100 mg/dL) in intention-to-treat analysis, which was 0.59 (0.51, 0.68) and 0.77 (0.74, 0.81) in per-protocol analysis, respectively. No significant increased risks were observed for the major adverse events. The absolute 10-year risk difference of overall CVD in per-protocol analysis was -7.1% (-10.7%, -3.6%) and -3.9% (-5.1%, -2.7%) in patients with baseline LDL-C 1.8-2.5 and ≥2.6 mmol/L, respectively. The effectiveness and safety were consistently observed in patients aged >75 years initiating statin at both LDL-C thresholds. CONCLUSIONS: Compared with the threshold of 2.6 mmol/L, initiating statin in patients with a lower baseline LDL-C level at 1.8-2.5 mmol/L can further reduce the risks of CVD and all-cause mortality without significantly increasing the risk of major adverse events in patients with T2DM, including patients aged >75 years.

Consensus statement on the management of hyperkalaemia-An Asia-Pacific perspective.

Hyperkalaemia is an electrolyte imbalance that impairs muscle function and myocardial excitability, and can potentially lead to fatal arrhythmias and sudden cardiac death. The prevalence of hyperkalaemia is estimated to be 6%-7% worldwide and 7%-10% in Asia. Hyperkalaemia frequently affects patients with chronic kidney disease, heart failure, and diabetes mellitus, particularly those receiving treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors. Both hyperkalaemia and interruption of RAAS inhibitor therapy are associated with increased risks for cardiovascular events, hospitalisations, and death, highlighting a clinical dilemma in high-risk patients. Conventional potassium-binding resins are widely used for the treatment of hyperkalaemia; however, caveats such as the unpalatable taste and the risk of gastrointestinal side effects limit their chronic use. Recent evidence suggests that, with a rapid onset of action and improved gastrointestinal tolerability, novel oral potassium binders (e.g., patiromer and sodium zirconium cyclosilicate) are alternative treatment options for both acute and chronic hyperkalaemia. To optimise the care for patients with hyperkalaemia in the Asia-Pacific region, a multidisciplinary expert panel was convened to review published literature, share clinical experiences, and ultimately formulate 25 consensus statements, covering three clinical areas: (i) risk factors of hyperkalaemia and risk stratification in susceptible patients; (ii) prevention of hyperkalaemia for at-risk individuals; and (iii) correction of hyperkalaemia for at-risk individuals with cardiorenal disease. These statements were expected to serve as useful guidance in the management of hyperkalaemia for health care providers in the region.

Limited impacts of biogenetic messaging on neural correlates of cognitive control and beliefs about depression.

During the past 60 years, perceptions about the origins of mental illness have shifted toward a biomedical model, depicting depression as a biological disorder caused by genetic abnormalities and/or chemical imbalances. Despite benevolent intentions to reduce stigma, biogenetic messages promote prognostic pessimism, reduce feelings of agency, and alter treatment preferences, motivations, and expectations. However, no research has examined how these messages influence neural markers of ruminative activity or decision-making, a gap this study sought to fill. In this pre-registered, clinical trial (NCT03998748), 49 participants with current or past depressive experiences completed a sham saliva test and were randomly assigned to receive feedback that they either have (gene-present; n = 24) or do not have (gene-absent; n = 25) a genetic predisposition to depression. Before and after receiving the feedback, resting-state activity and neural correlates of cognitive control (error-related negativity [ERN] and error positivity [Pe]) were measured using high-density electroencephalogram (EEG). Participants also completed self-report measures of beliefs about the malleability and prognosis of depression and treatment motivation. Contrary to hypotheses, biogenetic feedback did not alter perceptions or beliefs about depression, nor did it alter EEG markers of self-directed rumination nor neurophysiological correlates of cognitive control. Explanations of these null findings are discussed in the context of prior studies.

Age-specific associations between the number of co-morbidities, all-cause mortality and public direct medical costs in patients with type 2 diabetes: A retrospective cohort study.

