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Candida albicans , the most frequently isolated fungal pathogen in humans, forms biofilms that enhance resistance to antifungal drugs and host immunity, leading to frequent treatment failure. Understanding the molecular mechanisms governing biofilm formation is crucial for developing anti-biofilm therapies. In this study, we conducted a genetic screen to identify novel genes that regulate biofilm formation in C. albicans . One identified gene is ORF19.6693 , a homolog of the Saccharomyces cerevisiae SDD3 gene. The sdd3 ∆/∆ mutant exhibited severe defects in biofilm formation and significantly reduced chitin content in the cell wall. Overexpression of the constitutively active version of the Rho1 GTPase Rho1 G18V , an upstream activator of the protein kinase C (PKC)-mitogen-activated protein kinase (MAPK) cell-wall integrity pathway, rescued these defects. Affinity purification, mass spectrometry, and co-immunoprecipitation revealed Sdd3's physical interaction with Bem2, the GTPase-activating protein of Rho1. Deletion of SDD3 significantly reduced the amount of the active GTP-bound form of Rho1, thereby diminishing PKC-MAPK signaling and downregulating chitin synthase genes CHS2 and CHS8 . Taken together, our studies identify a new biofilm regulator, Sdd3, in C. albicans that modulates Rho1 activity through its inhibitory interaction with Bem2, thereby regulating the PKC-MAPK pathway to control chitin biosynthesis, which is critical for biofilm formation. As an upstream component of the pathway and lacking a homolog in mammals, Sdd3 has the potential to serve as an antifungal target for biofilm infections.IMPORTANCEThe human fungal pathogen Candida albicans is categorized as a critical priority pathogen on the World Health Organization's Fungal Priority Pathogens List. A key virulence attribute of this pathogen is its ability to form biofilms on the surfaces of indwelling medical devices. Fungal cells in biofilms are highly resistant to antifungal drugs and host immunity, leading to treatment failure. This study conducted a genetic screen to discover novel genes that regulate biofilm formation. We found that deletion of the SDD3 gene caused severe biofilm defects. Sdd3 negatively regulates the Rho1 GTPase, an upstream activator of the protein kinase C-mitogen-activated protein kinase pathway, through direct interaction with Bem2, the GTPase-activating protein of Rho1, resulting in a significant decrease in chitin content in the fungal cell wall. This chitin synthesis defect leads to biofilm formation failure. Given its essential role in biofilm formation, Sdd3 could serve as an antifungal target for biofilm infections., Competing Interests: The authors declare no conflict of interest.

Ductular reaction (DR) is the hallmark of cholestatic diseases manifested in the proliferation of bile ductules lined by biliary epithelial cells (BECs). It is commonly associated with an increased risk of fibrosis and liver failure. The receptor for advanced glycation end products (RAGE) was identified as a critical mediator of DR during chronic injury. Yet, the direct link between RAGE-mediated DR and fibrosis as well as the mode of interaction between BECs and hepatic stellate cells (HSCs) to drive fibrosis remain elusive. Here, we delineate the specific function of RAGE on BECs during DR and its potential association with fibrosis in the context of cholestasis. Employing a biliary lineage tracing cholestatic liver injury mouse model, combined with whole transcriptome sequencing and in vitro analyses, we reveal a role for BEC-specific Rage activity in fostering a pro-fibrotic milieu. RAGE is predominantly expressed in BECs and contributes to DR. Notch ligand Jagged1 is secreted from activated BECs in a Rage-dependent manner and signals HSCs in trans, eventually enhancing fibrosis during cholestasis., Competing Interests: Disclosure and competing interests statement. The authors declare no competing interests., (© 2024. The Author(s).)

Background: Hospital discharge for older adult patients carries risks. Effective patient-provider communication is crucial for postacute care. Technology-based communication tools are promising in improving patient experience and outcomes. However, there is limited evidence comparing patient and provider user experiences on a large-scale basis, hindering the exploration of true patient-provider shared understanding., Objective: This study aimed to evaluate an electronic health record-based discharge communication tool by examining and comparing patient and provider perspectives., Methods: This study comprised a cross-sectional self-administered staff survey and a pre-post cross-sectional patient survey. Physicians, nurses, and older adult patients aged 65 years and older discharged from 4 public hospitals were included. Patient-provider comparison items focused on 3 aspects of the design quality of the tool (information clarity, adequacy, and usefulness) and overall satisfaction with the tool. In addition, patients' experience of discharge information and their medication-taking behaviors before and after the program implementation were compared based on a validated local patient experience survey instrument. Providers' perceived usefulness of this tool to their work and implementation intentions were measured based on the technology acceptance model to enhance understanding of their experiences by conducting structural equation modeling analysis., Results: A total of 1375 and 2353 valid responses were received from providers and patients, respectively. Patients' overall satisfaction with this communication tool is significantly higher than providers', and patients rated the information clarity and usefulness presented by this tool higher as well (P<.001). However, patients rated information adequacy significantly lower than providers (P<.001). Meanwhile, patients reported a significant improvement in their experience of discharge medication information, and fewer patients reported side effects encounters after the program implementation (126/1083, 11.6% vs 111/1235, 9%; P=.04). However, providers showed inconsistent implementation fidelity. Providers' perceived quality of the tool design (β coefficient=0.24, 95% CI 0.08-0.40) and perceived usefulness to their work (β coefficient=0.57, 95% CI 0.43-0.71) significantly impacted their satisfaction. Satisfaction can significantly impact implementation intentions (β coefficient=0.40, 95% CI 0.17-0.64), which further impacts implementation behaviors (β coefficient=0.16, 95% CI 0.10-0.23)., Conclusions: A notable disparity exists between patients and health care providers. This may hinder the achievement of the tool's benefits. Future research should aim for a comprehensive overview of implementation barriers and corresponding strategies to enhance staff performance and facilitate patient-provider shared understanding., (© Dorothy Yingxuan Wang, Eliza Lai-Yi Wong, Annie Wai-Ling Cheung, Kam-Shing Tang, Eng-Kiong Yeoh. Originally published in JMIR Aging (https://aging.jmir.org).)

Context: Patients with younger onset of type 2 diabetes (YT2D) have increased risk for kidney failure compared to those with late onset. However, the mechanism of diabetic kidney disease (DKD) progression in this high-risk group is poorly understood., Objective: This work aimed to identify novel biomarkers and potential causal proteins associated with DKD progression in patients with YT2D., Methods: Among YT2D (T2D onset age <40 years), 144 DKD progressors (cases) were matched for T2D onset age, sex, and ethnicity with 292 nonprogressors (controls) and divided into discovery and validation sets. DKD progression was defined as decline of estimated glomerular filtration rate (eGFR) of 3 mL/min/1.73 m2 or greater or 40% decline in eGFR from baseline. A total of 1472 plasma proteins were measured through a multiplex immunoassay that uses a proximity extension assay technology. Multivariable logistic regression was used to identify proteins associated with DKD progression. Mendelian randomization (MR) was used to evaluate causal relationship between plasma proteins and DKD progression., Results: Forty-two plasma proteins were associated with DKD progression, independent of traditional cardiorenal risk factors, baseline eGFR, and urine albumin-to-creatinine ratio. The proteins identified were related to inflammatory and remodeling biological processes. Our findings suggest angiogenin as one of the top signals (odds ratio = 5.29; 95% CI, 2.39-11.73; P = 4.03 × 10-5). Furthermore, genetically determined plasma angiogenin level was associated with increased odds of DKD progression., Conclusion: Large-scale proteomic analysis identified novel proteomic biomarkers for DKD progression in YT2D. Genetic evidence suggest a causal role of plasma angiogenin in DKD progression., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: The adverse health impacts of ambient temperature have been well-documented, encompassing not only the mortality and morbidity burden but also mood and mental health disorders. However, the relationship between temperature and social isolation remains unexplored. The objective of the current study was to investigate the potential associations between ambient temperature and social isolation among the aging population., Methods: We took advantage of a cross-sectional survey conducted between January 2017 and November 2018 from a community service program special for older adults aged ≥60 who lived in a central community of Hong Kong. The personal social isolation was assessed by the validated Lubben Social Network Scale-6 (LSNS-6), with a score ranging from 0 to 30 and score of less than 12 indicating social isolation. The environmental exposures, including ambient temperature, sunshine hours, rainfalls, and air pollution, were obtained from the nearby monitoring stations. The association of ambient temperature with LSNS-6 score or social isolation was examined by the generalized linear models while adjusting the potential confounding from other environmental exposures and personal sociodemographic factors., Results: Among the 1616 participants, the distribution of LSNS-6 score was approximately normal and the mean score was a bit higher on cool days than on hot days (13.0 vs. 12.2). Compared with cool temperatures (14.4-19.5 o C), the independent effect estimates of hot ambient temperatures (24.5-28.7 o C) was associated with a 2.38 (95%CI: 1.63-3.13) decrease in LSNS-6 score. Meanwhile, we observed statistically significant associations of sunshine exposure, gender, health status, marital status, living alone, religion, and housing type with LSNS-6 score or social isolation., Conclusions: Our study revealed a clear association between ambient cool temperatures and reduced social isolation, as well as association between hot temperatures and social isolation among older Chinese adults residing in the urban community of Hong Kong., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors.)

