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Hok Sum Chan,1 Fanny Wai San Ko,2 Johnny Wai Man Chan,3 Kah Lin Choo,4 Loletta Kit Ying So,5 David Chi Leung Lam,6 Kit Man Sin,7 Wei Yin Wong,8 Yuk Lun Cheng,1 Maureen Mo Lin Wong9 1Department of Medicine, Alice Ho Miu Ling Nethersole Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 2Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 3Department of Medicine, Queen Elizabeth Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 4Department of Medicine, North District Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 5Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 6Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 7Department of Medicine and Geriatrics, Tuen Mun Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 8Department of Medicine, Haven of Hope Hospital, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China; 9Department of Medicine and Geriatrics, Caritas Medical Centre, Hong Kong Special Administrative Region (HKSAR), People’s Republic of ChinaCorrespondence: Hok Sum Chan, Department of Medicine, 6/F, Block J, Alice Ho Miu Ling Nethersole Hospital, 11 Chuen On Road, Tai Po, NT, Hong Kong Special Administrative Region (HKSAR), People’s Republic of China, Email chanhs@ha.org.hkBackground: Chronic obstructive pulmonary disease (COPD) is a common cause for hospital admission. This study aims to review the hospital burden of COPD in Hong Kong (HK) and the trend from year 2006 to 2014.Methods: A multi-center, retrospective study of the characteristics of COPD patients discharged from the public hospitals of HK from year 2006 to 2014. Anonymized data retrieval and analysis were performed. The demographic data of the subjects, use of health-care resources, ventilatory support, medications used and mortality of the subjects were analyzed.Results: Total patient headcount (HC) and admission number reduced from 10,425 and 23,362 in year 2006 to 9613 and 19,771, respectively, in 2014. There was a progressive reduction of female COPD HC from 2193 (21%) in year 2006 to 1517 (16%) in 2014. The utilization of non-invasive ventilation (NIV) increased rapidly and peaked in 2010 (29%) and decreased thereafter. There was a rapid increase in the prescription of long-acting bronchodilators (from 15% to 64%). COPD and pneumonia were the top causes of death, but death due to pneumonia was rapidly increasing while death due to COPD was progressively decreasing over the period.Conclusion: COPD HC and admission number (particularly in female patients) decreased progressively from year 2006 to 2014. There was also a decreasing trend of severity of disease as reflected by lower NIV use (after year 2010) and lower mortality rate due to COPD. Reduced smoking prevalence and tuberculosis (TB) notification rate in the community in the past might have reduced the incidence and severity of COPD and the hospital burden of disease. We observed an increasing trend of mortality due to pneumonia in COPD patients. Appropriate and timely vaccination programs are recommended for COPD patients as in the general elderly population.Keywords: hospital burden, mortality, smoking, old tuberculosis, pneumonia

The study aimed to test whether insight mediates decentering and cognitive coping processes in adaptive and maladaptive types. One hundred and fifty-five Chinese adult participants were recruited to complete an online survey, to report their level of decentering, insight, and cognitive coping strategies. The results of the simple regression analyses showed decentering positively predicted adaptive cognitive coping, and negatively predicted maladaptive cognitive coping process to a moderate degree. Mediation analyses revealed the mediating effect of insight only occurred in the relationship between decentering and maladaptive cognitive coping strategies, suggesting less decentering predicted greater maladaptive cognitive coping processes via a lower level of insight. The study contributed to the new understanding of the decentering mechanism of the cognitive coping process. Insight had a stronger effect on maladaptive cognitive coping than on adaptive cognitive coping strategies. The study provided recommendations to improve outcome effectiveness in mental health intervention. Keywords: Cognitive coping process, cognition, decentering, insight, metacognitive

