Development and validation of 10-year risk prediction models of cardiovascular disease in Chinese type 2 diabetes mellitus patients in primary care using interpretable machine learning-based methods.

AIM: To develop 10-year cardiovascular disease (CVD) risk prediction models in Chinese patients with type 2 diabetes mellitus (T2DM) managed in primary care using machine learning (ML) methods. METHODS: In this 10-year population-based retrospective cohort study, 141 516 Chinese T2DM patients aged 18 years or above, without history of CVD or end-stage renal disease and managed in public primary care clinics in 2008, were included and followed up until December 2017. Two-thirds of the patients were randomly selected to develop sex-specific CVD risk prediction models. The remaining one-third of patients were used as the validation sample to evaluate the discrimination and calibration of the models. ML-based methods were applied to missing data imputation, predictor selection, risk prediction modelling, model interpretation, and model evaluation. Cox regression was used to develop the statistical models in parallel for comparison. RESULTS: During a median follow-up of 9.75 years, 32 445 patients (22.9%) developed CVD. Age, T2DM duration, urine albumin-to-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), systolic blood pressure variability and glycated haemoglobin (HbA1c) variability were the most important predictors. ML models also identified nonlinear effects of several predictors, particularly the U-shaped effects of eGFR and body mass index. The ML models showed a Harrell's C statistic of >0.80 and good calibration. The ML models performed significantly better than the Cox regression models in CVD risk prediction and achieved better risk stratification for individual patients. CONCLUSION: Using routinely available predictors and ML-based algorithms, this study established 10-year CVD risk prediction models for Chinese T2DM patients in primary care. The findings highlight the importance of renal function indicators, and variability in both blood pressure and HbA1c as CVD predictors, which deserve more clinical attention. The derived risk prediction tools have the potential to support clinical decision making and encourage patients towards self-care, subject to further research confirming the models' feasibility, acceptability and applicability at the point of care.

Age-specific Multimorbidity Patterns and Burden on All-Cause Mortality and Public Direct Medical Expenditure: A Retrospective Cohort Study.

OBJECTIVE: To evaluate age-specific multimorbidity patterns and morbidity burden on mortality and healthcare expenditure across age groups. PATIENTS AND METHODS: Retrospective observational study between January 1, 2009 to December 31, 2017 using electronic health records in Hong Kong: Individuals were stratified by age (< 50, 50-64, 65-79, ≥ 80), and sub-classified by number of morbidities (0, 1, 2, 3, ≥ 4) out of 21 common chronic conditions. Clustering analyses were conducted to identify specific patterns of multimorbidity. Association between the number as well as combinations of morbidities and all-cause mortality and public expenditure was examined. RESULTS: 4,562,832 individuals with a median follow-up of 7 years were included. Mental disorders were the top morbidities among young individuals, while cardiovascular diseases were prevalent in the elderly. An increased number of morbidities was associated with a greater relative risk for mortality and medical expenditure, and this relationship was stronger among younger patients. Compared to individuals in the same age group without morbidity, the hazard ratios (HR; 95% CI) of all-cause mortality in patients aged < 50 and ≥ 80 with two comorbidities 3.81 (3.60-4.03) and 1.38 (1.36-1.40), respectively, which increased to 14.22 (9.87-20.47) and 2.20 (2.13-2.26), respectively, as the number of morbidities increased to ≥ 4. The stroke-hypertension cluster was shown to be associated with the highest HR of mortality 2.48 (2.43-2.53) among all identified clusters arising from the clustering analysis. CONCLUSION: Given the stronger association between multimorbidity and all-cause mortality and greater opportunity costs in younger populations, prevention and management of early-onset multimorbidity are warranted. (248 words).

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.

Associations and attributable burden between risk factors and all-cause and cause-specific mortality at different ages in patients with hypertension.

