Direct oral anticoagulants versus low-molecular-weight heparin in patients with cancer-associated venous thrombosis: a cost-effectiveness analysis.

Background: Direct oral anticoagulants (DOACs) have demonstrated clinical benefits and better patient adherence over low-molecular-weight heparin (LMWH) in treating patients with cancer-associated venous thrombosis (CAT). We aimed to compare the cost-effectiveness of DOACs against LMWH in patients with CAT from the perspective of the Hong Kong healthcare system. Methods: A Markov state-transition model was performed to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) for DOACs and LMWH in a hypothetical cohort of 10,000 patients with CAT over a 5-year lifetime horizon. The model was primarily based on the health states of no event, recurrent venous thromboembolism, bleeding, and death. Transition probabilities, relative risks, and utilities were derived from the literature. Resource cost data were obtained from the Hong Kong Hospital Authority. Deterministic and probabilistic sensitivity analyses tested the robustness of the results. Results: Relative to LMWH, DOACs were associated with increased QALYs (1.52 versus 1.50) at a lower medical cost of USD 2,232 versus 8,224 in five years. The cost of LMWH was the main contributor to the outcome. Out of 10,000 simulated cases, DOACs were dominant in 15.8% and cost-effective in 42.1%, at the willingness-to-pay threshold of USD 148,392 per additional QALY. Conclusions: DOACs were associated with greater QALY improvements and lower overall costs compared to LMWH. Accounting for uncertainty, DOACs were between cost-effective and dominant in 57.9% of cases. DOACs are a cost-effective alternative to LMWH in the management of CAT in Hong Kong.

Mechanical properties of concrete filled steel tube members constrained by carbon fiber reinforced materials under bidirectional coupled loading.

Carbon fiber reinforced composite structures have been a research hotspot in recent years, with 9 specimens designed for static tests under bending and torsion loads of CFRP concrete filled steel tubes. The torque angle (T-θ) curve was studied from an experimental perspective. Subsequently, a reasonable finite element model was established using ABAQUS software. In addition, the effects of changes in parameters such as the number of steel concrete strength, bending ratio, and steel ratio on C-CF-CFRP-ST bending and torsion specimens were studied through numerical parameter research. Finally, equations of bearing capacity of CFRP-concrete filled steel tube under coupled bending and torsion are proposed.

Study on the Bending-Shear Properties of Concrete-Filled Circular Carbon Fibre Reinforced Plastic Steel Tubes.

In order to study the bending-shear performance of CFRP concrete-filled steel tubes, static tests were conducted on 15 circular concrete-filled CFRP steel tube bending-shear specimens. For all specimens, Ds was 120 mm, ts was 2 mm, and ml was 1. The shear displacement (V-Δ) curve of the specimen and the collaborative work between the steel tube and CFRP are discussed. ABAQUS was applied to simulate the V-Δ curve and failure mode of the specimen. We explored the effects of CFRP layers, material strength, the steel ratio, and the shear span ratio on the bending-shear performance of components. The experimental results show that a steel tube and CFRP can work together. As the shear span ratio increased, the bearing capacity and stiffness of the specimen decreased. An increase in the number of transverse CFRP layers could improve the bearing capacity of the specimen, but it had no significant effect on the stiffness. Calculating the elastic stage stiffness and bearing capacity of 15 short columns of test and FE curves revealed an average error of 6.71% and a mean square error of 0.83 for the elastic stage stiffness. The simulation results of the established finite element model are in good agreement with the experimental results. The average error of the bearing capacity was 3.88%, with a mean square error of 0.94. Based on experimental and finite element results, the moment shear correlation equation for concrete-filled CFRP steel tube bending-shear members is presented.

Cost-Effectiveness of Biosimilars vs Leflunomide in Patients With Rheumatoid Arthritis.

