Current and Emerging Radiotherapy Options for Uveal Melanoma.

What treatment options are there for patients having uveal melanoma? A randomized, prospective, multi-institutional clinical trial (COMS) showed no difference in survival between brachytherapy and enucleation for medium-sized lesions. With the obvious benefit of retaining the eye, brachytherapy has flourished and many different approaches have been developed such as low-dose-rate sources using alternate low-energy photon-emitting radionuclides, different plaque designs and seed-loading techniques, high-dose-rate brachytherapy sources and applicators, and low- and high-dose-rate beta-emitting sources and applicators. There also have been developments of other radiation modalities like external-beam radiotherapy using linear accelerators with high-energy photons, particle accelerators for protons, and gamma stereotactic radiosurgery. This article examines the dosimetric properties, targeting capabilities, and outcomes of these approaches. The several modalities examined herein have differing attributes and it may be that no single approach would be considered optimal for all patients and all lesion characteristics.

Investigating viral and autoimmune T cell responses associated with post-acute sequelae of COVID-19.

Post-acute sequelae of COVID-19 (PASC), or Long COVID, is a chronic condition following acute SARS-CoV-2 infection. Symptoms include exertion fatigue, respiratory issues, myalgia, and neurological manifestations such as 'brain fog,' posing concern for their debilitating nature and potential role in other neurological disorders. However, the underlying potential pathogenic mechanisms of the neurological complications of PASC is largely unknown. Herein, we investigated differences in antigen-specific T cell responses from the peripheral blood towards SARS-CoV-2, latent viruses, or neuronal antigens in 14 PASC individuals with neurological manifestations (PASC-N) versus 22 individuals fully recovered from COVID-19. We employed Activation Induced Marker (AIM), ICS and FluoroSpot assays to determine the specificity and magnitude of CD4+ and CD8+ T cell responses towards SARS-CoV-2 (Spike and rest of proteome), latent viruses (CMV, EBV), and several neuronal antigens. Overall, we observed similar antigen-specific T cell frequencies and cytokine effector T cell responses between PASC donors compared to recovered controls for all antigens tested (viral or autoantigen) in both CD4+ and CD8+ T cell compartments. Our findings suggest that PASC-N does not appear to be associated with changes in antigen-specific T cell responses towards a subset of disease-relevant targets, but more studies in a larger cohort are needed to confirm these unaltered responses.

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

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

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

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

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.

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.

Comparison of Tumor Bed Delineation Using a Novel Radiopaque Filament Marker Versus Surgical Clips for Targeting Breast Cancer Radiotherapy.

BACKGROUND: Accuracy of tumor bed (TB) delineation is essential for targeting boost doses or partial breast irradiation. Multiple studies have shown high interobserver variability with standardly used surgical clip markers (CMs). We hypothesize that a radiopaque filament marker (FM) woven along the TB will improve TB delineation consistency. METHODS: An FDA-approved FM was intraoperatively used to outline the TB of patients undergoing lumpectomy. Between January 2020 and January 2022, consecutive patients with FM placed after either (1) lumpectomy or (2) lumpectomy with oncoplastic reconstruction were identified and compared with those with CM. Six "experts" (radiation oncologists specializing in breast cancer) across 2 institutions independently defined all TBs. Three metrics (volume variance, dice coefficient, and center of mass [COM] deviation). Two-tailed paired samples t tests were performed to compare FM and CM cohorts. RESULTS: Twenty-eight total patients were evaluated (14 FM and 14 CM). In aggregate, differences in volume between expert contours were 29.7% (SD ± 58.8%) with FM and 55.4% (SD ± 105.9%) with CM ( P < 0.001). The average dice coefficient in patients with FM was 0.54 (SD ± 0.15), and with CM was 0.44 (SD ± 0.22) ( P < 0.001). The average COM deviation was 0.63 cm (SD ± 0.53 cm) for FM and 1.05 cm (SD ± 0.93 cm) for CM; ( P < 0.001). In the subset of patients who underwent lumpectomy with oncoplastic reconstruction, the difference in average volume was 21.8% (SD ± 20.4%) with FM and 52.2% (SD ± 64.5%) with CM ( P <0.001). The average dice coefficient was 0.53 (SD ± 0.12) for FM versus 0.39 (SD ± 0.24) for CM ( P < 0.001). The average COM difference was 0.53 cm (SD ± 0.29 cm) with FM versus 1.25 cm (SD ± 1.08 cm) with CM ( P < 0.001). CONCLUSION: FM consistently outperformed CM in the setting of both standard lumpectomy and complex oncoplastic reconstruction. These data suggest the superiority of FM in TB delineation.

