Drug-induced agranulocytosis in Southern Chinese population: a twelve-year retrospective study

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Vitamin K intake reduces mortality in people with chronic kidney disease

Vitamin K intake reduces mortality in people with chronic kidney diseasepublished_or_final_versio

Association between treatment with apixaban, dabigatran, rivaroxaban, or warfarin and the risk of osteoporotic fractures among patients with atrial fibrillation: A population-based cohort study

Background: It is unclear whether anticoagulant type is associated with the risk for osteoporotic fracture, a deleterious complication of anticoagulants among patients with atrial fibrillation (AF). Objective: To compare the risk for osteoporotic fracture between anticoagulants. Design: Population-based cohort study. Setting: Territory-wide electronic health record database of the Hong Kong Hospital Authority. Participants: Patients newly diagnosed with AF between 2010 and 2017 who received a new prescription for warfarin or a direct oral anticoagulant (DOAC) (apixaban, dabigatran, or rivaroxaban). Follow-up ended on 31 December 2018. Measurements: Osteoporotic hip and vertebral fractures in anticoagulant users were compared using propensity score–weighted cumulative incidence differences (CIDs). Results: There were 23 515 patients identified (3241 apixaban users, 6867 dabigatran users, 3866 rivaroxaban users, and 9541 warfarin users). Overall mean age was 74.4 years (SD, 10.8), ranging from 73.1 years (warfarin) to 77.9 years (apixaban). Over a median follow-up of 423 days, 401 fractures were identified (crude event number [weighted rate per 100 patient-years]: apixaban, 53 [0.82]; dabigatran, 95 [0.76]; rivaroxaban, 57 [0.67]; and warfarin, 196 [1.11]). After 24-month follow-up, DOAC use was associated with a lower risk for fracture than warfarin use (apixaban CID, −0.88% [95% CI, −1.66% to −0.21%]; dabigatran CID, −0.81% [CI, −1.34% to −0.23%]; and rivaroxaban CID, −1.13% [CI, −1.67% to −0.53%]). No differences were seen in all head-to-head comparisons between DOACs at 24 months (apixaban vs. dabigatran CID, −0.06% [CI, −0.69% to 0.49%]; rivaroxaban vs. dabigatran CID, −0.32% [CI, −0.84% to 0.18%]; and rivaroxaban vs. apixaban CID, −0.25% [CI, −0.86% to 0.40%]). Limitation: Residual confounding is possible. Conclusion: Among patients with AF, DOAC use may result in a lower risk for osteoporotic fracture compared with warfarin use. Fracture risk does not seem to be altered by the choice of DOAC. These findings may help inform the benefit–risk assessment when choosing between anticoagulants. Primary Funding Source: The University of Hong Kong and University College London Strategic Partnership Fund

Randomized controlled trial of the effect of phytosterols-enriched low-fat milk on lipid profile in Chinese

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Exploring Swarm-Based Visual Effects

In this paper, we explore the visual effects of animated 2D line strokes and 3D cubes. A given 2D image is segmented into either 2D line strokes or 3D cubes. Each segmented object (i.e., line stroke or each cube) is initialised with the position and the colour of the corresponding pixel in the image. The program animates these objects using the boid framework. This simulates a flocking behavior of line strokes in a 2D space and cubes in a 3D space. In this implementation the animation runs in a cycle from the disintegration of the original image to a swarm of line strokes or 3D cubes, then the swarm moves about and then integrates back into the original image (an example clip has been uploaded to YouTube and can be viewed at https://www.youtube.com/watch?v=aV6h0VzTZ8)

Nitrogen-containing bisphosphonates are associated with reduced risk of pneumonia in patients with hip fracture

