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New antidiabetic agents (sodium-glucose cotransporter-2 inhibitor [SGLT2i] and glucagon-like peptide-1 receptor agonist [GLP-1RA]) and metabolic surgery have protective effects on metabolic syndromes.To compare the changes of metabolic parameters and costs among patients with obesity and type 2 diabetes undergoing metabolic surgery and initiating new antidiabetic agents over 12 months.Hong Kong Hospital Authority database from 2006-2017.This is a population-wide retrospective cohort study consisting of 2616 patients (1810 SGLT2i, 528 GLP-1RA, 278 metabolic surgery). Inverse probability treatment weighting of propensity score was applied to balance baseline covariates of patients with obesity and type 2 diabetes who underwent metabolic surgery, or initiated SGLT2i or GLP-1RA. Metabolic parameters and direct medical costs were measured and compared from baseline to 12 months in metabolic surgery, SGLT2i, and GLP-1RA groups.Patients in all 3 groups had improved metabolic parameters over a 12-month period. Patients with metabolic surgery achieved significantly better outcomes in BMI (-5.39, -.56, -.40 kg/mBeneficial weight loss and metabolic outcomes at 12 months were observed in all 3 groups, among which the metabolic surgery group showed the most remarkable effects but incurred the greatest medical costs. However, studies with a longer follow-up period are warranted to show long-term outcomes.

STUDY OBJECTIVES: The main cause of death in patients with obesity hypoventilation syndrome (OHS) is cardiac rather than respiratory failure. Here, we investigated autonomic-respiratory coupling and serum cardiac biomarkers in patients with OHS and obstructive sleep apnea (OSA) with comparable body mass index and apnea-hypopnea index. METHODS: Cardiopulmonary coupling (CPC) and cyclic variation of heart rate analysis was performed on the electrocardiogram signal from the overnight polysomnogram. Cardiac serum biomarkers were obtained in patients with OHS and OSA with a body mass index > 40 kg/m(2). Samples were obtained at baseline and after 3 months of positive airway pressure (PAP) therapy in both groups. RESULTS: Patients with OHS (n = 15) and OSA (n = 36) were recruited. No group differences in CPC, cyclic variation of heart rate, and serum biomarkers were observed at baseline and after 3 months of PAP therapy. An improvement in several CPC metrics, including the sleep apnea index, unstable sleep (low-frequency coupling and elevated low-frequency coupling narrow band), and cyclic variation of heart rate were observed in both groups with PAP use. However, distinct differences in response characteristics were noted. Elevated low-frequency coupling narrow band coupling correlated with highly sensitive troponin-T (P

Background and AimsInflammation drives progression of chronic liver disease. However, the triggers of inflammation remain undefined during chronic hepatitis B (CHB) because hepatic flares are spontaneous and difficult to capture. We used nucleoside analogue (NA) withdrawal to investigate early inflammatory events because liver damage after stopping therapy occurs in a predictable time frame. 11 CHB patients underwent 192 weeks of NA therapy before a protocol defined stop. Liver fine-needle aspirates (FNAs) were collected at baseline and 4-weeks post-withdrawal and analyzed using flow cytometry and single-cell RNA sequencing (scRNA-seq). Intrahepatic mononuclear cells (IHMCs) from uninfected livers were used to validate transcriptomic findings. At 4 weeks post NA-withdrawal, HBV DNA rebounded but alanine aminotransferase (ALT) levels remained normal, 7/11 patients developed ALT elevations (>2xULN) at later timepoints. There were no changes in cell frequencies between baseline and viral rebound. ScRNA-seq revealed upregulation of IFN stimulated genes (ISGs) and pro-inflammatory cytokineMIFupon viral rebound. In vitro experiments confirmed the type I IFN-dependent ISG profile whereasMIFwas induced primarily by IL-12. MIF exposure further amplified inflammatory cytokine production by myeloid cells. Our data show that innate immune activation is detectable in the liver before clinically-significant liver damage is detectable in the serum.

BACKGROUND The prevention of sexually transmitted infections (STIs) in China particularly among young adults, and Chlamydia trachomatis (CT) infections are the most common STIs in young women. One of the most effective ways to prevent STIs is the consistent use of condoms during sexual intercourse. There has been no economic evaluation for an interactive web-based sexual health program, Smart Girlfriend, in China. OBJECTIVE To evaluate the cost-effectiveness of the Smart Girlfriend (a web-based sexual health program) to prevent sexually transmitted infections (STIs) compared with the control (a one-page information sheet about condom use) in China. METHODS A decision-analytical model that included a decision tree followed by a Markov structure of Chlamydia trachomatis (CT) infections was developed since CT was the most prevalent of STIs in young women. The model represents the lifetime experience following receiving the intervention and the control. The one-way and probabilistic sensitivity analyses were conducted. The main outcomes were the number of CT infections, and the incremental cost per quality-adjusted life-year (QALY). RESULTS In the base-case analysis, the introduction of the Smart Girlfriend would avert 0.45% of CT infections, 0.3% of Pelvic Inflammatory Disease, and 0.04% Chronic Pelvic Pain, resulting in a gain of 70 discounted QALYs and cost savings of 4342 USD over a 4-year time horizon, compared with the control for a cohort of 10,000 sexually active nonpregnant young women. With more than 4,548 users, the intervention would be cost-effective, and with more than 8,315 users, the intervention would be cost-saving. A 99% probability of being cost-effective was detected with a willingness to pay 17,409 USD per QALY. CONCLUSIONS The Smart Girlfriend is cost-effective and possibly cost-saving. This result was particularly sensitive to the number of websites users and launching the website would be cost-effective if more than 4,548 people used it. Further work is warranted to explore if the findings could be expanded in women who have sex with women and other STIs.