AIM: To evaluate the association between the number of co-morbidities, all-cause mortality and public health system expenditure in patients with type 2 diabetes (T2D) across different age groups. MATERIALS AND METHODS: A retrospective observational study of T2D patients using electronic health records in Hong Kong was conducted. Patients were stratified by age (< 50, 50-64, 65-79, ≥ 80 years) and the number of co-morbidities (0, 1, 2, 3, ≥ 4), defined using the Charlson Comorbidity Index and prevalent chronic diseases identified in local surveys. The association between the number of co-morbidities, all-cause mortality and direct medical costs was examined using Cox proportional hazard regression and the gamma generalized linear model with log link function. RESULTS: A total of 262 212 T2D patients with a median follow-up of 10 years were included. Hypertension and dyslipidaemia were the most common co-morbidities in all age groups. After age stratification, cardiovascular diseases dominated the top pair of co-morbidities in the older age groups (65-79 and ≥ 80 years), while inflammatory and liver disease were predominant among younger individuals. Compared with co-morbidity-free T2D patients, the hazard ratios (95% CI) of death for patients aged younger than 50 and 80 years or older with two co-morbidities were 1.31 (1.08-1.59) and 1.25 (1.15-1.36), respectively, and increased to 3.08 (2.25-4.21) and 1.98 (1.82-2.16), respectively, as the number of co-morbidities increased to four or more. Similar trends were observed for medical costs. CONCLUSIONS: Age-specific co-morbidity patterns were observed for patients with T2D. A greater number of co-morbidities was associated with increased mortality and healthcare costs, with stronger relationships observed among younger patients.

Prognostic Utility of Cardiac MRI Myocardial Strain Parameters in Patients With Ischemic and Nonischemic Dilated Cardiomyopathy: A Multicenter Study.

BACKGROUND. Prior small single-center studies have yielded conflicting results regarding the prognostic significance of myocardial strain parameters derived from feature tracking (FT) on cardiac MRI in patients with dilated cardiomyopathy (DCM). OBJECTIVE. The purpose of this study was to evaluate the prognostic utility of FT parameters on cardiac MRI in patients with ischemic and nonischemic DCM and to determine the optimal strain parameter for outcome prediction. METHODS. This retrospective study included 471 patients (median age, 61 years; 365 men, 106 women) with ischemic (n = 233) or nonischemic (n = 238) DCM and left ventricular (LV) ejection fraction (EF) less than 50% who underwent cardiac MRI at any of four centers from January 2011 to December 2019. Cardiac MRI parameters were determined by manual contouring. In addition, software-based FT was used to calculate six myocardial strain parameters (LV and right ventricular [RV] global radial strain, global circumferential strain, and global longitudinal strain [GLS]). Late gadolinium enhancement (LGE) was also evaluated. Patients were assessed for a composite outcome of all-cause mortality and/or heart-failure hospitalization. Cox regression models were used to determine associations between strain parameters and the composite outcome. RESULTS. Mean LV EF was 27.5% and mean LV GLS was -6.9%. The median follow-up period was 1328 days. The composite outcome occurred in 220 patients (125 deaths, 95 heart-failure hospitalizations). All six myocardial strain parameters were significant independent predictors of the composite outcome (hazard ratio [HR] = 0.92-1.16; all p < .05). In multivariable models that included age, corrected LV and RV end-diastolic volume, LV and RV EF, and presence of LGE, the only strain parameter that was a significant independent predictor of the composite outcome was LV GLS (HR = 1.13, p = .006); LV EF and presence of LGE were not independent predictors of the composite outcome in the models (p > .05). A LV GLS threshold of -6.8% had sensitivity of 62.6% and specificity of 62.6% in predicting the composite outcome rate at 4.0 years. CONCLUSION. LV GLS, derived from FT on cardiac MRI, is a significant independent predictor of adverse outcomes in patients with DCM. CLINICAL IMPACT. This study strengthens the body of evidence supporting the clinical implementation of FT when performing cardiac MRI in patients with DCM.

Association of genetic variants related to combined exposure to higher BMI and waist-to-hip ratio on lifelong cardiovascular risk in UK Biobank.