It remains unclear the age-specific associations of risk factors with deaths and mortality burden attributable across age. In a territory-wide retrospective cohort, 1,012,228 adults with hypertension were identified. Comorbidities including diabetes, chronic kidney disease (CKD), cardiovascular disease (CVD), heart failure, and cancer, and risk factors including current smoking and suboptimal control of blood pressure (BP), glucose and low-density lipoprotein cholesterol were defined. Associations of comorbidities/risk factors with all-cause and cause-specific mortality across age groups (18-54, 55-64, 65-74, and ≥75 years) were assessed. Population attributable fractions were also quantified. During a median follow-up of 10.7 years, 244,268 (24.1%) patients died, with pneumonia (7.2%), cancer (5.1%), and CVD (4.2%) being the leading causes. Despite increasing deaths with age, relative risk of mortality related to comorbidities/risk factors decreased with age; similar patterns were found for cause-specific mortality. The assessed risk factors accounted for 24.0% (95% CI 22.5%, 25.4%) deaths, with highest proportion in the youngest group (33.5% [28.1%, 38.5%] in 18-54 years vs 19.4% [17.0%, 21.6%] in ≥75 years). For mortality burden, CKD was the overall leading risk factor (12.7% [12.4%, 12.9%]) with higher proportions in older patients (11.1-13.1% in ≥65 years), while diabetes was the leading risk factor in younger patients (15.9-13.5% in 18-54 years). The association of comorbidities or risk factors with mortality is stronger in younger patients with hypertension, despite lower absolute mortality in young patients than in the elderly. Leading risk factors differed across age, highlighting the importance of targeted and precise risk management.

Correction to Nb Doping and Alloying of 2D WS2 by Atomic Layer Deposition for 2D Transition Metal Dichalcogenide Transistors and HER Electrocatalysts.

[This corrects the article DOI: 10.1021/acsanm.4c00094.].

Recalibration of a Non-Laboratory-Based Risk Model to Estimate Pre-Diabetes/Diabetes Mellitus Risk in Primary Care in Hong Kong.

INTRODUCTION/OBJECTIVES: A non-laboratory-based pre-diabetes/diabetes mellitus (pre-DM/DM) risk prediction model developed from the Hong Kong Chinese population showed good external discrimination in a primary care (PC) population, but the estimated risk level was significantly lower than the observed incidence, indicating poor calibration. This study explored whether recalibrating/updating methods could improve the model's accuracy in estimating individuals' risks in PC. METHODS: We performed a secondary analysis on the model's predictors and blood test results of 919 Chinese adults with no prior DM diagnosis recruited from PC clinics from April 2021 to January 2022 in HK. The dataset was randomly split in half into a training set and a test set. The model was recalibrated/updated based on a seven-step methodology, including model recalibrating, revising and extending methods. The primary outcome was the calibration of the recalibrated/updated models, indicated by calibration plots. The models' discrimination, indicated by the area under the receiver operating characteristic curves (AUC-ROC), was also evaluated. RESULTS: Recalibrating the model's regression constant, with no change to the predictors' coefficients, improved the model's accuracy (calibration plot intercept: -0.01, slope: 0.69). More extensive methods could not improve any further. All recalibrated/updated models had similar AUC-ROCs to the original model. CONCLUSION: The simple recalibration method can adapt the HK Chinese pre-DM/DM model to PC populations with different pre-test probabilities. The recalibrated model can be used as a first-step screening tool and as a measure to monitor changes in pre-DM/DM risks over time or after interventions.

A comparison of cardiovascular disease, cancer, mortality, and Graves' ophthalmopathy following treatment for hyperthyroidism: A Bayesian network meta-analysis.

