Benefits and Risks Associated With Statin Therapy for Primary Prevention in Old and Very Old Adults : Real-World Evidence From a Target Trial Emulation Study.

BACKGROUND: There is little consensus on using statins for primary prevention of cardiovascular diseases (CVDs) and all-cause mortality in adults aged 75 years or older due to the underrepresentation of this population in randomized controlled trials. OBJECTIVE: To investigate the benefits and risks of using statins for primary prevention in old (aged 75 to 84 years) and very old (aged ≥85 years) adults. DESIGN: Sequential target trial emulation comparing matched cohorts initiating versus not initiating statin therapy. SETTING: Territory-wide public electronic medical records in Hong Kong. PARTICIPANTS: Persons aged 75 years or older who met indications for statin initiation from January 2008 to December 2015 were included. Participants with preexisting diagnosed CVDs at baseline, such as coronary heart disease (CHD), were excluded from the analysis. Among 69 981 eligible persons aged 75 to 84 years and 14 555 persons aged 85 years or older, 41 884 and 9457 had history of CHD equivalents (for example, diabetes) in the respective age groups. INTERVENTION: Initiation of statin therapy. MEASUREMENTS: Incidence of major CVDs (stroke, myocardial infarction, or heart failure), all-cause mortality, and major adverse events (myopathies and liver dysfunction). RESULTS: Of 42 680 matched person-trials aged 75 to 84 years and 5390 matched person-trials aged 85 years or older (average follow-up, 5.3 years), 9676 and 1600 of them developed CVDs in each age group, respectively. Risk reduction for overall CVD incidence was found for initiating statin therapy in adults aged 75 to 84 years (5-year standardized risk reduction, 1.20% [95% CI, 0.57% to 1.82%] in the intention-to-treat [ITT] analysis; 5.00% [CI, 1.11% to 8.89%] in the per protocol [PP] analysis) and in those aged 85 years or older (ITT: 4.44% [CI, 1.40% to 7.48%]; PP: 12.50% [CI, 4.33% to 20.66%]). No significantly increased risks for myopathies and liver dysfunction were found in both age groups. LIMITATION: Unmeasured confounders, such as lifestyle factors of diet and physical activity, may exist. CONCLUSION: Reduction for CVDs after statin therapy were seen in patients aged 75 years or older without increasing risks for severe adverse effects. Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older. PRIMARY FUNDING SOURCE: Health Bureau, the Government of Hong Kong Special Administrative Region, China, and National Natural Science Foundation of China.

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.

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.

Feasibility and acceptability of electronic EQ-5D-5L for routine measurement of HRQOL in patients with chronic musculoskeletal problems in Hong Kong primary care.

BACKGROUND: Information on HRQOL can enhance patient diagnosis and management but it is rarely available in routine clinical practice. This mixed-method study evaluated the feasibility and acceptability of the electronic EQ-5D-5L measurement of HRQOL in patients with chronic musculoskeletal problems in primary care. METHODS: In three primary care clinics, 665 patients with musculoskeletal problems completed the electronic EQ-5D-5L and Visual Analogue Scale (e-EQ-5D-5L/VAS), and a questionnaire on socio-demographics, perceived ease of use (PEOU), and perceived usefulness (PU) at baseline and two follow-ups. Patient completion and response rates, and time to complete the e-EQ-5D-5L/VAS were measured. During the same consultations, 49 doctors reviewed the e-EQ-5D-5L/VAS reports and completed a clinician questionnaire on PEOU, PU, and time spent to address each report. Individual interviews along with focus group discussions were conducted on patients, doctors, and research assistants for further exploration. RESULTS: Mean completion time reduced from baseline to first and second follow-up (120.66, 83.99, and 105.22 s, respectively). Completion and response rates were high at each follow-up visit (> 99.8% and > 91.11%, respectively). Doctors needed less than 2 min to read the report but felt the time required to address the report was a significant barrier. Some patients had difficulties using e-platforms, in understanding or answering questions; but, PEOU improved with time (p < 0.001). Most patients found the e-platforms useful (> 85.3%). Clinicians agreed a great majority of the reports were easy to use (76.0-85.1%) and useful (69.2-72.0%), particularly aiding with a holistic view of the patient's musculoskeletal problem. CONCLUSION: The e-EQ-5D-5L/VAS is a feasible and acceptable measurement of HRQOL of patients with chronic musculoskeletal problems in routine primary care in Hong Kong which can assist real-time management decisions. TRIAL REGISTRATION: NCT03609762.