OBJECTIVE: This study examines the individual and combined association of BMI and waist-to-hip ratio (WHR) with CVD risk using genetic scores of the obesity measurements as proxies. DESIGN: A 2 × 2 factorial analysis approach was applied, with participants divided into four groups of lifetime exposure to low BMI and WHR, high BMI, high WHR, and high BMI and WHR based on weighted genetic risk scores. The difference in CVD risk across groups was evaluated using multivariable logistic regression. SETTING: Cohort study. PARTICIPANTS: A total of 408 003 participants were included from the prospective observational UK Biobank study. RESULTS: A total of 58 429 CVD events were recorded. Compared to the low BMI and WHR genetic scores group, higher BMI or higher WHR genetic scores were associated with an increase in CVD risk (high WHR: OR, 1·07; 95 % CI (1·04, 1·10)); high BMI: OR, 1·12; 95 % CI (1·09, 1·16). A weak additive effect on CVD risk was found between BMI and WHR (high BMI and WHR: OR, 1·16; 95 % CI (1·12, 1·19)). Subgroup analysis showed similar patterns between different sex, age (<65, ≥65 years old), smoking status, Townsend deprivation index, fasting glucose level and medication uses, but lower systolic blood pressure was associated with higher CVD risk in obese participants. CONCLUSIONS: High BMI and WHR were associated with increased CVD risk, and their effects are weakly additive. Even though there were overlapping of effect, both BMI and WHR are important in assessing the CVD risk in the general population.

Differential T-Cell Reactivity to Endemic Coronaviruses and SARS-CoV-2 in Community and Health Care Workers.

Herein we measured CD4+ T-cell responses against common cold coronaviruses (CCC) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in high-risk health care workers (HCW) and community controls. We observed higher levels of CCC-reactive T cells in SARS-CoV-2-seronegative HCW compared to community donors, consistent with potential higher occupational exposure of HCW to CCC. We further show that SARS-CoV-2 T-cell reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses is consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC T-cell reactivity was decreased in SARS-CoV-2-infected HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses, either directly or indirectly. This result was unexpected, but consistently detected in independent cohorts derived from Miami and San Diego. CD4+ T-cell responses against common cold coronaviruses (CCC) are elevated in SARS-CoV-2 seronegative high-risk health care workers (HCW) compared to COVID-19 convalescent HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses and/or cross-reactivity associated with a protective effect.

The validity, reliability, sensitivity and responsiveness of a modified Patient Enablement Instrument (PEI-2) as a tool for serial measurements of health enablement.

BACKGROUND: Patient enablement is a core tenet of patient-centred and holistic primary care. The Patient Enablement Instrument (PEI) is a transitional measure limited in its ability to measure changes over time. A modified version, PEI-2, has been developed to measure enablement at a given time-point without comparison to a recalled baseline. OBJECTIVE: To assess the validity, reliability, sensitivity and responsiveness of PEI-2. METHODS: PEI-2 was modified from the Chinese PEI to assess enablement over 4 weeks in a prospective cohort study nested within a community support programme [Trekkers Family Enhancement Scheme (TFES)] in Hong Kong. Construct validity was assessed by factor analysis and convergent validity by Spearman's correlations with health-related quality of life and depressive symptoms. Internal reliability was assessed using Cronbach's alpha. Test-retest reliability was assessed by intraclass correlation (ICC), responsiveness by 12-24-month change in PEI-2 score and sensitivity by differences in change of PEI-2 score between TFES participants and a control group. RESULTS: PEI-2 demonstrated construct validity with all items loading on one factor (factor loadings >0.7). Convergent validity was confirmed by significant correlations with 12-item Short Form Questionnaire, version 2 (r = 0.1089-0.1919) and Patient Health Questionnaire-9 (r = -0.2030). Internal reliability was high (Cronbach's alpha = 0.9095) and test-retest reliability moderate (ICC = 0.520, P = 0.506). Significant improvements in PEI-2 scores among the TFES group suggested good responsiveness (P < 0.001). The difference in change of PEI-2 scores between TFES and control was significant (P = 0.008), indicating good sensitivity. CONCLUSIONS: This study supports the validity, reliability, sensitivity and responsiveness of PEI-2 in measuring changes in enablement, making it a promising tool for evaluating enablement in cohort and intervention studies.

Effects of continuity of care on health outcomes among patients with diabetes mellitus and/or hypertension: a systematic review.

