Lower risk of gout in sodium glucose cotransporter 2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors in type-2 diabetes.

OBJECTIVES: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) vs dipeptidyl peptidase-4 inhibitors (DPP4I) on the risk of new-onset gout remains unknown. This study aims to compare the effects of SGLT2I against DPP4I on gout risks. METHODS: This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus treated with SGLT2I or DPP4I between 1 January 2015 and 31 December 2020 in Hong Kong. The study outcomes are new-onset gout and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I was performed. Univariable and multivariable Cox regression models were conducted. Competing risks models and multiple approaches based on the propensity score were applied. RESULTS: This study included 43 201 patients [median age: 63.23 years old (Interquartile range, IQR): 55.21-71.95, 53.74% males; SGLT2I group: n = 16 144; DPP4I group: n = 27 057] with a median follow-up of 5.59 years (IQR: 5.27-5.81 years) since initial drug exposure. The incidence rate of developing gout [Incidence rate (IR): 2.5; 95% CI: 2.2, 2.9] among SGLT2I users was significantly lower than DPP4I users (IR: 5.2; 95% CI: 4.8, 5.8). SGLT2I was associated with 51% lower risks of gout (HR: 0.49; 95% CI: 0.42, 0.58; P-value < 0.0001) and 51% lower risks of all-cause mortality (HR: 0.49; 95% CI: 0.42, 0.58; P-value < 0.0001) after adjusting for significant demographics, past comorbidities, medications and laboratory results. The results remained consistent on competing risk and other propensity score approaches. CONCLUSIONS: SGLT2I use was associated with lower risks of new gout diagnosis compared with DPP4I use.

Comparison of Sodium-Glucose Cotransporter-2 Inhibitor and Dipeptidyl Peptidase-4 Inhibitor on the Risks of New-Onset Atrial Fibrillation, Stroke and Mortality in Diabetic Patients: A Propensity Score-Matched Study in Hong Kong.

OBJECTIVE: To compare the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) and dipeptidyl peptidase-4 inhibitors (DPP4Is) on adverse outcomes in diabetic patients in Hong Kong. METHODS: This was a retrospective population-based cohort study of type 2 diabetes mellitus patients (n = 72,746) treated with SGLT2I or DPP4I between January 1, 2015, and December 31, 2020, in Hong Kong. Patients with exposure to both DPP4I and SGLT2I therapy, without complete demographics or mortality data, or who had prior atrial fibrillation (AF) were excluded. The study outcomes were new-onset AF, stroke/transient ischemic attack, cardiovascular mortality and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I users was performed. RESULTS: The unmatched study cohort included 21,713 SGLT2I users and 39,510 DPP4I users (total: n = 61,233 patients; 55.37% males, median age: 62.7 years [interquartile range (IQR): 54.6-71.9 years]). Over a median follow-up of 2030 (IQR: 1912-2117) days, 2496 patients (incidence rate [IR]: 4.07%) developed new-onset AF, 2179 patients (IR: 3.55%) developed stroke/transient ischemic attack, 1963 (IR: 3.20%) died from cardiovascular causes and 6607 patients (IR: 10.79%) suffered from all-cause mortality. After propensity score matching (SGLT2I: n = 21,713; DPP4I: n = 21,713), SGLT2I users showed lower incidence of new-onset AF (1.96% vs. 2.78%, standardized mean difference [SMD] = 0.05), stroke (1.80% vs. 3.52%, SMD = 0.11), cardiovascular mortality (0.47% vs. 1.56%, SMD = 0.11) and all-cause mortality (2.59% vs. 7.47%, SMD = 0.22) compared to DPP4I users. Cox regression found that SGLT2I users showed lower risk of new-onset AF (hazard ratio [HR]: 0.68, 95% confidence interval [CI]: [0.56, 0.83], P = 0.0001), stroke (HR: 0.64, 95% CI: [0.53, 0.79], P < 0.0001), cardiovascular mortality (HR: 0.39, 95% CI: [0.27, 0.56], P < 0.0001) and all-cause mortality (HR: 0.44, 95% CI: [0.37, 0.51], P < 0.0001) after adjusting for significant demographics, past comorbidities, medications and laboratory tests. CONCLUSIONS: Based on real-world data of type 2 diabetic patients in Hong Kong, SGLT2I use was associated with lower risk of incident AF, stroke/transient ischemic attack, and cardiovascular and all-cause mortality outcomes compared to DPP4I use.