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.

The indirect impact of the COVID-19 pandemic on people with type 2 diabetes mellitus and without COVID-19 infection: Systematic review and meta-analysis.

BACKGROUND: The effect directly from the coronavirus disease 2019 (COVID-19) infection on health and fatality has received considerable attention, particularly among people with type 2 diabetes mellitus (T2DM). However, evidence on the indirect impact of disrupted healthcare services during the pandemic on people with T2DM is limited. This systematic review aims to assess the indirect impact of the pandemic on the metabolic management of T2DM people without a history of COVID-19 infection. METHODS: PubMed, Web of Science, and Scopus were systematically searched for studies that compared diabetes-related health outcomes between pre-pandemic and during-pandemic periods in people with T2DM and without the COVID-19 infection and published from January 1, 2020, to July 13, 2022. A meta-analysis was performed to estimate the overall effect on the diabetes indicators, including hemoglobin A1c (HbA1c), lipid profiles, and weight control, with different effect models according to the heterogeneity. RESULTS: Eleven observational studies were included in the final review. No significant changes in HbA1c levels [weighted mean difference (WMD), 0.06 (95% CI -0.12 to 0.24)] and body weight index (BMI) [0.15 (95% CI -0.24 to 0.53)] between the pre-pandemic and during-pandemic were found in the meta-analysis. Four studies reported lipid indicators; most reported insignificant changes in low-density lipoprotein (LDL, n = 2) and high-density lipoprotein (HDL, n = 3); two studies reported an increase in total cholesterol and triglyceride. CONCLUSIONS: This review did not find significant changes in HbA1c and BMI among people with T2DM after data pooling, but a possible worsening in lipids parameters during the COVID-19 pandemic. There were limited data on long-term outcomes and healthcare utilization, which warrants further research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022360433.

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

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

Diabetes with poor-control HbA1c is cardiovascular disease 'risk equivalent' for mortality: UK Biobank and Hong Kong population-based cohort study.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) has traditionally been considered a coronary heart disease 'risk equivalent' for future mortality, but significant heterogeneity exists across people with T2DM. This study aims to determine the risk of all-cause mortality of patients with cardiovascular disease (CVD) and T2DM in UK and Hong Kong, with stratifications for hemoglobin A1 (HbA1c) concentrations, compared with those without CVD and diabetes mellitus. RESEARCH DESIGN AND METHODS: This is a retrospective cohort study of 3 839 391 adults from Hong Kong and a prospective cohort study of 497 779 adults from the UK Biobank. Individuals were divided into seven disease groups: (1) no T2DM and CVD, (2) T2DM only with HbA1c <7%, (3) T2DM only with HbA1c 7%-7.9%, (4) T2DM only with HbA1c 8%-8.9%, (5) T2DM only with HbA1c ≥9%, (6) CVD only, and (7) T2DM and CVD. Differences in all-cause mortality between groups were examined using Cox regression. RESULTS: After around 10 years of median follow-up, 423 818 and 19 844 deaths were identified in the Hong Kong cohort and UK Biobank, respectively. Compared with individuals without T2DM and CVD, the adjusted HR for all-cause mortality in the other six disease groups for the Hong Kong cohort was 1.25 (95% CI 1.23 to 1.27) for T2DM only with HbA1c <7%, 1.21 (95% CI 1.19 to 1.23) for T2DM only with HbA1c 7%-7.9%, 1.36 (95% CI 1.33 to 1.39) for T2DM only with HbA1c 8%-8.9%, 1.82 (95% CI 1.78 to 1.85) for T2DM only with HbA1c ≥9%, 1.37 (95% CI 1.36 to 1.38) for CVD only, and 1.83 (95% CI 1.81 to 1.85) for T2DM and CVD, and for the UK Biobank the HR was 1.45 (95% CI 1.33 to 1.58), 1.50 (95% CI 1.32 to 1.70), 1.72 (95% CI 1.43 to 2.08), 2.51 (95% CI 2.05 to 3.08), 1.67 (95% CI 1.59 to 1.75) and 2.62 (95% CI 2.42 to 2.83), respectively. This indicates that patients with T2DM had an increased risk of mortality compared with those without T2DM and CVD, and in those with HbA1c ≥9% an even higher risk than people with CVD. CONCLUSIONS: Patients with T2DM with poor HbA1c control (8%-8.9% and ≥9%) were associated with similar and higher risk of mortality compared with patients with CVD, respectively. Optimal HbA1c, controlled for risk reduction and prevention of mortality and complications in diabetes management, remains important.