Importance: Among patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate, a treatment sequence initiated with biosimilar disease-modifying antirheumatic drugs (DMARDs) provides better clinical efficacy compared with conventional synthetic DMARDs recommended by current treatment guidelines; but its cost-effectiveness evidence remains unclear. Objective: To evaluate the cost-effectiveness of the treatment sequence initiated with biosimilar DMARDs after failure with methotrexate vs leflunomide and inform formulary listing decisions. Design, Setting, and Participants: This economic evaluation's cost-effectiveness analysis was performed at a Hong Kong public institution using the Markov disease transition model to simulate the lifetime disease progression and cost for patients with RA, using monetary value in 2022. Scenario and sensitivity analyses were performed to test the internal validity of the modeling conclusion. Participants included patients diagnosed with RA from 2000 to 2021 who were retrieved retrospectively from local electronic medical records to generate model input parameters. Statistical analysis was performed from January 2023 to March 2024. Interventions: The model assesses 3 competing treatment sequences initiated with biosimilar infliximab (CT-P13), biosimilar adalimumab (ABP-501), and leflunomide; all used in combination with methotrexate. Main Outcomes and Measures: Lifetime health care cost and quality-adjusted life-years (QALYs) of the simulated cohort. Results: In total, 25 099 patients with RA were identified (mean [SD] age, 56 [17] years; 19 469 [72.7%] women). In the base-case analysis, the lifetime health care cost and QALYs for the treatment sequence initiated with leflunomide were US $154 632 and 14.82 QALYs, respectively; for biosimilar infliximab, they were US $152 326 and 15.35 QALYs, respectively; and for biosimilar adalimumab, they were US $145 419 and 15.55 QALYs, respectively. Both biosimilar sequences presented lower costs and greater QALYs than the leflunomide sequence. In the deterministic sensitivity analysis, the incremental cost-effectiveness ratio (US$/QALY) comparing biosimilar infliximab sequence vs leflunomide sequence and biosimilar adalimumab sequence vs leflunomide sequence ranged from -15 797 to -8615 and -9088 to 10 238, respectively, all below the predefined willingness-to-pay threshold (US $48 555/QALY gain). In the probabilistic sensitivity analysis, the probability of treatment sequence initiated with leflunomide, biosimilar infliximab, and biosmilar adalimumab being cost-effective out of 10 000 iterations was 0%, 9%, and 91%, respectively. Conclusions and Relevance: In this economic evaluation study, the treatment sequences initiated with biosimilar DMARDs were cost-effective compared with the treatment sequence initiated with leflunomide in managing patients with RA who experienced failure with the initial methotrexate treatment. These results suggest the need to update clinical treatment guidelines for initiating biosimilars immediately after the failure of methotrexate for patients with RA.

Identification and validation of N-acetylputrescine in combination with non-canonical clinical features as a Parkinson's disease biomarker panel.

Parkinson's disease is a progressive neurodegenerative disorder in which loss of dopaminergic neurons in the substantia nigra results in a clinically heterogeneous group with variable motor and non-motor symptoms with a degree of misdiagnosis. Only 3-25% of sporadic Parkinson's patients present with genetic abnormalities that could represent a risk factor, thus environmental, metabolic, and other unknown causes contribute to the pathogenesis of Parkinson's disease, which highlights the critical need for biomarkers. In the present study, we prospectively collected and analyzed plasma samples from 194 Parkinson's disease patients and 197 age-matched non-diseased controls. N-acetyl putrescine (NAP) in combination with sense of smell (B-SIT), depression/anxiety (HADS), and acting out dreams (RBD1Q) clinical measurements demonstrated combined diagnostic utility. NAP was increased by 28% in Parkinsons disease patients and exhibited an AUC of 0.72 as well as an OR of 4.79. The clinical and NAP panel demonstrated an area under the curve, AUC = 0.9 and an OR of 20.4. The assessed diagnostic panel demonstrates combinatorial utility in diagnosing Parkinson's disease, allowing for an integrated interpretation of disease pathophysiology and highlighting the use of multi-tiered panels in neurological disease diagnosis.

Risk of carditis among adolescents after extending the interdose intervals of BNT162b2.