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.

Identifying and articulating the student experience in the Intercalated Enrichment Year.

BACKGROUND: Benefits of intercalation during an undergraduate medical degree are well-recognized. The University of Hong Kong implemented a compulsory Enrichment Year (EY) in its Bachelor of Medicine and Bachelor of Surgery degree programme (MBBS) in 2016. In their third year of study, students could work on an area of interest in any of three programme categories (i) intercalation/ university exchange (IC); (ii) research (RA); (iii) service/ humanitarian work (SH). This study aimed to explore the barriers, enablers, and overall student learning experiences from the first cohort of EY students in order to inform future development of the EY. METHODS: An exploratory sequential mixed-method study in 2019-20. Twenty students were purposively selected to attend three semi-structured focus group interviews. Conventional thematic analysis was employed and results assisted the design of a cross-sectional questionnaire. Sixty-three students completed the questionnaire. ANOVA or chi-square test was used to compare the difference in student's characteristics, barriers, enablers and perspectives on EY between programme categories. Adjusting student's characteristics, logistic regressions were conducted to identify the effect of programme categories on the EY experience. RESULTS: Most students (95% in the questionnaire) agreed that EY was worthwhile and more rewarding than expected. EY was positively regarded for enhancing personal growth and interpersonal relationships. The main barriers were financial difficulties, scholarship issues and insufficient information beforehand. A few students had practical (i.e. accommodation, cultural adaptation) problems. Potential enablers included better financial support, more efficient information exchange and fewer assignments and preparation tasks. Similar barriers were encountered by students across all three categories of EY activities. CONCLUSIONS: Personal growth was the most important benefit of the EY. Barriers were consistent with those identified in the literature except for cultural adaptation, which could be related to Hong Kong's unique historical context. Financial limitation was the most concerning barrier, as it could result in unequal access to educational opportunities. Better and timely access to scholarships and other funding sources need to be considered. TRIAL REGISTRATION: Ethics approval was obtained from the local Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 19-585 ).

Prediction models and nomograms for 10-year risk of end-stage renal disease in Chinese type 2 diabetes mellitus patients in primary care.

AIMS: To develop and validate 10-year risk prediction models, nomograms and charts for end-stage renal disease (ESRD) in Chinese patients with type 2 diabetes mellitus (T2DM) in primary care, in order to guide individualized treatment. MATERIALS AND METHODS: This was a 10-year population-based observational cohort study. A total of 141 516 Chinese T2DM patients without history of cardiovascular disease or ESRD who were managed in public primary care clinics in 2008 were included and followed up until December 2017. Two-thirds of these patients were randomly selected to develop sex-specific ESRD risk prediction models using Cox regressions. The validity and accuracy of the models were tested on the remaining third of patients using Harrell's C-index. We selected variables based on their clinical and statistical importance to construct the nomograms and charts. RESULTS: The median follow-up period was 9.75 years. The cumulative incidence of ESRD was 6.0% (men: 6.1%, women: 5.9%). Age, diabetes duration, systolic blood pressure (SBP), SBP variability, diastolic blood pressure, triglycerides, glycated haemoglobin (HbA1c), HbA1c variability, urine albumin to creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR) were significant predictors for both sexes. Smoking and total cholesterol to HDL cholesterol ratio were additional significant predictors for men and women, respectively. The models showed Harrell's C-statistics of 0.889/0.889 (women/men). Age, eGFR, UACR, SBP and HbA1c were selected for both sexes to develop nomograms and charts. CONCLUSIONS: Using routinely available variables, the 10-year ESRD risk of Chinese T2DM patients in primary care can be predicted with approximately 90% accuracy. We have developed different tools to facilitate routine ESRD risk prediction in primary care, so that individualized care can be provided to prevent or delay ESRD in T2DM patients.