Background: Visual arts-based interventions may have potential effects on post-stroke physical and psychosocial outcomes, but the current evidence is unclear. Objectives: (1)To determine the effects of visual arts-based interventions on physical and psychosocial outcomes among stroke survivors, and (2)to identify the best practice of visual arts-based interventions that have optimal effects on physical and psychosocial outcomes among stroke survivors. Methods: Seventeen databases were searched. Two reviewers independently screened for the eligible studies, appraised methodological quality assessment, and extracted data. Methodological quality was assessed using the revised Cochrane risk of bias tool for randomised trials. Meta-analysis was conducted using Review Manager 5.4, and narrative synthesis was performed if there was insufficient data for meta-analysis. Grading of Recommendations Assessment, Development and Evaluation was adopted to assess the certainty of evidence. Results: Seven studies were included in this review. The pooled results suggested that visual arts-based interventions had significant effects on activities of daily living (SMD: 0.96, 95%CI: 0.24 to 1.69, p =0.009, I 2 =87%), upper limb function (SMD: 0.83, 95%CI: 0.42 to 1.24, p I 2 =6%), and depressive symptoms (SMD: -1.14, 95%CI: -1.67 to -0.61, p I 2 =70%). While the effect on hand function (SMD: 0.47, 95% CI: -0.43 to 1.37, p =0.31; I 2 =82%) and anxiety (SMD: -0.80, 95%CI: -1.71 to 0.11, p =0.08; I 2 =86%) were non-significant. Narrative synthesis showed that the effects of visual arts-based intervention on self-efficacy, social participation, and quality of life were uncertain. This review also found that five non-visual art activities with education, task orientation, sharing, feedback, and support as parts of the component of visual arts-based interventions might contribute to the benefits of physical and psychosocial outcomes after stroke. Conclusion: This review found that stroke survivors may benefit from visual arts-based interventions to improve physical and psychosocial outcomes. However, the quality of evidence was relatively low, further rigorous randomised controlled trials are recommended to strengthen the current evidence.

OBJECTIVE Crohn’s Disease (CD) is a chronic disease characterized by transmural inflammation and may involve any portion of the gastrointestinal tract. Children with CD are more likely to present with extensive disease and have more rapid clinical progression than adults.1 This study aimed to compare the treatment patterns between pediatric and adult patients with CD. METHODS This is a retrospective claims-based study using the Merative L.P Marketscan® Research database (January 1, 2014 through December 31, 2021). Pediatric (≤ 17 years) and adult (≥ 18 years) patients with a CD diagnosis code and ≥12 months continuous enrollment with medical and pharmacy benefits before and after the first diagnosis of CD (index date) were included. Descriptive statistics described treatment patterns for pediatric and adult CD cohorts. RESULTS There were 2810 pediatric and 25,934 adult patients with CD included in the analysis. The mean (SD) ages in years for pediatric and adult patients were 13.5 (3.1) and 46.0 (15.9), respectively (Table 1). While females (53.6%) were slightly predominant in the adult cohort, there was a numerically higher proportion of males (59.5%) in the pediatric cohort. The most common monotherapy in children was corticosteroids (22.9%) or biologics (34.9%), while adult monotherapy was primarily corticosteroids (29.6%) or aminosalicylates (32.9%). The time from diagnosis to initiation of corticosteroids and immunomodulators was numerically shorter in children than adults (median days between index and corticosteroids or immunomodulators initiations: 14 vs. 54 and 26 vs 34, respectively). Combination therapies, including biologics and/or immunomodulators with corticosteroids, were numerically more often used in children than in adults (32.4% vs 15.0%). Among all biologic users, adalimumab (18.1%) was numerically more commonly prescribed for adults while infliximab (38.2%) was numerically more common in children. Pediatric patients showed numerically higher 6-month persistence from initiation of a biologic when compared with adult patients (persistence rate: 94.6% vs 87.2%; Table 2). Notably, a small proportion of pediatric patients were on either ustekinumab or vedolizumab (0.1% and 0.2%, respectively) as add-on therapy despite those medications not being currently approved in this population. CONCLUSION The study suggests that children with newly diagnosed CD receive combination therapies more frequently than adults. This may be related to greater disease severity in children. Children treated with biologics had numerically greater persistence, suggesting similar efficacy compared to adults. REFERENCE 1. Freeman H.J., Natural history and long-term clinical course of Crohn’s disease. World J Gastroenterol. 2014 Jan 7;20(1):31-6.

