Disease-related complications in patients with metastatic hormone-sensitive prostate cancer.

INTRODUCTION: Prostate-specific antigen-based screening for prostate cancer reportedly does not improve cancer-specific survival. However, there remain concerns about the increasing incidence of advanced disease at initial presentation. Here, we investigated the incidences and types of complications that occur during the course of disease in patients with metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: This study included 100 consecutive patients who were diagnosed with mHSPC at five hospitals from January 2016 to August 2017. Analyses were conducted using patient data extracted from a prospectively collected database, along with information about complications and readmission obtained from electronic medical records. RESULTS: The median patient age was 74 years and the median serum prostate-specific antigen level at diagnosis was 202.5 ng/mL. Ninety-nine patients received androgen deprivation therapy; 17 of these patients also received chemotherapy. During a mean follow-up period of 32.9 months, 41 patients reported bone pain; of these patients, 21 developed pathologic fractures and eight had cord compression. Twenty-eight patients developed retention of urine; of these patients, 10 (36%) required surgery and 11 (39%) required long-term urethral catheter use. Among 15 patients who developed ureteral obstruction, four (27%) required ureteral stenting and four (27%) required long-term nephrostomy drainage. Other complications included anaemia (41%) and deep vein thrombosis (4%). Fifty-nine (59%) patients had ≥1 unplanned hospital admission during the course of disease; 16% of such patients had >5 episodes of readmission. CONCLUSION: Among patients with mHSPC, 70% experienced disease-related complications and unplanned hospital admissions, which substantially burdened both patients and the healthcare system.

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.

Enlightenment of re-entry airflow: The path of the airflow and the airborne pollutants transmission in buildings.

Viable aerosols in the airflow may increase the risk of occupants contracting diseases. Natural ventilation is common in buildings and is accompanied by re-entry airflow during the ventilation process. If the re-entry airflow contains toxic or infectious species, it may cause potential harm to residents. One of the Covid-19 outbreaks occurred in a public residential building at Luk Chuen House (LC-House) in Hong Kong. It is highly suspected that the outbreak of the disease is related to the re-entry airflow. The study attempts to explain and discuss possible causes of the outbreak. In order to understand the impact of airflow on the outbreak, a public residential building similar to LC-House was used in the study. Two measurements M - I and M - II with the same settings were conducted for a sampling unit in the corridor under low and strong wind conditions respectively. The sampling unit and the tracer gas carbon dioxide (CO2) were used to simulate the index unit and infectious contaminated airflow respectively. The CO2 concentrations of the unit and corridor were measured simultaneously. Two models of Traditional Single-zone model (TSZ-model) and New Dual-zone model (NDZ-model) were used in the analysis. By comparing the ACH values obtained from the two models, it is indicated that the re-entry airflow of the unit is related to the corridor wind speeds and this provides a reasonable explanation for the outbreak in LC-House, and believes that the results can help understand the recent frequent cluster outbreaks in other residential buildings.

Multicentre study of hospitalised patients with sports- and recreational cycling-related traumatic brain injury in Hong Kong.

INTRODUCTION: Cycling is associated with a greater risk of traumatic brain injury (TBI) than other recreational activities. This study aimed to investigate the epidemiology of sports-related TBI in Hong Kong and to examine predictors for recreational cycling-induced intracranial haemorrhage. METHODS: This retrospective multicentre study included patients diagnosed with sports-related TBI in public hospitals in Hong Kong from 2015 to 2019. Computed tomography scans were reviewed by an independent assessor. The primary endpoint was traumatic intracranial haemorrhage. The secondary endpoint was an unfavourable Glasgow Outcome Scale (GOS) score at discharge from hospital. RESULTS: In total, 720 patients were hospitalised with sports-related TBI. The most common sport was cycling (59.2%). The crude incidence of cycling-related TBI was 1.1 per 100 000 population. Cyclists were more likely to exhibit intracranial haemorrhage and an unfavourable GOS score, compared with patients who had TBI because of other sports. Although 47% of cyclists had intracranial haemorrhage, only 15% wore a helmet. In multivariate analysis, significant predictors for intracranial haemorrhage were age ≥60 years, antiplatelet medication, moderate or severe TBI, and skull fracture. Among 426 cyclists, 375 (88%) had mild TBI, and helmet wearing was protective against intracranial haemorrhage, regardless of age, antiplatelet medication intake, and mechanism of injury. Of 426 cyclists, 31 (7.3%) had unfavourable outcomes on discharge from hospital. CONCLUSIONS: The incidence of sports-related TBI is low in Hong Kong. Although cycling-related head injuries carried greater risks of intracranial haemorrhage and unfavourable outcomes compared with other sports, most cyclists experienced good recovery. Helmet wearing among recreational cyclists with mild TBI was protective against intracranial haemorrhage and skull fracture.