Comparative Risks of Nonsteroidal Anti-inflammatory Drugs on Cardiovascular Diseases: A Population-Based Cohort Study.

Through examining the incidence of cardiovascular diseases (CVDs) among nonsteroidal anti-inflammatory drug (NSAID) users and nonusers, this study aims to compare the risks contributed by different NSAIDs in a Chinese population. The retrospective cohort including 4 298 368 adults without CVD from electronic health records between 2008 and 2017 in Hong Kong was adopted. A total of 4.5% of individuals received NSAIDs including celecoxib, etoricoxib, diclofenac, ibuprofen, indomethacin, mefenamic acid, or naproxen for ≥4 consecutive weeks at baseline. Cox regression, including NSAID use as a time-dependent covariate and adjusted with patient's characteristics, was conducted to examine the association between NSAID exposure and incident CVD. After a median follow-up of 6.9 years (30 million person-years), a total of 258 601 cases of incident CVD was recorded. NSAID use was shown to be associated with a significantly higher risk of CVD (hazard ratio [HR], 1.32 [95%CI, 1.28-1.37]) compared to non-NSAID use. Similar results in coronary heart disease (HR, 1.37 [95%CI, 1.31-1.43]), stroke (HR, 1.27 [95%CI, 1.21-1.33]), and heart failure (HR, 1.25 [95%CI, 1.16-1.34]) were obtained. Overall, similar CVD risk was observed across users of NSAIDs except for etoricoxib, which showed a higher risk (HR, 2.01 [95%CI, 1.63-2.48]). Considering that a higher CVD risk was consistently displayed among NSAID users, NSAIDs should be used cautiously, and the usage of etoricoxib in the Chinese population should be reviewed.

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

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

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.

Who reports insufficient and disturbed sleep? Results from a representative population-based health survey in Hong Kong.

OBJECTIVES: To highlight the prevalence of sleep problems and identify associated risk factors among a representative sample recruited from the general population of Hong Kong. DESIGN, SETTING AND PARTICIPANTS: Participants included 12 022 individuals (aged 15 or above) who took part in the Population Health Survey 2014/15, a territory-wide survey conducted by the Department of Health of the Government of the Hong Kong Special Administrative Region. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcomes were the prevalence of (1) insufficient sleep (<6 hours sleep per day) and (2) any sleep disturbance (difficulty initiating sleep, intermittent awakenings, early awakening) ≥3 times per week in the past 30 days. Multivariable logistic regression identified associations between sleep problems and sociodemographic, clinical and lifestyle factors. RESULTS: 9.7% of respondents reported insufficient sleep and 10.5% reported sleep disturbances ≥3 times a week. Female gender, monthly household income <$12 250 (Hong Kong dollar), lower education level, mental health condition and physical health condition were significantly associated with both insufficient and disturbed sleep (all p<0.05). Unemployment, homemaker, insufficient physical activity, current/former smoking status and harmful alcohol consumption were associated with sleep disturbances only (all p<0.01). CONCLUSIONS: Sleep problems are highly prevalent in Hong Kong. As such problems are associated with a range of health conditions, it is important to facilitate improvements in sleep. Our results show that harmful alcohol consumption, insufficient physical activity and current smoking are modifiable risk factors for sleep disturbances. Public health campaigns should focus on these risk factors in order to promote a healthy lifestyle and ultimately reduce sleep disturbances. Targeted interventions for high-risk groups may also be warranted, particularly for those with doctor-diagnosed physical and mental health conditions.

Immunological memory to common cold coronaviruses assessed longitudinally over a three-year period pre-COVID19 pandemic.