Microtubules are formed from heterodimers of alpha- and beta-tubulin, each of which has multiple isoforms encoded by separate genes. Pathogenic missense variants in multiple different tubulin isoforms cause brain malformations. Missense mutations in TUBB3, which encodes the neuron-specific beta-tubulin isotype, can cause congenital fibrosis of the extraocular muscles type 3 (CFEOM3) and/or malformations of cortical development, with distinct genotype–phenotype correlations. Here, we report fourteen individuals from thirteen unrelated families, each of whom harbors the identical NM_006086.4 (TUBB3):c.785G>A (p.Arg262His) variant resulting in a phenotype we refer to as the TUBB3 R262H syndrome. The affected individuals present at birth with ptosis, ophthalmoplegia, exotropia, facial weakness, facial dysmorphisms, and, in most cases, distal congenital joint contractures, and subsequently develop intellectual disabilities, gait disorders with proximal joint contractures, Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), and a progressive peripheral neuropathy during the first decade of life. Subsets may also have vocal cord paralysis, auditory dysfunction, cyclic vomiting, and/or tachycardia at rest. All fourteen subjects share a recognizable set of brain malformations, including hypoplasia of the corpus callosum and anterior commissure, basal ganglia malformations, absent olfactory bulbs and sulci, and subtle cerebellar malformations. While similar, individuals with the TUBB3 R262H syndrome can be distinguished from individuals with the TUBB3 E410K syndrome by the presence of congenital and acquired joint contractures, an earlier onset peripheral neuropathy, impaired gait, and basal ganglia malformations.

OBJECTIVE Ulcerative Colitis (UC) is a chronic disease characterized by continuous inflammation of the colonic and rectal mucosa. Children with UC are more likely to present with extensive disease and have more rapid clinical progression than adults.1 This study compared treatment patterns between pediatric and adult patients with UC. METHODS This retrospective, claims-based, cohort study used data from the Merative L.P Marketscan® Research Database to identify newly diagnosed patients with a confirmed UC diagnosis from January 1, 2014 through December 31, 2021. Pediatric (≤ 17 years) and adult (≥ 18 years) patients with continuous enrollment for 12 months before and 12 months following the first UC diagnosis (index date) who also received at least 1 medication related to inflammatory bowel disease (aminosalicylates, corticosteroids, immunomodulators, or biologics) after the first diagnosis date, were included. Descriptive statistics described treatment patterns for both cohorts. RESULTS This analysis included 1343 pediatric and 37,617 adult patients with UC. The mean (SD) ages (years) for pediatric and adult patients were 13.7 (3.3) and 48.8 (15.3) years, respectively (Table 1). The time from diagnosis to initiation of corticosteroids was numerically shorter in children in contrast to adults (median days between index date and corticosteroids initiation: 15 vs 56). Among all UC patients, aminosalicylates (74.0% adults vs 72.5% children) were the most prescribed monotherapy, followed by corticosteroids (16.6% adults vs 15.3% children) and immunomodulators (5.1% adults vs. 7.4% children). Additionally, children were started on combination therapies numerically more often than adults (32.3% vs 16.7%). The most used combination therapies for both cohorts were aminosalicylates plus corticosteroids (63.0% adults vs 62.4% children), followed by aminosalicylates and immunomodulators (15.3% adults vs 8.3% children). Children had numerically higher utilization of biologics than adults (22.6% vs 10.8%). The persistence rates of all drug therapies within 6 months following initiation in both cohorts were similar (Table 2). Notably, a small proportion of pediatric patients were on ustekinumab, vedolizumab, or tofacitinib as add-on therapy (0.2%, 2.0%, and 0.2%, respectively), despite those medications not being currently approved in this population. CONCLUSION More children with newly diagnosed UC receive combination therapies and have higher utilization of biologics compared to adults. This may reflect greater disease progression and complications in children. REFERENCE 1. Ruemmele, F., Turner, D. Differences in the management of pediatric and adult-onset ulcerative colitis – lessons from the joint ECCO and ESPGHAN consensus guidelines for the management of pediatric ulcerative colitis. Journal of Crohn’s and Colitis, 8(1), January 2014, pages 1-4.

