Depression amongst physicians can lead to poor individual and institutional outcomes. This study examined the prevalence and factors associated with depression and suicidal ideation amongst doctors ...in Hong Kong. Doctors who graduated from medical school at the University of Hong Kong between 1995 and 2014 were invited to participate in a survey measuring depressive symptoms, suicidal ideation and thoughts of self-harm, lifestyle behaviours, career satisfaction and socio-demographic characteristics. Data collection occurred between January and April 2016. The prevalence of screened-positive depression was 16.0% and 15.3% of respondents reported having suicidal ideation. Amongst those with positive depression screening scores, less than half reported having a diagnosed mood disorder. Sleeping fewer hours was associated with higher depression scores (P < 0.001) and an increased odds of meeting the cut-off for depression (P < 0.001). Factors associated with suicidal ideation included being unmarried (P = 0.012) and sleeping fewer hours (P = 0.022). Hong Kong doctors appear to have high rates of undiagnosed depression, and high levels of depressive symptoms and suicidal ideations. There is a need for greater awareness of the morbidity due to depression and to promote better mental health help-seeking among physicians. Barriers to mental health help-seeking need to be addressed and appropriate resources allocated to reduce suffering.
Objective
Patients with axial spondyloarthritis (SpA) are subjected to elevated cardiovascular risks, but assessment of early myocardial damage and clinical risk stratification remained obscure. The ...aim of this study was to evaluate the prognostic value of speckle-tracking strain analysis and serum high-sensitivity troponin I (hsTnI) in patients with axial SpA.
Methods
Two-dimensional speckle-tracking echocardiography was performed to derive longitudinal strain (LS), circumferential strain (CS), and radial strain (RS). Serum hsTnI was measured by validated immunoassay (Architect i1000SR Abbott) as indicator of subclinical myocardial damage.
Results
The mean Bath Ankylosing Spondylitis Disease Activity Index and median modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) were 3.8 and 15.5, respectively. Over a median follow-up of 81 months, major adverse cardiovascular events (MACE) occurred in 13% of subjects (
n
= 116). Univariate Cox regression showed that age, disease duration, Bath Ankylosing Spondylitis Functional Index, modified Schober test, mSASSS, hsTnI, interventricular septal thickness, E/E′, LS, RS, and carotid intima-media thickness were significant predictors of MACE (all
P
< 0.05). After adjustment for age, sex, and statistically significant disease-related parameters, only subclinically raised hsTnI and impaired LS remained independent predictors for MACE. Kaplan-Meier analysis showed that combined impaired LS ≥ − 17.5% and hsTnI ≥ 3.0 pg/ml significantly predicted MACE (log-rank test
P
< 0.01; sensitivity 50%; specificity 90%; positive predictive value 43%; negative predictive value 92%).
Conclusions
Depressed LS indicating subclinical left ventricular systolic dysfunction and elevated serum hsTnI both independently predicted MACE among young patients with axial SpA. Combined analysis of speckle-tracking-derived strain analysis and serum hsTnI improves risk stratification in these patients.
Key Points
• Both depressed longitudinal strain (LS) and elevated serum high-sensitivity troponin I (hsTnI) are promising independent predictors for cardiovascular (CV) events in axial SpA.
• Importantly, patients with LS ≥
−
17.5% and hsTnI ≥ 3.0 pg/ml had the highest risk of incident MACE.
• Axial SpA patients with concomitant impaired LS and raised hsTnI are at a high risk of CV events.
The unmet need in systemic lupus erythematosus (SLE) with the current standard of care is widely recognised, but few studies have quantified this. The recent definition of treat-to-target endpoints ...and other thresholds of uncontrolled disease activity provide an opportunity to formally define unmet need in SLE. In this study, we enumerated the prevalence of these states and examined their association with adverse outcomes.
Data were collected prospectively in a 13-country longitudinal SLE cohort between 2013 and 2019. Unmet need was defined as never attaining lupus low disease activity state (LLDAS), a time-adjusted mean SLEDAI-2K (AMS) > 4, or ever experiencing high disease activity status (HDAS; SLEDAI-2K ≥10). Health-related quality of life (HRQoL) was assessed using SF36 (v2) and damage accrual using the SLICC-ACR SLE Damage Index (SDI).
A total of 3384 SLE patients were followed over 30,313 visits (median IQR follow-up 2.4 0.4, 4.3 years). Eight hundred thirteen patients (24%) never achieved LLDAS. Median AMS was 3.0 1.4, 4.9; 34% of patients had AMS > 4. Twenty-five per cent of patients had episodes of HDAS. Each of LLDAS-never, AMS>4, and HDAS-ever was strongly associated with damage accrual, higher glucocorticoid use, and worse HRQoL. Mortality was significantly increased in LLDAS-never (adjusted HR 95% CI = 4.98 2.07, 12.0, p<0.001) and HDAS-ever (adjusted hazard ratio (HR) 95% CI = 5.45 2.75, 10.8, p<0.001) patients.