BackgroundEvidence evaluating real-world effectiveness of oral antivirals against Omicron variants is lacking.MethodsAn unselected, territory-wide cohort of all initially non-hospitalized patients with an officially registered diagnosis of SARS-CoV-2 infection between 26th February and 3rd May 2022 during the Omicron BA.2.2 wave in Hong Kong, was identified. We undertook a retrospective cohort design as primary analysis, and case-control design as sensitivity analysis. Outpatient oral antiviral users were matched with controls using 1:10 propensity-score matching. Study outcomes were mortality, COVID-19-related hospitalization, composite outcome of in-hospital disease progression (in-hospital mortality, invasive mechanical ventilation, or intensive care unit admission) and its individual outcomes. Hazard ratios (HR) were estimated by Cox regression, and odds ratios in oral antiviral users compared with non-users by logistic regression. Subgroup analyses evaluated the associations by vaccination status and age.FindingsAmong 1,072,004 non-hospitalized COVID-19 patients, 5,257 and 5,663 were initiated molnupiravir and nirmatrelvir/ritonavir in the community setting with a median follow-up of 42 and 38 days, respectively. Molnupiravir use was associated with lower risks of mortality (HR=0·61, 95%CI=0·46-0·82, pInterpretationAmid the Omicron BA.2.2 wave, early initiation of oral antivirals among non-institutionalised COVID-19 patients was associated with reduced risks of mortality and in-hospital outcomes. Nirmatrelvir/ritonavir use was associated with greater and more consistent protection than molnupiravir.FundingHealth and Medical Research Fund, Food and Health BureauResearch in contextEvidence before this studyOral antivirals have been initiating in non-hospitalized COVID-19 patients to lower their risks of hospitalization and death, and hence to reduce the burden on healthcare systems. We searched Scopus and PubMed for studies until 25 May 2022 using the search terms “SARS-CoV-2 OR COVID-19” AND “molnupiravir OR Lagevrio OR EIDD-2801” OR “nirmatrelvir OR Paxlovid OR PF-07321332”. Major studies examining the outpatient use of molnupiravir and nirmatrelvir/ritonavir are MOVe-OUT and EPIC-HR trials, respectively. Both have been conducted among unvaccinated, non-hospitalized patients with mild-to-moderate COVID-19 who are at risk of progression to severe disease, during a pandemic wave of SARS-CoV-2 Delta variant. Early initiation of molnupiravir or nirmatrelvir/ritonavir within five days of symptom onset has been associated with relative risk reduction of hospitalization or death by 30% and 88%, respectively. Considering the real-world evaluation of the two oral antivirals against the currently circulating Omicron variant, only one single-center, retrospective review of solid organ transplant recipients with COVID-19 has been conducted; yet their results are unlikely generalizable to other populations given its specific patient group and small sample size. Real-world effectiveness of oral antivirals is urgently needed to inform their clinical use in COVID-19 patients, considering their vaccination status and the variant of concern.Added value of this studyTo the best of our knowledge, this is one of the first real-world studies exploring the clinical use of oral antivirals during a pandemic wave dominated by SARS-CoV-2 Omicron variant. A territory-wide, retrospective cohort study was conducted to examine the effectiveness of molnupiravir and nirmatrelvir/ritonavir in community-dwelling COVID-19 patients. Early initiation of molnupiravir or nirmatrelvir/ritonavir within five days of symptom onset was associated with significant reduction of all-cause mortality risk by 39% and 75%, respectively, compared to not using any oral antivirals. Nirmatrelvir/ritonavir use was also associated with a reduced risk of COVID-19-related hospitalization by 31%, which was consistently observed across age and vaccination status. In terms of disease progression, both oral antivirals were effective in lowering the risk of in-hospital death, which was again more substantial with nirmatrelvir/ritonavir than molnupiravir. Intriguingly, the need for invasive ventilation might be reduced among molnupiravir users compared to matched controls.Implications of all the available evidenceBased on relative efficacy, our findings give support to current guidelines prioritizing nirmatrelvir/ritonavir use over molnupiravir in community-dwelling COVID-19 patients who are at high risk of hospitalization or progression to severe disease, should the former be accessible and clinically appropriate. Amid a pandemic wave of the Omicron variant, real-world effectiveness of oral antivirals in reducing the mortality risk of community-dwelling COVID-19 patients has been demonstrated in this study consisting mostly of the elderly and those who had not been fully vaccinated, extending beyond the evidence demonstrated in clinical trials among those of the Delta variant and who were at risk of severe COVID-19 from being overweight/obese. Several clinical trials (namely RECOVERY and PANORAMIC) and observational studies of the two oral antivirals are ongoing, and further research is needed to confirm our results in other patient populations and healthcare settings.