New-onset syncope in diabetic patients treated with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors: a Chinese population-based cohort study.

BACKGROUND AND AIMS: Syncope is a symptom that poses an important diagnostic and therapeutic challenge, and generates significant cost for the healthcare system. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated beneficial cardiovascular effects, but their possible effects on incident syncope have not been fully investigated. This study compared the effects of SGLT2i and dipeptidyl peptidase-4 inhibitors (DPP4i) on new-onset syncope. METHODS AND RESULTS: This was a retrospective, territory-wide cohort study enrolling type 2 diabetes mellitus (T2DM) patients treated with SGLT2i or DPP4i between 1 January 2015 and 31 December 2020, in Hong Kong, China. The outcomes were hospitalization of new-onset syncope, cardiovascular mortality, and all-cause mortality. Multivariable Cox regression and different approaches using the propensity score were applied to evaluate the association between SGLT2i and DPP4i with incident syncope and mortality. After matching, a total of 37 502 patients with T2DM were included (18 751 SGLT2i users vs. 18 751 DPP4i users). During a median follow-up of 5.56 years, 907 patients were hospitalized for new-onset syncope (2.41%), and 2346 patients died from any cause (6.26%), among which 471 deaths (1.26%) were associated with cardiovascular causes. Compared with DPP4i users, SGLT2i therapy was associated with a 51% lower risk of new-onset syncope [HR 0.49; 95% confidence interval (CI) 0.41-0.57; P < 0.001], 65% lower risk of cardiovascular mortality (HR 0.35; 95% CI 0.26-0.46; P < 0.001), and a 70% lower risk of all-cause mortality (HR 0.30; 95% CI 0.26-0.34; P < 0.001) in the fully adjusted model. Similar associations with syncope were observed for dapagliflozin (HR 0.70; 95% CI 0.58-0.85; P < 0.001), canagliflozin (HR 0.48; 95% CI 0.36-0.63; P < 0.001), and ertugliflozin (HR 0.45; 95% CI 0.30-0.68; P < 0.001), but were attenuated for empagliflozin (HR 0.79; 95% CI 0.59-1.05; P = 0.100) after adjusting for potential confounders. The subgroup analyses suggested that, compared with DPP4i, SGLT2i was associated with a significantly decreased risk of incident syncope among T2DM patients, regardless of gender, age, glucose control status, Charlson comorbidity index, and the association remained constant amongst those with common cardiovascular drugs and most antidiabetic drugs at baseline. CONCLUSION: Compared with DPP4i, SGLT2i was associated with a significantly lower risk of new-onset syncope in patients with T2DM, regardless of gender, age, degree of glycaemic control, and comorbidity burden.

Initiation of warfarin is associated with decreased mortality in patients with infective endocarditis: A population-based cohort study.