Generative adversarial networks for imputing missing data for big data clinical research.

BACKGROUND: Missing data is a pervasive problem in clinical research. Generative adversarial imputation nets (GAIN), a novel machine learning data imputation approach, has the potential to substitute missing data accurately and efficiently but has not yet been evaluated in empirical big clinical datasets. OBJECTIVES: This study aimed to evaluate the accuracy of GAIN in imputing missing values in large real-world clinical datasets with mixed-type variables. The computation efficiency of GAIN was also evaluated. The performance of GAIN was compared with other commonly used methods, MICE and missForest. METHODS: Two real world clinical datasets were used. The first was that of a cohort study on the long-term outcomes of patients with diabetes (50,000 complete cases), and the second was of a cohort study on the effectiveness of a risk assessment and management programme for patients with hypertension (10,000 complete cases). Missing data (missing at random) to independent variables were simulated at different missingness rates (20, 50%). The normalized root mean square error (NRMSE) between imputed values and real values for continuous variables and the proportion of falsely classified (PFC) for categorical variables were used to measure imputation accuracy. Computation time per imputation for each method was recorded. The differences in accuracy of different imputation methods were compared using ANOVA or non-parametric test. RESULTS: Both missForest and GAIN were more accurate than MICE. GAIN showed similar accuracy as missForest when the simulated missingness rate was 20%, but was more accurate when the simulated missingness rate was 50%. GAIN was the most accurate for the imputation of skewed continuous and imbalanced categorical variables at both missingness rates. GAIN had a much higher computation speed (32 min on PC) comparing to that of missForest (1300 min) when the sample size is 50,000. CONCLUSION: GAIN showed better accuracy as an imputation method for missing data in large real-world clinical datasets compared to MICE and missForest, and was more resistant to high missingness rate (50%). The high computation speed is an added advantage of GAIN in big clinical data research. It holds potential as an accurate and efficient method for missing data imputation in future big data clinical research. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03299010 ; Unique Protocol ID: HKUCTR-2232.

A pilot study on the validity and psychometric properties of the electronic EQ-5D-5L in routine clinical practice.

BACKGROUND: Electronic measurement of health-related quality of life (HRQOL) may facilitate timely and regular assessments in routine clinical practice. This study evaluated the validity and psychometric properties of an electronic version of the EQ-5D-5L (e-EQ-5D-5L) in Chinese patients with chronic knee and/or back problems. METHODS: 151 Chinese subjects completed an electronic version of the Chinese (Hong Kong) EQ-5D-5L when they attended a primary care or orthopedics specialist out-patient clinic in Hong Kong. They also completed the Chinese Western Ontario and McMaster University Osteoarthritis Index (WOMAC), a Pain Rating Scale, and a structured questionnaire on socio-demographics, co-morbidities and health service utilization. 32 subjects repeated the e-EQ-5D-5L two weeks after the baseline. 102 subjects completed e-EQ-5D-5L and 99 completed the Global Rating on Change Scale at three-month clinic follow up. Construct validity was assessed by the association of EQ-5D-5L scores with external criterion of WOMAC scores. We tested mean differences of WOMAC scores between adjacent response levels of the EQ-5D-5L dimensions by one-way ANOVA, test-retest reliability by intra-class correlation, sensitivity by known group comparisons and responsiveness by changes in EQ-5D-5L scores over 3 months. RESULTS: There was an association between EQ-5D-5L and WOMAC scores. Mean WOMAC scores increased with the increase in adjacent response levels of EQ-5D-5L dimensions. Test-retest intraclass correlation coefficient (ICC) of EQ-5D-5L utility and EQ-VAS scores were 0.76 and 0.83, respectively, indicating good reliability. There were significant differences in the proportions reporting limitations in the EQ-5D-5L dimensions, the utility and VAS scores between the mild and severe pain groups (utility = 0.28, p = 0.001; VAS = 11.46, p < 0.001), and between primary care and specialist out-patient clinic patients (utility = 0.15, p = 0.001; VAS = 10.21, p < 0.001), supporting sensitivity. Among those reporting 'better' global health at three-months, their EQ-5D-5L utility and EQ-VAS scores were significantly increased from baseline (utility = 0.18, p < 0.001; VAS = 10.75, p = 0.005). CONCLUSIONS: The electronic version of the EQ-5D-5L is valid, reliable, sensitive and responsive in the measurement of HRQOL in Chinese patients with chronic knee or back pain in routine clinical practice.

