Genetic association of COVID-19 severe versus non-severe cases by RNA sequencing in patients hospitalised in Hong Kong.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused extensive disruption of public health worldwide. There were reports of COVID-19 patients having multiple complications. This study investigated COVID-19 from a genetic perspective. METHODS: We conducted RNA sequencing (RNA-Seq) analysis of respiratory tract samples from 24 patients with COVID-19. Eight patients receiving mechanical ventilation or extracorporeal membrane oxygenation were regarded as severe cases; the remaining 16 patients were regarded as non-severe cases. After quality control, statistical analyses were performed by logistic regression and the Kolmogorov-Smirnov test to identify genes associated with disease severity. RESULTS: Six genes were associated with COVID-19 severity in both statistical tests, namely RPL15, BACE1-AS, CEPT1, EIF4G1, TMEM91, and TBCK. Among these genes, RPL15 and EIF4G1 played roles in the regulation of mRNA translation. Gene ontology analysis showed that the differentially expressed genes were mainly involved in nervous system diseases. CONCLUSION: RNA sequencing analysis showed that severe acute respiratory syndrome coronavirus 2 infection is associated with the overexpression of genes involved in nervous system disorders.

An interpretable knee replacement risk assessment system for osteoarthritis patients.

Objective: Knee osteoarthritis (OA) is a complex disease with heterogeneous representations. Although it is modifiable to prevention and early treatment, there still lacks a reliable and accurate prognostic tool. Hence, we aim to develop a quantitative and self-administrable knee replacement (KR) risk stratification system for knee osteoarthritis (KOA) patients with clinical features. Method: A total of 14 baseline features were extracted from 9592 cases in the Osteoarthritis Initiative (OAI) cohort. A survival model was constructed using the Random Survival Forests algorithm. The prediction performance was evaluated with the concordance index (C-index) and average receiver operating characteristic curve (AUC). A three-class KR risk stratification system was built to differentiate three distinct KR-free survival groups. Thereafter, Shapley Additive Explanations (SHAP) was introduced for model explanation. Results: KR incidence was accurately predicted by the model with a C-index of 0.770 (±0.0215) and an average AUC of 0.807 (±0.0181) with 14 clinical features. Three distinct survival groups were observed from the ten-point KR risk stratification system with a four-year KR rate of 0.79%, 5.78%, and 16.2% from the low, medium, and high-risk groups respectively. KR is mainly caused by pain medication use, age, surgery history, diabetes, and a high body mass index, as revealed by SHAP. Conclusion: A self-administrable and interpretable KR survival model was developed, underscoring a KR risk scoring system to stratify KOA patients. It will encourage regular self-assessments within the community and facilitate personalised healthcare for both primary and secondary prevention of KOA.

Awareness, perceptions, and acceptance of human papillomavirus vaccination among parents in Hong Kong.

INTRODUCTION: This study investigated the awareness, perceptions, and acceptance of human papillomavirus (HPV) vaccination for children among parents in Hong Kong. It also explored factors associated with, and differences in, vaccine acceptance and hesitancy between parents of girls and boys. METHODS: Parents of boys or girls in Primary 5 to 6 were invited to participate in an online survey through an established health and lifestyle e-platform. RESULTS: Overall, 851 parents completed the survey: 419 (49.2%) had daughters, 348 (40.9%) had sons, and 84 (9.9%) had children of both genders. Parents who enrolled their children into the Childhood Immunisation Programme were more likely to accept HPV vaccination (79.7% vs 33.7%, odds ratio [OR]=7.70; 95% confidence interval [CI]=5.39-11.01; P<0.001); parents of girls were more likely to accept than parents of boys (86.0% vs 71.8%, OR=2.40; 95% CI=1.67-3.46; P<0.001). Among parents of girls and boys, the main reasons for HPV vaccination acceptance were prevention of cancers (girls: 68.8% and boys: 68.7%), prevention of sexually transmitted diseases (girls: 67.3% and boys: 68.3%), and optimal timing before initiation of sexual activity (girls: 62.8% and boys: 59.8%). Vaccine hesitancy was mainly associated with concerns about serious side-effects (girls: 66.7% and boys: 68.0%) and the belief that their children were too young (girls: 60.0% and boys: 54.0%). CONCLUSION: Parents in Hong Kong are hesitant about HPV vaccination for their sons. This barrier could be removed by providing information to correct vaccine safety misconceptions and offering a gender-neutral vaccination programme through the school-based Childhood Immunisation Programme.

Pain Relief After Total Knee Arthroplasty with Intravenous and Periarticular Corticosteroid: A Randomized Controlled Trial.