IMPORTANCE: The use of warfarin to prevent thromboembolism in patients with infective endocarditis (IE) remains controversial due to potentially increased bleeding risks. DESIGN: Population-based retrospective cohort study. PARTICIPANTS: Patients aged 18 or older and diagnosed with IE in Hong Kong between January 1st, 1997 and August 31st, 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched for baseline characteristics using 1:1 propensity score matching. EXPOSURE: Warfarin use within 14 days of IE diagnosis. MAIN OUTCOMES AND MEASURES: Patients were followed up to 90 days for the outcomes of ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox regression was used to determine hazard ratios (HRs) [95 % confidence intervals (CIs)] between treatment groups. Fine-Gray competing risk regression with all-cause mortality as the competing event was performed as a sensitivity analysis. In addition to 90-day analyses, landmark analyses were performed at 30 days of follow-up. RESULTS: The matched cohort consisted of 675 warfarin users (57.0 % male, age 59 ± 16 years) and 675 warfarin non-users (53.5 % male, age 61 ± 19 years). Warfarin users had a 50 % decreased 90-day risk in all-cause mortality (HR:0.50 [0.39-0.65]), without significantly different 90-day risks of ischemic stroke (HR:1.04 [0.70-1.53]), intracranial hemorrhage (HR:1.25 [0.77-2.04]), and gastrointestinal bleeding (HR:1.04 [0.60-1.78]). Thirty-day landmark analysis showed similar results. Competing risk regression showed significantly higher 30-day cumulative incidence of intracranial hemorrhage in warfarin users (sub-HR:3.34 [1.34-8.31]), but not at 90-day (sub-HR:1.63 [0.95-2.81]). Results from Fine-Gray regression were otherwise congruent with those from Cox regression. CONCLUSIONS AND RELEVANCE: Warfarin initiated within 14 days of IE diagnosis was associated with significantly decreased risks of mortality but higher risks of intracranial hemorrhage, with similar risks of ischemic stroke and gastrointestinal bleeding, compared with non-use of warfarin with 14 days of IE diagnosis. KEY POINTS: Question: Is warfarin, initiated within 14 days of a diagnosis of infective endocarditis (IE), efficacious and safe? FINDINGS: In this propensity score-matched, population-based, prospective cohort study from Hong Kong, warfarin use within 14 days of IE diagnosis was associated with a 50 % decrease in the risk of all-cause mortality, albeit with higher risk of intracranial hemorrhage, and without significant differences in the risk of ischaemic stroke and gastrointestinal bleeding. Meaning: In patients with IE, warfarin use within 14 days of diagnosis may have mortality benefits, despite increased risks of intracranial hemorrhage.

Clinical characteristics, risk factors and outcomes of cancer patients with COVID-19: A population-based study.

INTRODUCTION: Cancer patients may be susceptible to poorer outcomes in COVID-19 infection owing to the immunosuppressant effect of chemotherapy/radiotherapy and cancer growth, along with the potential for nosocomial transmission due to frequent hospital admissions. METHODS: This was a population-based retrospective cohort study of COVID-19 patients who presented to Hong Kong public hospitals between 1 January 2020 and 8 December 2020. The primary outcome was a composite endpoint of requirement for intubation, ICU admission and 30-day mortality. RESULTS: The following study consisted of 6089 COVID-19 patients (median age 45.9 [27.8.1-62.7] years; 50% male), of which 142 were cancer subjects. COVID-19 cancer patients were older at baseline and tended to present with a higher frequency of comorbidities, including diabetes mellitus, hypertension, chronic obstructive pulmonary disease, ischemic heart disease, ventricular tachycardia/fibrillation and gastrointestinal bleeding (p < 0.05). These subjects also likewise tended to present with higher serum levels of inflammatory markers, including D-dimer, lactate dehydrogenase, high sensitivity troponin-I and C-reactive protein. Multivariate Cox regression showed that any type of cancer presented with an almost four-fold increased risk of the primary outcome (HR: 3.77; 95% CI: 1.63-8.72; p < 0.002) after adjusting for significant demographics, Charlson comorbidity index, number of comorbidities, past comorbidities and medication history. This association remained significant when assessing those with colorectal (HR: 5.07; 95% CI: 1.50-17.17; p < 0.009) and gastrointestinal malignancies (HR: 3.79; 95% CI: 1.12-12.88; p < 0.03), but not with lung, genitourinary, or breast malignancies, relative to their respective cancer-free COVID-19 counterparts. CONCLUSIONS: COVID-19 cancer patients are associated with a significantly higher risk of intubation, ICU admission and/or mortality.

Predictive value of neutrophil-to-lymphocyte ratio for atrial fibrillation and stroke in type 2 diabetes mellitus: The Hong Kong Diabetes Study.