Spatial and temporal variations of coastal microplastic pollution in Hong Kong.

Further to our 2015-16 investigation, this study revealed the repeated presence of microplastics (MPs) in the coastal environment (Deep Bay, Tolo Harbour, Tsing Yi and Victoria Harbour) of Hong Kong from July 2016 to March 2017. The highest level of MPs in coastal surface water (17,182 particles/100 m3) was detected in Tsing Yi. Microplastic abundance in sediments of different sites (59 to 225 plastic particles/kg), however, did not vary significantly. MPs in the size of ≤1 mm were predominated in surface waters (53.3% to 98.6%) and sediments (79.1% to 96.8%). MPs in the shape of pellets and fragments were prevalent in surface waters and sediments respectively. Seasonal pattern of microplastic pollution was consistently observed in Victoria Harbour and Tsing Yi, where the number of MPs was always higher in dry season than in wet season for two consecutive years.

Malaysia Stroke Council guide on acute stroke care service during COVID-19 Pandemic.

On the 18th of March 2020, the Malaysia government declared a movement control order (MCO) due to the unprecedented COVID-19 pandemic. Although the majority of patients presented with respiratory-related symptoms, COVID-19 patients may present atypically with neurological manifestations and may even have an increased risk of stroke. The Malaysia Stroke Council is concerned regarding the level of care given to stroke patients during this pandemic. During the recent National Stroke Workflow Steering Committee meeting, a guide was made based on the currently available evidences to assist Malaysian physicians providing acute stroke care in the hospital setting in order to provide the best stroke care while maintaining their own safety. The guide comprises of prehospital stroke awareness, hyperacute stroke care, stroke care unit and intensive care unit admission, post-stroke rehabilitation and secondary prevention practice. We urge continuous initiative to provide the best stroke care possible and ensure adequate safety for both patients and the stroke care team.

Survey on common reference intervals for general chemistry analytes in Hong Kong.

INTRODUCTION: Reference intervals (RIs) are essential tool for proper interpretation of results. There is a global trend towards implementing common RIs to avoid confusion and enhance patient management across different laboratories. However, local practices with respect to RIs lack harmonisation. METHODS: We have conducted the first local survey regarding RIs for 14 general chemistry analytes in 10 chemical pathology laboratories that employ four different analytical platforms (Abbott Architect, Beckman Coulter AU, Roche Cobas, and Siemens Dimension EXL). Analytical bias was assessed by an inter-laboratory results comparison of external quality assurance programmes. RESULTS: Sufficient inter-laboratory and inter-platform agreement regarding the 10 analytes (albumin, alanine aminotransferase, aspartate aminotransferase, chloride, gamma-glutamyl transferase, phosphate, potassium, sodium, total protein, and urea) were demonstrated. However, the RIs were heterogeneous across all laboratories, with percentage differences of the upper RI value of up to 47% for aspartate aminotransferase (absolute difference of 16 U/L), 29% for urea (1.8 mmol/L), and 18% for potassium (0.8 mmol/L). The percentage difference between lower RI values was up to 24% for urea (0.6 mmol/L), 22% for phosphate (0.16 mmol/L), and 8% for total protein (5 g/L). The coefficients of variation of the upper RI values of potassium and sodium were 1.2 times and 1.0 times of their corresponding between-subject biological variation, respectively, representing unnecessary variations that are overlooked and unchecked in current practice. CONCLUSIONS: We recommend the use of common RIs for general chemistry analytes in Hong Kong to prevent interpreter confusion, improve electronic data transfer, and unite laboratory practice. This is the first local study on this topic, and our data can lay the groundwork for increasing harmonisation of RIs across more laboratory tests.

Sudden arrhythmia death syndrome in young victims: a five-year retrospective review and two-year prospective molecular autopsy study by next-generation sequencing and clinical evaluation of their first-degree relatives.