Previous studies indicate an increased carditis risk among adolescents following the two-dose messenger RNA COVID-19 vaccine. Several jurisdictions have extended the interdose interval between the first and second doses to reduce the risk. However, the effectiveness of such an extension policy remains inconclusive. Using the territory-wide vaccine record-linked electronic health records in Hong Kong, we conducted a nested case-control study from February 23, 2021 to August 15, 2022. Adolescents aged between 12 and 17 who received two-dose BNT162b2 were included for comparing risks between standard interdose interval (21-27 days) versus extended interdose interval ( ≥ 56 days). The carditis cumulative incidence within 28 days following the second dose was calculated. The adjusted odds ratio was estimated from multivariable conditional logistic regression. We identified 49 adolescents with newly diagnosed carditis within 28 days following the second dose. The crude cumulative incidence is 37.41 [95% confidence interval (CI): 27.68-49.46] per million vaccinated adolescents. Compared to the standard interdose interval group, adolescents with an extended interval had a significantly lower risk of carditis [adjusted odds ratio (aOR) 0.34 (95% CI: 0.16-0.73)]. Sensitivity analysis of carditis occurring within 14 days following the second dose yielded a similar estimate [aOR 0.30 (95% CI: 0.13-0.73)]. Extending the interdose interval of the BNT162b2 vaccine from 21 to 27 days to 56 days or longer is associated with 66% lower risk of incident carditis among adolescents. Our findings contribute towards an evidence-based vaccination strategy for a vulnerable population and potentially informs product label updates.

Mirrorless MEMS imaging: a nonlinear vibrational approach utilizing aerosol-jetted PZT-actuated fiber MEMS scanner for microscale illumination.

This study introduces a novel image capture and lighting techniques using a cutting-edge hybrid MEMS scanner system designed for compact microscopic imaging. The scanner comprises a tapered optical fiber waveguide and innovative aerosol-jet printed PZT (lead zirconate titanate) bimorph push-pull actuators on a stainless-steel substrate, effectively addressing issues that are commonly associated with PZT on silicon substrates such as fracture and layer separation. By leveraging nonlinear vibration, the scanner achieves a spiral scan pattern from a single signal input, in addition to the expected two-dimensional scanning and target illumination from two phase-shifted inputs. This capability is further enhanced by a novel process to taper the optical fiber, which reduces illumination scattering and tunes the fiber to the resonant frequencies of the scanner. The precisely tapered tip enables large fields of view while maintaining independent 2-axis scanning through one-degree-of-freedom actuation. Experimental validation showcases the successful generation of a spiral scan pattern with a 60 µm diameter scan area and a 10 Hz frame rate, effectively reconstructing scanned images of 5 µm lines, cross patterns (15 µm in length with a 5 µm gap), and structures of a Psychodidae wing.

Double-blind, randomized, placebo-controlled study to evaluate erenumab-specific central effects: an fMRI study.

OBJECTIVE: Given the findings of central effects of erenumab in the literature, we aimed to conduct a rigorous placebo-controlled, double-blind, randomized study to elucidate whether the observed changes are directly attributable to the drug. METHODS: We recruited 44 patients with migraine, randomly assigning them to either the erenumab 70 mg or the placebo group. 40 patients underwent fMRI scanning using a trigeminal nociceptive paradigm both, pre- and four weeks post-treatment. Participants kept a headache diary throughout the whole study period of two months in total. A clinical response was defined as a ≥30% reduction in headache frequency at follow-up. Details of this study have been preregistered in the open science framework: https://osf.io/ygf3t . RESULTS: Seven participants of the verum group (n=33.33%) and 4 of the placebo group (21.05%) experienced improvements in migraine activity, characterized by a minimum of 30% reduction in monthly headache frequency compared to baseline. The imaging data show an interaction between the verum medication and the response. Whilst numbers were too small for individual analyses (Verum vs. Placebo and Responder vs. Non-Responder), the variance-weighted analysis (Verum vs Placebo, scan before vs after weighted for response) revealed specific decrease in thalamic, opercular and putamen activity. INTERPRETATION: The central effects of erenumab could be reproduced in a placebo randomized design, further confirming its central role in migraine modulation. The mechanism, whether direct or secondary to peripheral mode of action, needs further exploration. It is important to note that the response rate to erenumab 70mg in this study was not as substantial as anticipated in 2019, when this study was planned. This resulted in a too small sample size for a subgroup analysis based on the responder status was associated with both the verum drug and the relative reduction in headache days.