INTRODUCTION: Neutrophil-to-lymphocyte ratio (NLR) is a routinely available biomarker that reflects systemic inflammation. The study evaluated the predictive value of NLR for ischemic stroke and atrial fibrillation (AF) in patients with type 2 diabetes mellitus. METHODS: This was a population-based cohort study of patients with type 2 diabetes mellitus and complete blood count tests at baseline between 1 January 1st, 2009, and 31 December, 2009, at government-funded hospitals/clinics in Hong Kong. Follow-up was until 31 December, 2019, or death. RESULTS: A total of 85,351 patients (age = 67.6 ± 13.2 years old, male = 48.8%, follow-up = 3101 ± 1441 days) were included. Univariable Cox regression found that increased NLR at quartiles 2, 3 and 4 was significantly associated with higher risks of new-onset ischemic stroke (hazard ratio [HR]: 1.28 [1.20-1.37], p < .001, HR: 1.41 [1.32-1.51], p < .001 and HR: 1.38 [1.29-1.47], p < .001) and AF (HR: 1.09 [1.02-1.17], p < .015; HR: 1.28 [1.20-1.37], p < .001; HR: 1.39 [1.31-1.49], p < .001) compared to quartile 1. On multivariable analysis, NLR remained a significant predictor of ischemic stroke risk for quartiles 2 and 3 (quartile 2: HR: 1.14 [1.05, 1.22], p = .001; quartile 3: HR: 1.14 [1.06, 1.23], p < .001) but not quartile 4 (HR: 1.08 [0.994, 1.17], p = .070). NLR was not predictive of AF after adjusting for confounders (quartile 2: HR: 0.966 [0.874, 1.07], p = .499; quartile 3: HR: 0.978 [0.884, 1.08], p = .661; quartile 4: HR: 1.05 [0.935, 1.16], p = .462). CONCLUSION: NLR is a significant predictor of new-onset ischaemic stroke after adjusting for significant confounders in Chinese type 2 diabetes patients.

The Association Between Neutrophil-Lymphocyte Ratio and Variability with New-Onset Dementia: A Population-Based Cohort Study.

BACKGROUND: Previous studies identified that neutrophil-to-lymphocyte ratio (NLR) may be a predictor of dementia. However, the associations between NLR and dementia at the population level were less explored. OBJECTIVE: This retrospective population-based cohort study was designed to identify the associations between NLR and dementia among patients visiting for family medicine consultation in Hong Kong. METHODS: The patients were recruited from January 1, 2000, to December 31, 2003, and followed up until December 31, 2019. The demographics, prior comorbidities, medications, and laboratory results were collected. The primary outcomes were Alzheimer's disease and related dementia and non-Alzheimer's dementia. Cox regression and restricted cubic spline were applied to identify associations between NLR and dementia. RESULTS: A cohort of 9,760 patients (male: 41.08% ; baseline age median: 70.2; median follow-up duration: 4756.5 days) with complete NLR were included. Multivariable Cox regression identified that patients with NLR >5.44 had higher risks of developing Alzheimer's disease and related dementia (hazard ratio [HR]: 1.50, 95% Confidence interval [CI]: 1.17-1.93) but not non-Alzheimer's dementia (HR: 1.33; 95% CI: 0.60-2.95). The restricted cubic splines demonstrated that higher NLR was associated with Alzheimer's disease and related dementia. The relationship between the NLR variability and dementia was also explored; of all the NLR variability measures, only the coefficient of variation was predictive of non-Alzheimer's dementia (HR: 4.93; 95% CI: 1.03-23.61). CONCLUSION: In this population-based cohort, the baseline NLR predicts the risks of developing dementia. Utilizing the baseline NLR during family medicine consultation may help predict the risks of dementia.

Metformin versus sulphonylureas for new onset atrial fibrillation and stroke in type 2 diabetes mellitus: a population-based study.

AIMS: To gain insights on the cardiovascular effects of metformin and sulphonylurea, the present study compares the rates of incident atrial fibrillation, stroke, cardiovascular mortality and all-cause mortality between metformin and sulphonylurea users in type 2 diabetes mellitus. METHODS: This was a retrospective population-based cohort study of type 2 diabetes mellitus patients receiving either sulphonylurea or metformin monotherapy between January 1, 2000, and December 31, 2019. The primary outcome was new-onset AF or stroke. Secondary outcomes were cardiovascular, non-cardiovascular and all-cause mortality. Propensity score matching (1:2 ratio) between sulphonylurea and metformin users was performed, based on demographics, CHA-DS-VASc score, past comorbidities and medication use. Cox regression was used to identify significant risk factors. Competing risk analysis was conducted using cause-specific and subdistribution hazard models. Sensitivity analyses using propensity score stratification, high-dimensional propensity score and inverse probability of treatment weighting were conducted. Subgroup analyses were conducted for age and gender in the matched cohort. RESULTS: A total of 36,228 sulphonylurea users and 72,456 metformin users were included in the propensity score-matched cohort. Multivariable Cox regression showed that sulphonylurea users had higher risks of incident AF (hazard ratio [HR]: 2.89, 95% confidence interval [CI]: 2.75-3.77; P < 0.0001), stroke (HR: 3.23, 95% CI: 3.01-3.45; P < 0.0001), cardiovascular mortality (HR: 3.60, 95% CI: 2.62-4.81; P < 0.0001) and all-cause mortality (HR: 4.35, 95% CI: 3.16-4.75; P < 0.0001) compared to metformin users. Similarly, significant results were observed using cause-specific and subdistribution hazard models. Sensitivity analysis using techniques based on the propensity score also yielded similar results. CONCLUSIONS: Sulphonylurea use was associated with higher risks of incident AF, stroke, cardiovascular mortality and all-cause mortality compared to metformin. Males and patients older than 65 years with sulphonylurea use were exposed to the highest risks.