OBJECTIVE: Sudden arrhythmia death syndrome (SADS) accounts for about 30% of causes of sudden cardiac death (SCD) in young people. In Hong Kong, there are scarce data on SADS and a lack of experience in molecular autopsy. We aimed to investigate the value of molecular autopsy techniques for detecting SADS in an East Asian population. METHODS: This was a two-part study. First, we conducted a retrospective 5-year review of autopsies performed in public mortuaries on young SCD victims. Second, we conducted a prospective 2-year study combining conventional autopsy investigations, molecular autopsy, and cardiac evaluation of the first-degree relatives of SCD victims. A panel of 35 genes implicated in SADS was analysed by next-generation sequencing. RESULTS: There were 289 SCD victims included in the 5-year review. Coronary artery disease was the major cause of death (35%); 40% were structural heart diseases and 25% were unexplained. These unexplained cases could include SADS-related conditions. In the 2-year prospective study, 21 SCD victims were examined: 10% had arrhythmogenic right ventricular cardiomyopathy, 5% had hypertrophic cardiomyopathy, and 85% had negative autopsy. Genetic analysis showed 29% with positive heterozygous genetic variants; six variants were novel. One third of victims had history of syncope, and 14% had family history of SCD. More than half of the 11 first-degree relatives who underwent genetic testing carried related genetic variants, and 10% had SADS-related clinical features. CONCLUSION: This pilot feasibility study shows the value of incorporating cardiac evaluation of surviving relatives and next-generation sequencing molecular autopsy into conventional forensic investigations in diagnosing young SCD victims in East Asian populations. The interpretation of genetic variants in the context of SCD is complicated and we recommend its analysis and reporting by qualified pathologists.

Epidemiology of myopia and prevention of myopia progression in children in East Asia: a review.

INTRODUCTION: Myopia (short-sightedness) exhibits high prevalence in East Asia. Methods to mitigate myopia progression are important in preventing the vision-threatening complications associated with high myopia. In this review, we examine the regional epidemiology of myopia and provide updated evidence regarding interventions to slow myopia progression in children. METHODS: We performed a literature search using PubMed from the date of inception through 25 June 2018. Studies involving myopia epidemiology and control of myopia progression were selected; only studies published in English were reviewed. Preference was given to prospective studies, as well as those conducted in Hong Kong or East Asia. RESULTS: Atropine eye drops and pirenzepine eye gel are highly effective for controlling myopia progression in children. Orthokeratology, peripheral defocus contact lenses, bifocal or progressive addition spectacles, and increased involvement in outdoor activities are also effective for controlling myopia progression; however, myopia undercorrection and single vision contact lenses are ineffective. CONCLUSION: Although various methods are effective for controlling myopia progression in children, no curative remedy exists for myopia. Health care professionals should be aware of the available methods, as well as their risks and benefits. Treatment should be individualised and based on the preferences of the patient's family, after full discussion of the risks and benefits of each modality.

Clinical and genetic profile of congenital long QT syndrome in Hong Kong: a 20-year experience in paediatrics.

INTRODUCTION: Congenital long QT syndrome (LQTS) is a genetically transmitted cardiac channelopathy that can lead to sudden cardiac death. This study aimed to report the clinical and genetic characteristics of all young patients diagnosed with LQTS in the only tertiary paediatric cardiology centre in Hong Kong. METHODS: This is a retrospective review of all paediatric and young adult patients diagnosed at our centre with LQTS from January 1997 to December 2016. The diagnosis of LQTS was established with a corrected QT interval (QTc) ≥480 ms, Schwartz score of >3 points, or the presence of a pathogenic mutation. RESULTS: Fifty-nine patients (33 males) from 52 families were included, with a mean age of 8.17 years (range, 0.00-16.95 years) at presentation. Five patients had concomitant congenital heart diseases. The mean follow-up duration was 5.33 ± 4.65 years. The mean QTc in the cohort was 504 ± 47 ms. They presented with syncope and convulsion (49%), cardiac arrest (10%), bradycardia and neonatal atrioventricular block (12%). Fifteen (25%) patients were asymptomatic at diagnosis. Thirty-eight (64.4%) patients were confirmed to have a pathogenic mutation for LQTS genes. Forty-five (76.3%) patients received beta blocker therapy. Thirteen (22.0%) patients required implantable cardioverter defibrillator. There was no mortality in the study period. The 1-, 5-, and 10-year breakthrough cardiac event-free rates were 93.0%, 80.7%, and 72.6%, respectively. CONCLUSION: Identification of the disorder, administration of beta blockers, and lifestyle modification can prevent subsequent cardiac events in LQTS. Genotyping in patients with LQTS is essential in guiding medical therapy and improving prognosis.