BACKGROUND: The rising prevalence of non-communicable diseases (NCDs) such as diabetes mellitus (DM) and hypertension (HT) has placed a tremendous burden on healthcare systems around the world, resulting in a call for more effective service delivery models. Better continuity of care (CoC) has been associated with improved health outcomes. This review examines the association between CoC and health outcomes in patients with DM and/or HT. METHODS: This was a systematic review with searches carried out on 13 March 2021 through PubMed, Embase, MEDLINE and CINAHL plus, clinical trials registry and bibliography reviews. Eligibility criteria were: published in English; from 2000 onwards; included adult DM and/or HT patients; examined CoC as their main intervention/exposure; and utilised quantifiable outcome measures (categorised into health indicators and service utilisation). The study quality was evaluated with Critical Appraisal Skills Programme (CASP) appraisal checklists. RESULTS: Initial searching yielded 21,090 results with 42 studies meeting the inclusion criteria. High CoC was associated with reduced hospitalisation (16 out of 18 studies), emergency room attendances (eight out of eight), mortality rate (six out of seven), disease-related complications (seven out of seven), and healthcare expenses (four out of four) but not with blood pressure (two out of 13), lipid profile (one out of six), body mass index (zero out of three). Six out of 12 studies on diabetic outcomes reported significant improvement in haemoglobin A1c by higher CoC. Variations in the classification of continuity of care and outcome definition were identified, making meta-analyses inappropriate. CASP evaluation rated most studies fair in quality, but found insufficient adjustment on confounders, selection bias and short follow-up period were common limitations of current literatures. CONCLUSION: There is evidence of a strong association between higher continuity of care and reduced mortality rate, complication risks and health service utilisation among DM and/or HT patients but little to no improvement in various health indicators. Significant methodological heterogeneity in how CoC and patient outcomes are assessed limits the ability for meta-analysis of findings. Further studies comprising sufficient confounding adjustment and standardised definitions are needed to provide stronger evidence of the benefits of CoC on patients with DM and/or HT.

Cardiac magnetic resonance for asymptomatic patients with type 2 diabetes and cardiovascular high risk (CATCH): a pilot study.

BACKGROUND: Stress cardiovascular magnetic resonance (CMR) to screen for silent myocardial ischaemia in asymptomatic high risk patients with type 2 diabetes mellitus (DM) has never been performed, and its effectiveness is unknown. Our aim was to determine the feasibility of a screening programme using stress CMR by obtaining preliminary data on the prevalence of silent ischaemia caused by obstructive coronary artery disease (CAD) and quantify myocardial perfusion in asymptomatic high risk patients with type 2 diabetes. METHODS: In this prospective cohort study, we recruited 63 asymptomatic DM patients (mean age 66 years ± 4.4 years; 77.8% male); with Framingham risk score ≥ 20% from 3 sites from June 2017 to August 2018. Normal volunteers were recruited to determine normal global myocardial perfusion reserve index (MPRI). Adenosine stress CMR and global MPRI was performed and measured in all subjects. Positive stress CMR cases were referred for catheter coronary angiography (CCA) with/without fractional flow reserve (FFR) measurements. Positive CCA was defined as an FFR ≤ 0.8 or coronary narrowing ≥ 70%. Patients were followed up for major adverse cardiovascular events. Prevalence is presented as patient numbers and percentage. Mann-Whitney U test was used to compare global MPRI between patients and normal volunteers. RESULTS: 13 patients had positive stress CMR with positive CCA (20.6% of patient population), while 9 patients with positive stress CMR examinations had a negative CCA. 5 patients (7.9%) had infarcts detected of which 2 patients had no stress perfusion defects. 12 patients had coronary artery stents inserted, whilst 1 patient declined stent placement. DM patients had lower global MPRI than normal volunteers (n = 7) (1.43 ± 0.27 vs 1.83 ± 0.31 respectively; p < 0.01). After a median follow-up of 653 days, there was no death, heart failure, acute coronary syndrome hospitalisation or stroke. CONCLUSION: 20.6% of asymptomatic DM patients (with Framingham risk ≥ 20%) had silent obstructive CAD. Furthermore, asymptomatic patients have reduced global MPRI than normal volunteers. TRIAL REGISTRATION: ClinicalTrials.gov Registration Number: NCT03263728 on 28th August 2017; https://clinicaltrials.gov/ct2/show/NCT03263728.