The objective of this work was to study the risk of pneumonia and pneumonia mortality among patients receiving nitrogen‐containing bisphosphonates (N‐BPs), non‐N‐BP anti‐osteoporosis medications, and no anti‐osteoporosis medications after hip fracture. We studied a historical cohort using a population‐wide database. Patients with first hip fracture during 2005–2015 were identified and matched by time‐dependent propensity score. The cohort was followed until December 31, 2016, to capture any pneumonia and pneumonia mortality. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox‐proportional hazards regression. Absolute risk difference (ARD) and number needed to treat (NNT) were calculated. We identified 54,047 patients with hip fracture. Of these, 4041 patients who received N‐BPs and 11,802 without anti‐osteoporosis medication were propensity score–matched. N‐BPs were associated with a significantly lower risk of pneumonia compared with no treatment (6.9 versus 9.0 per 100 person‐years; HR 0.76; 95% CI, 0.70 to 0.83), resulting in an ARD of 0.02 and NNT of 46. A similar association was observed with pneumonia mortality (HR 0.65; 95% CI, 0.56 to 0.75). When N‐BPs were compared with non‐N‐BP anti‐osteoporosis medications, the association remained significant. N‐BPs were associated with lower risks of pneumonia and pneumonia mortality. Randomized controlled trials are now required to determine whether N‐BPs, non–vaccine‐based medications, can reduce pneumonia incidence in high risk groups

Effectiveness of denosumab for fracture prevention in real-world postmenopausal women with osteoporosis: a retrospective cohort study

Summary: To determine denosumab’s effectiveness for fracture prevention among postmenopausal women with osteoporosis in East Asia, the risk of fracture was compared between patients continuing denosumab therapy versus patients discontinuing denosumab after one dose. The real-world effectiveness was observed to be consistent with the efficacy demonstrated in the phase III trial. Introduction: After therapeutic efficacy is demonstrated for subjects in global clinical trials, real-world evidence may provide complementary knowledge of therapeutic effectiveness in a heterogeneous mix of patients seen in clinical practice. This retrospective cohort study was conducted to compare the fracture risk in real-world clinical care received in Taiwan and Hong Kong between a treatment cohort (patients receiving denosumab 60 mg subcutaneously every 6 months) versus an off-treatment cohort (patients discontinuing after 1 dose of denosumab, which has no known clinical benefit) among real-world postmenopausal women. Methods: This study included 38,906 and 2,835 postmenopausal women receiving denosumab in Taiwan and Hong Kong, respectively. The primary endpoint was hip fracture, and secondary endpoints were clinical vertebral and nonvertebral fractures. Propensity-score-matched analysis, adjusting for known covariates, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The robustness of findings was evaluated with a series of sensitivity and quantitative bias analyses. Results: In this study, 554 hip fractures were included in the primary Taiwan population analysis. The crude incidence rate was 0.9 per 100 person-years in the treatment cohort (n = 25,059) and 1.7 per 100 person-years in the off-treatment cohort (n = 13,847). After adjusting for prognostic differences between cohorts, denosumab reduced the risk of hip fractures by 38% (HR = 0.62, CI:0.52–0.75). Risk reductions of similar magnitude were observed for the secondary endpoints and for the analysis of the smaller Hong Kong population. Conclusion: The effectiveness of denosumab for fracture reduction among real-world postmenopausal women with osteoporosis was consistent with the efficacy demonstrated in a global clinical trial