SummaryBackgroundEffectiveness of oral antivirals in mild-to-moderate COVID-19 patients is urgently needed. This retrospective cohort study aims to evaluate the clinical and virologic outcomes associated with molnupiravir and nirmatrelvir/ritonavir use in COVID-19 patients during a pandemic wave dominated by the Omicron BA.2 subvariant.MethodsWe analyzed data from a territory-wide retrospective cohort of hospitalized patients with confirmed diagnosis of SARS-CoV-2 infection from 26th February 2022 to 26th April 2022 in Hong Kong. Oral antiviral users were matched with controls using propensity-score matching in a ratio of 1:1. Study outcomes were all-cause mortality, a composite outcome of disease progression (all-cause mortality, initiation of invasive mechanical ventilation [IMV], intensive care unit admission, or the need for oxygen therapy) and their individual outcomes, and time to achieving lower viral burden of cycle threshold (Ct) value ≥30 cycles. Hazard ratios (HR) of event outcomes were estimated using Cox regression models.ResultsAmong 40,776 hospitalized patients with SARS-CoV-2 infection over a mean follow-up of 41.3 days with 925,713 person-days, this study included 1,856 molnupiravir users, 890 nirmatrelvir/ritonavir users and 2,746 control patients not initially requiring oxygen therapy at baseline after propensity-score matching. Oral antiviral use was associated with significantly lower risks of all-cause mortality (molnupiravir: HR=0.48, 95%CI=0.40-0.59, pConclusionsAgainst Omicron BA.2, initiation of novel oral antiviral treatment in hospitalized patients not requiring any oxygen therapy was associated with lower risks of all-cause mortality and disease progression, in addition to achieving low viral burden faster. Our findings support the early use of oral antivirals in COVID-19 patients who do not require supplemental oxygen on admission.FundingHealth and Medical Research Fund, Food and Health Bureau, Government of the Hong Kong SARResearch in contextEvidence before this studyThe medical and research community are actively exploring the use of oral antivirals in COVID-19 patients to lower their risks of hospitalization and death, and to reduce the burden on healthcare systems. We searched Scopus and PubMed for studies until 13th May 2022 using the search terms “SARS-CoV-2 OR COVID-19” AND “molnupiravir OR Lagevrio OR EIDD-2801” OR “nirmatrelvir OR Paxlovid OR PF-07321332”. Major studies examining the safety and efficacy of molnupiravir include MOVe-IN and MOVe-OUT trials conducted in hospitalized and non-hospitalized COVID-19 patients, respectively. Clinical evidence for the use of ritonavir-boosted nirmatrelvir came from the EPIC-HR trial conducted among non-hospitalized adults with COVID-19. While no clinical benefits have been observed with molnupiravir use in the inpatient setting among patients with moderate-to-severe COVID-19, early initiation of molnupiravir or nirmatrelvir/ritonavir within 5 days of symptom onset in non-hospitalized patients with mild-to-moderate COVID-19 and risk factors for progression to severe disease has been associated with relative risk reduction of hospitalization or death by 30% and 88%, respectively. Notably, these clinical trials were conducted prior to the prevalence of Omicron variant, and the efficacy of oral antivirals against this current variant of concern can only be inferred from experimental evidence to date. Real-world evidence of oral antiviral use in patients with SARS-CoV-2 infection of Omicron variant is lacking.Added value of this studyTo the best of our knowledge, this is the first real-world study exploring the inpatient use of oral antivirals during a pandemic wave dominated by SARS-CoV-2 Omicron variant. We conducted a territory-wide, retrospective cohort study to examine the effectiveness of molnupiravir and nirmatrelvir/ritonavir in COVID-19 patients who did not require supplemental oxygen on admission in Hong Kong. Early initiation of oral antivirals within 2 days of admission was associated with significantly lower risks of all-cause mortality and disease progression, in addition to achieving low viral burden faster than their respective matched controls. Oral antiviral use was also associated with a reduced need for oxygen therapy than non-use.Implications of all the available evidenceCurrent guidelines are now prioritizing the distribution of oral antivirals to those who do not require supplemental oxygen, but who are at the highest risk of disease progression. Our study cohort reflected such prescription pattern in real-world clinical practice, consisting of mostly the elderly with multiple pre-existing comorbidities and who had not been fully vaccinated. The antiviral effect and mortality benefit observed in this patient cohort support the use of oral antivirals in COVID-19 patients who do not require supplemental oxygen on admission during a pandemic wave of Omicron variant. Ongoing research will inform the safety and effectiveness of oral antivirals in specific patient populations (by vaccination status and viral variants), drug combinations, and different healthcare settings.

Objective School-performance difficulties (SPD) are common in children with epilepsy. The objectives of this study were to determine if the rate of SPD in children with seizures change from seizure-onset to follow-up and differ from children with psychiatric disorders. Methods School-aged children who required an initial electroencephalography (EEG) test in 2016 were reviewed and separated into two groups based on the presence or absence of seizures. Developmental delay and SPD were compared between groups at initial assessment and SPD was assessed after 2–4 years of follow-up. Analysis was also performed on a sub-set of patients with psychiatric disorders. Results At baseline, the rate of SPD was similar between the seizure (n = 146) and non-seizure (n = 332) groups [26% vs. 27%]. At follow-up, the seizure (n = 119) group had a significantly higher rate of SPD than the non-seizure (n = 215) group (54% vs. 43%). There was no difference in the rate of SPD between the seizure (n = 119) and psychiatric (n = 69) groups at baseline (31% vs. 43%) or follow-up (54% vs. 55%). Conclusion Over time, children with recurrent seizures experience more SPD than children without seizures, but similar SPD to children with psychiatric disorders.

To conduct a systematic review and meta-analysis to summarize evidence regarding differential changes in physical activity (PA) involvements and exercise habits in people with and without chronic diseases during the COVID-19 outbreak.MEDLINE, Embase, SPORTDiscus, Cumulative Index to Nursing and Allied Health, PsycINFO, Cochrane Library, and Physiotherapy Evidence Database were searched from November 2019 to May 2021.Two reviewers independently screened cross-sectional and longitudinal studies that investigated changes in PA-related outcomes in people with and without chronic diseases during the pandemic.PA-related outcomes and sedentary time were extracted from the included studies. Relevant risk of bias were assessed. Meta-analyses were conducted for each PA-related outcome, if applicable. Quality of evidence of each PA-related outcome was evaluated by Grading of Recommendations Assessment, Development, and Evaluation.Of 1226 identified citations, 36 articles (28 with and 8 without chronic diseases) with 800,256 participants were included. Moderate evidence from wearable sensors supported a significant reduction in pooled estimates of step count (standardized mean differences [SMD]=-2.79, P.01). Very limited to limited evidence substantiated significant decreases in self-reported PA-related outcomes and significant increases in sedentary behaviors among people with and without chronic diseases. Specifically, pooled estimates of metabolic equivalent-minute per week (SMD=-0.16, P=.02) and PA duration (SMD=-0.07, P.01) were significantly decreased, while sedentary time (SMD=0.09, P=.04) showed significant increases in the general population (small to large effects). Very limited evidence suggested no significant PA changes among people in a country without lockdown.During the pandemic, objective and self-reported assessments showed significant reductions in PA in people with and without chronic diseases globally. This mainly occurred in countries with lockdowns. Although many countries have adopted the "live with the coronavirus" policy, authorities should implement population-based strategies to revert the potential lockdown-related long-term deleterious effects on people's health.