OBJECTIVES: This network meta-analysis aimed to evaluate the association of anti-thyroid drugs (ATD), radioactive iodine (RAI), and thyroidectomy with subsequent outcomes in patients with newly-diagnosed hyperthyroidism. METHODS: The Ovid Medline, Ovid Embase, and Cochrane Library databases were searched for observational studies and randomized controlled trials. Included studies were published on or before 1st May 2022 involving at least two of the treatments among ATD, RAI, and thyroidectomy for hyperthyroidism. Pairwise comparisons and Bayesian network meta-analysis were used to estimate hazard ratios (HRs) and their credible interval (CrI) of outcomes, including cardiovascular disease (CVD), cancer, overall mortality, and Graves' ophthalmopathy (GO). RESULTS: A total of 22 cohort studies with 131,297 hyperthyroidism patients were included. Thyroidectomy was associated with lower risks of mortality and GO than ATD (HR = 0.54, 95% CrI: 0.31, 0.96; HR = 0.31, 95% CrI: 0.12, 0.64) and RAI (HR = 0.62, 95% CrI: 0.41, 0.95; HR = 0.18, 95% CrI: 0.07, 0.35). RAI had a higher risk of GO (HR = 1.70, 95% CrI: 1.02, 2.99) than ATD treatment. CONCLUSIONS: This Bayesian network meta-analysis indicated that thyroidectomy was associated with lower risks of mortality and GO in newly-diagnosed hyperthyroid patients compared to ATD and RAI. Relative to ATD, RAI therapy increased the risk of GO.

Nb Doping and Alloying of 2D WS2 by Atomic Layer Deposition for 2D Transition Metal Dichalcogenide Transistors and HER Electrocatalysts.

We utilize plasma-enhanced atomic layer deposition to synthesize two-dimensional Nb-doped WS2 and NbxW1-xSy alloys to expand the range of properties and improve the performance of 2D transition metal dichalcogenides for electronics and catalysis. Using a supercycle deposition process, films are prepared with compositions spanning the range from WS2 to NbS3. While the W-rich films form crystalline disulfides, the Nb-rich films form amorphous trisulfides. Through tuning the composition of the films, the electrical resistivity is reduced by 4 orders of magnitude compared to pure ALD-grown WS2. To produce Nb-doped WS2 films, we developed a separate ABC-type supercycle process in which a W precursor pulse precedes the Nb precursor pulse, thereby reducing the minimum Nb content of the film by a factor of 3 while maintaining a uniform distribution of the Nb dopant. Initial results are presented on the electrical and electrocatalytic performances of the films. Promisingly, the NbxW1-xSy films of 10 nm thickness and composition x ≈ 0.08 are p-type semiconductors and have a low contact resistivity of (8 ± 1) × 102 Ω cm to Pd/Au contacts, demonstrating their potential use in contact engineering of 2D TMD transistors.

Effectiveness of a 5-year health empowerment programme on promoting cardiovascular health for adults from low-income families in Hong Kong.

OBJECTIVE: This study aimed to evaluate the effectiveness of a health empowerment programme (HEP) to enhance cardiovascular health for adults from low-income families. METHODS: A prospective cohort study (N = 219, Intervention group: n = 103, comparison group: n = 116) was conducted with participants recruited from January 2013 to November 2015 and followed up until January 2022. Throughout the study duration, intervention group were invited to participate in the HEP. The cardiovascular health status of both groups at baseline and follow-up were assessed using the adapted Ideal Cardiovascular Health Index (ICHI) defined by the American Heart Association. After inverse propensity score weighting, multiple linear regression and Poisson regression were employed to examine the effects of the HEP. RESULTS: The HEP was associated with a greater increase in ICHI total score (B = 0.33, p < 0.001), and the increase of proportion of people achieving a normal blood pressure (Incidence rate ratio: 3.39, p < 0.05). CONCLUSION: HEP can be an effective and sustainable strategy to reduce social disparities in cardiovascular health of adults from low-income families, as indicated by improvement in the ICHI total score and blood pressure status. PRACTICAL IMPLICATIONS: The sustainable HEP in the community setting has potential for generalizability and scalability to other financially challenged families.

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.