Migraine prodromes and migraine triggers.

Migraine is characterized by a well-defined premonitory phase occurring hours or even days before the headache. Also, many migraineurs report typical triggers for their headaches. Triggers, however, are not consistent in their ability to precipitate migraine headaches. When looking at the clinical characteristics of both premonitory symptoms and triggers, a shared pathophysiological basis seems evident. Both seem to have their origin in basic homeostatic networks such as the feeding/fasting, the sleeping/waking, and the stress response network, all of which strongly rely on the hypothalamus as a hub of integration and are densely interconnected. They also influence the trigeminal pain processing system. Additionally, thalamic and hormonal mechanisms are involved. Activity within all those networks is influenced by various endogenous and external factors and might even cyclically change dependent on physiological internal rhythms. This might affect the threshold for the generation of migraine headaches. Premonitory symptoms thus appear as the result of an already ongoing alteration within those networks, whereas triggers might in this special situation only be able to further stress the system over the threshold for attack generation as catalysts of a process already in motion.

Torsional Behavior of Concrete-Filled Circular Steel Tubes Strengthened with CFRP.

In order to study the torsional performance of steel tube concrete after reinforcement with a carbon-fiber-reinforced polymer (CFRP), the mechanical properties of 18 specimens were studied from both experimental and finite element perspectives. The T-θ curve and τ-γ curve of the specimen were measured in the experiment, and the failure mode of the specimen was analyzed. Subsequently, a reasonable finite element model was established using ABAQUS software, and the variation in various parameters surrounding the performance of the specimen was analyzed. Based on the experimental and finite element results, a formula for calculating the bearing capacity of the specimen was established. According to both the experimental and numerical results, the torsional bearing capacity of C-CF-CFRP-ST, defined as the torque endured by the specimen with maximum shear strain, was determined to be 15,000 µÎµ, together with its corresponding calculation formula. After the test, it was demonstrated that the main components of the concrete-filled CFRP-steel tube composite material-the steel tube and the concrete-could be used as reusable resources.

Factors influencing choice of b/ts DMARDs in managing inflammatory arthritis from a patient perspective: a systematic review of global evidence and a patient-based survey from Hong Kong.

OBJECTIVES: To investigate factors concerning patients regarding biological/target synthetic disease-modifying antirheumatic drugs (b/ts DMARDs) in treating inflammatory arthritis (IA). DESIGN: This study consists of a systematic review and a cross-sectional survey in Hong Kong. A systematic review of literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses was conducted on PubMed, Web of Science, Cochrane and Embase between 1 January 2000 and 1 January 2022. Content analysis was conducted to summarise factors grouped by four themes-social aspects (SA), clinical aspects (CA), medicine characteristics (MC) and financial aspects (FA) in the decision-making process. One cross-sectional survey among Hong Kong patients with IA was conducted to add to global evidence. SETTING: A systematic review of global evidence and a patient-based survey in Hong Kong to complement scarce evidence in Asia regions. RESULTS: The systematic review resulted in 34 studies. The four themes were presented in descending order consistently but varied with frequency throughout decision-making processes. During decision-making involving medication initiation, preference and discontinuation, MC (reported frequency: 83%, 86%, 78%), SA (56%, 43%, 78%) and FA (39%, 33%, 56%) were the three most frequently reported factors, whereas CA was less studied. Local survey also revealed that MC factors such as treatment efficacy and the probability of severe adverse events, and SA factors such as the availability of government or charity subsidy, influenced patients' initiation and preference for b/ts DMARDs. Meanwhile, self-estimated improvement in disease conditions (SA), drug side effects (MC) and drug costs (FA) were associated with treatment discontinuation. CONCLUSIONS: Global and local evidence consistently indicate that MC and SA are important considerations in patients' decisions regarding novel DMARDs. Health policies that reduce patients' financial burden and enhances healthcare professionals' engagement in decision-making and treatment delivery should be in place with an efficient healthcare system for managing IA optimistically.

Risk of autoimmune diseases following COVID-19 and the potential protective effect from vaccination: a population-based cohort study.