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an established technique for lung cancer staging and the diagnosis of mediastinal diseases. Recently, the paradigm of EBUS guided mediastinal sampling with conventional cytology has shifted over to histology specimens through the use of cryobiopsy. This case series explores the novel technique, key enablers, and potential advantages of endoscopic ultrasound with bronchoscope-guided transesophageal cryobiopsy (EUS-B-TEC). The findings of this case series suggest that EUS-B-TEC is a safe and valuable addition to the bronchoscopic procedural armamentarium. Further studies are warranted to validate the potential of EUS-B-TEC., Competing Interests: Dr. Sze Shyang Kho has received travel grant from ERBE Elektromedizin GmbH. Dr. Chun Ian Soo has received speaker honoraria from Cook Medical. All other authors have no conflict of interest., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Background: Human papillomavirus (HPV) infection is prevalent among people who are sexually active. This study aimed to compare the levels of behavioral intention to receive free clinician-collected and self-collected samples for HPV DNA testing and its determinants between heterosexual males and females in Hong Kong, China., Methods: This is a secondary analysis of a territory-wide survey conducted in Hong Kong between May 2021 and March 2022. Participants were sexually active adult Hong Kong residents who were able to communicate in English or Chinese. Invitation letters were mailed to residential addresses that were geographically randomly selected. All sexually active adult household members were invited to complete a self-administered online survey. Multivariate logistic regression analyses were fitted., Results: Out of 45,394 invitations, 1265 surveys were collected, and 487 heterosexual males and 741 females were included in the analysis. More females than heterosexual males intended to take up free clinician-collected samples for HPV DNA testing (76.7% versus 62.2%, p < 0.001). Similar proportion of heterosexual males and females intended to receive free self-collected samples for HPV DNA testing (67.8% versus 72.6%, p = 0.20). Perceived existing treatment could control sexually transmitted infections (STI) (treatment control), more concerned about STI (concern), perceived more benefits, cue to action (suggested by significant others), and self-efficacy related to HPV testing were associated with higher intention to receive clinician-collected samples for HPV testing in both groups. Heterosexual males who perceived more severe symptoms if contracted STI (identity), longer duration of STI (timeline), more negative effects of STI on their lives (consequences), more understanding of STI (coherence), and stronger negative emotions if contracted STI (emotions) also had higher behavioral intention to take up clinician-collected samples for HPV testing. In addition, perceived more benefits, cue to action, and self-efficacy related to self-collected samples for HPV DNA testing were associated with behavioral intention to take up such testing in both groups., Conclusions: HPV DNA testing was under-utilized in Hong Kong. Free self-collected samples for HPV testing were highly acceptable by both heterosexual males and females. Illness representation of STI and the Health Belief Model could explain intentions to take up HPV DNA testing., Competing Interests: Declarations. Ethics approval and consent to participate: Before starting the online survey, the participants read a statement that participation was voluntary, refusal to participate would have no effect on them, and the data would be kept strictly confidential and would only be used for research purposes. Online informed consent was sought. Ethical approval was obtained from the Joint Chinese University of Hong Kong – New Territories East Cluster Clinical Research Ethics Committee (reference number: CREC 2020.436). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: This study aimed to investigate how doctor-patient communication, trust in doctors impacted patients' experience and satisfaction in shared decision-making (SDM)., Methods: This study is based on the data from a cross-sectional survey (n = 12,401) conducted in 27 public specialist outpatient clinics in Hong Kong., Results: The multivariable regression models revealed that doctors' better communication skills were associated with lower decision-making involvement (odd ratio, 0.75 [95 % CI, 0.88-0.94], P < .001) but higher satisfaction with involvement (odd ratio, 6.88 [95 % CI, 5.99-7.93], P < .001). Similarly, longer consultation durations were associated with reduced involvement in decision-making (odd ratio, 0.71 [95 % CI, 0.66-0.73], P < .001) but increased satisfaction with involvement (odd ratio, 1.91 [95 % CI, 1.80-2.04], P < .001). Trust in doctors significantly mediated these associations, except for the association between consultation duration and patients' satisfaction with decision-making involvement., Conclusion: Doctors' better communication skills and longer consultations might not necessarily increase patient involvement in SDM but correlated with increased satisfaction with involvement. Trust in doctors emerged as a mediator for participation and satisfaction in decision-making., Practice Implications: Clinics should consider patients' preferences and capabilities when tailoring communication strategies about decision-making and optimizing patient satisfaction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Mucoepidermoid carcinoma is a rare primary tumour of the lung. Diagnosis can be made after careful exclusion of other lung neoplasms, especially those with overlapping histological and radiological features. https://bit.ly/4fcISSm., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©ERS 2024.)

Cag type IV secretion system (CagT4SS) translocates oncoprotein cytotoxin-associated gene A (CagA) into host cells and plays a key role in the pathogenesis of Helicobacter pylori. The structure of the outer membrane core complex (OMCC) in CagT4SS consists of CagX, CagY, CagM, CagT, and Cag3 in a stoichiometric ratio of 1:1:2:2:5 with 14-fold symmetry. However, the assembly pathway of OMCC remains elusive. Here, we report the crystal structures of CagT and Cag3-CagT complex, and the structural dynamics of Cag3 and CagT using hydrogen deuterium exchange-mass spectrometry (HDX-MS). The interwoven interaction of Cag3 and CagT involves conformational changes of CagT and β strand swapping. In conjunction with biochemical and biophysical assays, we further demonstrate the different oligomerization states of Cag3 and Cag3-CagT complex. Additionally, the association with CagM requires the pre-formation of Cag3-CagT complex. These results demonstrate the generation of different intermediate sub-assemblies and their structural flexibility, potentially representing different building blocks for OMCC assembly., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Upregulation of IL-6 has been associated with worse prognosis in COVID-19 patients. Impact on IL-6 signalling has mostly been limited to clinical outcomes in IL-6 receptor antagonist trials., Methods: We performed a phase 2, randomised, double-blind, placebo-controlled trial (NCT04380961) of US-based hospitalised adults (<85 years) with laboratory-confirmed SARS-CoV-2 infection and severe (low levels of supplemental oxygen) or critical disease (high levels of oxygen supplementation). Patients received sirukumab 5 mg/kg or placebo single dose IV on Day 1 plus standard of care. The primary endpoint was time to sustained clinical improvement up to Day 28 based on an ordinal scale. Secondary endpoints included clinical improvement, all-cause mortality, and safety. Following an interim analysis, the protocol was amended to only recruit patients with critical COVID-19., Findings: From May 2020 to March 2021, 209 patients were randomised; 112 had critical disease (72 sirukumab, 40 placebo) at baseline. Median time to sustained clinical improvement in critical patients was 17 and 23 days in the sirukumab and placebo groups (HR, 1∙1; 95% CI, 0∙66-1∙88; p > 0∙05). At Day 28, 59∙4% versus 55∙0% of patients achieved clinical improvement with sirukumab versus placebo and rates of all-cause mortality were 24∙6% versus 30∙0%, respectively. Rates of grade ≥3 adverse events were comparable between the sirukumab and placebo groups (25∙9% vs 32∙9%; all patients)., Interpretation: In critical COVID-19 patients who received sirukumab, there was no statistically significant difference in time to sustained clinical improvement versus placebo despite objective sequestration of circulating IL-6, questioning IL-6 as a key therapeutic target in COVID-19., Competing Interests: Declaration of Competing Interest Robert L. Gottlieb served as coordinating national principal investigator and as a consultant for this trial. He reports service on scientific advisory boards for AbbVie, AstraZeneca, Eli Lilly, Gilead Sciences, GSK, and Roche, and consulting via his institution for Kinevant Sciences, also related to COVID-19. Service on speakers bureau with Alnylam Pharmaceuticals and Pfizer, consultancy to Alnylam, research support from CareDx, and a gift-in-kind to his institution from Gilead Sciences to support NCT03383419 are also reported, all outside the submitted work. Meredith Clement has received research support (grants to institution) from Gilead Sciences and ViiV Healthcare, has served on advisory boards for Roche Diagnostics Corporation and ViiV Healthcare. Paul Cook is a PI for the following: NIH, Janssen, Gilead, ViiV, Seres, and Finch. Audra Deveikis, Kap Sum Foong, Philip Robinson, and Cedric W. Spak have nothing to declare. Jihad Slim serves on speakers bureaus for Gilead, ViiV, Merck, Janssen, AbbVie, and Thera. Katleen Callewaert is an employee of Janssen Pharmaceutica NV. Annemie Buelens, Sandra De Meyer, Liesbeth Van Wesenbeeck, and Erika Van Landuyt are employees of Janssen Pharmaceutica NV and own stock in Johnson & Johnson. Wai Ling Mo is an employee of Janssen-Cilag Limited. Inge Verbrugge and Magda Opsomer were employees of Janssen Pharmaceutica NV at the time of the study. Yanli Zhuang and Jacon Chien were employees of Janssen Research & Development, LLC at the time of the study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Current evidence supports the use of integrative oncology (IO) interventions in cancer supportive care. The demand for outpatient IO services in Hong Kong is expected to soar following the surge in cancer incidence due to population ageing. This study identified the factors influencing the delivery and utilisation of outpatient IO from local stakeholders' perspectives and developed corresponding implementation strategies., Methods: This study involved two sequential stages. First, with individual semi-structured interviews guided by the Theoretical Domains Framework (TDF), we explored stakeholders' views on the barriers to and facilitators for implementing IO. Second, guided by a TDF-based qualitative data analysis of interview transcripts, we performed intervention mapping to develop Behaviour Change Wheel-based implementation strategies that may overcome the barriers and strengthen the facilitators., Results: We interviewed 31 stakeholders, including traditional Chinese medicine (TCM) practitioners ( n  = 8), biomedically-trained doctors ( n  = 7), nurses ( n  = 6), administrators ( n  = 4), caregivers ( n  = 4), and pharmacists ( n  = 2). The key local factors influencing outpatient IO are (1) lacking nursing and administrative workforce supporting IO service delivery, (2) lacking awareness of IO services among healthcare professionals, administrators, patients, and caregivers, and (3) lacking knowledge among healthcare professionals of herb-drug interaction and herbal toxicities., Conclusion: We recommended a multi-faceted implementation strategies package that included arranging funding to train, recruit, and retain nursing and administrative staff, devolving resources into promoting interprofessional collaborations and evidence on IO effectiveness and safety, integrating evidence on herb-drug interactions and herbal toxicities into automated electronic health record systems monitored by pharmacists with dual qualifications in TCM and conventional pharmacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ho, Kwong, Li, Nilsen, Ho, Zhong, Wong, Lin and Chung.)