COVID-19 vaccines are important for patients with heart failure (HF) to prevent severe outcomes but the safety concerns could lead to vaccine hesitancy. This study aimed to investigate the safety of two COVID-19 vaccines, BNT162b2 and CoronaVac, in patients with HF.We conducted a self-controlled case series analysis using the data from the Hong Kong Hospital Authority and the Department of Health. The primary outcome was hospitalization for HF and the secondary outcomes were major adverse cardiovascular events (MACE) and all hospitalization. We identified patients with a history of HF before February 23, 2021 and developed the outcome event between February 23, 2021 and March 31, 2022 in Hong Kong. Incidence rate ratios (IRR) were estimated using conditional Poisson regression to evaluate the risks following the first three doses of BNT162b2 or CoronaVac.We identified 32,490 patients with HF, of which 3035 were vaccinated and had a hospitalization for HF during the observation period (BNT162b2 = 755; CoronaVac = 2280). There were no increased risks during the 0-13 days (IRR 0.64 [95% confidence interval 0.33-1.26]; 0.94 [0.50-1.78]; 0.82 [0.17-3.98]) and 14-27 days (0.73 [0.35-1.52]; 0.95 [0.49-1.84]; 0.60 [0.06-5.76]) after the first, second and third doses of BNT162b2. No increased risks were observed for CoronaVac during the 0-13 days (IRR 0.60 [0.41-0.88]; 0.71 [0.45-1.12]; 1.64 [0.40-6.77]) and 14-27 days (0.91 [0.63-1.32]; 0.79 [0.46-1.35]; 1.71 [0.44-6.62]) after the first, second and third doses. We also found no increased risk of MACE or all hospitalization after vaccination.Our results showed no increased risk of hospitalization for HF, MACE or all hospitalization after receiving BNT162b2 or CoronaVac vaccines in patients with HF.The project was funded by a Research Grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (Ref. No. COVID19F01). F.T.T.L. (Francisco T.T. Lai) and I.C.K.W. (Ian C.K. Wong)'s posts were partly funded by the D24H; hence this work was partly supported by AIR@InnoHK administered by Innovation and Technology Commission.

Upfront next-generation sequencing (NGS) in patients with metastatic NSCLC has been associated with cost savings and shorter time-to-test results in the United States. Nevertheless, this may not apply in jurisdictions where the prevalence of patients with actionable mutations, cost of health care, and reimbursement models differ.A decision analytical model was built to compare sequential, panel, exclusionary, and upfront NGS testing in patients with metastatic NSCLC in Hong Kong. In sequential and panel testing, patients were tested for genomic alterations (GAs) with treatment followed by sequential or NGS. In exclusionary testing,Exclusionary testing required the shortest time-to-results (1.6 wk) and was most cost saving. In the scenario where all patients used exclusionary testing, a cost saving of $4.6 million was expected relative to current practice, with 90.7% of actionable and 46.5% of nonactionable GAs detected; when all patients used NGS, it would be $2.9 million more expensive with a 100% GA detection rate. Results were sensitive to testing costs and the proportion of patients that continued testing.Exclusionary testing is the best option in terms of cost and time-to-results in Hong Kong. This finding may be applicable for other Asian countries; however, exclusionary testing does not capture all possible GAs. As more GAs become actionable and the cost of NGS declines, NGS may become a cost-saving option.

Over the last 10 years, with the development of culture-free bacterial identification techniques, understanding of how the microbiome influences diseases has increased exponentially and has highlighted potential opportunities for its use as a diagnostic biomarker and interventional target in many diseases including malignancy. Initial research focused on the faecal microbiome since it contains the densest bacterial populations and many other mucosal sites, such as the lungs, were until recently thought to be sterile. However, in recent years, it has become clear that the lower airways are home to a dynamic bacterial population sustained by the migration and elimination of microbes from the gastrointestinal and upper airway tracts. As in the gut, the lung microbiome plays an important role in regulating mucosal immunity and maintaining the balance between immune tolerance and inflammation. Studies to date have all shown that the lung microbiome undergoes significant changes in the setting of pulmonary disease. In lung cancer, animal models and small patient cohort studies have suggested that microbiome dysbiosis may not only impact tumour progression and response to therapy, particularly immunotherapy, but also plays a key role in cancer pathogenesis by influencing early carcinogenic pathways. These early results have led to concerted efforts to identify microbiome signatures that represent diagnostic biomarkers of early-stage disease and to consider modulation of the lung microbiome as a potential therapeutic strategy. Lung microbiome research is in its infancy and studies to date have been small, single centre with significant methodological variation. Large, multicentre longitudinal studies are needed to establish the clinical potential of this exciting field.