BACKGROUND: Total knee arthroplasty (TKA) is a cost-effective procedure, but it is also associated with substantial postoperative pain. The present study aimed to compare pain relief and functional recovery after TKA among groups that received intravenous corticosteroids, periarticular corticosteroids, or a combination of both. METHODS: This randomized, double-blinded clinical trial in a local institution in Hong Kong recruited 178 patients who underwent primary unilateral TKA. Six of these patients were excluded because of changes in surgical technique; 4, because of their hepatitis B status; 2, because of a history of peptic ulcer; and 2, because they declined to participate in the study. Patients were randomized 1:1:1:1 to receive placebo (P), intravenous corticosteroids (IVS), periarticular corticosteroids (PAS), or a combination of intravenous and periarticular corticosteroids (IVSPAS). RESULTS: The pain scores at rest were significantly lower in the IVSPAS group than in the P group over the first 48 hours (p = 0.034) and 72 hours (p = 0.043) postoperatively. The pain scores during movement were also significantly lower in the IVS and IVSPAS groups than in the P group over the first 24, 48, and 72 hours (p ≤ 0.023 for all). The flexion range of the operatively treated knee was significantly better in the IVSPAS group than in the P group on postoperative day 3 (p = 0.027). Quadriceps power was also greater in the IVSPAS group than in the P group on postoperative days 2 (p = 0.005) and 3 (p = 0.007). Patients in the IVSPAS group were able to walk significantly further than patients in the P group in the first 3 postoperative days (p ≤ 0.003). Patients in the IVSPAS group also had a higher score on the Elderly Mobility Scale than those in the P group (p = 0.036). CONCLUSIONS: IVS and IVSPAS yielded similar pain relief, but IVSPAS yielded a larger number of rehabilitation parameters that were significantly better than those in the P group. This study provides new insights into pain management and postoperative rehabilitation following TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Effects of strict public health measures on seroprevalence of anti-SARS-CoV-2 antibodies during pregnancy.

INTRODUCTION: A substantial number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain asymptomatic throughout the course of infection. Nearly half of pregnant women with coronavirus disease 2019 (COVID-19) are asymptomatic upon diagnosis; these cases are not without risk of maternal morbidity. Here, we investigated the seroprevalence of anti-SARS-CoV-2 antibodies in an unselected sample of pregnant women in Hong Kong. METHODS: This prospective cohort study included pregnant women who presented for routine Down syndrome screening (DSS) between November 2019 and October 2020; all women subsequently delivered at the booking hospitals. Serum antibodies against SARS-CoV-2 were analysed using a qualitative serological assay in paired serum samples taken at DSS and delivery for all participants. RESULTS: In total, 1830 women were recruited. Six women (0.33%) were seropositive at the DSS visit; this seropositivity persisted until delivery. Of the six women, none reported relevant symptoms during pregnancy; one reported a travel history before DSS and one reported relevant contact history. The interval between sample collections was 177 days (range, 161-195). Among women with epidemiological risk factors, 1.79% with travel history, 50% with relevant contact history, and 0.77% with community SARS-CoV-2 testing history, were seropositive. CONCLUSION: The low seroprevalence in this study suggests that strict public health measures are effective for preventing SARS-CoV-2 transmission. However, these measures cannot be maintained indefinitely. Until a highly effective therapeutic drug targeting SARS-CoV-2 becomes available, vaccination remains the best method to control the COVID-19 pandemic.

Effects of enhanced recovery after surgery practices on postoperative recovery and length of stay after unilateral primary total hip or knee arthroplasty in a private hospital.

INTRODUCTION: Enhanced recovery after surgery (ERAS) practices improve postoperative recovery and reduce postoperative length of stay (LOS) in patients undergoing primary total hip arthroplasty (THA) or total knee arthroplasty (TKA). Our study investigated whether these promising results could be reproduced in a private hospital setting. METHODS: In total, 228 patients were included in the study cohort: the conventional group comprised 117 patients from 2012 to 2014, while the ERAS group comprised 111 patients from 2017 to 2018. All patients had undergone unilateral primary THA or TKA at a private hospital in Hong Kong. The outcome was postoperative LOS; factors affecting LOS were also investigated. RESULTS: No significant differences were found in any baseline parameters between the two groups of patients. The mean LOS was significantly shorter in the ERAS group than in the conventional group (3.28 ± 1.04 vs 5.16 ± 2.06 days, P<0.001). Moreover, a significantly greater proportion of patients could be discharged on or before postoperative day 3 in the ERAS group, compared with the conventional group (77.5% vs 13.7%, P<0.001). A significant difference in LOS was observed between general ward and private ward patients (3.06 ± 0.59 vs 3.66 ± 1.46 days, P=0.003). Sex, age, and nature of surgery (TKA vs THA) did not have significant effects on LOS. CONCLUSIONS: The ERAS practices yielded a significant improvement in postoperative LOS, compared to conventional practices, among patients who underwent unilateral primary THA or TKA in a private hospital.