Hip fractures risks in edoxaban versus warfarin users: A propensity score-matched population-based cohort study with competing risk analyses.

OBJECTIVE: The three direct oral anticoagulants (DOAC), rivaroxaban, apixaban and dabigatran have been associated with lower risks of fractures compared to warfarin. However, no large scale studies have explored the associations with the newest DOAC, edoxaban, with fracture risk. The present study aims to elucidate the effects of edoxaban on the risk of hip fracture amongst elderly patients by comparing the incidence of new onset hip fracture between edoxaban and warfarin users in a Chinese population. METHODS: This was a retrospective population-based cohort study of patients with edoxaban or warfarin use between January 1st, 2016 and December 31st, 2019 in Hong Kong, China. Patients with less than one-month exposure, medication switching between warfarin and edoxaban, those who died within 30 days after drug exposure, prior human immunodeficiency virus infection, age <50 years old, and those with prior hip fractures were excluded. Propensity score matching (1:2) between edoxaban and warfarin users using the nearest neighbour method was performed based on demographics, prior comorbidities, and use of different medications. The study outcomes were new onset hip fractures, medically attended falls and all-cause mortality. RESULTS: A total of 5014 patients including 579 edoxaban users and 4435 warfarin users (median age: 70 years old [interquartile range (IQR): 62-79], 56.66% males) with a median follow-up of 637.5 (IQR: 320-1073) days were included. In the matched cohort, edoxaban users had significantly lower rates of new onset hip fractures, medically attended falls and all-cause mortality. The protective value of edoxaban use against new onset hip fracture (hazard ratio [HR]: 0.13, 95% confidence interval [CI]: [0.03-0.54], p = 0.0051), medically attended falls (HR: 0.47, [0.29-0.75], p = 0.0018) and all-cause mortality (HR: 0.61, [0.42-0.87], p = 0.0059) in comparison to warfarin use persisted after matching. The significant relationship between edoxaban use and lower fracture risk was preserved in all sensitivity analyses using different approaches using the propensity score. CONCLUSIONS: Edoxaban use is associated with lower risks of new onset hip fractures, medically attended falls and mortality risks compared to warfarin after propensity score matching.

Gender-specific clinical risk scores incorporating blood pressure variability for predicting incident dementia.

INTRODUCTION: The present study examined the gender-specific prognostic value of blood pressure (BP) and its variability in the prediction of dementia risk and developed a score system for risk stratification. MATERIALS AND METHODS: This was a retrospective, observational population-based cohort study of patients admitted to government-funded family medicine clinics in Hong Kong between January 1, 2000 and March 31, 2002 with at least 3 blood pressure measurements. Gender-specific risk scores for dementia were developed and tested. RESULTS: The study consisted of 74 855 patients, of whom 3550 patients (incidence rate: 4.74%) developed dementia over a median follow-up of 112 months (IQR= [59.8-168]). Nonlinear associations between diastolic/systolic BP measurements and the time to dementia presentation were identified. Gender-specific dichotomized clinical scores were developed for males (age, hypertension, diastolic and systolic BP and their measures of variability) and females (age, prior cardiovascular, respiratory, gastrointestinal diseases, diabetes mellitus, hypertension, stroke, mean corpuscular volume, monocyte, neutrophil, urea, creatinine, diastolic and systolic BP and their measures of variability). They showed high predictive strengths for both male (hazard ratio [HR]: 12.83, 95% confidence interval [CI]: 11.15-14.33, P value < .0001) and female patients (HR: 26.56, 95% CI: 14.44-32.86, P value < .0001). The constructed gender-specific scores outperformed the simplified systems without considering BP variability (C-statistic: 0.91 vs 0.82), demonstrating the importance of BP variability in dementia development. CONCLUSION: Gender-specific clinical risk scores incorporating BP variability can accurately predict incident dementia and can be applied clinically for early disease detection and optimized patient management.