Statin intolerance, primarily myalgia, is not uncommon in patients treated for elevated low-density lipoprotein cholesterol. Nonstatin drugs, such as ezetimibe, can spare patients from statin exposure, while still reducing low-density lipoprotein cholesterol. Ezetimibe is generally very well tolerated, although gastrointestinal and musculoskeletal symptoms have been occasionally reported. We describe an extremely rare case of an ezetimibe-associated liver injury who required protracted treatment with prednisone and azathioprine. Ezetimibe-associated liver injury should be suspected with development of hepatic abnormalities concurrent with the timing of ezetimibe treatment and in the absence of other possible precipitating factors. Résumé: L’intolérance aux statines, se manifestant principalement par une myalgie, n’est pas rare chez les patients traités pour des taux élevés de cholestérol à lipoprotéines à basse densité (LDL). Des médicaments n’appartenant pas à la classe des statines, comme l’ézétimibe, permettent d’éviter l’exposition aux statines chez les patients, tout en réduisant le taux le cholestérol LDL. L’ézétimibe est généralement bien toléré, bien que des symptômes gastro-intestinaux et musculosquelettiques aient été signalés à l’occasion. Nous décrivons un cas extrêmement rare de lésion hépatique associée à l’ézétimibe ayant nécessité un traitement prolongé par la prednisone et l’azathioprine. Il faut soupçonner une lésion hépatique liée à l’ézétimibe lors de la survenue d’anomalies hépatiques pendant le traitement par l’ézétimibe en l’absence d’autres facteurs déclencheurs.

Background An intracardiac foreign body causing recurrent fungemia is a rare clinical situation. Clinicians should be that aware of rare sources of sepsis despite a thorough history and examination. Results The authors describe a 63 year-old man, with unremarkable past medical history, who presented with a fever for 2 weeks. Blood cultures persistently grew Candida albicans and Streptococcus constellatus. Echocardiogram assessment showed a suspected vegetation over the tricuspid valve. Surgical exploration with median sternotomy and cardiopulmonary bypass revealed a tooth-pick impacted within the right atrium surrounded by vegetation. The authors postulate accidental ingestion of the foreign body and translocation into the right atrium via the esophagus and thoracic cavity. Conclusion Surgical removal of symptomatic intracardiac foreign bodies is highly recommended.

Concerns regarding the autoimmune safety of COVID-19 vaccines may negatively impact vaccine uptake. We aimed to describe the incidence of autoimmune conditions following BNT162b2 and CoronaVac vaccination and compare these with age-standardized incidence rates in non-vaccinated individuals.This is a descriptive cohort study conducted in public healthcare service settings. Territory-wide longitudinal electronic medical records of Hong Kong Hospital Authority users (≥16 years) were linked with COVID-19 vaccination records between February 23, 2021 and June 30, 2021. We classified participants into first/second dose BNT162b2 groups, first/second dose CoronaVac groups and non-vaccinated individuals for incidence comparison. The study outcomes include hospitalized autoimmune diseases (16 types of immune-mediated diseases across six body systems) within 28 days after first and second dose of vaccination. Age-standardized incidence rate ratios (IRRs) with exact 95% confidence intervals (CIs) were estimated using Poisson distribution.This study included around 3.9 million Hong Kong residents, of which 1,122,793 received at least one dose of vaccine (BNT162b2: 579,998; CoronaVac: 542,795), and 721,588 completed two doses (BNT162b2: 388,881; CoronaVac: 332,707). Within 28 days following vaccination, cumulative incidences for all autoimmune conditions were below 9 per 100,000 persons, for both vaccines and both doses. None of the age-standardized incidence rates were significantly higher than the non-vaccinated individuals, except for an observed increased incidence of hypersomnia following the first dose of BNT162b2 (standardized IRR: 1.47; 95% CI: 1.10-1.94).Autoimmune conditions requiring hospital care are rare following mRNA and inactivated COVID-19 vaccination with similar incidence to non-vaccinated individuals. The association between first dose BNT162b2 vaccination and immune-related sleeping disorders requires further research. Population-based robust safety surveillance is essential to detect rare and unexpected vaccine safety events.

CASE A 34-year-old man spontaneously presented with bilateral thoracic outlet syndrome over 1 year. He was a gymnast active in rowing and weightlifting, with "slanted" shoulders, narrowed costoclavicular spaces, and well-developed scalene muscles. Imaging revealed fractures of multiple bilateral upper ribs in various degrees of nonunion. The patient's symptoms improved after activity modification and physiotherapy. CONCLUSIONS Atraumatic spontaneous rib fracture-nonunions are an uncommon cause of thoracic outlet syndrome; this diagnosis should be considered in physically active patients presenting with typical symptoms with atypical anatomy.

Although Virtual Reality (VR) was first mentioned in the 60s, the research interest into the technology and its application are still gaining much attention globally. VR technology had evolved and had found niche application in many fields including entertainment, tourism, healthcare, manufacturing, education and more. A notable characteristic of the VR technology is that it seeks to immerse the user into the intended environment and narrative, allowing high user interaction and involvement. These qualities are very beneficial for engineering education. In the past, cost, hardware capabilities and availability, connectivity and other issues had hindered VR wider adoption and application. However, it is changing with the advent of more devices, the involvement of more consumer electronic players and the growth of digitization. This paper seeks to report on the research on virtual reality in engineering education over the past 26 years. The study conducts a bibliometric analysis to reflect the trend of VR in engineering education settings, thus identifying the possible emerging trends. An extensive literature search was conducted using the Scopus database and was analyzed using Vosviewer and Excel. There is an increasing trend of VR research related to the engineering education settings with an evident increase in the scope, the coverage and the citations figures. There is tremendous growth in the number of publications and citations in the recent past four years of the study. The most active author in the field is Sampaio, and the top universities where the publications are affiliated with are Purdue University and Clemson University. The majority of the publications were also found to be affiliated with the "ASEE Annual Conference and Exposition Conference Proceedings". The United States had the honor of being the country with the majority of publications from this study. There is a continuous shift of research interest observed through the publications keywords, and this provides an indication of the dynamic progression of research direction among researcher in the field of study. The findings of this study provide a good overview of the trend in research related to VR in engineering education and can serve as a guide to academics seeking to research or adapt the usage of VR in engineering settings.