Autistic spectrum disorder (ASD) is a neurodevelopmental disability characterised by the impairment of social interaction and communication ability. The alarming increase in its prevalence in children urged researchers to obtain a better understanding of the causes of this disease. Genetic factors are considered to be crucial, as ASD has a tendency to run in families. In recent years, with technological advances, the importance of structural variations (SVs) in ASD began to emerge. Most of these studies, however, focus on the Caucasian population. As a populated ethnicity, ASD shall be a significant health issue in China. This systematic review aims to summarise current case-control studies of SVs associated with ASD in the Chinese population. A list of genes identified in the nine included studies is provided. It also reveals that similar research focusing on other genetic backgrounds is demanded to manifest the disease etiology in different ethnic groups, and assist the development of accurate ethnic-oriented genetic diagnosis.

Background: Older adult patients are particularly vulnerable to medication-related issues during the discharge process. To enhance medication discharge education and patient experience, a written medication reminder, incorporating crucial medication side effects and warning signs, was implemented in medicine wards. This study aimed to examine the influence of this reminder on patient experience and medication-taking behaviors among older adults in public healthcare settings., Methods: Two separate rounds of cross-sectional surveys were conducted before and after the program implementation among different discharged patients in each round. The study enrolled older adult patients aged ≥ 65 or their caregivers discharged from the medical wards of four pilot public hospitals in Hong Kong. A structured questionnaire was administered via telephone within 14 days of the patient's discharge. The survey assessed patients' experience with the provided medication information during discharge, including the clarity, adequacy, and usefulness of the information, as well as their overall experience with inpatient services. The self-reported medication-taken behaviors, including adherence and side-effect encounters, were also measured., Results: A total of 1,265 responses were collected before the implementation of the medication reminder, and 1,426 responses were obtained after the implementation. Pre/post-implementation survey comparison showed significant improvement in patient experience regarding the clarity of the provided medication information (7.93 ± 1.84 vs. 8.18 ± 1.69, P = 0.002), adequacy (7.92 ± 1.93 vs. 8.15 ± 1.76, P = 0.014), and usefulness (8.06 ± 1.80 vs. 8.26 ± 1.70, P = 0.017), significantly positive experience on the overall discharge information (β coefficient, 0.43 [95%CI, 0.30 to 0.56]) and inpatient service (β coefficient, 0.47 [95%CI, 0.32 to 0.61]). In addition, the side effects encounters were significantly lower in the post-implementation survey group (11.6% vs. 9.0%, P = 0.04) and no statistical difference was found in self-reported medication adherence between the two groups., Conclusions: The provision of written medication reminders on key medication risks effectively improved older adult patients' experience and reduced side effects without any unintended negative consequences. The findings can serve as a reference for similar settings seeking to enhance post-discharge care among older adult patients. Future studies could investigate the influence in other specialties and age groups and include clinical outcomes to test the program's effectiveness., (© 2024. The Author(s).)

Background: Electronic mental health literacy (eMHL) is critical for accessing and effectively using digital mental health resources. However, there is a paucity of research on how eMHL varies across age groups., Objective: This study aimed to investigate differences in eMHL among young, middle-aged, and older adults; provide insights into the needs, behaviors, and attitudes of different age groups in relation to digital mental health resources; and ultimately, inform the improvement of mental health services., Methods: A qualitative investigation was conducted to examine the differences in eMHL across different age demographics in the Chinese population in 2023. The study sample comprised 3 distinct age groups: 18-34 years, 35-64 years, and 65 years and older. Participants were recruited through purposive sampling to ensure a diverse representation of the population. Data were collected through semistructured one-on-one interviews, which allowed for in-depth exploration of individual experiences and perceptions. The gathered data were subsequently subjected to rigorous thematic analysis to enable the identification and interpretation of recurring patterns and themes., Results: The principal outcomes derived from these interviews were synthesized into 5 distinct dimensions: emotional needs, use of digital mental health resources, assessment of digital mental health information, engagement with social media to regulate emotions, and coping strategies. These dimensions were uniformly observed across the 3 age groups., Conclusions: We identified differences in knowledge, skills, and attitudes regarding the use of web-based information for managing mental health problems between the 3 age groups. The findings highlight the importance of age-specific strategies for improving eMHL., (©Richard Huan Xu, Lidan Tian, Liling Zhu, Yuan Cao, Sherry Kit-wa Chan, Dong Dong, Wai-ling Annie Cheung, Eliza Lai-yi Wong. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 16.07.2024.)