Failure to achieve LLDAS, high average disease activity, and episodes of HDAS were prevalent in SLE and were significantly associated with poor outcomes including organ damage, glucocorticoid exposure, poor quality of life, and mortality.
Background Rheumatic diseases are related to both abnormal bone turnover and atherogenesis, but a mechanistic link was missing. Methods and Results We investigated the effect of cumulative rheumatic ...inflammation ( CRI ) on risk of coronary calcification in a retrospective cohort of 145 rheumatoid arthritis patients. A time-adjusted aggregate CRI score was derived by conglomerating all quarterly biomarker encounters of serum C-reactive protein over 60 months immediately preceding computed tomography coronary angiography. Flow cytometry was performed to measure the osteocalcin-positive ( OCN
) CD 34
KDR
and OCN
CD 34
circulating endothelial progenitor cells ( EPCs ). Conventional early circulating EPCs CD 34
CD 133
KDR
was determined. Coronary calcification was defined as any Agatston score >0. 50% of patients (n=72/145) had coronary calcification. CRI score was associated with presence of coronary calcification ( P=0.004) (multivariable-adjusted: highest versus lowest quartile: odds ratio=5.6 95% CI 1.1-28.9, P=0.041). Receiver operating characteristics curve revealed divergent behavior of OCN -expressing circulating EPCs ( OCN
CD 34
EPCs : area under the curve=0.60, P=0.034; OCN
CD 34
KDR
EPCs : area under the curve=0.59, P=0.053, positive predictors) versus conventional early EPCs ( CD 34
CD 133
KDR
: area under the curve=0.60, P=0.034, negative predictor) for coronary calcification, which persisted after multivariable adjustments ( OCN
CD 34
KDR
>75th percentile: odds ratio=7.2 95% CI 1.8-27.9, P=0.005; OCN
CD 34
EPCs >75th percentile: odds ratio=6.0 95% CI 1.5-23.3, P=0.010; CD 34
CD 133
KDR
>75th percentile: odds ratio=0.3 95% CI 0.1-1.0, P=0.053). Intriguingly, the CRI score was associated with increased OCN
CD 34
EPCs (highest versus lowest quartile: B=+25.6 95% CI 0.8-50.5 ×10
/mL peripheral blood, P=0.043), but reduced CD 34
CD 133
KDR
EPCs (highest versus lowest quartile: B=-16.2 95% CI -31.5 to -0.9, P=0.038). Conclusions Preceding 60 months of CRI is associated with increased risk of coronary calcification and altered OCN expression in circulating EPCs .
Adult antibody deficiency remains under-recognised and under-studied - especially among Asian populations. Patterns of immunoglobulin use and the feasibility of subcutaneous immunoglobulin (SCIg) ...replacement among Chinese patients remains unclear.
To investigate the trends of immunoglobulin use, burden of adult antibody deficiency and the outcomes of patients on SCIg compared to intravenous immunoglobulin (IVIg) replacement in Hong Kong through a retrospective observational study.
Population-wide data of immunoglobulin recipients in Hong Kong between 2012 and 2021, and longitudinal clinical data of adult immunodeficiency patients at Queen Mary Hospital were collected and analysed.
Total immunoglobulin consumption and recurrent immunoglobulin recipients increased continuously from 175,512g to 298,514g (ρ=0.99, p<0.001) and 886 to 1,508 (ρ=0.89, p=0.001) between 2012-21 in Hong Kong. Among 469 immunoglobulin recipients at Queen Mary Hospital in 2021, 344 (73.3%) were indicated for replacement. Compared to those on IVIg (n=14), patients on SCIg replacement (n=8) had fewer immunodeficiency-related hospitalisations (IRR=0.11) and shorter duration of hospitalisation stay (IRR=0.10) per year, as well as better quality of life (SF-36v2 Health Survey and Life Quality Index). Estimated annual healthcare cost of SCIg replacement per patient was lower than that of IVIg (HKD196,850 USD25,096 vs HKD222,136 USD28,319).
There was a significantly increasing burden of adult antibody deficiency and immunoglobulin consumption in Hong Kong. SCIg was feasible and more cost-effective when compared to IVIg, with SCIg patients experiencing better clinical outcomes and quality of life. Future prospective studies to confirm the long-term efficacy and superiority of SCIg are required.
