The impact of ischemic stroke on atrial fibrillation-related healthcare cost: a systematic review

Aim: To summarize healthcare costs incurred by patients with atrial fibrillation (AF) who developed ischemic stroke, explore factors associated with increased cost and highlight the importance of anticoagulation therapy for stroke prophylaxis. / Methods: A systematic literature search of PubMed, EMBASE, Web of Science and the health economic evaluation database was conducted up to December 2015. Studies focused on the cost and/or resource utilization of ischemic stroke in patients with AF were included. Reported costs were converted to international dollars (I$) and adjusted to 2015 values. Alongside the narrative review of included studies, Spearman’s correlation, independent-samples t-test and one-way ANOVA were used to explore factors associated with cost differences between studies. / Results: Sixteen studies published from nine countries were identified. Based on currency conversion rates in 2015, ischemic stroke related healthcare costs were estimated to be I$41,420, I$12,895 and I$8,184 for high-income, upper middle-income and lower middle-income economies respectively. Local GDP per capita accounted for approximately 50% of the healthcare cost variation among countries. Major component of overall cost was from hospitalization. Ischemic stroke incurring in patients with AF ≥75 years were 2.3 times that of their younger peers (p=0.049). / Conclusions: The economic burden from ischemic stroke in patients with AF is considerable with positive association to country income. Clinicians and stakeholders should be aware of the importance of anticoagulation therapies in stroke prophylaxis, the occurrence of stroke and the downstream economic burden on an increasingly aging population

Influenza vaccination and hospitalisation in Elderly Health Centres.

1. A cohort of Elderly Health Centres was examined to determine whether influenza vaccination decreased hospitalisation and mortality. 2. In the influenza season, influenza vaccination reduced all-cause mortality by half and cardiorespiratory hospitalisation by a quarter. The extent to which influenza vaccination protects older people from serious morbidity and mortality needs to be confirmed in appropriately designed studies, so that scarce health care resources can be used effectivelypublished_or_final_versio

RhoE/ROCK signaling modulates chemoresistance in HCC through IL6/JAK2/STAT3 pathways

Conference Theme: New Horizons in Cancer Research Conference: Harnessing Breakthroughs - Targeting CuresPoster Session B: Tumor Biology: no. B40Liver cancer (hepatocellular carcinoma, HCC) is a major malignancy worldwide and the second commonest fatal cancer in Southeast Asia and China including Hong Kong, due to the high prevalence of hepatitis B viral infection. HCC is highly chemoresistant, limiting treatment options to patients. There is an urgent need to delineate the underlying molecular mechanism of HCC chemoresistance so as to identify novel therapeutic targets for this aggressive cancer. Deregulation of Rho GTPase pathway is demonstrated to play important roles in HCC tumorigenesis. RhoE/Rnd3 belongs to the Rnd subfamily of the Rho GTPase which lacks the intrinsic GTPase activity. In our previous study, we have shown that RhoE is frequently downregulated in human HCCs and acts as a metastasis suppressor, whereas ROCK2 is upregulated in human HCCs. In this study, we aimed to investigate whether RhoE is also involved in the regulation of chemoresistance in HCC. Using short-hairpin RNA and ...published_or_final_versio

Infrastructures, processes of insertion and the everyday: towards a new dialogue in critical policy studies

This forum argues that the complex assemblages of infrastructures, and their reproduction in our everyday worlds, offer a privileged lens through which to explore the practices of much of what critical policy studies holds dear. It draws attention to processes of insertion that reproduce infrastructure in everyday lives, arguing that such processes cast new light on the work of the state, governance, and democratic struggles. It discerns three avenues as a means of exploring such infrastructural processes: first, an invitation to transcend the physical form and reflect on infrastructural temporalities; second on the transformation of spatial governance and policy through infrastructure; and third, a re-assessment in the relationship between infrastructures and the ‘modernist ideal’. Through these avenues, light can be shed on the often ‘hidden’ practices of policymaking. We conclude by calling for a dialogue across diverse disciplines, side-stepping embedded divides between academics-activists, cities-towns, and the global south-north

Cost-Effectiveness of Apixaban versus Warfarin in Chinese Patients with Non-Valvular Atrial Fibrillation: A Real-Life and Modelling Analyses