Introduction: Upper limb problems have a significant impact on the global population leading to pain and restricted joint mobility, ultimately impacting their quality of life. Traditional treatments, such as non-steroidal anti-inflammatory drugs and corticosteroids, often come with undesirable side effects, prompting patients to seek alternative therapies. In this trial, we hypothesise that soothing cream gel (SCG) will improve range of motion and chronic pain in the shoulder and elbow. The objective of this trial is to evaluate the efficacy of SCG in improving the range of motion and chronic pain in the shoulder and elbow., Methods and Analysis: A double-blinded, randomised, placebo-controlled trial is conducted to compare the effects of SCG and placebo gel. SCG contains Vitis vinifera essence, Melaleuca viridiflora essential oil, etc, and is manufactured according to Good Manufacturing Practice standards. The placebo gel will be processed with similar appearance, texture and scent but will lack active ingredients. 70 participants with upper limb problems will be recruited from four study sites, including clinical centres and a sport department at the Chinese University of Hong Kong (CUHK). Participants will be randomly assigned to either treatment group or placebo group for 2 weeks. Primary outcome will be the range of motion in the upper limb, assessed by a goniometer, to measure active flexion and abduction for the shoulder, and active flexion and extension for the elbow. The primary efficacy analyses will be based on the full analysis set following the intention-to-treat principle., Ethics and Dissemination: The trial has obtained approval from the joint CUHK-New Territories East Cluster (CRE-2023.142), and the patient enrolment commenced in July 2023. Written informed consent will be obtained from all participants prior to participation. Study results will be disseminated through publication in peer-reviewed journals and presentations at conference., Trial Registration Number: NCT05799391., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Discharging older adult patients from the hospital poses risks due to their vulnerable conditions, complex instructions and limited health literacy. Insufficient information about medication side effects adds to patient concerns. To address this, a post-discharge information summary system was developed. While it has shown positive impacts, concerns exist regarding implementation fidelity., Objective: This study employed a theory-driven approach to understand health providers' perspectives on effective implementation., Method: Individual semi-structured interviews were conducted via telephone with nurses, doctors and pharmacists from local public hospitals. All interviews were audio-recorded and transcribed verbatim. Theoretical Domains Framework (TDF) was applied for direct content analysis. Belief statements were generated by thematic synthesis under each of the TDF domains., Results: A total of 98 participants were interviewed. Out of the 49 belief statements covering eight TDF domains, 19 were determined to be highly relevant to the implementation of the post-discharge information summary system. These TDF domains include knowledge, skills, social/professional role and identity, beliefs about consequences, intentions, memory, attention and decision processes, environmental context and resources and social influences., Conclusion: Our study contributes to the understanding of determinants in implementing discharge interventions for older adult patients' self-care. Our findings can inform tailored strategies for frontline staff, including aligning programme rationale with stakeholders, promoting staff engagement through co-creation, reinforcing positive programme outcomes and creating default settings. Future research should employ rigorous quantitative designs to examine the actual impact and relationships among these determinants., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: The introduction of bolt-on dimensions in EQ-5D instruments is growing common, but most bolt-on studies have targeted the diseased population and obtained bolt-on from other existing Health-related Quality of Life (HRQoL) instruments. As the qualitative approach offers important evidence to support the consistency and design of the potential bolt-on items, this paper studies the Hong Kong SAR community's perception of the current EQ-5D-5 L instrument and identifies potential bolt-on via a qualitative approach., Methods: A representative sample mix was recruited based on the age group, gender, and education level composition of the Hong Kong SAR community by quota sampling. Semi-structured interviews were conducted and the interviews were transcribed and coded to identify emergent and recurrent themes., Results: Thirty interviews were conducted and the majority of the interviewees considered the EQ-5D-5 L insufficiently comprehensive to illustrate their HRQoL. While some key HRQoL aspects included in the EQ-5D matched with the community's HRQoL perception, respondents showed concern about the potential overlap of the existing HRQoL dimension, the optimal number or attributes, and the appropriateness of the EQ-VAS. Among the potential bolt-on dimensions that emerged, 'Sleep', 'Interpersonal Relationship', and 'Satisfaction' were the key potential bolt-on dimensions identified and emphasized in the interviews., Conclusions: The qualitative findings of the study illustrate the possible gap between EQ-5D-5 L measurements and community HRQoL perception, while the findings support the development of EQ-5D bolt-on dimensions in the target community with content and face validity., (© 2024. The Author(s).)

Cellular RNA is asymmetrically distributed in cells and the regulation of RNA localization is crucial for proper cellular functions. However, limited chemical tools are available to capture dynamic RNA localization in complex biological systems with high spatiotemporal resolution. Here, we developed a new method for RNA proximity labeling activated by near-infrared (NIR) light, which holds the potential for deep penetration. Our method, termed FAP-seq, utilizes a genetically encoded fluorogen activating protein (FAP) that selectively binds to a set of substrates known as malachite green (MG). FAP binding restricts the rotation of MG and rapidly activates its fluorescence in a wash-free manner. By introducing a monoiodo modification to MG, we created a photosensitizer (MG-HI) with the highest singlet oxygen generation ability among various MG derivatives, enabling both protein and RNA proximity labeling in live cells. New insights are provided in the transcriptome analysis with FAP-seq, while a deeper understanding of the symmetry-breaking structural arrangement of FAP-MG-HI was obtained through molecular dynamics simulations. Overall, our wash-free and NIR light-inducible RNA proximity labeling method (FAP-seq) offers a powerful and versatile approach for investigating complex mechanisms underlying RNA-related biological processes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objectives: To compare the prevalence of anxiety/depression, resilience, and social support among nurses, foreign domestic helpers (FDHs), and residents living in subdivided units (SDUs), and to examine their associations in these high-risk groups in Hong Kong during Omicron waves., Methods: We recruited 1,014 nurses, 621 FDHs, and 651 SDU residents from December 2021 to May 2022 in this cross-sectional survey. The depression, anxiety, social support, and resilience levels were measured by the validated scales. The multivariate binary logistic regression and causal mediation analysis were applied to examine the associations., Results: We observed a prevalence of 17.7% in anxiety and 21.6% in depression which were the highest in SDU residents, followed by FDHs, and lowest in nurses. Social support was associated with increased resilience levels and decreased risks of anxiety/depression. The association of social support with mental disorders was partly mediated by resilience, accounting for 30.9% and 20.9% of the total effect of social support on anxiety and depression, respectively., Conclusion: Public health strategies should target improving social support and providing resilience-promoting interventions to help reduce mental disorders in vulnerable groups., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Wong, Qiu, Sun, Mo, Lai, Yam, Miao, Cheung and Yeoh.)

Biocatalytic oxidations are an emerging technology for selective C-H bond activation. While promising for a range of selective oxidations, practical use of enzymes catalyzing aerobic hydroxylation is presently limited by their substrate scope and stability under industrially relevant conditions. Here, we report the engineering and practical application of a non-heme iron and α-ketoglutarate-dependent dioxygenase for the direct stereo- and regio-selective hydroxylation of a non-native fluoroindanone en route to the oncology treatment belzutifan, replacing a five-step chemical synthesis with a direct enantioselective hydroxylation. Mechanistic studies indicated that formation of the desired product was limited by enzyme stability and product overoxidation, with these properties subsequently improved by directed evolution, yielding a biocatalyst capable of >15,000 total turnovers. Highlighting the industrial utility of this biocatalyst, the high-yielding, green, and efficient oxidation was demonstrated at kilogram scale for the synthesis of belzutifan., (© 2024 Wiley-VCH GmbH.)

Objective: To investigate the relationship between obstructive sleep apnea (OSA) with and without excessive daytime sleepiness (EDS) and behavioral and emotional outcomes in non-obese prepubertal children., Methods: This was a retrospective analysis of children aged 5-11 years who presented to our unit for assessment of their sleep-related complaints. All children underwent polysomnography (PSG). They also completed the Pediatric Daytime Sleepiness Scale (PDSS) and a sleep diary. OSA was diagnosed if the obstructive apnea-hypopnea index (OAHI) was ≥1 event/hour. EDS was defined as PDSS >15. Behavioral and emotional outcomes were assessed using the Child Behavioral Checklist (CBCL)., Results: Data from 391 children (mean age of 8.6 ± 1.7 years; 67 % male) were analyzed. Seventy children did not have OSA or EDS, 137 had OSA, 50 had reported having EDS but without OSA, and 134 children had both OSA and EDS. There were significantly higher CBCL total problems score in the combined group (61 ± 9) compared to the non-OSA/EDS group (54 ± 10), and the OSA-only group (54 ± 10) (p < 0.001). The presence of EDS was significantly associated with higher CBCL T score and higher odds for clinically significant behavioral problems (T score ≥65) after adjusting for age, sex, BMI z-score and average sleep duration (p < 0.001)., Conclusion: Excessive daytime sleepiness is an important contributory factor associated with suboptimal behavioral and emotional outcomes in children with OSA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This short report evaluated the accuracy and quality of information provided by ChatGPT regarding the use of complementary and integrative medicine for cancer. Using the QUality Evaluation Scoring Tool, a panel of 12 reviewers assessed ChatGPT's responses to 8 questions. The study found that ChatGPT provided moderate-quality responses that were relatively unbiased and not misleading. However, the chatbot's inability to reference specific scientific studies was a significant limitation. Patients with cancer should not rely on ChatGPT for clinical advice until further systematic validation. Future studies should examine how patients perceive ChatGPT's information and its impact on communication with health care professionals.

Background: The Coronavirus disease 2019 (COVID-19) is the largest global epidemic in recent time. Chinese medicine has been recognized by the World Health Organization as an effective treatment for COVID-19, but there is still a lack of high-quality randomized, double-blind trials using placebo as the control to support its application, which may hinder its further promotion locally and internationally. Objectives: This study will evaluate the efficacy and safety of Yinqiao Powder-Maxing Ganshi Decoction with variation in relieving major symptoms of mild and moderate COVID-19 by telemedicine. Methods and design: This clinical study is a randomized, double-blind, placebo-controlled trial that applies telemedicine to evaluate the efficacy and safety of Yinqiao Powder-Maxing Ganshi Decoction in the treatment of mild and moderate COVID-19. Eligible subjects will be randomly divided into either treatment or placebo groups for up to 14 days after stratification according to age (A:18-49, B:50-65) and the number of vaccinations (a: ≥3 doses, b: ≤2 doses). The treatment group will receive Yinqiao Powder-Maxing Ganshi Decoction granules along with certain variation based on their symptoms, and the placebo group will receive the same amount of placebo granules. Subjects will be prescribed different additions based on their symptoms and pathogenesis at the inclusion. The oral temperature, oximeter, result of rapid antigen test and symptom score will be recorded by subjects until they have stopped the medication. Subjects are required to have follow-up assessment by video-conference on days 7, 14 and 35. The time for the body temperature returning to normal will be used as the primary outcome. Discussion: This trial will provide scientific evidence on the use of Yinqiao Powder-Maxing Ganshi Decoction for the treatment of COVID-19, and the results would help raise the awareness in Hong Kong and the international community on the use of Chinese herbal medicine for treating COVID-19. Clinical Trial Registration: clinicaltrials.gov, identifier NCT05787327., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sum, Li, Zhang, Hung, Fong, Lin, Chow, Leung, Lo, Chia, Chan and Lin.)