Optimizing the frequency of physician encounters in follow - up care for patients with type 2 diabetes mellitus: a systematic review.

BACKGROUND: Decisions on the frequency of physician encounters for patients with type 2 diabetes mellitus (T2DM) have significant impacts on both patients' health outcomes and burden on health systems, whereas definitive intervals for physician encounters are still lacking in most clinical guidelines. This study systematically reviewed the existing evidence evaluating different frequencies of physician encounters among T2DM patients. METHODS: Systematic search of studies evaluating different visit frequencies for follow - up care in T2DM patients was performed in MEDLINE Ovid, Embase Ovid, and Cochrane library from database inception to 25 March 2022. Studies on the follow - up encounters driven by non - physicians and those on the episodic visits in the acute care settings were excluded in the screening. Citation searching was conducted via Google Scholar on the identified papers after screening. The risk of bias was assessed using Cochrane RoB2 tool for randomized controlled trials and Newcastle - Ottawa Scale for cohort studies. Findings were summarized narratively. RESULTS: Among 6363 records from the database search and 231 references from the citation search, 12 articles were eligible for in - depth review. The results showed that for patients who had not achieved cardiometabolic control, intensifying encounter frequency could enhance medication adherence, shorten the time to achieve the treatment target, and improve the patients' quality of life. However, for the patients who had already achieved the treatment targets, less frequent encounters were equivalent to intensive encounters in maintaining their cardiometabolic control, and could save considerable healthcare costs without substantially lowering the quality of care and patients' satisfaction. CONCLUSION: Existing evidence suggested that the optimal frequency of physician encounters for patients with T2DM should be individualized, which can be stratified by patients' risk levels based on the cardiometabolic control to guide the differential scheduling of physician encounters in the follow - up. More research is needed to determine how to optimize the frequency of physician encounters for this large and heterogeneous population.

Association of eGFR slope with all-cause mortality, macrovascular and microvascular outcomes in people with type 2 diabetes and early-stage chronic kidney disease.

AIMS: The association of estimated glomerular filtration rate (eGFR) slope with progression of complications in people with type 2 diabetes (T2D) and early-stage chronic kidney disease (CKD) is less clear. METHODS: We identified 115,139 T2D participants without decreased eGFR (>60 mL/min/1.73 m2) between 2008 and 2015 from the electronic database of the Hong Kong Hospital Authority. eGFR slope calculated by linear-mixed effects model using 3-year eGFR measurements was categorized into quintiles. With Quintile 3 of eGFR slope as the reference group, we used Cox proportional or cause-specific models to investigate the association between eGFR slope and all-cause mortality, macrovascular and microvascular complications, as appropriate. RESULTS: Over a median follow-up of 7.8 years, fastest eGFR declines (Quintile 1 with median eGFR slope: -4.32 mL/min/1.73 m2/year) were associated with increased risk of all adverse outcomes (adjusted hazard ratio [aHR] 1.36 to 2.97, all P < 0.0001), compared with less steep eGFR declines (Quintile 3: -1.08 mL/min/1.73 m2/year). Substantial eGFR increases (Quintile 5: 1.34 mL/min/1.73 m2/year) were associated with decreased risk of CKD and ≥ 40 % decline in eGFR (aHR [95 % CI] 0.65 [0.63, 0.67] and 0.85 [0.82, 0.89], respectively) and higher risk of death, CVD, DR and DN (aHR [95 % CI] 1.48 [1.40, 1.56], 1.19 [1.14, 1.25], 1.07 [1.004, 1.15] and 1.62 [1.37, 1.91], respectively). CONCLUSIONS: In a cohort of T2D people without decreased eGFR, accelerated declines and increases in eGFR were associated with all-cause mortality, macrovascular and microvascular complications, supporting the potential prognostic utility of eGFR slope in T2D people with early-stage CKD.

Opioid prescribing, pain, and hospital stay of general surgery patients with oxycodone allergies in South Australia.