OBJECTIVES: Many of the cost-effectiveness analyses of apixaban against warfarin focused on Western populations but Asian evidence remains less clear. The present study aims to evaluate the cost-effectiveness of apixaban against warfarin in Chinese patients with non-valvular atrial fibrillation (NVAF) from a public institutional perspective in Hong Kong. METHODS: We used a Markov model incorporating 12 health state transitions, and simulated the disease progression of NVAF in 1,000 hypothetical patients treated with apixaban/warfarin. Risks of clinical events were based on the ARISTOTLE trial and were adjusted with local International Normalized Ratio control, defined as the time in therapeutic range. Real-life input for the model, including patients' demographics and clinical profiles, post-event treatment patterns, and healthcare costs, were determined by a retrospective cohort of 40,569 incident patients retrieved from a Hong Kong-wide electronic medical database. Main outcome measurements included numbers of thromboembolic and bleeding events, life years, quality-adjusted life years (QALYs) and direct healthcare cost. When comparing apixaban and warfarin, treatment with incremental cost-effectiveness ratio (ICER) less than one local GDP per capita (USD 33,534 in 2014) was defined to be cost-effective. RESULTS: In the lifetime simulation, fewer numbers of events were estimated for the apixaban group, resulting in reduced event-related direct medical costs. The estimated ICER of apixaban was USD 7,057 per QALY at base-case analysis and ranged from USD 1,061 to 14,867 per QALY under the 116 tested scenarios in deterministic sensitivity analysis. While in probabilistic sensitivity analysis, the probability of apixaban being the cost-effective alternative to warfarin was 96% and 98% at a willingness to pay threshold of USD 33,534 and 100,602 per QALY, respectively. CONCLUSIONS: Apixaban is likely to be a cost-effective alternative to warfarin for stroke prophylaxis in Chinese patients with NVAF in Hong Kong

Rapid assessment of visual impairment (RAVI) in marine fishing communities in South India - study protocol and main findings

<p>Abstract</p> <p>Background</p> <p>Reliable data are a pre-requisite for planning eye care services. Though conventional cross sectional studies provide reliable information, they are resource intensive. A novel rapid assessment method was used to investigate the prevalence and causes of visual impairment and presbyopia in subjects aged 40 years and older. This paper describes the detailed methodology and study procedures of Rapid Assessment of Visual Impairment (RAVI) project.</p> <p>Methods</p> <p>A population-based cross-sectional study was conducted using cluster random sampling in the coastal region of Prakasam district of Andhra Pradesh in India, predominantly inhabited by fishing communities. Unaided, aided and pinhole visual acuity (VA) was assessed using a Snellen chart at a distance of 6 meters. The VA was re-assessed using a pinhole, if VA was < 6/12 in either eye. Near vision was assessed using N notation chart binocularly. Visual impairment was defined as presenting VA < 6/18 in the better eye. Presbyopia is defined as binocular near vision worse than N8 in subjects with binocular distance VA of 6/18 or better.</p> <p>Results</p> <p>The data collection was completed in <12 weeks using two teams each consisting of one paramedical ophthalmic personnel and two community eye health workers. The prevalence of visual impairment was 30% (95% CI, 27.6-32.2). This included 111 (7.1%; 95% CI, 5.8-8.4) individuals with blindness. Cataract was the leading cause of visual impairment followed by uncorrected refractive errors. The prevalence of blindness according to WHO definition (presenting VA < 3/60 in the better eye) was 2.7% (95% CI, 1.9-3.5).</p> <p>Conclusion</p> <p>There is a high prevalence of visual impairment in marine fishing communities in Prakasam district in India. The data from this rapid assessment survey can now be used as a baseline to start eye care services in this region. The rapid assessment methodology (RAVI) reported in this paper is robust, quick and has the potential to be replicated in other areas.</p

Knock-in models related to Alzheimer’s disease: synaptic transmission, plaques and the role of microglia

Background: Microglia are active modulators of Alzheimer’s disease but their role in relation to amyloid plaques and synaptic changes due to rising amyloid beta is unclear. We add novel findings concerning these relationships and investigate which of our previously reported results from transgenic mice can be validated in knock-in mice, in which overexpression and other artefacts of transgenic technology are avoided. Methods: AppNL-F and AppNL-G-F knock-in mice expressing humanised amyloid beta with mutations in App that cause familial Alzheimer’s disease were compared to wild type mice throughout life. In vitro approaches were used to understand microglial alterations at the genetic and protein levels and synaptic function and plasticity in CA1 hippocampal neurones, each in relationship to both age and stage of amyloid beta pathology. The contribution of microglia to neuronal function was further investigated by ablating microglia with CSF1R inhibitor PLX5622. Results: Both App knock-in lines showed increased glutamate release probability prior to detection of plaques. Consistent with results in transgenic mice, this persisted throughout life in AppNL-F mice but was not evident in AppNL-G-F with sparse plaques. Unlike transgenic mice, loss of spontaneous excitatory activity only occurred at the latest stages, while no change could be detected in spontaneous inhibitory synaptic transmission or magnitude of long-term potentiation. Also, in contrast to transgenic mice, the microglial response in both App knock-in lines was delayed until a moderate plaque load developed. Surviving PLX5266-depleted microglia tended to be CD68-positive. Partial microglial ablation led to aged but not young wild type animals mimicking the increased glutamate release probability in App knock-ins and exacerbated the App knock-in phenotype. Complete ablation was less effective in altering synaptic function, while neither treatment altered plaque load. Conclusions: Increased glutamate release probability is similar across knock-in and transgenic mouse models of Alzheimer’s disease, likely reflecting acute physiological effects of soluble amyloid beta. Microglia respond later to increased amyloid beta levels by proliferating and upregulating Cd68 and Trem2. Partial depletion of microglia suggests that, in wild type mice, alteration of surviving phagocytic microglia, rather than microglial loss, drives age-dependent effects on glutamate release that become exacerbated in Alzheimer’s disease