Associations between usual glycated haemoglobin and cardiovascular disease in patients with type 2 diabetes mellitus: A 10-year diabetes cohort study.

AIM: To investigate the assocation between glycated haemoglobin (HbA1c) level and cardiovascular disease (CVD) risk among patients with type 2 diabetes. MATERIALS AND METHODS: This retrospective cohort study conducted in Hong Kong selected patients aged 45 to 84 years with type 2 diabetes mellitus and without CVD from primary care clinics during the period 2008 to 2010. Usual HbA1c measurement was calculated using a mixed-effects model to minimize regression dilution bias. The association between usual HbA1c and CVD risk was assessed by Cox regression, with adjustment for baseline covariates. Subgroup analyses by patient characteristics were also conducted. RESULTS: After a median follow-up period of 8.4 years (1.4 million person-years), 174 028 patients with 34 074 CVD events were observed. A curvilinear association was found between usual HbA1c and total CVD, stroke, heart failure and CVD mortality risk. No significant difference was found among patients with usual HbA1c <53 mmol/mol (7%). A positive linear association was found between usual HbA1c and the risks of outcomes when the usual HbA1c was 53 mmol/mol (7%) or above. The adjusted hazard ratios (HRs) for CVD risk per 1% increment in usual HbA1c >7% was 21% (HR 1.21, 95% confidence interval [CI] 1.18-1.23) (HR for CVD per 1mmol/mol increment in usual HbA1c > 53 mmol/mol was 1.7% (HR 1.017, CI 1.015-1.019)). A similar pattern was identified in a patient subgroup analysis, but the effects of usual HbA1c in younger patients were more prominent than in older patients. CONCLUSIONS: Usual HbA1c increments for levels >53 mmol/mol (7.0%) were associated with elevated CVD risk, but no difference was found in the population with usual HbA1c <53 mmol/mol (7.0%), irrespective of patient characteristics. For CVD prevention, strict adherence to an HbA1c target of <53 mmol/mol (7%) should apply to younger patients.

Age-specific associations of glycated haemoglobin variability with cardiovascular disease and mortality in patients with type 2 diabetes mellitus: A 10- year cohort study.

AIMS: To investigate the associations of increased variability in glycated haemoglobin (HbA1c) with cardiovascular disease (CVD) and mortality risk in patients with diabetes. MATERIALS AND METHODS: This prospective cohort study included 147 811 patients aged 45 to 84 years with type 2 diabetes mellitus, without CVD and with at least three HbA1c values recorded before baseline in the period 2008 to 2010. HbA1c variability was evaluated using a mixed effects model to reduce regression dilution bias. Age-specific associations (45- 54, 55- 64, 65- 74 and 75- 84 years) between HbA1c variability and risk of CVD and mortality were assessed by Cox regression, adjusted for patient characteristics and usual HbA1c. RESULTS: After a median follow-up of 7.4 years(1.02 million person-years), an overall incidence of 40 785 events including CVD (incidence 27 793) and all-cause mortalities (incidence 23 175) were identified. Positive log-linear associations between HbA1c variability and CVD and mortality were identified in all age groups. The hazard ratios (HRs) for the composite of CVD and all-cause mortality showed that age was inversely associated with HbA1c variability, with a 28% higher risk per 1% increase in HbA1c variability in the age group 45 to 54 years (all composite outcomes: HR 1.28, 95% confidence interval [CI] 1.21, 1.35), whereas only a 14% higher risk in the 75- 84 age group (all composite outcomes: HR 1.14, 95% CI 1.11, 1.17). Subgroup analysis showed the risk in patients with usual HbA1c <53mmol/mol was about eight times higher than in those with usual HbA1c ≥64mmol/mol. CONCLUSIONS: HbA1c variability was strongly related to CVD and mortality in patients with diabetes across all age groups. Whilst pursuing optimal HbA1c targets, attention should be given to patients with high HbA1c variability, especially younger patients with good HbA1c control.

Greater variability in lipid measurements associated with cardiovascular disease and mortality: A 10-year diabetes cohort study.