High volume, labour-intensive manufacturing operations pose several challenges for successful operations. It is an even bigger challenge to move away from manual dependency and shift towards automation of production processes. There seems to be no general agreement among researchers on what are the critical success factors (CSFs) on the implementation of advanced automation and robotics processes in the manufacturing environment. Success factors vary across the manufacturing industry and also organizational units. This paper attempts to elicit the opinion and perception of academic professionals with links to high volume labour-intensive manufacturing industry. A systematic literature search was conducted on the topic and semi-structured interviews were conducted with experts to gather their views on CSFs. Results from the literature search and interviews revealed that factors related to Organization Strategy, Culture, and Structure; Top management support; Past experience, staffing, and learning; Project management, planning, and control; Finance, and resource availability; Technology maturity and vendor support; to be critical for the success of the production process automation project initiatives. Findings from this study can be used as guidelines to ascertain CSFs for organizations and strategy planning. Manufacturing organizations can also use this study to evaluate their organizational readiness and enhance the level of automation further.

Case reports and small series of the surgical and radiological management of median arcuate ligament syndrome (MALS) have been described, however, long-term outcome data are lacking. The purpose of this study was to review our experience of the laparoscopic management of MALS, and describe the long-term outcomes after surgical intervention.Data were collected between 2005 and 2016 in a single U.K. institution. All patients with MALS who underwent laparoscopic decompression of the celiac artery were included. Surgical outcomes were recorded from a prospectively collected database. Long-term outcomes were determined by outpatient review and the Gastrointestinal Quality of Life Index (GIQLI).Six patients were included. Five were female with a median age of 30 years (22.3-48.3). All six presented with abdominal pain and a bruit. Length of symptoms on presentation was 41 months (19-69). Duplex ultrasonography indicated celiac trunk stenosis in each case, with an elevated peak velocity flow in the celiac trunk of 230 cm/s (210-287.5). All six underwent successful laparoscopic decompression of the celiac artery with no conversions to open. Operating time was 137.3 minutes (95.6-166.3) and intraoperative blood loss was 110 mL (65-225). Length of stay was one day (1-2.3), with no postoperative complications or mortality. Median follow-up was 109.5 months (78-113.5). At this point, all patients remained symptom free with an overall GIQLI score of 129/144 (123.8-134.5).MALS is a rare condition. Laparoscopic decompression of the median arcuate ligament is safe and offers long-term resolution of symptoms, and improvement in patient quality of life.

In this study, we estimate PM2.5-caused health costs in Hong Kong and examine spatio-temporal boundary effects on the estimated results. During the period between 2012 and 2016, mean annual...

Ten of thousands of aircraft are expected to retire in the next 20 years. Aircraft manufacturers are gearing up for a new wave of recycling challenges as these aircrafts contain significant higher amount of carbon fibre reinforced polymer composite, which cannot be recycled by the conventional processes designed for metallic alloys. Aircraft manufacturers have been working with the recycling industry to limit unsustainable dismantling that is harmful to the environment and the potential liability risk of re-entry of un-certified salvaged parts back to the aviation market. An organised recycling network and procedures have already been set up for the conventional metallic alloys and will soon be required to include the composite waste. This paper reports the existing aircraft recycling practice and reviews the key recycling technologies for thermoset composites. Energy consumptions of these technologies are sought from the literature and are reported in this paper. Progress in development of reuse options for the recycled fibre is also included with discussion of their advantages and drawbacks. The challenge of working with the fluffy fibre is considered and the benefit of fibre alignment is highlighted for encouraging a widespread use of the fibre.

The current global manufacturing landscape is fast changing with growing worldwide demand for better, more innovative, value added and satisfying products. Therefore, industrial and manufacturing system must rise to meet these challenges and fulfil the appetite of consumers worldwide for the products efficiently. Manufacturing industries value creation must be geared towards higher efficiency and productivity. Industry 4.0 sets about bringing manufacturing capabilities to the next level, the fourth stage of the industrial revolution. This paper reviews the literature available on the Industry 4.0 (Industrie 4.0) initiative and sets out to identify the highly cited papers examples. Later, a review of the impact of Industry 4.0 technologies on Lean Manufacturing effectiveness, in particular, the elimination of different wastes was also presented. It is clearly established from this review and assessment exercise that there are much potential for Industry 4.0 environment to further improve the effectiveness of Lean Manufacturing initiatives to drive efficiency and productivity better.

Carbon fibre composites have great potential for vehicle lightweighting but the high cost and environmental impact of their production tends to largely undermine the advantages in non-aerospace applications. Recycled fibre has the potential to significantly reduce both cost and environmental impact but has yet it has not been widely accepted by the composites industry due to reduced mechanical performance in components as well as the difficulties in handling and processing caused by the fluffy discontinuous form which is quite unlike any current material formats which suit existing processing methods. The developed alignment process allows discontinuous random recycled carbon fibre to be processed into tapes with a highly aligned orientation distribution. This allows composites with high fibre content to be manufactured at lower moulding pressures with the added benefit of keeping fibre length degradation to a minimum. To evaluate the effects of process factors on fibre orientation, a two-level full factorial experimental plan was designed. This represents the first time a systematic study of input parameters on final part performance has been published in the open literature. With further improvements to the process, it is shown that it is possible to manufacture a composite achieving high fibre volume content (46%) under 7 bar moulding pressure in an autoclave, exhibiting competitive mechanical properties with almost 100 GPa tensile modulus and over 800 MPa tensile strength.