Objective: The EQ-VAS is an important component of the EQ-5D questionnaire. However, there is limited evidence comparing its performance to the EQ-5D utility score, which restricts its use in the population. This study aimed to EQ-5D-5L utility score and EQ-visual analogue scale (EQ-VAS) in primary care patients in Hong Kong (HK)., Methods: Secondary data analysis was performed on the data collected from a cross-sectional survey to investigate patient engagement in HK. Participants were recruited through random sampling from a single general outpatient clinic. Trained investigators conducted face-to-face interviews with all eligible patients attending the clinic. Patients who were: 1) ≥ 18 years old, 2) have visited the clinic at least once in the last 6 months, 3) no cognitive problems, and 4) can speak and understand the local language. Pearson correlation was used to explore the association between EQ-5D utility and EQ-VAS score. Ordinary least squares regression and heteroscedastic Tobit regression models were adopted to analyze the EQ-VAS and EQ-5D utility data, respectively., Results: The analysis included data from 1,004 responses (response rate = 65%). Around 52.7% of participants were female, 25.9% completed tertiary or above education, and 75.1% living with chronic disease. The mean EQ-5D utility and EQ-VAS score were 0.92 (SD = 0.13) and 72.27 (SD = 14.69), respectively. A significant association was found between EQ-5D utility and EQ-VAS score, with coefficients ranging from 0.335 (participants who divorced) to 0.744 (participants living alone). Around 98.5% reported having no problems with 'Self-care', followed by 'Usual activities' (96.3%), 'Mobility' (91.5%) and 'Anxiety/depression' (79.9%). The correlation between EQ-VAS score and EQ-5D utility was positive for each dimension of the EQ-5D instrument (correlation coefficients ranged between 0.211 and 0.623). Age strongly influenced the magnitude and trajectory of EQ-VAS score and utility, as observed in the changes. The regression model showed that 'Mobility', 'Pain/discomfort', and 'Anxiety/depression' have considerable influence on EQ-VAS score., Conclusions: This study compared the EQ-5D utility score and EQ-VAS in HK primary care setting. Although heterogeneity existed, the EQ-VAS and utility score are significantly correlated and reliable for evaluating health-related quality of life in this population., (© 2024. The Author(s).)

Through genome mining efforts, two lasso peptide biosynthetic gene clusters (BGCs) within two different species of Achromobacter , a genus that contains pathogenic organisms that can infect patients with cystic fibrosis, were discovered. Using gene-refactored BGCs in E. coli , these lasso peptides, which were named achromonodin-1 and achromonodin-2, were heterologously expressed. Achromonodin-1 is naturally encoded by certain isolates from the sputum of patients with cystic fibrosis. The NMR structure of achromonodin-1 was determined, demonstrating that it is a threaded lasso peptide with a large loop and short tail structure, reminiscent of previously characterized lasso peptides that inhibit RNA polymerase (RNAP). Achromonodin-1 inhibits RNAP in vitro and has potent, focused activity toward Achromobacter pulmonis , another isolate from the sputum of a cystic fibrosis patient. These efforts expand the repertoire of antimicrobial lasso peptides and provide insights into how Achromobacter isolates from certain ecological niches interact with each other.

An efficacious tuberculosis (TB) vaccine is critical to reducing the global burden of TB. TB vaccine trials require the identification of multiple sites globally that have both a high incidence of TB and the capacity to conduct a clinical trial. To expand the diversity of potential phase III TB vaccine trial sites to be considered for inclusion, we describe a novel epidemiologic method that incorporates approaches from a variety of public health practices. Our approach incorporates analytic methodology to enable quantification and validation of qualitative information from disparate data sources, and epidemiologic analysis to systematically assess site-specific TB epidemiology. The integration of robust data-driven practices, and more quantitatively focused analysis, allowed for the objective evaluation of sites, which resulted in the identification of sites and catchment areas with high TB burden that may not have been previously considered. This suggests that an integrated epidemiologic methodology, not traditionally utilized for clinical trial site evaluations, could be integrated into site feasibility assessments as it results in more rapid site identification and reduces unintended bias., Competing Interests: The authors have declared that no competing interests exist. ACS, AFD, CP are employees of the Bill & Melinda Gates Medical Research Institute, a non-profit organization dedicated to the development and effective use of novel biomedical interventions aimed at reducing the burden of TB, malaria, diarrheal diseases, and maternal, newborn, and child illnesses worldwide., (Copyright: © 2023 Mui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: The COVID-19 pandemic has a huge impact on the healthcare system and affects the normal delivery of routine healthcare services to hospitalized patients. This study aimed to examine the differences in patient experience of hospital service before and during COVID-19 among the discharged adult population., Methods: A territory-wide patient experience survey was conducted before and during COVID-19 (between October 2019 and April 2020) among patients discharged from the main acute and rehabilitation public hospitals in Hong Kong. A hierarchical ordinal logistic model was employed to examine the difference in multiple dimensions of patient experience, with adjustments of covariates., Results: In total, 9,800 participants were recruited. During the pandemic, there was a marginally significant increase in overall care rating (AOR: 1.12, 95% CI: 0.99-1.27), and an improvement in the timeliness of admission. However, significant reductions in patients' confidence in nurses were observed. Communication of information regarding medication side effects reduced significantly (AOR: 0.72, 95% CI: 0.64-0.82)., Conclusion: The patients hospitalized during the pandemic reported worse responsiveness in communication in their patient journey than those admitted before the pandemic. These findings will help develop appropriate strategies to address patients' concerns in the new normal., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wong, Wang, Cheung, Graham and Yeoh.)

Rasmussen's aneurysm is a rare yet fatal cause of massive haemoptysis in pulmonary tuberculosis. Early identification and timely intervention are of utmost importance to reduce the associated mortality. A girl in early adolescence presented with persistent fever and massive haemoptysis who required intubation and was subsequently confirmed to have tuberculosis. CT pulmonary angiogram showed the presence of pseudoaneurysms in the left upper and lower lobes. The haemoptysis resolved following the embolisation of the culprit's vessel. Residual lung destruction was evident on CT after a 12-month course of antituberculosis therapy. Rasmussen's aneurysm is a significant vascular complication of cavitary tuberculosis and needs to be considered in patients presenting with massive haemoptysis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Hong Kong government distributed rapid antigen test (RAT) kits to households across the city and called for a universal voluntary testing exercise for three consecutive days during the Omicron wave to identify infected persons early for quarantine and disrupt transmission chains in the community. We conducted a survey to evaluate the participation rates and explore the determinants of voluntary RAT adoption and hesitancy., Methods: This cross-sectional survey was conducted through computer-assisted telephone interviews from 19 May to 16 June 2022 using an overlapping dual-frame telephone number sampling design. Information on willingness to adopt voluntary RAT, four themes of personal qualities, attitudes toward the government's health policies, incentives to motivate RAT adoption, and personal sociodemographic factors were collected. Logistic regression analysis was used to examine the factors associated with RAT adoption., Results: Of the 1010 participants, 490 successfully responded to the fixed-line and 520 to the mobile phone survey, with response rates of 1.42% and 1.63% and screen hesitancy rates of 36.1% and 39.3%, respectively. Participants of adoption RAT were those aged 30-49 years, with high perceived COVID-19 infection severity, ≥ 3 doses of COVID-19 vaccination, and more agreement with the health policies on material resources and quarantine orders. Individuals who were less risk seeking and more altruistic reported a higher adoption of voluntary RAT., Conclusions: Understanding the willingness to participate in a voluntary universal testing programme might shed light on effective ways to minimise screening hesitancy in future public health strategies and campaigns., Competing Interests: Declaration of Competing Interest We have no conflict of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Diabetic corneal neuropathy (DCN) is a common complication of diabetes. However, there are very limited therapeutic options. We investigated the effects of a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, fenofibrate, on 30 patients (60 eyes) with type 2 diabetes. On in vivo confocal microscopy evaluation, there was significant stimulation of corneal nerve regeneration and a reduction in nerve edema after 30 days of oral fenofibrate treatment, as evidenced by significant improvement in corneal nerve fiber density (CNFD) and corneal nerve fiber width, respectively. Corneal epithelial cell morphology also significantly improved in cell circularity. Upon clinical examination, fenofibrate significantly improved patients' neuropathic ocular surface status by increasing tear breakup time along with a reduction of corneal and conjunctival punctate keratopathy. Tear substance P (SP) concentrations significantly increased after treatment, suggesting an amelioration of ocular surface neuroinflammation. The changes in tear SP concentrations was also significantly associated with improvement in CNFD. Quantitative proteomic analysis demonstrated that fenofibrate significantly upregulated and modulated the neurotrophin signaling pathway and linolenic acid, cholesterol, and fat metabolism. Complement cascades, neutrophil reactions, and platelet activation were also significantly suppressed. Our results showed that fenofibrate could potentially be a novel treatment for patients with DCN., (© 2023 by the American Diabetes Association.)