Background: Case reports suggest that SARS-CoV-2 infection could lead to immune dysregulation and trigger autoimmunity while COVID-19 vaccination is effective against severe COVID-19 outcomes. We aim to examine the association between COVID-19 and development of autoimmune diseases (ADs), and the potential protective effect of COVID-19 vaccination on such an association. Methods: A retrospective cohort study was conducted in Hong Kong between 1 April 2020 and 15 November 2022. COVID-19 was confirmed by positive polymerase chain reaction or rapid antigen test. Cox proportional hazard regression with inverse probability of treatment weighting was applied to estimate the risk of incident ADs following COVID-19. COVID-19 vaccinated population was compared against COVID-19 unvaccinated population to examine the protective effect of COVID-19 vaccination on new ADs. Findings: The study included 1,028,721 COVID-19 and 3,168,467 non-COVID individuals. Compared with non-COVID controls, patients with COVID-19 presented an increased risk of developing pernicious anaemia [adjusted Hazard Ratio (aHR): 1.72; 95% Confidence Interval (CI): 1.12-2.64]; spondyloarthritis [aHR: 1.32 (95% CI: 1.03-1.69)]; rheumatoid arthritis [aHR: 1.29 (95% CI: 1.09-1.54)]; other autoimmune arthritis [aHR: 1.43 (95% CI: 1.33-1.54)]; psoriasis [aHR: 1.42 (95% CI: 1.13-1.78)]; pemphigoid [aHR: 2.39 (95% CI: 1.83-3.11)]; Graves' disease [aHR: 1.30 (95% CI: 1.10-1.54)]; anti-phospholipid antibody syndrome [aHR: 2.12 (95% CI: 1.47-3.05)]; immune mediated thrombocytopenia [aHR: 2.1 (95% CI: 1.82-2.43)]; multiple sclerosis [aHR: 2.66 (95% CI: 1.17-6.05)]; vasculitis [aHR: 1.46 (95% CI: 1.04-2.04)]. Among COVID-19 patients, completion of two doses of COVID-19 vaccine shows a decreased risk of pemphigoid, Graves' disease, anti-phospholipid antibody syndrome, immune-mediated thrombocytopenia, systemic lupus erythematosus and other autoimmune arthritis. Interpretation: Our findings suggested that COVID-19 is associated with an increased risk of developing various ADs and the risk could be attenuated by COVID-19 vaccination. Future studies investigating pathology and mechanisms would be valuable to interpreting our findings. Funding: Supported by RGC Collaborative Research Fund (C7154-20GF).

Management of cluster headache: Treatments and their mechanisms.

BACKGROUND: The management of cluster headache is similar to that of other primary headache disorders and can be broadly divided into acute and preventive treatments. Acute treatments for cluster headache are primarily delivered via rapid, non-oral routes (such as inhalation, nasal, or subcutaneous) while preventives include a variety of unrelated treatments such as corticosteroids, verapamil, and galcanezumab. Neuromodulation is becoming an increasingly popular option, both non-invasively such as vagus nerve stimulation when medical treatment is contraindicated or side effects are intolerable, and invasively such as occipital nerve stimulation when medical treatment is ineffective. Clinically, this collection of treatment types provides a range of options for the informed clinician. Scientifically, this collection provides important insights into disease mechanisms. METHODS: Two authors performed independent narrative reviews of the literature on guideline recommendations, clinical trials, real-world data, and mechanistic studies. RESULTS: Cluster headache is treated with acute treatments, bridge treatments, and preventive treatments. Common first-line treatments include subcutaneous sumatriptan and high-flow oxygen as acute treatments, corticosteroids (oral or suboccipital injections) as bridge treatments, and verapamil as a preventive treatment. Some newer acute (non-invasive vagus nerve stimulation) and preventive (galcanezumab) treatments have excellent clinical trial data for episodic cluster headache, while other newer treatments (occipital nerve stimulation) have been specifically tested in treatment-refractory chronic cluster headache. Most treatments are suspected to act on the trigeminovascular system, the autonomic system, or the hypothalamus. CONCLUSIONS: The first-line treatments have not changed in recent years, but new treatments have provided additional options for patients.