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.

Five-year effectiveness of bariatric surgery on disease remission, weight loss, and changes of metabolic parameters in obese patients with type 2 diabetes: A population-based propensity score-matched cohort study.

AIMS: To compare disease remission rates, weight loss, and changes of metabolic parameters of patients after bariatric surgery with nonsurgical patients. METHODS: Based on the 2006-2017 Hospital Authority database, a population-based retrospective cohort of obese type 2 diabetes mellitus (T2DM) patients with and without bariatric surgery were identified. Surgical patients were matched with nonsurgical patients on 1-to-5 propensity score. Remission rates of diabetes, hypertension, and dyslipidaemia were reported annually up to 60 months. Changes in weight loss measurements (Body Mass Index [BMI], percentage of total weight loss [%TWL], percentage of excess weight loss [%EWL], and percentage of rebound in excess weight loss [%REWL]) and metabolic parameters (haemoglobin A1c [HbA1c ], systolic blood pressure [SBP], diastolic blood pressure [DBP], and low-density lipoprotein cholesterol [LDL-C]) were measured for both groups. RESULTS: Four hundred one surgical patients (310 restrictive surgeries; 91 bypass surgeries) and 1894 nonsurgical patients were included. Surgical patients had higher remission rates in diabetes and dyslipidaemia and better glycaemic control at 12 to 60 months (all Ps < .01). SBP and DBP were significantly lower for surgical group up to 12 months and similar between two groups after 12 months. Surgical patients had significantly lower BMI during follow-up period. %TWL and %EWL were higher in the surgery group (15.7% vs 3.7%; 48.8% vs 12.0%) at 60 months (P < .001); differences in %REWL between two groups were insignificant. The effectiveness of restrictive and bypass surgeries was similar at 60 months, although restrictive surgeries were slightly more effective in T2DM remission. CONCLUSIONS: Bariatric surgery was effective in weight loss, remission of diabetes, and dyslipidaemia in 5-year post-surgery.

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.

Lower urinary tract symptoms and health-related quality of life in Hong Kong primary care: a cross-sectional study.

PURPOSE: To estimate the prevalence of lower urinary tract symptoms (LUTS) in primary care using the International Continence Society symptom definition; to evaluate the association between LUTS and health-related quality of life (HRQOL); and to evaluate the treatment gaps. METHODS: Patients aged 40 and above were randomly recruited in a Hong Kong public primary care. Patients were asked (i) how often they experienced 18 individual LUTS during the past 4 weeks and (ii) whether they had sought treatments for their LUTS. The 12-Item Short Form Health Survey version 2 (SF-12 v2) and the modified Incontinence Impact Questionnaire-Short Form (IIQ-7) were used to measure HRQOL. RESULTS: 500 patients completed the survey. 75.8% of the patients had at least one LUTS "at least sometimes", with patients with a combination of storage, voiding, and post-micturition symptoms being the most prevalent (22.2%), followed by a combination of voiding and storage symptoms (14%). Only 14% of LUTS patients had sought treatments for their LUTS. LUTS was associated with a negative effect in all domains of the SF-12 v2 and IIQ-7 and patients with a combination of storage, voiding, and post-micturition symptoms had the worst HRQOL. Finally, having a combination of storage, voiding, and post-micturition symptoms and poorer HRQOL were factors associated with having sought treatments for LUTS. CONCLUSION: A high prevalence of LUTS but low treatment-seeking rates implied possible unmet needs of LUTS patients in primary care, suggesting the potential for more active interventions to alleviate the negative impact of LUTS on patients' HRQOL.