Epidemiology of Acute Myocarditis/Pericarditis in Hong Kong Adolescents Following Comirnaty Vaccination

BACKGROUND: Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. METHODS: This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for COVID-19 vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine Adverse Event Response and Evaluation Programme. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analysed. RESULTS: Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. 29 (87.88%) were males and 4 (12.12%) were females, with a median age of 15.25 years. 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management.The overall incidence of acute myocarditis/pericarditis was 18.52 (95% Confidence Interval [CI], 11.67-29.01) per 100,000 persons vaccinated. The incidence after the first and second doses were 3.37 (95%CI 1.12-9.51) and 21.22 (95%CI 13.78-32.28 per 100,000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI 2.38-12.53) and 37.32 (95% CI 26.98-51.25) per 100,000 persons vaccinated. CONCLUSIONS: There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose

Tendon Is Covered by a Basement Membrane Epithelium That Is Required for Cell Retention and the Prevention of Adhesion Formation

The ability of tendons to glide smoothly during muscle contraction is impaired after injury by fibrous adhesions that form between the damaged tendon surface and surrounding tissues. To understand how adhesions form we incubated excised tendons in fibrin gels (to mimic the homeostatic environment at the injury site) and assessed cell migration. We noticed cells exiting the tendon from only the cut ends. Furthermore, treatment of the tendon with trypsin resulted in cell extravagation from the shaft of the tendons. Electron microscopy and immunolocalisation studies showed that the tendons are covered by a novel cell layer in which a collagen type IV/laminin basement membrane (BM) overlies a keratinised epithelium. PCR and western blot analyses confirmed the expression of laminin β1 in surface cells, only. To evaluate the cell retentive properties of the BM in vivo we examined the tendons of the Col4a1+/Svc mouse that is heterozygous for a G-to-A transition in the Col4a1 gene that produces a G1064D substitution in the α1(IV) chain of collagen IV. The flexor tendons had a discontinuous BM, developed fibrous adhesions with overlying tissues, and were acellular at sites of adhesion formation. In further experiments, tenotomy of wild-type mice resulted in expression of laminin throughout the adhesion. In conclusion, we show the existence of a novel tendon BM-epithelium that is required to prevent adhesion formation. The Col4a1+/Svc mouse is an effective animal model for studying adhesion formation because of the presence of a structurally-defective collagen type IV-containing BM

Novel Expression Patterns of Metabotropic Glutamate Receptor 6 in the Zebrafish Nervous System

The metabotropic glutamate receptor 6 (mGluR6 or GRM6) belongs to the class III of the metabotropic glutamate receptor family. It is the only known mGluR that mediates direct synaptic transmission in the nervous system and is thought to mediate the ON-response in the ON-pathway of the vertebrate retina. Phylogenetic and gene structure analysis indicated that the zebrafish genome harbours two mglur6 paralogs, mglur6a and mglur6b. Besides expression in the inner nuclear layer and distinct regions in the brain, both mglur6 paralogs are expressed in ganglion cells of the retina, an expression pattern which can also be observed in the downstream effector molecules gnaoa and gnaob. This unexpected expression pattern is consistent with immunohistological labeling using a peptide antibody specific for the mGluR6b paralog. These expression patterns contradict the existing view that mGluR6 is solely located on ON-bipolar cells where it functions in signal transmission. Consistent with expression in ON-bipolar cells, we report a decreased b-wave amplitude in the electroretinogram after morpholino-based downregulation of mGluR6b, showing a function in the ON response. Our data suggest more widespread functions of mGluR6 mediated signaling in the central nervous system, possibly including sign reversing synapses in the inner retina