In vivo photothermal therapy monitored by multi-position calibrated photoacoustic thermometer.

With the ability of monitoring both temperature and photothermal agents, the photoacoustic (PA) imaging is a promising guiding tool for the photothermal therapy (PTT). The calibration line which depicts the relative variation of PA amplitude with the temperature should be obtained before using PA thermometer. In existing study, a calibration line was generated based on the data from one spatial position, and used in the whole region of interesting (ROI). However, the generalization of this calibration line in ROI was not verified, especially for ROI with heterogeneous tissues. Moreover, the relationship between the distributions of photothermal agents and effective treatment area is not clear, hindering using photothermal agents' distribution to optimize the administration-therapy interval. In this study, the distribution of effective photothermal agents and temperature in subcutaneously transplanted tumor mouse models were continuously monitored by 3D photoacoustic/ ultrasonic dual-modality imaging in 8 h after administration. With multiple micro-temperature probes in tumor and surrounding normal tissue, the PA thermometer was calibrated and evaluated at multiple spatial positions for the first time. The generalization in homologous tissue and tissue specificity in heterogeneous tissues of the PA thermometer calibration line were verified. Our study not only validated the effectivity of PA thermometer by proving the generalization of calibration line, but also removes a major obstacle that prevents applying the PA thermometer to a heterogeneous tissues ROI. The positive correlation between the proportion of effective treatment area and the proportion of effective photothermal agent area in the tumor was observed. Since the latter can be monitored with fast PA imaging, PA imaging can be employed as a convenient tool for seeking optimal administration-treatment interval.

Migraine triggers in Asian countries: a narrative review.

Background: Migraine is one of the most common neurological disorders worldwide. Clinical characteristics of migraine may be somewhat different across ethnic groups. Although factors such as stress, lack of sleep, and fasting are known as migraine triggers, the discussion about geographical differences of migraine triggers in Asia is lacking. Methods: In this study, we performed a narrative review on migraine triggers in Asia. We searched PubMed for relevant papers published between January 2000 and February 2022. Results: Forty-two papers from 13 Asian countries were included. Stress and sleep are the most frequently reported migraine triggers in Asia. There were some differences in migraine triggers in Asian countries: fatigue and weather common in Eastern Asia and fasting common in Western Asia. Conclusion: Majority of the common triggers reported by patients with migraine in Asia were stress and sleep, similar to those reported globally, thus showing they are universally important. Some triggers linked to internal homeostasis are influenced by culture (e.g., alcohol, food/eating habit), and triggers related to environmental homeostasis, such as weather, are highly heterogenous between regions.

Cost-Effectiveness of Direct Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation in Hong Kong.

OBJECTIVES: The emergence of direct oral anticoagulants (DOACs) has revolutionized the prevention of stroke related to nonvalvular atrial fibrillation (NVAF). Several DOACs are available on the market, while the cost-effectiveness comparison among DOACs and vitamin K antagonist (warfarin) in NVAF management in Hong Kong market remains scarce. The objective of this study was to assess the cost-effectiveness of DOACs and warfarin from a Hong Kong public institutional perspective to inform formulary listing decisions. METHODS: A previously developed Markov model was adapted to simulate the lifetime disease progression of a hypothetical cohort of 1000 patients. Net monetary costs, quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio were computed for the following competing alternatives: warfarin, apixaban (5 mg twice daily), dabigatran (110 mg or 150 mg twice daily), and rivaroxaban (20 mg once daily). Probabilistic sensitivity analyses were conducted to address study uncertainties. RESULTS: In base-case results, all DOACs were associated with greater QALYs improvements and lower costs than warfarin. Rivaroxaban, apixaban, dabigatran 150 mg, dabigatran 110 mg, and warfarin resulted in net costs US dollar (USD) 8088, USD 8240, USD 8566, USD 8653, and USD 16 363 and net QALY 5.87, 6.017, 6.022, 5.98, and 5.829, respectively. In probabilistic sensitivity analysis, the probabilities of warfarin, rivaroxaban 20 mg, dabigatran 110 mg, dabigatran 150 mg, and apixaban 5 mg being cost-effective of 2000 iterations were 0%, 0%, 29.4%, 33.2%, and 37.4%, respectively. CONCLUSION: Apixaban was the most cost-effective option compared with other DOACs and warfarin in the management of NVAF; this conclusion is consistent under all the tested uncertainty scenarios.