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.

Tree analysis modeling of the associations between PHQ-9 depressive symptoms and doctor diagnosis of depression in primary care.

BACKGROUND: The aim of this study was to explore the relationship between patient self-reported Patient Health Questionnaire-9 (PHQ-9) symptoms and doctor diagnosis of depression using a tree analysis approach. METHODS: This was a secondary analysis on a dataset obtained from 10 179 adult primary care patients and 59 primary care physicians (PCPs) across Hong Kong. Patients completed a waiting room survey collecting data on socio-demographics and the PHQ-9. Blinded doctors documented whether they thought the patient had depression. Data were analyzed using multiple logistic regression and conditional inference decision tree modeling. RESULTS: PCPs diagnosed 594 patients with depression. Logistic regression identified gender, age, employment status, past history of depression, family history of mental illness and recent doctor visit as factors associated with a depression diagnosis. Tree analyses revealed different pathways of association between PHQ-9 symptoms and depression diagnosis for patients with and without past depression. The PHQ-9 symptom model revealed low mood, sense of worthlessness, fatigue, sleep disturbance and functional impairment as early classifiers. The PHQ-9 total score model revealed cut-off scores of >12 and >15 were most frequently associated with depression diagnoses in patients with and without past depression. CONCLUSIONS: A past history of depression is the most significant factor associated with the diagnosis of depression. PCPs appear to utilize a hypothetical-deductive problem-solving approach incorporating pre-test probability, with different associated factors for patients with and without past depression. Diagnostic thresholds may be too low for patients with past depression and too high for those without, potentially leading to over and under diagnosis of depression.

The mediating role of sleep quality in the association between nocturia and health-related quality of life.

BACKGROUND: Even though the negative impacts of nocturia on sleep quality and health-related quality of life (HRQOL) have been documented in previous research, their interrelationship has been poorly studied. This study aimed to explore whether nocturia would affect sleep quality, which in turn affects HRQOL. METHODS: Participants aged 40 and above were randomly recruited from a Hong Kong public primary care clinic. Participants were asked to report the average number of nocturia (waking up at night to void) pisodes per night over a 1-month period. The Pittsburgh Sleep Quality Index (PSQI) and the 12-Item Short Form Health Survey version 2 (SF-12 v2) were administered. The mediation analysis was tested using multistage regression approach and bootstrap method. RESULTS: Of the 500 subjects who completed the survey, 31.2% reported symptomatic nocturia (having ≥2 nocturia episodes per night), and 60.4% experienced poor sleep quality (a PSQI global score > 5). Respondents with symptomatic nocturia had a poorer HRQOL in the domains of physical functioning (PF), role physical (RP) and social functioning (SF), general health (GH), vitality (VT) and physical component summary (PCS) of the SF-12 v2 than those without. Compared with the respondents without poor sleep quality, those with poor sleep quality had poorer HRQOL across all domains and summaries of the SF-12 v2. Mediation analysis found that sleep quality fully mediated the association between nocturia and the PF, RP and SF domains of the SF-12 v2, respectively, and partially mediated the association between nocturia and the GH, VT and PCS domains of the SF-12 v2, respectively. CONCLUSIONS: We found that sleep quality mediated the association between nocturia and HRQOL. To enhance the HRQOL of patients with nocturia, clinicians should not only focus on nocturia symptoms, but also on their sleep quality.

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.