Background: Patient feedback is an important way for healthcare providers to understand patient experience and improve the quality of care effectively and facilitate patient-centered care in the healthcare system. This study aimed to suggest a validated instrument by evaluating the psychometric properties of the Accident and Emergency Experience Questionnaire (AEEQ) for measuring patient experience in the accident and emergency department (AED) service among the adult Chinese population., Methods: Attendances aged 18 or above from all public hospitals with AEDs during 16-30 June 2016 were targeted and a cross-sectional telephone survey was conducted using AEEQ. Preliminary AEEQ consisted of 92 items, including 53 core evaluative items and 19 informative items, and the other 20 items covered socio-demographics, self-perceived health status, and free open-ended comments on AED service. Psychometric properties of the evaluative items were evaluated for practicability, content and structure validity, internal consistency, and test-retest reliability in this study., Results: A total of 512 patients were recruited with a response rate of 54% and a mean age of 53.2 years old. The exploratory factor analysis suggested removing 7 items due to weak factor loadings and high cross-loading and then leaving 46 items grouped into 5 dimensions, which were care and treatment (14 items), environment and facilities (16 items), information on medication and danger signals (5 items), clinical investigation (3 items), and overall impression (8 items) to represent patient experience on AED service. The internal consistency and test-retest reliability were high with Cronbach's alpha coefficient and Spearman's correlation coefficient of the suggested scale of 0.845 and 0.838, respectively., Conclusion: The AEEQ is a valid and reliable instrument to evaluate the AED service which helps to build the engagement platform for promoting patient-centered care between patients and frontline healthcare professionals and improving healthcare quality in the future., (© 2023. The Author(s).)

Background: Defined as having few social relationships or infrequent social contact with family, friends, and the community, social isolation is a public health crisis. We aimed to evaluate the prevalence of social isolation and explore the association between social isolation and health status among community-dwelling Chinese Older Adults living with homecare services., Methods: This is a cross-sectional survey with a structured questionnaire conducted among older adults aged ≥60 in the Central Kowloon District of Hong Kong during 2017-2018. Social isolation was assessed by the Lubben Social Network Scale-6 and a score less than 12 was defined as socially isolated. Six aspects of health status including fall risk, cognitive function, depression, activities of daily living (ADL), instrumental activities of daily living (IADL), and functional mobility were measured by standardized instruments. Multi-criteria decision analysis (MCDA) was applied to estimate an index to represent the overall health status of the respondents. Multivariate logistic/linear regression models were applied to examine the associations between social isolation and health status after adjusting the sociodemographic characteristics., Results: Among the 1,616 participants included in this analysis, the mean age was 80.9 years, 66.3% were female and 41.4% were identified as socially isolated. Compared with the non-isolated group, the socially isolated group had higher proportions of males, divorced or unmarried, ever smoking and drinking, living alone, and living in public housing without religion. After adjusting for confounders, the odds ratios (OR) comparing the socially isolated vs. non-isolated groups were 2.52 (95%CI: 1.79, 3.56) for high fall risk, 1.51 (1.17, 1.94) for cognitive impairment, and 1.78 (1.31, 2.43) for depression. The socially isolated group increased the odds of abnormal ADL, IADL, and functional mobility by 105-150%, and decreased the overall health score by 5.30 (3.42, 7.18)., Conclusion: We demonstrated the association of social isolation with poorer physical function and mental health and overall health status among the community-dwelling Chinese older adults living with homecare services. These findings provided new knowledge about the association of social isolation with both physical and mental function for daily living even for those receiving an integrated homecare service in the community. It implies that an unmet healthcare need existed when comparing the service scope of the current homecare services in the community. It also highlighted the need for targeted prevention and intervention initiatives among community-dwelling old adults to alleviate social isolation for better health and good functioning in the community., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wong, Qiu, Cheung, Leung, Chen and Yeoh.)

Background: Various strategies of weaning V-A ECMO have been described. PCRTO is a weaning technique which involves serial decremental pump revolutions until a retrograde flow from the arterial to venous ECMO cannula is achieved. It has been reported as a feasible weaning strategy in the pediatric population, but its application in adults has not been widely reported., Methods: This was a case series including all adult patients who underwent PCRTO during weaning from V-A ECMO at a tertiary ECMO center between January 2019 and July 2021. The primary end point was the successful weaning from V-A ECMO support., Results: A total of 57 runs of PCRTO in 36 patients were analyzed-45 (78.9%) of the trials were concluded successfully. The median retrograde blood flow rate during PCRTO was 0.6 ± 0.2 L/min, and the median duration of each PCRTO was 180 (120-240) min. Of the 35 patients who had at least one session of successful PCRTO, 31 (88.6%) were ultimately weaned from ECMO. There were no major complications from PCRTO including systemic or circuit thrombosis., Conclusions: PCRTO is a feasible strategy for assessing readiness for weaning from V-A ECMO with a low risk of adverse events and high rate of predicting eventual successful ECMO decannulation. Further investigation including comparison with alternative weaning strategies in prospective studies is required to confirm the approach., (© 2023 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

The global high prevalence of COVID-19 is a major challenge for health professionals and patients. SARS-CoV-2 virus has four structural protein components: the spike protein, envelope protein, membrane protein, and nucleocapsid protein. The SARS-CoV-2 virus mutates predominantly in the spike proteins, whilst the other key viral components usually remain stable. Essentially the pathological functions of the SARS-CoV-2 virus on different cell types are still largely unknown. Previous studies have shown that the human oral cavity can potentially act as reservoir of the SARS-CoV-2 virus. However, the consequence of SARS-CoV-2 viral infection on human oral health has not been systematically examined. COVID-19 can cause severe oral mucosa lesions and is likely to be connected with poor periodontal conditions. Fibroblasts are the major cell type inside periodontal ligament (PDL) and express the SARS-CoV-2 receptor: Angiotensin-converting enzyme 2 (ACE2), whose expression level can increase upon bacterial infection hence potentially provide a direct route of SARS-CoV-2 infection to PDL fibroblasts. In this research, we aimed to study the pathogenicity of SARS-CoV-2 viral components on human fibroblasts. We found that by exposing to SARS-CoV-2, especially to the viral envelope and membrane proteins, the human periodontal fibroblasts could develop fibrotic pathogenic phenotypes, including hyperproliferation that was simultaneously induced with increased apoptosis and senescence. The fibrotic degeneration was mediated by a down-regulation of mitochondrial β-oxidation in the fibroblasts. Fatty acid β-oxidation inhibitor, etomoxir treatment could mirror the same pathological consequence on the cells, similar to SARS-CoV-2 infection. Our results therefore provide novel mechanistic insights into how SARS-CoV-2 infection can affect human periodontal health at the cell and molecular level with potential new therapeutic targets for COVID-19 induced fibrosis., (© 2023. The Author(s).)