The first pilot study of expanded newborn screening for inborn errors of metabolism and survey of related knowledge and opinions of health care professionals in Hong Kong.

INTRODUCTION: Newborn screening is important for early diagnosis and effective treatment of inborn errors of metabolism (IEM). In response to a 2008 coroners' report of a 14-year-old boy who died of an undiagnosed IEM, the OPathPaed service model was proposed. In the present study, we investigated the feasibility of the OPathPaed model for delivering expanded newborn screening in Hong Kong. In addition, health care professionals were surveyed on their knowledge and opinions of newborn screening for IEM. METHODS: The present prospective study involving three regional hospitals was conducted in phases, from 1 October 2012 to 31 August 2014. The 10 steps of the OPathPaed model were evaluated: parental education, consent, sampling, sample dispatch, dried blood spot preparation and testing, reporting, recall and counselling, confirmation test, treatment and monitoring, and cost-benefit analysis. A fully automated online extraction system for dried blood spot analysis was also evaluated. A questionnaire was distributed to 430 health care professionals by convenience sampling. RESULTS: In total, 2440 neonates were recruited for newborn screening; no true-positive cases were found. Completed questionnaires were received from 210 respondents. Health care professionals supported implementation of an expanded newborn screening for IEM. In addition, there is a substantial need of more education for health care professionals. The majority of respondents supported implementing the expanded newborn screening for IEM immediately or within 3 years. CONCLUSION: The feasibility of OPathPaed model has been confirmed. It is significant and timely that when this pilot study was completed, a government-led initiative to study the feasibility of newborn screening for IEM in the public health care system on a larger scale was announced in the Hong Kong Special Administrative Region Chief Executive Policy Address of 2015.

Genetic basis of channelopathies and cardiomyopathies in Hong Kong Chinese patients: a 10-year regional laboratory experience.

INTRODUCTION: Hereditary channelopathies and cardiomyopathies are potentially lethal and are clinically and genetically heterogeneous, involving at least 90 genes. Genetic testing can provide an accurate diagnosis, guide treatment, and enable cascade screening. The genetic basis among the Hong Kong Chinese population is largely unknown. We aimed to report on 28 unrelated patients with positive genetic findings detected from January 2006 to December 2015. METHODS: Sanger sequencing was performed for 28 unrelated patients with a clinical diagnosis of channelopathies or cardiomyopathies, testing for the following genes: KCNQ1,KCNH2,KCNE1,KCNE2, and SCN5A, for long QT syndrome; SCN5A for Brugada syndrome; RYR2 for catecholaminergic polymorphic ventricular tachycardia; MYH7 and MYBPC3 for hypertrophic cardiomyopathy; LMNA for dilated cardiomyopathy; and PKP2 and DSP for arrhythmogenic right ventricular dysplasia/cardiomyopathy. RESULTS: There were 17 males and 11 females; their mean age at diagnosis was 39 years (range, 1-80 years). The major clinical presentations included syncope, palpitations, and abnormal electrocardiography findings. A family history was present in 13 (46%) patients. There were 26 different heterozygous mutations detected, of which six were novel-two in SCN5A (NM_198056.2:c.429del and c.2024-11T>A), two in MYBPC3 (NM_000256.3:c.906-22G>A and c.2105_2106del), and two in LMNA (NM_170707.3:c.73C>A and c.1209_1213dup). CONCLUSIONS: We have characterised the genetic heterogeneity in channelopathies and cardiomyopathies among Hong Kong Chinese patients in a 10-year case series. Correct interpretation of genetic findings is difficult and requires expertise and experience. Caution regarding issues of non-penetrance, variable expressivity, phenotype-genotype correlation, susceptibility risk, and digenic inheritance is necessary for genetic counselling and cascade screening.

Arthroscopic approach to the spring (calcaneonavicular) ligament.