BACKGROUND: The frequency of oxycodone adverse reactions, subsequent opioid prescription, effect on pain and patient care in general surgery patients are not well known. This study aimed to determine prevalence of documented oxycodone allergy and intolerances (independent variables) in a general surgical cohort, and association with prescribing other analgesics (particularly opioids), subjective pain scores, and length of hospital stay (dependent variables). METHODS: This retrospective cohort study included general surgery patients from two South Australian hospitals between April 2020 and March 2022. Multivariable logistic regression evaluated associations between previous oxycodone allergies and intolerances, prescription records, subjective pain scores, and length of hospital stay. RESULTS: Of 12 846 patients, 216 (1.7%) had oxycodone allergies, and 84 (0.7%) oxycodone intolerances. The 216 oxycodone allergy patients had lower odds of receiving oxycodone (OR 0.17, P < 0.001), higher odds of tramadol (OR 3.01, P < 0.001) and tapentadol (OR 2.87, P = 0.001), but 91 (42.3%) still received oxycodone and 19 (8.8%) morphine. The 84 with oxycodone intolerance patients had lower odds of receiving oxycodone (OR 0.23, P < 0.001), higher odds of fentanyl (OR 3.6, P < 0.001) and tramadol (OR 3.35, P < 0.001), but 42 (50%) still received oxycodone. Patients with oxycodone allergies and intolerances had higher odds of elevated subjective pain (OR 1.60, P = 0.013; OR 2.36, P = 0.002, respectively) and longer length of stay (OR 1.36, P = 0.038; OR 2.24, P = 0.002, respectively) than patients without these. CONCLUSIONS: General surgery patients with oxycodone allergies and intolerances are at greater risk of worse postoperative pain and longer length of stay, compared to patients without. Many still receive oxycodone, and other opioids that could cause cross-reactivity.

Team-based continuity of care for patients with hypertension: a retrospective primary care cohort study in Hong Kong.

BACKGROUND: Continuity of care (COC) is associated with improved health outcomes in patients with hypertension. Team-based COC allows more flexibility in service delivery but there is a lack of research on its effectiveness for patients with hypertension. AIM: To investigate the effectiveness of team-based COC on the prevention of cardiovascular disease (CVD) and mortality in patients with hypertension. DESIGN AND SETTING: A retrospective cohort study in a primary care setting in Hong Kong. METHOD: Eligible patients included those visiting public primary care clinics in Hong Kong from 2008 to 2018. The usual provider continuity index (UPCI) was used to measure the COC provided by the most visited physician team. Cox regression and restricted cubic splines were applied to model the association between the COC and the risk for CVDs and all-cause mortality. RESULTS: This study included 421 640 eligible patients. Compared with participants in the lowest quartile of UPCI, the hazard ratios for overall CVD were 0.94 (95% CI = 0.92 to 0.96), 0.91(95% CI = 0.89 to 0.93), and 0.90 (95% CI = 0.88 to 0.92) in the second, third, and fourth quartiles, respectively. A greater effect size on CVD risk reduction was observed among the patients with unsatisfactory blood pressure control, patients aged <65 years, and those with a Charlson comorbidity index of <4 at baseline (Pinteraction<0.05 in these subgroup analyses), but the effect was insignificant among the participants with an estimated glomerular filtration rate of <60 ml/ min/1.73 m2 at baseline. CONCLUSION: Team-based COC via a coordinated physician team was associated with reduced risks of CVD and all-cause mortality among patients with hypertension, especially for the patients with unsatisfactory blood pressure control. Early initiation of team-based COC may also achieve extra benefits.

Patient enablement and health-related quality of life for patients with chronic back and knee pain: a cross-sectional study in primary care.