Interleukin 17 (IL-17) was recently linked to pathogenesis of systemic lupus erythematosus (SLE), but its relation to disease activity has not been well characterized. We examined the relation ...between serum levels of Th17 (IL-17, IL-23), Th1 (IL-12, interferon-γ), Th2 (IL-10, IL-6, IL-4) cytokines and disease activity in patients with SLE.
Serum cytokines were measured by enzyme linked immunosorbent assays. Disease activity was determined by SLE disease activity index (SLEDAI), anti-dsDNA antibody, and C3 and C4 levels.
Serum levels of IL-17 (p < 0.001), IL-6 (p = 0.006) and IL-10 (p < 0.001) were higher in SLE patients (n = 70) compared to healthy controls (n = 36). Higher serum IL-23 level was found in patients with active disease with cutaneous manifestations (p = 0.004) and serositis (p = 0.04) compared to those without. Serum IL-17 level above the detection limit was more frequently found in patients who had active lupus nephritis (11/23, 47.8%) (p = 0.002), nonrenal active disease (9/15, 60%) (p = 0.001), and inactive lupus (21/32, 65.6%) (p < 0.001) compared to healthy controls (0%). Serum IL-17 levels were otherwise comparable between these 3 groups of patients and were not related to SLEDAI, glomerular filtration rate, activity or chronicity score and ISN/RPS criteria class among patients with active lupus nephritis. There was no significant correlation between serum IL-17/IL-23 and Th1 or Th2 cytokine levels.
SLE patients had higher serum IL-17 levels than healthy controls. Elevated serum IL-23 was found in patients with inflammatory manifestations including cutaneous involvement and serositis. The lack of correlation between Th17, Th1, and Th2 cytokines suggested independent regulatory mechanisms for these cytokines.
Abstract
Background
There is little data on mycophenolic acid (MPA) pharmacokinetics and pharmacogenomics and optimal MPA exposure in lupus nephritis (LN) patients during long-term maintenance.
...Methods
We measured blood MPA levels at 1, 2, 4, 8, 10 and 12-h post-dose (i.e. C1, C2, C4, C8, C10 and C12) in 88 stable LN patients receiving maintenance prednisolone and mycophenolate mofetil, repeated every 6 months. The relationship between MPA exposure and single nucleotide polymorphisms (SNPs) of adenosine triphosphate–binding cassette subfamily C member 2 (ABCC2; rs2273697, rs3740066, rs717620 and rs17222723), organic anion-transporting polypeptides (OATPs; rs7311358 and rs4149117) and uridine diphosphate glucuronosyltransferase (UGT; rs17863762, rs6714486, rs17868320 and rs72551330) was also investigated.
Results
C1, C2 and C12 were 8.3 ± 6.6 , 7.2 ± 5.2 and 2.0 ± 1.4 mg/L and all correlated with the 12-h area under the curve (AUC0–12; r = 0.51, 0.85 and 0.73; P = 0.02, <0.001 and <0.001, respectively). C12 inversely correlated with hemoglobin, immunoglobulins and leukocyte levels (P < 0.05 for all). Five renal flares, 11 episodes of infection and 10 episodes of anemia (hemoglobin <10 g/dL) occurred over 96 weeks, with a corresponding C12 of 1.3 ± 0.5, 4.3 ± 2.6 and 2.9 ± 1.5 mg/L, respectively (versus 2.4 ± 1.2, 1.8 ± 1.2 and 1.7 ± 1.1 mg/L in patients without these complications; P = 0.041, <0.001 and 0.004). SNP rs2273697 A/G in the ABCC2 gene was associated with lower MPA exposure compared with G/G (1075.9 ± 239.9 versus 1891.5 ± 918.9 mgh/L per g/kg; P = 0.003). SNPs of OATP and UGT were unrelated to MPA level.
Conclusion
MPA C12 correlates with the AUC0–12 and is related to renal flare, infection and anemia. SNP rs2273697 A/G is associated with lower MPA exposure.
•Real-world head-to-head comparisons of BNT162b2 and CoronaVac are limited.•Target trial emulation study using electronic health records in Hong Kong.•BNT162b2 demonstrated almost 50% lower risk of ...mortality compared with CoronaVac.•BNT162b2 showed a higher risk of myocarditis after two doses compared to CoronaVac.
To evaluate the difference between BNT162b2 and CoronaVac in vaccine effectiveness and safety.
This target trial emulation study included individuals aged ≥12 during 2022. Propensity score matching was applied to ensure group balance. The Cox proportional hazard model was used to compare the effectiveness outcomes including COVID-19 infection, severity, 28-day hospitalization, and 28-day mortality after infection. Poisson regression was used for safety outcomes including 32 adverse events of special interests between groups.