The Impact of Cardiac Comorbidity Sequence at Baseline and Mortality Risk in Type 2 Diabetes Mellitus: A Retrospective Population-Based Cohort Study.

Introduction: The presence of multiple comorbidities increases the risk of all-cause mortality, but the effects of the comorbidity sequence before the baseline date on mortality remain unexplored. This study investigated the relationship between coronary heart disease (CHD), atrial fibrillation (AF) and heart failure (HF) through their sequence of development and the effect on all-cause mortality risk in type 2 diabetes mellitus. Methods: This study included patients with type 2 diabetes mellitus prescribed antidiabetic/cardiovascular medications in public hospitals of Hong Kong between 1 January 2009 and 31 December 2009, with follow-up until death or 31 December 2019. The Cox regression was used to identify comorbidity sequences predicting all-cause mortality in patients with different medication subgroups. Results: A total of 249,291 patients (age: 66.0 ± 12.4 years, 47.4% male) were included. At baseline, 7564, 10,900 and 25,589 patients had AF, HF and CHD, respectively. Over follow-up (3524 ± 1218 days), 85,870 patients died (mortality rate: 35.7 per 1000 person-years). Sulphonylurea users with CHD developing later and insulin users with CHD developing earlier in the disease course had lower mortality risks. Amongst insulin users with two of the three comorbidities, those with CHD with preceding AF (hazard ratio (HR): 3.06, 95% CI: [2.60−3.61], p < 0.001) or HF (HR: 3.84 [3.47−4.24], p < 0.001) had a higher mortality. In users of lipid-lowering agents with all three comorbidities, those with preceding AF had a higher risk of mortality (AF-CHD-HF: HR: 3.22, [2.24−4.61], p < 0.001; AF-HF-CHD: HR: 3.71, [2.66−5.16], p < 0.001). Conclusions: The sequence of comorbidity development affects the risk of all-cause mortality to varying degrees in diabetic patients on different antidiabetic/cardiovascular medications.

The association between blood pressure variability and hip or vertebral fracture risk: A population-based study.

BACKGROUND: The present study evaluated the association between blood pressure variability and the risk of hip/vertebral fractures in middle aged and elderly patients. METHODS: This was a retrospective observational study of patients attending family medicine outpatient clinics, recruited from 1st January 2000 to 31st December 2003 and were followed up until 31st December 2019. Standard deviation (SD), root mean square (RMS), coefficient of variation (CV) and a variability score (defined as the number of changes in blood pressure (diastolic and systolic) of 5 mm Hg or more) were used as measures of blood pressure variability. The primary outcome was a composite of new onset hip or vertebral fractures. RESULTS: A total of 57,810 patients were included. Over a median follow-up of 5894 days (interquartile range: 3505-6487), 3285 patients (5.68%) developed new onset hip/vertebral fractures. The crude incidence rates were 4.95%, 5.31%, and 7.2% for diastolic blood pressure-CV and 5.0%, 5.28%, and 7.08% for systolic blood pressure-CV in the first, second, and third tertiles, respectively. Survival analysis demonstrated differences in hip/vertebral fracture amongst the tertiles of systolic and diastolic blood pressure variability (P < 0.0001). CONCLUSIONS: Measures of blood pressure variability were significantly associated with incident hip/vertebral fractures. They can be incorporated into existing clinical scores to improve risk stratification.

Risk stratification of cardiac arrhythmias and sudden cardiac death in type 2 diabetes mellitus patients receiving insulin therapy: A population-based cohort study.