BACKGROUND: Chronic back and knee pain impairs health- related quality of life (HRQoL) and patient enablement can improve HRQoL. AIM: To determine whether enablement was a moderator of the effect of chronic back and knee pain on HRQoL. DESIGN AND SETTING: A cross-sectional study of Chinese patients with chronic back and knee problems in public primary care clinics in Hong Kong. METHOD: Each participant completed the Chinese Patient Enablement Instrument-2 (PEI-2), the Chinese Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Pain Rating Scale (PRS). Multivariable regression examined the effects of PRS score and PEI-2 score on WOMAC total score. A moderation regression model and simple slope analysis were used to evaluate whether the interaction between enablement (PEI-2) and pain (PRS) had a significant effect on HRQoL (WOMAC). RESULTS: Valid patient-reported outcome data from 1306 participants were analysed. PRS score was associated with WOMAC total score (ß = 0.326, P<0.001), whereas PEI-2 score was associated inversely with WOMAC total score (ß = -0.260, P<0.001) and PRS score. The effect of the interaction between PRS and PEI-2 (PRS × PEI-2) scores on WOMAC total score was significant (ß = -0.191, P<0.001) suggesting PEI-2 was a moderator. Simple slope analyses showed that the relationship between PRS and WOMAC was stronger for participants with a low level of PEI-2 (gradient 3.056) than for those with a high level of PEI-2 (gradient 1.746). CONCLUSION: Patient enablement moderated the impact of pain on HRQoL. A higher level of enablement can lessen impairment in HRQoL associated with chronic back and knee pain.

Bariatric surgery, novel glucose-lowering agents, and insulin for type 2 diabetes and obesity: Bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: This network meta-analysis aimed to compare the effects of bariatric surgery, novel glucose-lowering agents (SGLT2i, GLP1RA, DPP4i), and insulin for patients with type 2 diabetes mellitus (T2DM) and obesity. METHODS: Four databases were searched from inception to April 2023 to identify randomized controlled trials (RCTs) comparing bariatric surgery, SGLT2i, GLP1RA, DPP4i, insulin, and/or placebo/usual care among patients with T2DM and obesity in the achievement of HbA1c < 7.0 per cent within one year, and 12-month changes in HbA1c and body weight. RESULTS: A total of 376 eligible RCTs (149 824 patients) were analysed. Bariatric surgery had significantly higher rates of achieving HbA1c < 7.0 per cent than SGLT2i (RR = 2.46, 95 per cent c.i. = 1.28, 4.92), DPP4i (RR = 2.59, 95 per cent c.i. = 1.36, 5.13), insulin (RR = 2.27, 95 per cent c.i. = 1.18, 4.58) and placebo/usual care (RR = 4.02, 95 per cent c.i. = 2.13, 7.93), but had no statistically significant difference from GLP1RA (RR = 1.73, 95 per cent c.i. = 0.91, 3.44), regardless of oral (RR = 1.33, 95 per cent c.i. = 0.66, 2.79) or injectable (RR = 1.75, 95 per cent c.i. = 0.92, 3.45) administration. Significantly more GLP1RA patients achieved HbA1c < 7.0 per cent than other non-surgical treatments. Bariatric surgery had the greatest reductions in HbA1c (∼1 per cent more) and body weight (∼15 kg more) at 12 months. Among novel glucose-lowering medications, GLP1RA was associated with greater reductions in HbA1c than SGLT2i (-0.39 per cent, 95 per cent c.i. = -0.55, -0.22) and DPP4i (-0.51 per cent, 95 per cent c.i. = -0.64, -0.39) at 12 months, while GLP1RA (-1.74 kg, 95 per cent c.i. = -2.48, -1.01) and SGLT2i (-2.23 kg, 95 per cent c.i. = -3.07, -1.39) showed greater reductions in body weight than DPP4i at 12 months. CONCLUSION: Bariatric surgery showed superiority in glycaemic control and weight management compared to non-surgical approaches. GLP1RA administered by oral or injectable form demonstrated reduced HbA1c and body weight at 12 months, and was preferable over other non-surgical treatments among patients with T2DM and obesity. PROSPERO REGISTRATION NO: CRD42020201507.