Background: Studies have shown increasing COVID-19 vaccination hesitancy among migrant populations in certain settings compared to the general population. Hong Kong has a growing migrant population with diverse ethnic backgrounds. Apart from individual-level factors, little is known about the migrants' preference related to COVID-19 vaccines., Objective: This study aims to investigate which COVID-19 vaccine-related attributes combined with individual factors may lead to vaccine acceptance or refusal among the migrant population in Hong Kong., Methods: An online discrete choice experiment (DCE) was conducted among adults, including Chinese people, non-Chinese Asian migrants (South, Southeast and Northeast Asians), and non-Asian migrants (Europeans, Americans, and Africans) in Hong Kong from February 26 to April 26, 2021. The participants were recruited using quota sampling and sent a link to a web survey. The vaccination attributes included in 8 choice sets in each of the 4 blocks were vaccine brand, safety and efficacy, vaccine uptake by people around, professionals' recommendation, vaccination venue, and quarantine exemption for vaccinated travelers. A nested logistic model (NLM) and a latent-class logit (LCL) model were used for statistical analysis., Results: A total of 208 (response rate 62.1%) migrant participants were included. Among the migrants, those with longer local residential years (n=31, 27.7%, for ≥10 years, n=7, 20.6%, for 7-9 years, n=2, 6.7%, for 4-6 years, and n=3, 9.7%, for ≤3 years; P=.03), lower education level (n=28, 28.3%, vs n=15, 13.9%, P=.01), and lower income (n=33, 25.2%, vs n=10, 13.2%, P=.04) were more likely to refuse COVID-19 vaccination irrespective of vaccination attributes. The BioNTech vaccine compared with Sinovac (adjusted odds ratio [AOR]=1.75, 95% CI 1.14-2.68), vaccine with 90% (AOR=1.44, 95% CI 1.09-1.91) and 70% efficacy (AOR=1.21, 95% CI 1.03-1.44) compared with 50% efficacy, vaccine with fewer serious adverse events (1/100,000 compared with 1/10,000; AOR=1.12, 95% CI 1.00-1.24), and quarantine exemption for cross-border travelers (AOR=1.14, 95% CI 1.01-1.30) were the vaccine attributes that could increase the likelihood of vaccination among migrants. For individual-level factors, full-time homemakers (AOR=0.44, 95% CI 0.29-0.66), those with chronic conditions (AOR=0.61, 95% CI 0.41-0.91) and more children, and those who frequently received vaccine-related information from the workplace (AOR=0.42, 95% CI 0.31-0.57) were found to be reluctant to accept the vaccine. Those with a higher income (AOR=1.79, 95% CI 1.26-2.52), those knowing anyone infected with COVID-19 (AOR=1.73, 95% CI 1.25-2.38), those having greater perceived susceptibility of COVID-19 infection (AOR=3.42, 95% CI 2.52-4.64), those who received the influenza vaccine (AOR=2.15, 95% CI 1.45-3.19), and those who frequently received information from social media (AOR=1.52, 95% CI 1.12-2.05) were more likely to accept the vaccine., Conclusions: This study implies that migrants have COVID-19 vaccination preference heterogeneity and that more targeted and tailored approaches are needed to promote vaccine acceptance for different subgroups of the migrant population in Hong Kong. Vaccination promotion strategies are needed for low-education and low-income migrant groups, migrants with chronic diseases, the working migrant population, homemakers, and parents., (©Saba Asim, Kailu Wang, Elena Nichini, Faustina Fu Yip, Liling Zhu, Hin Chung Eddy Fung, Yan Zeng, Zhilan Fang, Annie Wai-Ling Cheung, Eliza Lai-yi Wong, Dong Dong, Eng-Kiong Yeoh. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 27.03.2023.)

This study investigates how health literacy (HL) and trust in health information affected COVID-19 vaccine hesitancy among Chinese Hong Kong adults. A cross-sectional study was conducted in August 2022. A total of 401 participants completed the study. Participants completed a newly developed Hong Kong HL scale and self-reported their trust levels in health information from different resources. The proportions of early uptake of the first dose and booster dose of COVID-19 vaccine were 69.1% and 71.8%, respectively. The risk of delaying the first dose was higher among participants with inadequate functional HL (OR = 0.58, p = 0.015), adequate levels of two subdomains of critical HL (OR = 1.82, p = 0.013; OR = 1.91, p < 0.01), and low-level trust in health information from the government (OR = 0.57, p = 0.019). Respondents with adequate interactive HL (OR = 0.52, p = 0.014) and inadequate level of one subdomain of critical HL (OR =1.71, p = 0.039) were more likely to delay the booster dose. This negative association between critical HL and vaccination was suppressed by trust in health information from the government. This study shows that HL and trust in health information from the government are associated with COVID-19 vaccine hesitancy. Efforts should be directed at providing tailored communication strategies with regard to people's HL and increasing public confidence in health authorities to decrease vaccine hesitancy.

This large-scale patient study investigated the rate, unique signatures associated with acquired reading impairments, its neurocognitive correlates, and long-term outcome in 731 acute stroke patients using the sentence and non-word reading subtests of Birmingham Cognitive Screen (BCoS). The objectives for the study were to explore the (i) potentially different error patterns among adult patients, (ii) associative relationship between the different subclasses of reading impairment and performance in other cognitive domains, and (iii) recovery rates in patients nine months post-lesion compared with their initial performance. The study revealed distinctive reading impairment profiles in patients with left hemisphere (LH) and right hemisphere (RH) lesions. Some interesting associations between reading disorder and other cognitive functions were observed. Nine months post-lesion, both groups showed some recovery in reading performance compared with their baseline performance, but the rate of improvement was higher for the LH group. The study reveals unique reading profiles and impairment patterns among left and right hemisphere lesions. The findings of the study provide a deeper understanding of reading deficits that will inform clinical practice, planning of rehabilitative interventions of brain injured patients, and the scientific community.

Introduction: Health literacy (HL) refers to individuals' abilities to process and use health information to promote health. This study aimed to develop the first HL measurement tool for the Chinese Hong Kong population., Methods: A two-phase methodology was adopted. In Phase I, evidence synthesis with a deductive method was conducted to formulate the item list from the literature. In Phase II, a modified e-Delphi survey was conducted among stakeholders (i.e., healthcare providers and healthcare consumers) to confirm the content validity of the item list. The stakeholders were invited to rate the relevance of each draft item on a 4-point scale and provide suggestions for revisions, removal or adding new items., Results: In Phase I, a total of 34 items covering functional, interactive and critical HL were generated. In Phase II, to obtain a balanced view from experts and laypeople, healthcare professionals (n = 12) and consumers (n = 12) were invited to participate in the Delphi panel. The response rates of the three rounds were 100%. After the third round, the consensus was reached for 31 items, and no further comments for adding or revising items were received. All items exhibited excellent content validity (item content validity index: 0.79-1.00; K*: 0.74-1.00)., Conclusions: A Health Literacy Scale for Hong Kong was developed. Compared with existing HL scales, the scale fully operationalized the skills involved in functional, interactive and critical HL. The Delphi study shows evidence supporting the high content validity of all items in the scale. In future studies, these items should undergo rigorous testing to examine their psychometric properties in our target population groups. By illuminating the details in the development process, this paper provides a deeper understanding of the scale's scope and limitations for others who are interested in using this tool., Patient or Public Contribution: Public as healthcare consumers, in addition to healthcare providers, were involved in developing a new HL scale for this study. The input from the public contributed to examining the scale's content validity by judging whether all items reflected the skills that they need to find and use health-related information in their daily life., (© 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Backgrounds: Vaccination remains one of the most effective ways to protect populations from COVID-19 infection, severe conditions, and death. This study aims to examine whether the gain/loss-framing of information, provision of subsidized pre-vaccination physician consultation, and cash incentives can improve COVID-19 acceptance amongst adults., Methods: A survey experiment was conducted within a broader cross-sectional survey of people aged 18-64 years in Hong Kong, China. The participants were randomly assigned to one of the eight groups derived from full-factorial design of the three strategies with stratification by age and sex. The vaccine acceptance rate was compared between people with and without any of the strategies. The heterogeneous effects of these strategies were identified for those with different perceptions of the pandemics and vaccine in multiple logistic regressions., Results: The survey experiment collected 1,000 valid responses. It found that loss-framed information and provision of subsidized physician consultation to assess suitability to be vaccinated, can improve vaccine acceptance, while cash incentives did not make a difference. The improvement effect of loss-framing information and physician consultation is stronger among those with higher perceived infection risk and severity of condition, as well as unvaccinated people with lower confidence in vaccine safety., Conclusions: The findings indicated that individualized loss-framing messages and equitable provision of subsidized pre-vaccination physician consultations can be incorporated in efforts to promote vaccine acceptance and vaccination roll-out speed. However, it remains inconclusive whether and how universal cash incentives may be deployed to support vaccination promotion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Wong, Cheung, Dong and Yeoh.)