BACKGROUND: This research studied the safety and efficacy of a new portal to the spring ligament. This portal is located just plantar to the insertion of the posterior tibial tendon and above the fibrous septum between the posterior tibial and the flexor digitorum longus tendons. METHODS: Twelve fresh frozen foot and ankle specimens were used. The distance between the accessory medial portal and the medial plantar nerve was measured. The relation between the medial plantar nerve and the spring ligament was studied. The depth that can be reached through the portal was also assessed. RESULTS: The average distance between the insertion point of the 3mm diameter metal rod and the medial plantar nerve was 20(6-27)mm. The medial plantar nerve located at lateral third of the ligament in 8 specimens (67%), middle third in 2 specimens (17%) and medial third in 2 specimens (17%). The tip of rod can reach Zone A in all specimens. CONCLUSION: This study demonstrated that arthroscopic approach and repair of the spring ligament can injure the medial plantar nerve. CLINICAL RELEVANCE: The clinical relevance of this cadaver study is that it confirmed the feasibility of arthroscopic approach to the whole span of the spring ligament and alerted the potential risk of injury to the medial plantar nerve during arthroscopic assisted repair of the ligament.

Optimising the utility of pleural fluid adenosine deaminase for the diagnosis of adult tuberculous pleural effusion in Hong Kong.

INTRODUCTION: Pleural fluid adenosine deaminase level can be applied to rapidly detect tuberculous pleural effusion. We aimed to establish a local diagnostic cut-off value for pleural fluid adenosine deaminase to identify patients with tuberculous pleural effusion, and optimise its utility. METHODS: We retrospectively reviewed the medical records of consecutive adults with pleural fluid adenosine deaminase level measured by the Diazyme commercial kit (Diazyme Laboratories, San Diego [CA], United States) during 1 January to 31 December 2011 in a cluster of public hospitals in Hong Kong. We considered its level alongside early (within 2 weeks) findings in pleural fluid and pleural biopsy, with and without applying Light's criteria in multiple scenarios. For each scenario, we used the receiver operating characteristic curve to identify a diagnostic cut-off value for pleural fluid adenosine deaminase, and estimated its positive and negative predictive values. RESULTS: A total of 860 medical records were reviewed. Pleural effusion was caused by congestive heart failure, chronic renal failure, or hypoalbuminaemia caused by liver or kidney diseases in 246 (28.6%) patients, malignancy in 198 (23.0%), non-tuberculous infection in 168 (19.5%), tuberculous pleural effusion in 157 (18.3%), and miscellaneous causes in 91 (10.6%). All those with tuberculous pleural effusion had a pleural fluid adenosine deaminase level of ≤100 U/L. When analysis was restricted to 689 patients with pleural fluid adenosine deaminase level of ≤100 U/L and early negative findings for malignancy and non-tuberculous infection in pleural fluid, the positive predictive value was significantly increased and the negative predictive value non-significantly reduced. Using this approach, neither additionally restricting analysis to exudates by Light's criteria nor adding closed pleural biopsy would further enhance predictive values. As such, the diagnostic cut-off value for pleural fluid adenosine deaminase is 26.5 U/L, with a sensitivity of 87.3%, specificity of 93.2%, positive predictive value of 79.2%, negative predictive value of 96.1%, and accuracy of 91.9%. Sex, age, and co-morbidity did not significantly affect prediction of tuberculous pleural effusion using the cut-off value. CONCLUSION: We have established a diagnostic cut-off level for pleural fluid adenosine deaminase in the diagnosis of tuberculous pleural effusion by restricting analysis to a level of ≤100 U/L, and considering early pleural fluid findings for malignancy and non-tuberculous infection, but not Light's criteria.

Okur-Chung neurodevelopmental syndrome: Eight additional cases with implications on phenotype and genotype expansion.

Okur-Chung syndrome is a neurodevelopmental condition attributed to germline CSNK2A1 pathogenic missense variants. We present 8 unreported subjects with the above syndrome, who have recognizable dysmorphism, varying degrees of developmental delay and multisystem involvement. Together with 6 previously reported cases, we present a case series of 7 female and 7 male subjects, highlighting the recognizable facial features of the syndrome (microcephaly, hypertelorism, epicanthic fold, ptosis, arched eyebrows, low set ears, ear fold abnormality, broad nasal bridge and round face) as well as frequently occurring clinical features including neurodevelopmental delay (93%), gastrointestinal (57%), musculoskeletal (57%) and immunological (43%) abnormalities. The variants reported in this study are evolutionary conserved and absent in the normal population. We observed that the CSNK2A1 gene is relatively intolerant to missense genetic changes, and most variants are within the protein kinase domain. All except 1 variant reported in this cohort are spatially located on the binding pocket of the holoenzyme. We further provide key recommendations on the management of Okur-Chung syndrome. To conclude, this is the second case series on Okur-Chung syndrome, and an in-depth review of the phenotypic features and genomic findings of the condition with suggestions on clinical management.