A total of 639,818 and 1804,388 individuals were identified for the 2-dose and 3-dose comparison, respectively. In 2-dose and 3-dose comparison, the hazard ratios (95% confidence intervals CI) were 0.844 0.833-0.856 and 0.749 0.743-0.755 for COVID-19 infection, 0.692 0.656-0.731 and 0.582 0.559-0.605 for hospitalization, 0.566 0.417-0.769 and 0.590 0.458-0.76 for severe COVID-19, and 0.563 0.456-0.697 and 0.457 0.372-0.561 for mortality for BNT162b2 recipients versus CoronaVac recipients, respectively. Regarding safety, 2-dose BNT162b2 recipients had a significantly higher incidence of myocarditis (incidence rate ratio IRR 95% CI: 8.999 1.14-71.017) versus CoronaVac recipients, but the difference was insignificant in 3-dose comparison (IRR 95% CI: 2.000 0.500-7.996).
BNT162b2 has higher effectiveness among individuals aged ≥12 against COVID-19-related outcomes for SARS-CoV-2 omicron compared to CoronaVac, with almost 50% lower mortality risk.
Interleukin-18 receptor accessory protein (IL18RAP) is an indispensable subunit for the IL-18 receptor (IL-18R) complex's ability to mediate high-affinity IL-18 binding and signalling transduction. ...Interest in IL-18 in systemic lupus erythematosus (SLE) has been mostly focused on its role as a type 1 T helper cell-driving cytokine. The functional significance of IL18RAP in mediating the IL-18-driven response in myeloid cells in SLE remains largely unexplored. This study aimed to investigate the expression and function significance of IL18RAP in neutrophils of SLE patients. By qRT-PCR and Western blot analyses, elevated expressions of IL18RAP mRNA and protein were observed in neutrophils from SLE patients-particularly those with a history of nephritis. IL18RAP expression correlated negatively with complement 3 level and positively with disease activity, with higher expression in patients exhibiting renal and immunological manifestations. The increased IL18RAP expression in SLE neutrophils could be attributed to elevated type I interferon level in sera. Functionally, neutrophils from SLE patients showed higher IL-18-mediated enhancement in reactive oxygen species (ROS) generation, which showed positive correlation with IL18RAP expression and could be neutralized by anti-IL18RAP blocking antibodies. Taken together, our findings suggest that IL-18 could contribute to SLE pathogenesis through mediation of neutrophil dysfunction via the upregulation of IL18RAP expression.
ObjectiveTo estimate the prevalence and severity of burnout and explore the factors associated with burnout among Hong Kong medical graduates up to 20 years post-graduation.DesignCross-sectional ...survey.SettingHong Kong.ParticipantsDoctors who graduated from the University of Hong Kong between 1995 and 2014.Primary and secondary outcome measuresBurnout as measured by the Copenhagen Burnout Inventory (CBI), alcohol consumption as measured by the Alcohol Use Disorders Identification Test Version C, lifestyle behaviours (hours of sleep and work, exercise, smoking, substance use), career satisfaction and sociodemographic characteristics were obtained using paper or online questionnaires.ResultsResponse rate was 30.9% (496/1607). Prevalence of CBI burnout was 63.1% (personal), 55.9% (work-related) and 35.4% (patient-related). The mean CBI subscale scores were 57.4±21.4 (personal), 48.9±7.4 (work-related) and 41.5±21.8 (client-related). Factors associated with personal and patient-related burnout included age (coeff −0.437, 95% CI −0.779 to −0.095 and coeff −0.596, 95% CI −0.965 to −0.228, respectively), practice setting (coeff −5.759, 95% CI −10.665 to −0.853 and coeff −5.317, 95% CI −10.602 to −0.032, respectively) and regular exercise (coeff −6.855, 95% CI −11.102 to −2.608 and coeff −6.769, 95% CI −11.333 to −2.205, respectively). Gender (coeff 5.1, 95% CI 1.382 to 8.818), average hours of sleep per night (coeff −5.200, 95% CI −7.139 to −3.262) and work hours per week (coeff 0.226, 95% CI 0.099 to 0.353) were associated with personal burnout only. No factors were significantly associated with work-related burnout.ConclusionBurnout is highly prevalent among Hong Kong medical graduates. Younger doctors, women and those working in the public sector appear to be at higher risk for burnout and may benefit from targeted interventions. Policymakers and healthcare authorities should consider measures to help reduce burnout by enabling adequate sleep, reducing work hours and encouraging exercise.
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