Total knee arthroplasty is safe for patients aged ≥80 years in Hong Kong.

INTRODUCTION: Total knee arthroplasty (TKA) is an efficacious operation that improves pain and function in patients with knee arthritis. Because of the population ageing trend in Hong Kong, there is a need to determine the safety profile of TKA in older patients. This study examined the age of patients who underwent TKA in the past 10 years in Hong Kong; the aim was to investigate the mortality safety profile and clinical outcomes of TKA in patients aged ≥80 years. METHODS: This study included all patients who underwent primary TKA in the Hospital Authority (HA) from 2010 to 2019. Incidences of 30-day, 90-day, and 1-year mortality were established. Clinical outcomes of patients aged ≥80 years in one cluster of HA hospitals were assessed. RESULTS: Between 2010 and 2019, 25 040 TKA procedures were conducted in all HA hospitals; 2491 were conducted in patients aged ≥80 years. The median age at operation was higher during 2015-2019 than during 2010-2014 (70 vs 69 years; P<0.001); furthermore, an increase was observed in the proportion of patients aged ≥80 years at the time of operation. Incidences of 30-day, 90-day, and 1-year mortality were 0.156%, 0.35%, and 1.09%, respectively. CONCLUSIONS: In this first study to examine the safety profile of TKA in older patients in Hong Kong, the mean age at the time of TKA and proportion of patients aged ≥80 years have steadily risen in the past decade. Even in older patients, TKA is a reasonably safe procedure.

A machine learning-based approach to decipher multi-etiology of knee osteoarthritis onset and deterioration.

Objectives: By deploying a novel combination of machine learning approaches, we aim to investigate the contributions of each local and systemic risk factors in multi-etiology of knee osteoarthritis (KOA) to disease onset and deterioration. Methods: A machine-learning-based KOA progression prediction model is developed using the data from the National Institute of Health Osteoarthritis Biomarkers Consortium. According to Kellgren-Lawrence (KL) grade of plain radiographs at baseline, the subjects are divided into either KOA onset or deterioration study groups. The disease progression is defined as the changes in both joint space width (JSW) and WOMAC pain score. In addition to radiographic and symptomatic data, the anthropological particulars, history of the knee injury and surgery, metabolic syndrome and living habits were deployed in a multi-layer perceptron (MLP) to predict disease progression in each study group. The relative contributions of each risk factors were weighted via DeepLIFT gradient. Additionally, statistical interactions among risk factors were identified compared. Results: Our model achieved AUC of 0.843 (95% CI 0.824, 0.862) and 0.765 (95% CI 0.756, 0.774) in prediction of KOA onset and deterioration, respectively. For KOA onset prediction, history of injury has attained the highest DeepLIFT gradient except medial joint space narrowing; while for KOA deterioration prediction, diabetes and habit of smoking obtained second and third highest gradients respectively aside from medial joint space narrowing, surpassing the impact of the injury. Conclusion: We developed a machine learning workflow which effectively dissects the risk factors' contributions and their mutual interactions for onset and deterioration of KOA respectively.

Universal haemoglobin A1c screening reveals high prevalence of dysglycaemia in patients undergoing total knee arthroplasty.

INTRODUCTION: Diabetes mellitus is an established modifiable risk factor for periprosthetic joint infection (PJI). Haemoglobin A1c (HbA1c) is a glycaemic marker that correlates with diabetic complications and PJI. As diabetes and prediabetes are frequently asymptomatic, and there is increasing evidence to suggest a correlation between dysglycaemia and osteoarthritis, it is reasonable to provide HbA1c screening before total knee arthroplasty (TKA). The aim of the present study was to determine the prevalence of dysglycaemia in patients who underwent TKA and investigate whether HbA1c screening and optimisation of glycaemic control before TKA affects the incidence of PJI after TKA. METHODS: Patients who underwent primary TKA before and after routine HbA1c screening was introduced in our unit were reviewed. Prediabetes and diabetes were defined according to the American Diabetes Association. Patients with HbA1c ≥7.5% were referred to an endocrinologist for optimisation of glycaemic control before TKA. The incidence PJI, defined according to the Musculoskeletal Infection Society criteria, was recorded. RESULTS: A total of 729 patients (934 knees) had HbA1c screening before TKA. Of them, 17 (2.3%) and 184 (25.2%) patients had known prediabetes and diabetes, respectively, and 265 (36.4%) and 12 (1.6%) had undiagnosed prediabetes and diabetes, respectively. The incidence of PJI was significantly lower in all patients who received HbA1c screening compared with those who did not (0.2% vs 1.02%, P=0.027). CONCLUSION: Screening for HbA1c before TKA provides a cost-effective opportunity to identify undiagnosed dysglycaemia. Patients identified as having dysglycaemia receive modified treatment, significantly reducing the rate of PJI when compared with historical controls.