AIM: To examine the associations between variability in lipids and the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes based on low-density lipoprotein-cholesterol (LDL-C), the total cholesterol (TC) to high-density lipoprotein-cholesterol (HDL-C) ratio and triglycerides (TG). MATERIALS AND METHODS: A retrospective cohort study included 125 047 primary care patients with type 2 diabetes aged 45-84 years without CVD during 2008-2012. The variability of LDL-C, TC to HDL-C and TG was determined using the standard deviation of variables in a mixed effects model to minimize regression dilution bias. The associations between variability in lipids and CVD and mortality risk were assessed by Cox regression. Subgroup analyses based on patients' baseline characteristics were also conducted. RESULTS: A total of 19 913 CVD events and 15 329 mortalities were recorded after a median follow-up period of 77.5 months (0.8 million person-years), suggesting a positive linear relationship between variability in lipids and the risk of CVD and mortality. Each unit increase in the variability of LDL-C (mmol/L), the TC to HDL-C ratio and TG (mmol/L) was associated with a 27% (HR: 1.27 [95% CI: 1.20-1.34]), 31% (HR:1.31 [95% CI: 1.25-1.38]) and 9% (HR: 1.09 [95% CI: 1.04-1.15]) increase in the risk of composite endpoint of CVD and mortality, respectively. Age-specific effects were also found when comparing LDL-C variability, with patients aged 45-54 years (HR: 1.70 [95% CI: 1.42-2.02]) exhibiting a 53% increased risk for the composite endpoints than those aged 75-84 years (HR: 1.11 [95% CI: 1.01-1.23]). Similar age effects were observed for both the TC to HDL-C ratio and TG variability. Significant associations remained consistent among most of the subgroups. CONCLUSIONS: Variability in respective lipids are significant factors in predicting CVD and mortality in primary care patients with type 2 diabetes, with the strongest effects related to LDL-C and the TC to HDL-C ratio and most significant in the younger age group of patients aged 45-54 years. Further study is warranted to confirm these findings.

Trend in health-related quality of life and health utility and their decrements due to non-communicable diseases and risk factors: analysis of four population-based surveys between 1998 and 2015.

PURPOSE: To revisit the population norms of health-related quality of life (HRQoL) and health utility for the Hong Kong general population, compare these scores over past health surveys, and assess the association of scores with non-communicable diseases (NCDs) and their risk factors. METHODS: HRQoL data measured by the standard Short Form 12 Health Survey-version 2 (SF-12v2) were extracted from the surveys in 1998, 2003/2004, 2008/2009 and 2014/2015. SF-12v2 data were mapped to the Short-form 6-dimension (SF-6D) preference-based measure to generate the health utility scores. Population weighting based on the sex and age in the second quarter of 2015 was applied when generating population normative values. Linear regression models were fitted to assess the effect of the number of NCDs and modifiable lifestyle factors on HRQoL and health utility. RESULTS: The general population mean scores of SF-12v2 domains and SF-6D in 2014/15 were higher compared to past surveys. Linear increases in General Health, Vitality and Mental Health domains were observed from 1998 to 2014/15. More doctor-diagnosed NCDs, insufficient physical activity and fruit/vegetable consumption, poor sleep quality and insufficient or excessive amount of sleep (< 6/≥ 10 h) were all associated with worse physical- and mental-related HRQoL and health utility. CONCLUSION: This study compared HRQoL and health utility in the Hong Kong general population derived from multiple surveys and found an improving trend over twenty years. More NCDs were associated with worse HRQoL. It is suggested that promoting adequate physical activity, consumption of fruit/vegetable and 6-9 h of sleep could improve health.

Development and pilot evaluation of a mobile app on parent-child exercises to improve physical activity and psychosocial outcomes of Hong Kong Chinese children.