Introduction: Health literacy (HL) refers to an individual's ability to process and use health information to make health-related decisions. However, previous HL scales did not fully cover all aspects of this concept. This study aimed to develop a comprehensive Hong Kong HL scale (HLS-HK) and evaluate its psychometric properties among Chinese adults., Methods: A scale of 31-item covering Nutbeam's framework, namely functional and interactive HL (FHL and IHL), and critical HL (CHL) within three subdomains: critical appraisal of information, understanding of social determinants of health, and actions to address social determinants of health, was developed based on previous literature review and Delphi survey. Cognitive interviews were performed to examine all items' face validity in terms of three aspects: comprehensiveness, clarity, and acceptability. A cross-sectional survey was conducted to investigate the scale's psychometric properties, including its internal consistency reliability, factorial structure validity, convergent validity, and predictive validity., Results: Nine interviewees participated in the cognitive interviews in October 2021. Based on the input from respondents, two items were deleted, two items were combined, and several items' wording was revised. The other items were clear and readable. Finally, 28 items remained. A total of 433 adults completed the questionnaire survey between December 2021 and February 2022. After excluding one item with low inter-item correlations, the scale's internal consistency reliability was acceptable, with a Cronbach's alpha of 0.89. Exploratory factor analysis produced a five-factor model, as shown in the original theoretical framework. These factors accounted for 53% of the total variance. Confirmatory factor analysis confirmed that the fit indices for this model were acceptable (comparative fit index = 0.91, root mean square error of approximation = 0.06, and root mean square residual = 0.06). The scale is also significantly correlated with theoretically selected variables, including education and self-rated health., Conclusion: The HLS-HK is a valid and reliable tool for evaluating HL. Compared with existing tools, this scale extended the operationalization of FHL, IHL, and CHL and fully operationalized the CHL via three subdomains. It can be used to understand the difficulties and barriers that people may encounter when they use health-related information and services., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tian, Mo, Dong, Cheung and Wong.)

Background: Real-world data is currently limited on the association between oral antiviral therapy and healthcare system burden in patients with mild-to-moderate COVID-19. This study aims to evaluate the clinical and cost effectiveness of Molnupiravir and Nirmatrelvir-ritonavir use in reducing mortality in this population., Methods: This is a retrospective cohort study involving 54,355 COVID-19 patients during February 22-March 31,2022 in Hong Kong. Inverse probability of treatment weighting (IPTW) was used to adjust patient characteristics. Our exposure of interest was Molnupiravir/Nirmatrelvir-Ritonavir prescription, with all-cause mortality as the primary outcome. IPTW-adjusted multivariate regressions were used to estimate treatment impact on clinic re-attendance and unplanned admissions. Finally, attributed cost and incremental cost-effectiveness ratios (ICER) were estimated., Findings: In the outpatient cohort ( N = 33,217, 61.1%), 16.1% used Molnupiravir and 13.4% used Nirmatrelvir-Ritonavir, while in the inpatient cohort ( N = 21,138, 38.9%), 3.8% used Molnupiravir and 1.3% used Nirmatrelvir-Ritonavir. IPTW-adjusted Cox model estimated that Molnupiravir (hazard ratio (HR)(95%CI)=0.31 (0.24-0.40), P< 0.0001) and Nirmatrelvir-Ritonavir (HR=0.10 (95%CI 0.05-0.21), P< 0.0001) were significantly associated with a reduced mortality hazard. In the outpatient cohort, both antiviral prescriptions were associated with reduced odds for unplanned hospital admissions (Molnupiravir: odds ratio (OR) =0.72 (0.52-0.98), P=0.039; Nirmatrelvir-Ritonavir: OR=0.37 (0.23-0.60), P< 0.0001). Among hospitalised patients, both antiviral prescriptions were associated with significant reductions in the odds ratios for 28-days readmission (Molnupiravir: OR=0.71 (0.52-0.97), P= 0.031; Nirmatrelvir-Ritonavir: OR=0.47 (0.24-0.93), P= 0.030). ICERs for death averted for Molnupiravir stood at USD493,345.09 in outpatient settings and USD2,629.08 in inpatient settings. In outpatient settings, Nirmatrelvir-ritonavir cost USD331,105.27 to avert one death, but saved USD5,502.53 to avert one death in comparison with standard care., Interpretation: In high-risk patients in Hong Kong with mild-to-moderate COVID-19, Molnupiravir and Nirmatrelvir-Ritonavir prescriptions were associated with reduced all-cause mortality and significant cost savings., Funding: Centre for Health Systems & Policy Research is funded by The Tung's Foundation; and The Laboratory of Data Discovery for Health Limited(D24H) is funded the AIR@InnoHK platform administered by the Innovation and Technology Commission of Hong Kong. Funders did not have any role in study design, data collection, data analysis, interpretation and writing of this manuscript., Competing Interests: No conflict of interest existed for AKCW, SCLC, TTLL, OWKT, KWYC, SL, CKT, TY, THR. CYC, AWLC, KW, ELYW of Centre for Health Systems & Policy Research are supported by funding from The Tung's Foundation. LYFL, ETFY, JWKH of The Laboratory of Data Discovery for Health Limited (D24H) are supported by funding from the AIR@InnoHK platform administered by the Innovation and Technology Commission of Hong Kong., (© 2022 The Authors.)

Background: Western studies have found that nurses are likely to experience both positive and negative emotions in their job, as a helping profession [professional quality of life (ProQoL)] during the coronavirus disease 2019 (COVID-19) pandemic, and that psychosocial and work-related variables (e.g. pandemic-related stressors, interpersonal and organizational support, coping strategies) are associated with such outcomes. However, relevant studies on nurses in the Asian context are limited., Objective: This study examined the psychosocial correlates of three indicators of ProQoL, i.e. compassion satisfaction, secondary traumatic stress (STS), and burnout, among nurses during the fifth wave of the COVID-19 pandemic in Hong Kong., Method: Nurses in Hong Kong ( N  = 220) working in hospitals and community settings during the COVID-19 pandemic were recruited between 24 May and 27 June 2022 through nursing associations to complete an online survey measuring the aforementioned psychosocial variables., Results: Hierarchical regression results found that stressors from clinical work environments, insufficient emotional support, and less positive reframing were associated with poorer ProQoL (i.e. lower compassion satisfaction; higher STS and burnout) ( β from 0.16, p  > .05, to 0.44, p  > .001). In addition, COVID-19-related worries/uncertainties and emotional processing were associated with higher STS ( β from 0.21 to 0.23, p  < .01), whereas insufficient organizational support for communication with the healthcare system was associated with higher burnout ( β  = 0.12, p  < .05)., Conclusions: Our findings identified the important psychosocial determinants in ProQoL among nurses in Hong Kong and provide recommendations for services supporting the mental health of these nurses. Providing workshops for nurses to train their skills in coping with COVID-19-related uncertainties, worries, and stressors from the clinical work environment, in using adaptive coping strategies (e.g. positive reframing), and in soliciting emotional support from important others could facilitate their ProQoL. Moreover, the provision of organizational support through timely and transparent communication with the healthcare system could reduce STS in nurses.

Objectives: To examine the level of resilience among the frontline healthcare workers (HCWs) in four different Southeast Asian jurisdictions and identify the potential factors that may enhance healthcare workers resilience. Methods: An online cross-sectional survey was carried out among 3,048 eligible healthcare workers in Hong Kong, Nepal, Vietnam, and Taiwan from May 2021 to July 2022, and information on individual resilience, socio-demographic characteristics, organizational supports, and personal exposures were collected. A binary logistic regression model was used to identify the factors that were associated with a high resilience level. Results: The resilience score was the highest among healthcare workers of Vietnam, followed by Taiwan and Hong Kong, with Nepal scoring the lowest. Participants with old age, part-time work, higher education level, more satisfaction with workplace policy, better organizational supports, and fewer COVID-specific worries were associated with higher resilience. Healthcare workers who were satisfied with the overall organizational policy support had an OR of 1.48 (95% CI: 1.25-1.76) for a high resilience level. Conclusion: Implementing satisfying organizational policies and establishing supportive work environments for frontline healthcare workers can increase individual resilience and organizational stability., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2022 Wong, Qiu, Chien, Wong, Chalise, Hoang, Nguyen, Wang, Lee, Chen, Chan, Wong, Cheung and Yeoh.)

Introduction: Psychosis is a prominent neuropsychiatric symptom of Parkinson's disease (PD) and is associated with negative outcomes, such as poorer quality of life and greater rate of functional impairment. Early identification of patients with PD at risk of developing psychosis facilitates appropriate management to improve outcomes. However, this phenomenon has not been examined locally. This study aimed to examine the prevalence of PD-associated psychosis in the local setting, identify any associated risk factors, as well as characterise the cognitive trajectory of patients with PD with psychosis., Methods: A retrospective cohort of 336 patients with PD, who presented to the National Neuroscience Institute, Singapore, in 2006 and 2007 and attended follow-up visits through to 2013 was analysed. The data analysed included scores from clinician assessments of cognitive function, disease severity and presence of psychotic symptoms, conducted when clinically appropriate during patients' medical visits. Survival analysis and logistic and linear regression analysis were performed., Results: Psychosis was diagnosed in 63 patients with PD, indicating a prevalence of 18.8% for PD-associated psychosis. Incidence of psychosis in PD was calculated to be 40 per 1,000 person-years. No significant association was found between demographic variables and the odds of developing psychosis in PD. Regression analyses found that the presence of psychosis significantly predicted greater cognitive decline and disease severity., Conclusion: Psychosis has a significant presence among the PD population in Singapore, possibly serving as an indicator of more rapid cognitive decline and progression of PD severity., Competing Interests: None