Wind energy has been considered as one of the greenest renewable energy sources over the last two decades. However, attention is turning to reducing the possible environmental impacts from this sector. We argue that wind energy would not be effectively "green" if anthropogenic materials are not given attention in a responsible manner. Using the concept of the circular economy, this paper considers how anthropogenic materials in the form of carbon fibers can reenter the circular economy system at the highest possible quality. This paper first investigates the viability of a carbon-fiber-reinforced polymer extraction process using thermal pyrolysis to recalibrate the maximum carbon fiber value by examining the effect of (a) heating rate, (b) temperature, and (c) inert gas flow rate on char yield. With cleaner and higher quality recovered carbon fibers, this paper discusses the economic preconditions for the takeoff and growth of the industry and recommends the reuse of extracted carbon fibers to close the circular economy loop.

Thoracic surgery has evolved throughout the decades. The difficulty of accessing the intrathoracic organs through the bony rib-cage has been a challenge for thoracic surgeons. In the past, large incisions stretching across the chest, such as posterolateral thoracotomies with rib spreading was the standard approach to access the lungs. These methods cause large amounts of trauma to the patient, with high rates of mortality and morbidity. However, with the advances in technology and the improvements in surgical technique, thoracic surgery has progressed to minimise trauma to the patient while still maintaining oncological and surgical principles. State-of-the-art technology, combined with wide variety of old and new surgical techniques give the thoracic surgeon a formidable armamentarium. Although there has been a focus on reducing the number and size of surgical wounds, considerations other than surgical approach can reduce the trauma suffered by the patient. Preservation of pulmonary function via organ preservation and anaesthetic techniques to further minimise the systemic inflammation such as non-intubated anaesthesia have also been shown to improve patient outcomes. This article aims to review the recent advances in minimally invasive thoracic surgery.

The high cost and energy intensity of virgin carbon fibre manufacture provides an opportunity to recover substantial value from carbon fibre reinforced plastic wastes. In this study, we assess the life cycle environmental implications of recovering carbon fibre and producing composite materials as substitutes for conventional and proposed lightweight materials in automotive applications (e.g., steel, aluminium, virgin carbon fibre). Key parameters for the recycled carbon fibre materials, including fibre volume fraction and fibre alignment, are investigated to identify beneficial uses of recycled carbon fibre in the automotive sector. Recycled carbon fibre components can achieve the lowest life cycle environmental impacts of all materials considered, although the actual impact is highly dependent on the design criteria (λ value) of the specific component. Low production impacts associated with recycled carbon fibre components are observed relative to lightweight competitor materials (e.g., aluminium, virgin carbon fibre reinforced plastic). In addition, recycled carbon fibre components have low in-use energy use due to mass reductions and associated reduction in mass-induced fuel consumption. The results demonstrate environmental feasibility of the CFRP recycling materials, supporting the emerging commercialisation of CF recycling technologies and identifying significant potential market opportunities in the automotive sector.

Colonoscopy remains the gold standard for colorectal cancer screening. Many barriers to the procedure exist including the possibility of abdominal discomfort that may occur with insufflation. Carbon dioxide (CO2), which is rapidly absorbed in the blood stream, is an alternate method used to distend the lumen during colonoscopy. The goal of this study was to compare patient discomfort, abdominal girth, and recovery time in 2 groups of patients randomized to CO2 versus room air insufflation during colonoscopy. Using a Wong-Baker score, we found statistical difference in postprocedural discomfort levels (CO2 Group: 1.15 ± 2.0 vs. room air: 0.41 ± 0.31, p = .015) and a significantly greater increase in abdominal girth over CO2 immediately postprocedure (room air: 1.06 ± 1.29 inches vs. CO2: 0.56 ± 0.73 inches, p = .054) girth immediately postprocedure; however, recovery time was similar between the 2 study arms (CO2: 9.1 ± 16.2 minutes vs. room air: 10.2 ± 18.6 minutes, p = .713). Further studies are needed to determine whether CO2 is cost-effective and improves patient satisfaction with colonoscopy.

Introduction/Background This study was conducted in Tuen Mun Hospital (TMH) to evaluate the effects of rTMS and tDCS on upper limb functional recovery in acute stroke patients. Material and method Patients with acute stroke were randomly assigned to rTMS, tDCS or control group. For rTMS group, patient received 1 Hz rTMS at 90% of resting motor threshold to M1 of the unaffected hemisphere for 1200 pulses. For tDCS group, patient received 1 mA anodal stimulation to hand area of the affected hemisphere for 20 minutes. Five consecutive sessions of rTMS or tDCS together with intensive physiotherapy upper limb training were given. For control group, only intensive physiotherapy upper limb training were given. The upper extremity section of Fugl–Meyer Scale (UE-FM) was used as outcome measure. Results Twenty-nine patients (17 female and 12 male) were assigned to the rTMS ( n = 9), tDCS ( n = 11) and control ( n = 9) group. The mean age was 62.7 ± 12.0 years old and the mean time between stroke onset and the first UE-FM assessment was 9.14 ± 3.30 days. There was no statistically significant difference in mean age, baseline UE-FM mean score, mean time between stroke onset and the first UE-FM assessment among three groups [X 2 (2) = 4.81, P = 0.09] [X 2 (2) = 1.56, P = 0.457] [X 2 (2) = 0.04, P = 0.98]. No adverse effects of rTMS or tDCS were reported. For between-group comparison, the changes in mean score of UE-FM in rTMS (20.8 ± 6.59) and tDCS group (16.1 ± 4.97) were statistically significantly larger than that in control group (10.6 ± 4.13) (U = −2.97, P = 0.002) (U = −2.29, P = 0.02). However, there was no significant difference between rTMS and tDCS group (U = −1.49, P = 0.152). Conclusion Findings of the present study showed that both rTMS and tDCS could augment physiotherapy treatment in enhancing upper limb motor functional recovery in acute stroke patients. These positive findings warrant further investigation of the application of non-invasive brain stimulation techniques to neurorehabilitation.