Psychometric properties of EQ-5D-5L for use in patients with Graves' disease.

BACKGROUND: The EQ-5D-5 L is a commonly used generic measure of health. This study aimed to evaluate the psychometric properties of the EQ-5D-5 L in patients with Graves' disease (GD). METHODS: A prospective cohort of patients with GD recruited at three public hospitals in Hong Kong completed the EQ-5D-5 L and ThyPRO-39 questionnaires at baseline, 1-month, and 6-month follow-ups. Convergent validity was tested by examining the Spearman correlation between EQ-5D-5 L and ThyPRO-39 scores at baseline. 1-month test-retest reliability was assessed by Intraclass Correlation Coefficient (ICC), Gwet's Agreement Coefficient 2 (AC2), and percentage agreement. Responsiveness of EQ-5D-5 L index and EQ-VAS scores was assessed using effect size statistics (standardized effect size [SES] and standardized response mean [SRM]). RESULTS: Of 125 recruited patients, 101 (80.8%) and 100 (80.0%) patients were followed up at 1- and 6-month, respectively. For convergent validity, there was a moderate negative correlation between EQ-5D-5 L index or EQ-VAS score and ThyPRO-39 overall QoL-impact score (-0.350, -0.451), between EQ-VAS score and composite score (-0.483), and strong negative correlation between EQ-5D-5 L index score and composite score (-0.567). The Gwet's AC2 and percentage agreement were the highest in self-care (0.964 and 0.967), followed by mobility (0.952 and 0.962), usual activities (0.934 and 0.948), pain/discomfort (0.801 and 0.887), and anxiety/depression (0.788 and 0.882). The ICC for the EQ-5D-5 L index and the EQ-VAS was 0.707 and 0.700. For patients who reported having 'worsened' health at 6-month follow-up, the SES and SRM were - 0.66 and - 0.42 for EQ-5D-5 L index and - 1.15 and - 1.00 for EQ-VAS, respectively. CONCLUSIONS: The EQ-5D-5 L demonstrated convergent validity, test-retest reliability, and responsiveness to worsened health status among patients with GD.

Trends of clinical parameters and incidences of diabetes mellitus complications among patients with type 2 diabetes mellitus in Hong Kong, 2010-2019: a retrospective cohort study.

Background: Diabetes mellitus-related characteristics, including available medications, onset ages, and newly-introduced management program, have been changing recently in Hong Kong, especially after the introduction of the Risk Assessment and Management Program-Diabetes Mellitus in all outpatient clinics in 2009. To understand the plural change and improve the management of patients with Type 2 Diabetes Mellitus (T2DM) based on the latest data, we examined the trends of clinical parameters, T2DM complications and mortality in patients with T2DM in Hong Kong from 2010 to 2019. Methods: In this retrospective cohort study, we acquired data from the Clinical Management System of the Hospital Authority in Hong Kong. Among adults with T2DM diagnosed on or before Sept 30, 2010, and with at least one attendance in general outpatient clinics between Aug 1, 2009, to Sept 30, 2010, we investigated the age-standardised trends of clinical parameters including haemoglobin A1c, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol (LDL-C), body mass index and estimated glomerular filtration rate (eGFR), complications including cardiovascular disease (CVD), peripheral vascular disease (PVD), sight-threatening diabetic retinopathy (STDR), neuropathy, eGFR<45 mL/min/1.73 m2 and end-stage renal disease (ESRD), and all-cause mortality from 2010 to 2019 and tested the statistical significance of the trends using generalised estimating equation by sex, level of clinical parameters and age groups. Findings: In total, 82,650 males and 97,734 females with T2DM were identified. LDL-C decreased from 3 to 2 mmol/L in both males and females, while other clinical parameters changed within 5% over the full decade from 2010 to 2019. CVD, PVD, STDR, and neuropathy had declining incidences, while ESRD and all-cause mortality had increasing incidences from 2010 to 2019. The incidence of eGFR<45 mL/min/1.73 m2 increased in males but decreased in females. The odds ratio (OR) of ESRD (1.13, 95% CI [1.12, 1.15]) was highest in both males and females while the ORs of STDR (0.94, 95% CI [0.92, 0.96]) and neuropathy (0.90, 95% CI [0.88, 0.92]) were lowest in males and females, respectively. Complications and all-cause mortality trends varied among baseline HbA1c, eGFR, and age subgroups. In contrast to the findings in other age groups, the incidence of any outcomes did not decrease in younger patients (<45 years) from 2010 to 2019. Interpretation: Improvements were observed in LDL-C and incidences of most complications from 2010 to 2019. Worse performance in the younger age group and increasing incidence of renal complications and mortality need more attention in managing patients with T2DM. Funding: The Health and Medical Research Fund, the Health Bureau, and Government of the Hong Kong Special Administrative Region.