BACKGROUND: Parent-child exercises involve children and parents to do workout together and have positive effects on physical and mental health. We developed a mobile app on parent-child exercises called Family Move, which combines coaching videos with game features such as points and level system to enhance the health and wellbeing of both children and parents through parent-child exercises. This pilot pre-post study investigated whether the Family Move app-based intervention had a positive effect on children's health-related quality of life (HRQOL), psychosocial wellbeing, and physical activity (PA) level. METHODS: We recruited 67 parent-child pairs. During the 8-week intervention, these pairs were invited to perform parent-child exercises using the Family Move app. Points were automatically added to the user account after viewing a coaching video. In-game ranking was available to enhance user engagement. Parent proxy-report questionnaires on children's HRQOL, psychosocial wellbeing, and PA were administered at baseline and 1- and 6-month follow-up. Paired samples t-tests were conducted to evaluate post-intervention changes in child outcomes (HRQOL, psychosocial wellbeing, and PA). Multiple linear regressions were used to examine these changes as a function of in-game ranking. RESULTS: 52 (78%) viewed at least one coaching video in the Family Move app. Children's PA level significantly increased at 1-month (d = 0.32, p = 0.030) and 6-month (d = 0.30, p = 0.042) follow-up, whereas their psychosocial problems declined at 6-month follow-up (d = 0.35, p = 0.005). Higher in-game ranking was significantly associated with fewer psychosocial problems at 1-month follow-up (ß = - 0.15, p = 0.030). CONCLUSIONS: Our findings suggest that the Family Move app could be a possible intervention to increase children's PA level and psychosocial wellbeing through parent-child exercise. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03279354 , registered September 11, 2017 (Prospectively registered).

Burden of CKD and Cardiovascular Disease on Life Expectancy and Health Service Utilization: a Cohort Study of Hong Kong Chinese Hypertensive Patients.

BACKGROUND: The relative effects of combinations of CKD, heart disease, and stroke on risk of mortality, direct medical costs, and life expectancy are unknown. METHODS: In a retrospective cohort study of 506,849 Chinese adults in Hong Kong with hypertension, we used Cox regressions to examine associations between all-cause mortality and combinations of moderate CKD (eGFR of 30-59 ml/min per 1.73 m2), severe CKD (eGFR of 15-29 ml/min per 1.73 m2), heart disease (coronary heart disease or heart failure), and stroke, and modeling to estimate annual public direct medical costs and life expectancy. RESULTS: Over a median follow-up of 5.8 years (2.73 million person-years), 55,666 deaths occurred. Having an increasing number of comorbidities was associated with incremental increases in mortality risk and medical costs and reductions in life expectancy. Compared with patients who had neither CKD nor cardiovascular disease, patients with one, two, or three conditions (heart disease, stroke, and moderate CKD) had relative risk of mortality increased by about 70%, 160%, and 290%, respectively; direct medical costs increased by about 70%, 160%, and 280%, respectively; and life expectancy at age 60 years decreased by about 5, 10, and 15 years, respectively. Burdens were higher with severe CKD. CONCLUSIONS: This study demonstrated extremely high mortality risk and medical cost increases for severe CKD, exceeding the combined effects from heart disease and stroke. Mortality risks and costs for moderate CKD, heart disease, and stroke were similar individually and roughly multiplicative for any combination. These findings suggest that to reduce mortality and health care costs in patients with hypertension, CKD prevention and intervention merits priority equal to that of cardiovascular disease.

Acute sleep deprivation enhances susceptibility to the migraine substrate cortical spreading depolarization.

BACKGROUND: Migraine is a common headache disorder, with cortical spreading depolarization (CSD) considered as the underlying electrophysiological event. CSD is a slowly propagating wave of neuronal and glial depolarization. Sleep disorders are well known risk factors for migraine chronification, and changes in wake-sleep pattern such as sleep deprivation are common migraine triggers. The underlying mechanisms are unknown. As a step towards developing an animal model to study this, we test whether sleep deprivation, a modifiable migraine trigger, enhances CSD susceptibility in rodent models. METHODS: Acute sleep deprivation was achieved using the "gentle handling method", chosen to minimize stress and avoid confounding bias. Sleep deprivation was started with onset of light (diurnal lighting conditions), and assessment of CSD was performed at the end of a 6 h or 12 h sleep deprivation period. The effect of chronic sleep deprivation on CSD was assessed 6 weeks or 12 weeks after lesioning of the hypothalamic ventrolateral preoptic nucleus. All experiments were done in a blinded fashion with respect to sleep status. During 60 min of continuous topical KCl application, we assessed the total number of CSDs, the direct current shift amplitude and duration of the first CSD, the average and cumulative duration of all CSDs, propagation speed, and electrical CSD threshold. RESULTS: Acute sleep deprivation of 6 h (n = 17) or 12 h (n = 11) duration significantly increased CSD frequency compared to controls (17 ± 4 and 18 ± 2, respectively, vs. 14 ± 2 CSDs/hour in controls; p = 0.003 for both), whereas other electrophysiological properties of CSD were unchanged. Acute total sleep deprivation over 12 h but not over 6 h reduced the electrical threshold of CSD compared to controls (p = 0.037 and p = 0.095, respectively). Chronic partial sleep deprivation in contrast did not affect CSD susceptibility in rats. CONCLUSIONS: Acute but not chronic sleep deprivation enhances CSD susceptibility in rodents, possibly underlying its negative impact as a migraine trigger and exacerbating factor. Our findings underscore the importance of CSD as a therapeutic target in migraine and suggest that headache management should identify and treat associated sleep disorders.