The immune memory to common cold coronaviruses (CCCs) influences SARS-CoV-2 infection outcome, and understanding its effect is crucial for pan-coronavirus vaccine development. We performed a longitudinal analysis of pre-COVID19-pandemic samples from 2016-2019 in young adults and assessed CCC-specific CD4+ T cell and antibody responses. Notably, CCC responses were commonly detected with comparable frequencies as with other common antigens and were sustained over time. CCC-specific CD4+ T cell responses were associated with low HLA-DR+CD38+ signals, and their magnitude did not correlate with yearly CCC infection prevalence. Similarly, CCC-specific and spike RBD-specific IgG responses were stable in time. Finally, high CCC-specific CD4+ T cell reactivity, but not antibody titers, was associated with pre-existing SARS-CoV-2 immunity. These results provide a valuable reference for understanding the immune response to endemic coronaviruses and suggest that steady and sustained CCC responses are likely from a stable pool of memory CD4+ T cells due to repeated earlier exposures and possibly occasional reinfections.

Ten-Year Effectiveness of the Multidisciplinary Risk Assessment and Management Programme-Diabetes Mellitus (RAMP-DM) on Macrovascular and Microvascular Complications and All-Cause Mortality: A Population-Based Cohort Study.

OBJECTIVE: The Risk Assessment and Management Programme-Diabetes Mellitus (RAMP-DM) is a protocol-driven, risk-stratified, and individualized management program offered by a multidisciplinary team in addition to usual care for primary care patients with diabetes. This study aimed to evaluate the effectiveness of RAMP-DM for preventing complications and mortality over 10 years. RESEARCH DESIGN AND METHODS: A population-based, prospective cohort study of adult patients with type 2 diabetes managed in the Hong Kong public primary health care system between 2009 and 2010 was conducted. RAMP-DM participants and usual care patients were matched using one-to-one propensity score matching and followed for 10 years. Risks of macrovascular and microvascular complications and all-cause mortality were estimated by Cox proportional hazards regression. RESULTS: A total of 36,746 patients (18,373 in each group) were included after propensity score matching, with a median follow-up of 9.5 years and 306,802 person-years. RAMP-DM participants had significantly lower risks of macrovascular (hazard ratio [HR] 0.52, 95% CI 0.50-0.54) and microvascular (HR 0.68, 95% CI 0.64-0.72) complications and all-cause mortality (HR 0.45, 95% CI 0.43-0.47) than patients who received usual care only. However, the effect of RAMP-DM on macrovascular and microvascular complications attenuated after the 9th and 8th year of follow-up, respectively. RAMP-DM participants also showed better control of hemoglobin A1c, blood pressure, triglycerides, and BMI and a slower decline in renal function. CONCLUSIONS: Significant reductions in diabetes-related complications and all-cause mortality were observed among RAMP-DM participants over a 10-year follow-up, yet the effect of preventing complications attenuated after 8 years.

Long-term spill-over impact of COVID-19 on health and healthcare of people with non-communicable diseases: a study protocol for a population-based cohort and health economic study.

INTRODUCTION: The COVID-19 pandemic has a significant spill-over effect on people with non-communicable diseases (NCDs) over the long term, beyond the direct effect of COVID-19 infection. Evaluating changes in health outcomes, health service use and costs can provide evidence to optimise care for people with NCDs during and after the pandemic, and to better prepare outbreak responses in the future. METHODS AND ANALYSIS: This is a population-based cohort study using electronic health records of the Hong Kong Hospital Authority (HA) CMS, economic modelling and serial cross-sectional surveys on health service use. This study includes people aged ≥18 years who have a documented diagnosis of diabetes mellitus, hypertension, cardiovascular disease, cancer, chronic respiratory disease or chronic kidney disease with at least one attendance at the HA hospital or clinic between 1 January 2010 and 31 December 2019, and without COVID-19 infection. Changes in all-cause mortality, disease-specific outcomes, and health services use rates and costs will be assessed between pre-COVID-19 and-post-COVID-19 pandemic or during each wave using an interrupted time series analysis. The long-term health economic impact of healthcare disruptions during the COVID-19 pandemic will be studied using microsimulation modelling. Multivariable Cox proportional hazards regression and Poisson/negative binomial regression will be used to evaluate the effect of different modes of supplementary care on health outcomes. ETHICS AND DISSEMINATION: The study was approved by the institutional review board of the University of Hong Kong, the HA Hong Kong West Cluster (reference number UW 21-297). The study findings will be disseminated through peer-reviewed publications and international conferences.

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.