Highlights • Developed two simple-to use nomograms for identifying COVID-19 positive patients. • Probabilities are provided to allow healthcare leaders to decide suitable cut-offs. • Variables are age, white cell count, chest x-ray appearances and contact history. • Model variables are easily available in the general hospital setting., Objectives To develop:(1) two validated risk prediction models for COVID-19 positivity using readily available parameters in a general hospital setting; (2) nomograms and probabilities to allow clinical utilisation. Methods Patients with and without COVID-19 were included from 4 Hong Kong hospitals. Database was randomly split 2:1 for model development database (n = 895) and validation database (n = 435). Multivariable logistic regression was utilised for model creation and validated with the Hosmer-Lemeshow (H-L) test and calibration plot. Nomograms and probabilities set at 0.1, 0.2, 0.4, 0.6 were calculated to determine sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results 1330 patients (mean age 58.2 ± 24.5 years; 50.7% males; 296 COVID-19 positive) were recruited. First prediction model developed had age, total white blood cell count, chest x-ray appearances and contact history as significant predictors (AUC = 0.911 [CI = 0.880-0.941]). Second model developed has same variables except contact history (AUC = 0.880 [CI = 0.844-0.916]). Both were externally validated on H-L test (p = 0.781 and 0.155 respectively) and calibration plot. Models were converted to nomograms. Lower probabilities give higher sensitivity and NPV; higher probabilities give higher specificity and PPV. Conclusion Two simple-to-use validated nomograms were developed with excellent AUCs based on readily available parameters and can be considered for clinical utilisation.

A proper interaction between muscle-derived collagen XXV and its motor neuron-derived receptors protein tyrosine phosphatases sigma and delta (PTP sigma/delta) is indispensable for intramuscular motor innervation. Despite this, thus far, pathogenic recessive variants in the COL25A1 gene had only been detected in a few patients with isolated ocular congenital cranial dysinnervation disorders. Here we describe five patients from three unrelated families with recessive missense and splice site COL25A1 variants presenting with a recognizable phenotype characterized by arthrogryposis multiplex congenita with or without an ocular congenital cranial dysinnervation disorder phenotype. The clinical features of the older patients remained stable over time, without central nervous system involvement. This study extends the phenotypic and genotypic spectrum of COL25A1 related conditions, and further adds to our knowledge of the complex process of intramuscular motor innervation. Our observations indicate a role for collagen XXV in regulating the appropriate innervation not only of extraocular muscles, but also of bulbar, axial, and limb muscles in the human.

Background Amiodarone is one of the most commonly used anti-arrhythmic agents. Amiodarone pulmonary toxicity is a potentially fatal adverse effect associated with amiodarone use. Previous studies on the epidemiology and risk factors for amiodarone pulmonary toxicity showed diverse results. Methods A multicenter retrospective cohort study was conducted to identify clinic-epidemiologic markers associated with amiodarone pulmonary toxicity for development of a prediction rule. Patients taking amiodarone who were managed in 3 centres in Hong Kong from 2005 to 2015 were included in this study. Penalized logistic regression was used to model the outcome as it is rare. Results A total of 34 cases with amiodarone pulmonary toxicity were identified among 1786 patients taking amiodarone for at least 90 days from 2005 to 2015. The incidence of amiodarone pulmonary toxicity was estimated to be 1.9%. The risk factors for amiodarone pulmonary toxicity included advanced age (OR 1.047, 95% CI 1.010–1.085, p = 0.013), ventricular arrhythmia (OR 2.703, 95% CI 1.053–6.935, p = 0.039), underlying lung disease (OR 2.511, 95% CI 1.146–5.501, p = 0.021) and cumulative dose of amiodarone (OR 4.762, 95% CI 1.310–17.309 p = 0.018). Conclusions The incidence of amiodarone pulmonary toxicity in Chinese patients in Hong Kong is estimated to be 1.9% in this study. Age, underlying lung disease, ventricular arrhythmia and cumulative dose of amiodarone are associated with the development of amiodarone pulmonary toxicity. A prediction rule was developed to inform the risk of developing amiodarone pulmonary toxicity.