Assessment of Hypertension Complications and Health Service Use 5 Years After Implementation of a Multicomponent Intervention.

Importance: There is a lack of information regarding the impact of implementing a protocol-driven, team-based, multicomponent intervention in public primary care settings on hypertension-related complications and health care burden over the long term. Objective: To compare hypertension-related complications and health service use at 5 years among patients managed with Risk Assessment and Management Program for Hypertension (RAMP-HT) vs usual care. Design, Setting, and Participants: In this population-based prospective matched cohort study, patients were followed up until the date of all-cause mortality, an outcome event, or last follow-up appointment before October 2017, whichever occurred first. Participants included 212 707 adults with uncomplicated hypertension managed at 73 public general outpatient clinics in Hong Kong between 2011 and 2013. RAMP-HT participants were matched to patients receiving usual care using propensity score fine stratification weightings. Statistical analysis was conducted from January 2019 to March 2023. Interventions: Nurse-led risk assessment linked to electronic action reminder system, nurse intervention, and specialist consultation (as necessary), in addition to usual care. Main Outcomes and Measures: Hypertension-related complications (cardiovascular diseases, end-stage kidney disease), all-cause mortality, public health service use (overnight hospitalization, attendances at accident and emergency department, specialist outpatient clinic, and general outpatient clinic). Results: A total of 108 045 RAMP-HT participants (mean [SD] age: 66.3 [12.3] years; 62 277 [57.6%] female) and 104 662 patients receiving usual care (mean [SD] age 66.3 [13.5] years; 60 497 [57.8%] female) were included. After a median (IQR) follow-up of 5.4 (4.5-5.8) years, RAMP-HT participants had 8.0% absolute risk reduction in cardiovascular diseases, 1.6% absolute risk reduction in end-stage kidney disease, and 10.0% absolute risk reduction in all-cause mortality. After adjusting for baseline covariates, the RAMP-HT group was associated with lower risk of cardiovascular diseases (hazard ratio [HR], 0.62; 95% CI, 0.61-0.64), end-stage kidney disease (HR, 0.54; 95% CI, 0.50-0.59), and all-cause mortality (HR, 0.52; 95% CI, 0.50-0.54) compared with the usual care group. The number needed to treat to prevent 1 cardiovascular disease event, end-stage kidney disease, and all-cause mortality was 16, 106, and 17, respectively. RAMP-HT participants had lower hospital-based health service use (incidence rate ratios ranging from 0.60 to 0.87) but more general outpatient clinic attendances (IRR, 1.06; 95% CI, 1.06-1.06) compared with usual care patients. Conclusions and Relevance: In this prospective matched cohort study involving 212 707 primary care patients with hypertension, participation in RAMP-HT was associated with statistically significant reductions in all-cause mortality, hypertension-related complications, and hospital-based health service use after 5 years.