Evaluation of the responsiveness of Short Form-12 Health Survey version 2 (SF-12v2) in Chinese patients with hypertension in primary care.

PURPOSE: There is limited evidence on the responsiveness of the Short Form-12 Health Survey version 2 (SF-12v2) in hypertensive patients. This study aimed to evaluate both the responsiveness of the SF-12 measures in Chinese hypertensive patients. METHODS: A prospective longitudinal study was conducted on hypertensive patients managed in public primary care clinics between 2012 and 2013. A total of 583 and 431 patients were surveyed and completed SF-12v2 at baseline and at 12-month follow-up interviews, respectively. Using global rating of change scale as an external anchor, the responsiveness was assessed by linear mixed effect models, multiple linear regression models, and receiver operating characteristic (ROC) curve analysis. RESULTS: SF-12v2 managed to detect negative changes among hypertensive patients in worsened general health group but failed to identify changes among hypertensive patients in improved general health group. Meanwhile, some domains of SF-12v2 detected a significant difference in difference between patients of worsened and stable/improved group and between patients of stable and improved group, but none of the domains and the summary scales reached the recommended standard of 0.7 in any comparisons in ROC analysis. CONCLUSIONS: The SF-12v2 was responsive to worsening of HRQOL but not to improvements in HRQOL among hypertensive patients. The overall responsiveness of SF-12v2 in hypertensive patients is unsatisfactory. Further studies are needed to identify HRQOL measures with good internal and external responsiveness for hypertensive patients.

Temporal trends in quality of primary care for patients with type 2 diabetes mellitus: A population-based retrospective cohort study after implementation of a quality improvement initiative.

BACKGROUND: This study examined whether temporal trends exist in treatment of patients with type 2 diabetes (T2D) and quality of diabetes care after implementation of quality improvement initiative in primary care setting. METHODS: We conducted a population-based retrospective cohort study of 202,284 patients with T2D who were routinely managed in primary care clinics. We examined the change over time and the variability between clinics in quality of care from Hospital Authority administrative data over a 5-year period (2009-2013) and used multilevel logistic regression to adjust for patient and clinic characteristics. Observational period was partitioned in 5 calendar years. Ten quality-of-care criteria were selected: adherence to 7 process of care criteria (HbA1c test, renal function test, full lipid profile, urine protein analysis, retinal screening, lipid-lowering agent prescriptions among patients with hypercholesterolaemia, and angiotensin converting enzyme inhibitor/angiotensin receptor blocker prescriptions among patients with microalbuminuria) and 3 outcome of care criteria (HbA1c  ≤ 7%, BP ≤ 130/80 mmHg, and LDL-C ≤ 2.6 mmol/L). Variability of standards between clinics was assessed by using intracluster correlation coefficients. RESULTS: Characteristics of patients with T2D managed in primary care changed substantially during the observational period, with increasing age and usage of insulin and longer duration of diabetes but improved metabolic profiles (all P trend < .001). Performance rates of the 7 process and 3 clinical outcomes of care criteria increased remarkably over time (all P trend < .001). Variations in retinal screening delivery between clinics were considerable, albeit decreasing over time. CONCLUSIONS: Coinciding with implementation of quality improvement initiative, quality of diabetes care improved significantly in the past 5 years, in part attributable to benefits of integrated multidisciplinary diabetes management.