A hydrodynamic alignment process has been developed for converting discontinuous random carbon fibers into tapes with a highly aligned orientation distribution to greatly improve the applicability of recovered fibers to composite parts. In hydrodynamic alignment processes short fibers are aligned by the velocity gradient along the flow direction in a convergent nozzle. Thereafter the jet of fiber suspension is deposited on a nylon mesh and the now redundant dispersion medium is drained away to leave an aligned fiber tape. The fundamental physical principles at work in the process have not been widely studied and are shown in the present work to greatly influence the properties of the resulting materials. In this work, the influence of suspension jet stability on the fiber orientation distribution was examined and the liquid jet break-up regime was determined. To explore the factors which can affect the suspension jet stability, different nozzle geometries, viscosities of dispersion media, fiber lengths and Reynolds numbers were applied in experimental work. The shear rate profiles inside different nozzles were simulated by Computational Fluid Dynamics methods and the results described in this paper.

Patients with clinical symptoms of esophageal dysfunction and dense eosinophilic infiltration of the esophageal mucosa are suspected to have eosinophilic esophagitis (EoE). Topical steroids are often used as first-line therapy for EoE, although some patients respond clinically to proton pump inhibitors (PPIs). The purpose of this study was to compare the histological and clinical response of patients with esophageal eosinophilia treated with aerosolized swallowed fluticasone propionate vs. esomeprazole.This prospective single-blinded randomized controlled trial enrolled newly diagnosed patients with suspected EoE, defined as having clinical symptoms related to esophageal dysfunction with at least 15 eosinophils/high power field (hpf). Patients underwent 24-h pH/impedance monitoring to establish gastroesophageal reflux disease (GERD). Patients were stratified by the presence of GERD and randomized to receive fluticasone 440 mcg twice daily or esomeprazole 40 mg once daily for 8 weeks followed by repeat endoscopy with biopsies. The primary outcome was histological response of esophageal eosinophilia, defined as7 eosinophils/hpf. Secondary outcomes included clinical change in symptoms using the validated Mayo dysphagia questionnaire (MDQ) and interval change in endoscopic findings following treatment.Forty-two patients (90% male, 81% white, mean age 38 ± 10 years) were randomized into fluticasone (n = 21) and esomeprazole (n = 21) treatment arms. In all, 19% (8/42) of patients had coexisting GERD and were equally stratified into each arm (n = 4). Overall, there was no significant difference in resolution of esophageal eosinophilia between fluticasone and esomeprazole (19 vs. 33%, P = 0.484). In patients with established GERD, resolution of esophageal eosinophilia was noted in 0% (0/4) of the fluticasone group compared with 100% (4/4) of the esomeprazole group (P = 0.029). In GERD-negative patients, there was no significant difference in resolution of esophageal eosinophilia between treatment arms with fluticasone and esomeprazole (24 vs.18%, P = 1.00). The MDQ score significantly decreased after treatment with esomeprazole (19 ± 21 vs. 1.4 ± 4.5, P0.001), but not with fluticasone (17 ± 18 vs. 12 ± 16, P = 0.162). Improvement in endoscopic findings and other histological markers were similar between treatment groups.Fluticasone and esomeprazole provide a similar histological response for esophageal eosinophilia. With regard to clinical response, esomeprazole was superior to fluticasone, particularly in patients with established GERD.

Polypropylene (PP) composites reinforced with recycled carbon fibre have been prepared through extrusion compounding and injection moulding. The reinforcing potential of the recycled fibre was increased by improving the interfacial adhesion between the fibre and PP matrix and this was done by the addition of maleic anhydride grafted polypropylene (MAPP) coupling agents. Three MAPP couplers with different molecular weights and maleic anhydride contents were considered. The effects on the mechanical properties of the composite were studied, and scanning electron microscopy (SEM) was used to study the fracture morphology of the tensile specimens. It was observed that with the addition of MAPP the interfacial adhesion was improved as fewer fibres were pulled-out and less debonding was seen. A microbond test was performed and a significant improvement in interfacial shear strength was measured. This resulted in composites with higher tensile and flexural strengths. The maximum strength was achieved from MAPP with the highest molecular weight. Increased modulus was also achieved with certain grades of MAPP. It was also found that the composite impact strength was improved significantly by MAPP, due to a higher compatibility between the fibre and matrix, which reduced crack initiation and propagation.

The mechanical response of a recycled CFRP is investigated experimentally. A complex multiscale microstructure is revealed, with both dispersed fibres (with fractured-sections) and fibre-bundles. The specific properties of the recyclate compare favourably with those of aluminium and glass–fibre composites. Micromechanical studies show that tensile failure follows the pre-existing fractured-sections on the dispersed-fibres, while compressive failure occurs by shear-banding. Fracture toughness measurements coupled with SEM evidence how bundles considerably toughen the composite by complex failure mechanisms. This analysis can guide the optimisation of recycling processes and support the development of design methods for recycled CFRP; it also provides insight on the mechanical response of other multiphase short-fibre reinforced materials.

This paper describes the development of an electromagnetic interference shielding material using recycled carbon fibre. Fibre recycled from a fluidised bed process was transformed into a non-woven veil and was moulded into a glass-fibre reinforced polymer plaque to provide shielding. Factors affecting shielding performance were established using a virgin fibre and the result was compared with veil made of the recycled fibre. Shielding performance increased with veil areal densities. The influence of fibre length on shielding seemed insignificant provided the fibre was distributed evenly. Sandwiching the plaque between fibre veils enhanced the shielding performance. A shielding value of 40 dB was attained from a layer of 80 g/m 2 recycled fibre veil and it was increased to 70 dB when the plaque was sandwiched between two layers of 30 g/m 2 recycled fibre veil. The correlation between veil formation and shielding effectiveness was established and found that shielding effectiveness increased with the degree of fibre dispersion.