Safety Profiles of Iron Chelators in Young Patients with Haemoglobinopathies

BACKGROUND: This review describes the safety of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), and combined therapy in young patients less than 25 years of age with haemoglobinopathies. METHOD: Searches in electronic literature databases were performed. Studies reporting adverse events associated with iron chelation therapy were included. Study and reporting quality was assessed using AHRQ Risk of Bias Assessment Tool and McMaster Quality Assessment Scale of Harms. Prospective clinical studies were pooled in a random-effects meta-analysis of proportions. RESULTS: Safety data of 2,040 patients from 34 studies were included. 92 case reports of 246 patients were identified. DFX (937 patients) and DFP (667 patients) possess the largest published safety evidence. Fewer studies on combination regimens are available. Increased transaminases were seen in all regimens (3.9-31.3%) and gastrointestinal disorders with DFP and DFX (3.7-18.4% and 5.8-18.8%, respectively). Therapy discontinuations due to adverse events were low (0-4.1%). Reporting quality was selective and poor in most of the studies. CONCLUSION: Iron chelation therapy is generally safe in young patients and published data corresponds to summary of product characteristics. Each iron chelation regimen has its specific safety risks. DFO seems not to be associated with serious adverse effects in recommended doses. In DFP and DFX rare, but serious adverse reactions can occur. Data on combined therapy is scarce, but it seems equally safe compared to monotherapy. This article is protected by copyright. All rights reserved

Serum calcium and incident diabetes: an observational study and meta-analysis

SUMMARY: The study aimed to prospectively evaluate if serum calcium is related to diabetes incidence in Hong Kong Chinese. The results showed that serum calcium has a significant association with increased risk of diabetes. The result of meta-analysis reinforced our findings. INTRODUCTION: This study aimed to evaluate the association of serum calcium, including serum total calcium and albumin-corrected calcium, with incident diabetes in Hong Kong Chinese. METHODS: We conducted a retrospective cohort study in 6096 participants aged 20 or above and free of diabetes at baseline. Serum calcium was measured at baseline. Incident diabetes was determined from several electronic databases. We also searched relevant databases for studies on serum calcium and incident diabetes and conducted a meta-analysis using fixed-effect modeling. RESULTS: During 59,130.9 person-years of follow-up, 631 participants developed diabetes. Serum total calcium and albumin-corrected calcium were associated with incident diabetes in the unadjusted model. After adjusting for demographic and clinical variables, the association remained significant only for serum total calcium (hazard ratio (HR), 1.32 (95 % confidence interval (CI), 1.02-1.70), highest vs. lowest quartile). In a meta-analysis of four studies including the current study, both serum total calcium (pooled risk ratio (RR), 1.38 (95 % CI, 1.15-1.65); I (2) = 5 %, comparing extreme quantiles) and albumin-corrected calcium (pooled RR, 1.29 (95 % CI, 1.03-1.61); I (2) = 0 %, comparing extreme quantiles) were associated with incident diabetes. Penalized regression splines showed that the association of incident diabetes with serum total calcium and albumin-correlated calcium was non-linear and linear, respectively. CONCLUSIONS: Elevated serum calcium concentration is associated with incident diabetes. The mechanism underlying this association warrants further investigation

Direct imaging of the coexistence of ferromagnetism and superconductivity at the LaAlO3/SrTiO3 interface

LaAlO3 and SrTiO3 are insulating, nonmagnetic oxides, yet the interface between them exhibits a two-dimensional electron system with high electron mobility,1 superconductivity at low temperatures,2-6 and electric-field-tuned metal-insulator and superconductorinsulator phase transitions.3,6-8 Bulk magnetization and magnetoresistance measurements also suggest some form of magnetism depending on preparation conditions5,9-11 and suggest a tendency towards nanoscale electronic phase separation.10 Here we use local imaging of the magnetization and magnetic susceptibility to directly observe a landscape of ferromagnetism, paramagnetism, and superconductivity. We find submicron patches of ferromagnetism in a uniform background of paramagnetism, with a nonuniform, weak diamagnetic superconducting susceptibility at low temperature. These results demonstrate the existence of nanoscale phase separation as suggested by theoretical predictions based on nearly degenerate interface sub-bands associated with the Ti orbitals.12,13 The magnitude and temperature dependence of the paramagnetic response suggests that the vast majority of the electrons at the interface are localized, and do not contribute to transport measurements.3,6,7 In addition to the implications for magnetism, the existence of a 2D superconductor at an interface with highly broken inversion symmetry and a ferromagnetic landscape in the background suggests the potential for exotic superconducting phenomena.Comment: Edited version to appear in Nature Physic