INTRODUCTION: Metabolic abnormalities may exacerbate the risk of adverse outcomes in patients with type 2 diabetes mellitus. The present study aims to assess the predictive value of HbA1c and lipid variability on the risks of sudden cardiac death (SCD) and incident atrial fibrillation (AF). METHODS: The retrospective observational study consists of type 2 diabetic patients prescribed with insulin, who went to publicly funded clinics and hospitals in Hong Kong between January 1, 2009 and December 31, 2009. Variability in total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, and HbA1c were assessed through their SD and coefficient of variation. The primary outcomes were incident (1) ventricular tachycardia/ventricular fibrillation, actual or aborted SCD and (2) AF. RESULTS: A total of 23 329 patients (mean ± SD age: 64 ± 14 years old; 51% male; mean HbA1c 8.6 ± 1.3%) were included. On multivariable analysis, HbA1c, total cholesterol, LDL-C and triglyceride variability were found to be predictors of SCD (p < .05). CONCLUSION: HbA1c and lipid variability were predictive of SCD. Therefore, poor glucose control and variability in lipid parameters in diabetic patients are associated with aborted or actual SCD. These observations suggest the need to re-evaluate the extent of glycemic control required for outcome optimization.

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors vs. Dipeptidyl Peptidase-4 (DPP4) Inhibitors for New-Onset Dementia: A Propensity Score-Matched Population-Based Study With Competing Risk Analysis.

Introduction: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors (DPP4I) on new-onset cognitive dysfunction in type 2 diabetes mellitus remain unknown. This study aimed to evaluate the effects of the two novel antidiabetic agents on cognitive dysfunction by comparing the rates of dementia between SGLT2I and DPP4I users. Methods: This was a population-based cohort study of type 2 diabetes mellitus patients treated with SGLT2I and DPP4I between January 1, 2015 and December 31, 2019 in Hong Kong. Exclusion criteria were <1-month exposure or exposure to both medication classes, or prior diagnosis of dementia or major neurological/psychiatric diseases. Primary outcomes were new-onset dementia, Alzheimer's, and Parkinson's. Secondary outcomes were all-cause, cardiovascular, and cerebrovascular mortality. Results: A total of 13,276 SGLT2I and 36,544 DPP4I users (total n = 51,460; median age: 66.3 years old [interquartile range (IQR): 58-76], 55.65% men) were studied (follow-up: 472 [120-792] days). After 1:2 matching (SGLT2I: n = 13,283; DPP4I: n = 26,545), SGLT2I users had lower incidences of dementia (0.19 vs. 0.78%, p < 0.0001), Alzheimer's (0.01 vs. 0.1%, p = 0.0047), Parkinson's disease (0.02 vs. 0.14%, p = 0.0006), all-cause (5.48 vs. 12.69%, p < 0.0001), cerebrovascular (0.88 vs. 3.88%, p < 0.0001), and cardiovascular mortality (0.49 vs. 3.75%, p < 0.0001). Cox regression showed that SGLT2I use was associated with lower risks of dementia (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: [0.27-0.61], P < 0.0001), Parkinson's (HR:0.28, 95% CI: [0.09-0.91], P = 0.0349), all-cause (HR:0.84, 95% CI: [0.77-0.91], P < 0.0001), cardiovascular (HR:0.64, 95% CI: [0.49-0.85], P = 0.0017), and cerebrovascular (HR:0.36, 95% CI: [0.3-0.43], P < 0.0001) mortality. Conclusions: The use of SGLT2I is associated with lower risks of dementia, Parkinson's disease, and cerebrovascular mortality compared with DPP4I use after 1:2 ratio propensity score matching.

Gender- and Age-Specific Associations of Visit-to-Visit Blood Pressure Variability With Anxiety.