Preoperative optimization to prevent periprosthetic joint infection in at-risk patients.

Periprosthetic joint infection (PJI) remains an important complication with devastating consequences after total joint arthroplasties. With the increasing number of arthroplasties worldwide, the number of PJI will increase correspondingly with a significant economic burden to our healthcare system. It is likely impossible to completely eradicate PJI; hence, assessment and optimization of its risk factors to preventing such a disastrous complication will be the key. There are many strategies to prevent PJI in the preoperative, intraoperative, or postoperative phases. The preoperative assessment provides a unique opportunity to screen and diagnose underlying comorbidities and optimize modifiable risk factors before elective surgeries. In this review, we will focus on current literature in preoperative assessment of various modifiable risk factors and share the experience and practical approach in our institution in preoperative optimization to reduce PJI in total joint arthroplasties.

Blood transfusions in total knee arthroplasty: a retrospective analysis of a multimodal patient blood management programme.

PURPOSE: Transfusion is associated with increased perioperative morbidity and mortality in patients undergoing total knee arthroplasty (TKA). Patient blood management (PBM) is an evidence-based approach to maintain blood mass via haemoglobin maintenance, haemostasis optimisation, and blood loss minimisation. The aim of the present study was to assess the effectiveness of a multimodal PBM approach in our centre. METHODS: This was a single-centre retrospective study of patients who underwent primary TKA in Queen Mary Hospital in Hong Kong in 2013 or 2018, using data from the Clinical Data Analysis and Reporting System and a local joint registry database. Patient demographics, preoperative haemoglobin, length of stay, readmission, mean units of transfusion, postoperative prosthetic joint infection, and mortality data were compared between groups. RESULTS: In total, 262 and 215 patients underwent primary TKA in 2013 and 2018, respectively. The mean transfusion rate significantly decreased after PBM implementation (2013: 31.3%; 2018: 1.9%, P<0.001); length of stay after TKA also significantly decreased (2013: 14.49±8.10 days; 2018: 8.77±10.14 days, P<0.001). However, there were no statistically significant differences in readmission, early prosthetic joint infection, or 90-day mortality rates between the two groups. CONCLUSION: Our PBM programme effectively reduced the allogeneic blood transfusion rate in patients undergoing TKA in our institution. Thus, PBM should be considered in current TKA protocols to reduce rates of transfusions and related complications.

Faecal microbiota transplantation for treatment of recurrent or refractory Clostridioides difficile infection in Hong Kong.

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong. METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected. RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported. CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.

Non-surgical treatment of knee osteoarthritis.

Knee osteoarthritis is one of the most common degenerative diseases causing disability in elderly patients. Osteoarthritis is an increasing problem for ageing populations, such as that in Hong Kong. It is important for guidelines to be kept up to date with the best evidence-based osteoarthritis management practices available. The aim of this study was to review the current literature and international guidelines on non-surgical treatments for knee osteoarthritis and compared these with the current guidelines in Hong Kong, which were proposed in 2005. Internationally, exercise programmes for non-surgical management of osteoarthritis have been proven effective, and a pilot programme in Hong Kong for comprehensive non-surgical knee osteoarthritis management has been successful. Long-term studies on the effectiveness of such exercise programmes are required, to inform future changes to guidelines on osteoarthritis management.

Comparison of high-flow nasal cannula versus oxygen face mask for environmental bacterial contamination in critically ill pneumonia patients: a randomized controlled crossover trial.

Whereas high-flow nasal cannula use is gaining prevalence, its high gas flow raises concerns about aerosolization of infectious particles and spread of infection. This randomized controlled crossover non-inferiority trial (N = 20) evaluated the degree of environmental contamination by viable bacteria associated with the use of high-flow nasal cannula compared with conventional oxygen mask for critically ill patients with Gram-negative pneumonia. The results show that high-flow nasal cannula use was not associated with increased air or contact surface contamination by either Gram-negative bacteria or total bacteria, suggesting that additional infection control measures are not required.