Treatment-resistant depression and risk of autoimmune diseases: evidence from a population-based cohort and nested case-control study.

Recent literature indicates that patients with depression had increased immune activation. We hypothesised that treatment-resistant depression (TRD), an indicator of non-responsive depression with long-term dysregulated inflammation, could be an independent risk factor for subsequent autoimmune diseases. We performed a cohort study and a nested case-control study to examine the association between TRD and risk of autoimmune diseases, and to explore potential sex-specific difference. Using electronic medical records in Hong Kong, we identified 24,576 patients with incident depression between 2014 and 2016 without autoimmune history and followed up from diagnosis to death or December 2020 to identify TRD status and autoimmune incidence. TRD was defined as having at least two antidepressant regimens and the third regimen to confirm previous treatment failures. Based on age, sex and year of depression, we matched TRD patients 1:4 to the non-TRD in the cohort analysis using nearest-neighbour matching, and matched cases and controls 1:10 using incidence density sampling in the nested case-control analysis. We conducted survival analyses and conditional logistic regression respectively for risk estimation, adjusting for medical history. Across the study period, 4349 patients without autoimmune history (17.7%) developed TRD. With 71,163 person-years of follow-up, the cumulative incidence of 22 types of autoimmune diseases among the TRD patients was generally higher than the non-TRD (21.5 vs. 14.4 per 10,000 person-years). Cox model suggested a non-significant association (HR:1.48, 95% CI: 0.99-2.24, p = 0.059), whereas conditional logistic model showed a significant association (OR: 1.67, 95% CI: 1.10-2.53, p = 0.017) between TRD status and autoimmune diseases. Subgroup analysis showed that the association was significant in organ-specific diseases but not in systemic diseases. Risk magnitudes were generally higher among men compared to women. In conclusion, our findings provide evidence for an increased risk of autoimmune diseases in patients with TRD. Controlling chronic inflammation in hard-to-treat depression might play a role in preventing subsequent autoimmunity.

Impact of Introducing Infliximab Biosimilars on Total Infliximab Consumption and Originator Infliximab Prices in Eight Regions: An Interrupted Time-Series Analysis.

OBJECTIVE: We aimed to assess whether the introduction of the first infliximab biosimilar was associated with changes in overall infliximab consumption (originator and biosimilars) and price changes to the originator infliximab. METHODS: An interrupted time series analysis using infliximab sales data from 2010 to 2020 from the IQVIA Multinational Integrated Data Analysis System for eight selected regions: Australia, Canada, Hong Kong, Korea, India, Japan, the UK, and the USA. Quarterly measures of infliximab consumption and list prices were respectively defined as the number of standard units (SU)/1000 inhabitants and as 2020 USA dollars (USD)/SU. RESULTS: Following the introduction of infliximab biosimilars, overall infliximab consumption increased in Australia [immediate change: 0.145 SU/1000 inhabitants (P = 0.014); long-term change: 0.022 SU/1000 inhabitants per quarter (P < 0.001)], Canada [immediate change 0.415 (P = 0.008)], the UK [long-term change 0.024 (P < 0.001)], and Hong Kong [immediate change: 0.042 (P < 0.001)]. The list price of originator infliximab also decreased following biosimilar introduction in Australia [immediate change: - 187.84 USD/SU (P < 0.001); long-term change - 6.46 USD/SU per quarter (P = 0.043)], Canada [immediate change: - 145.58 (P < 0.001)], the UK [immediate change: - 34.95 (P = 0.010); long-term change: - 4.77 (P < 0.001)], and Hong Kong [long-term change: - 4.065 (P = 0.046)]. Consumption and price changes were inconsistent in India, Japan, Korea, and the USA. CONCLUSIONS: Introduction of the first infliximab biosimilar was not consistently associated with increased consumption across regions. Additional policy and healthcare system interventions to support biosimilar infliximab adoption are needed.