Background: There is a bidirectional relationship between blood pressure variability (BPV) and anxiety, but few studies have examined the gender- and age-specific effects of visit-to-visit BPV on incident anxiety. We examined the predictive value of BPV for the incidence of anxiety in a family clinic cohort. Methods: Consecutive patients with a first attendance to family medicine clinics in Hong Kong between January 1, 2000, and December 31, 2002, with at least three blood pressure measurements available thereafter were included. The primary endpoint was incident anxiety as identified by ICD-9 coding. Results: This study included 48,023 (50% males) patients with a median follow-up of 224 [interquartile range (IQR): 217-229] months. Females were more likely to develop incident anxiety compared to males (incidence rate: 7 vs. 2%), as were patients of older age. Significant univariate predictors were female gender, older age, preexisting cardiovascular diseases, respiratory diseases, diabetes mellitus, hypertension, and gastrointestinal diseases, various laboratory examinations, and the number of blood pressure measurements. Higher baseline, maximum, minimum, standard deviation (SD), coefficient of variation (CV), and variability score of diastolic blood pressure significantly predicted incident anxiety, as did all systolic blood pressure measures [baseline, latest, maximum, minimum, mean, median, variance, SD, root mean square (RMS), CV, and variability score]. Conclusions: The relationships between longer-term visit-to-visit BPV and incident anxiety were identified. Female and older patients with higher blood pressure and higher BPV were at the highest risks of incident anxiety.

Video-assisted thoracic surgery thymectomy for nonthymomatous myasthenia gravis.

STUDY OBJECTIVES: Minimal-access thymectomy has become increasingly popular as surgical treatment for patients with nonthymomatous myasthenia gravis (NTMG) because of its comparable efficacy, safety, and lesser degree of tissue trauma compared with conventional open surgery. We reviewed and analyzed our data on video-assisted thoracic surgery (VATS) thymectomy and present the clinical outcomes according to the Myasthenia Gravis Foundation of America classification. DESIGN: A retrospective review of VATS thymectomy for NTMG in a university hospital over a 12-year period. Data were collected from the medical records and supplemented with telephone surveys. The impact of surgery and other variables potentially affecting complete stable remission (CSR) were calculated using Kaplan-Meier survival curves; comparisons between survival curves was performed using the log-rank test. RESULTS: A total of 38 consecutive patients underwent VATS thymectomy for NTMG. Median postoperative stay was 3 days. Pathologic examination revealed thymic hyperplasia in 61.1% of cases, normal thymus in 22.2%, and thymic atrophy in 16.6%. There was no perioperative mortality; complications occurred in four patients. After a median follow-up of 69 months, 91.6% of patients experienced improvement, with crude CSR achieved in 22.2%. Kaplan-Meier survival curve demonstrated a 75% CSR rate at 10-year follow-up. On univariate analysis, only disease duration < or = 12 months (p = 0.03) was associated with a statistically significant improvement in CSR. CONCLUSIONS: VATS thymectomy for NTMG results in symptomatic improvement in the vast majority of patients, with a high rate of CSR. The procedure is associated with low morbidity and no perioperative mortality. Future studies on thymectomy for myasthenia gravis should be reported in a standardized manner to allow accurate comparisons between results in the absence of randomized prospective trials.

Neuroimaging determinants of cognitive performances in stroke associated with small vessel disease.

BACKGROUND AND PURPOSE: Controversies still exist as to the neuroimaging determinants of cognitive impairment in cerebral small vessel disease (SVD). The authors studied the neuroimaging correlates of cognitive performances among patients with stroke associated with SVD. METHODS: The authors per formed cerebral computed tomography, magnetic resonance imaging, and diffusion-weighted imaging among 74 consecutive patients admitted to the acute stroke unit because of stroke associated with SVD. They examined the association between cognitive performances and the following neuroimaging features: volume of white matter changes (WMC), multiplicity of lacunae, location of lacunae, total cerebral atrophy, and frontal and medial temporal lobe atrophy. RESULTS: Apart from age and education, univariate linear regression analyses revealed that WMC volume, presence of thalamic lacunae, cerebral atrophy, and left frontal lobe atrophy predicted performance on the Mini-Mental State Examination while WMC volume, presence of thalamic infarcts, cerebral atrophy, and frontal lobe atrophy of both sides predicted performance on the Mattis Dementia Rating Scale-Initiation/Preservation subscale. In the multivariate analyses, education (R2=0.22, P<.001), left frontal lobe atrophy (R2=0.10, P=.004), and presence of thalamic lacunae (R2=0.04, P=.049) were found to predict performance on the Mini-Mental State Examination while age (R2=0.23, P<.001) and presence of thalamic lacunae (R2=0.08, P=.011) were found to predict performance on the Mattis Dementia Rating Scale-Initiation/Preservation. CONCLUSIONS: Among patients with stroke associated with SVD, thalamic lacunae and frontal lobe atrophy are key determinants of cognitive performances.