Variants in multiple tubulin genes have been implicated in neurodevelopmental disorders, including malformations of cortical development (MCD) and congenital fibrosis of the extraocular muscles (CFEOM). Distinct missense variants in the beta-tubulin encoding genes TUBB3 and TUBB2B cause MCD, CFEOM, or both, suggesting substitution-specific mechanisms. Variants in the alpha tubulin-encoding gene TUBA1A have been associated with MCD, but not with CFEOM. Using exome sequencing (ES) and genome sequencing (GS), we identified 3 unrelated probands with CFEOM who harbored novel heterozygous TUBA1A missense variants c.1216C>G, p.(His406Asp); c.467G>A, p.(Arg156His); and c.1193T>G, p.(Met398Arg). MRI revealed small oculomotor-innervated muscles and asymmetrical caudate heads and lateral ventricles with or without corpus callosal thinning. Two of the three probands had MCD. Mutated amino acid residues localize either to the longitudinal interface at which α and β tubulins heterodimerize (Met398, His406) or to the lateral interface at which tubulin protofilaments interact (Arg156), and His406 interacts with the motor domain of kinesin-1. This series of individuals supports TUBA1A variants as a cause of CFEOM and expands our knowledge of tubulinopathies.

Congenital fibrosis of the extraocular muscles (CFEOM) is a congenital cranial dysinnervation disorder caused by developmental abnormalities affecting cranial nerves/nuclei innervating the extraocular muscles. Autosomal dominant CFEOM arises from heterozygous missense mutations of KIF21A or TUBB3. Although spatiotemporal expression studies have shown KIF21A and TUBB3 expression in developing retinal ganglion cells, it is unclear whether dysinnervation extends beyond the oculomotor system. We aimed to investigate whether dysinnervation extends to the visual system by performing high-resolution optical coherence tomography (OCT) scans characterizing retinal ganglion cells within the optic nerve head and retina. Sixteen patients with CFEOM were screened for mutations in KIF21A, TUBB3, and TUBB2B. Six patients had apparent optic nerve hypoplasia. OCT showed neuro-retinal rim loss. Disc diameter, rim width, rim area, and peripapillary nerve fiber layer thickness were significantly reduced in CFEOM patients compared to controls (p &lt, 0.005). Situs inversus of retinal vessels was seen in five patients. Our study provides evidence of structural optic nerve and retinal changes in CFEOM. We show for the first time that there are widespread retinal changes beyond the retinal ganglion cells in patients with CFEOM. This study shows that the phenotype in CFEOM extends beyond the motor nerves.

BACKGROUND: Congenital fibrosis of the extraocular muscles(CFEOM) is characterized by ptosis and non-progressive restrictive ophthalmoplegia. CFEOM1 is a stereotypical phenotype with isolated bilateral ptosis, bilateral ophthalmoplegia, absent upgaze, and globe infraduction. CFEOM3 is a more variable phenotype that can include unilateral disease, absent ptosis, residual upgaze, and/or orthotropia. Most cases of CFEOM1 result from recurrent heterozygous KIF21A missense mutations and less commonly from recurrent heterozygous TUBB3 missense mutations. While most cases of CFEOM3 result from recurrent heterozygous TUBB3 missense mutations, several pedigrees harbored pathogenic variants in KIF21A. Here, we asked if Lebanese pedigrees with CFEOM3 harbor pathogenic variants in TUBB3 or KIF21A. MATERIALS AND METHODS: Families affected with congenital cranial dysinnervation disorders were prospectively recruited from the American University of Beirut pediatric ophthalmology clinic and included two probands with CFEOM. KIF21A hotspot exons and TUBB3 coding sequence were sequenced. Available family members were sequenced for co-segregation analysis. RESULTS: Both families were found to have CFEOM3 and to harbor pathogenic variants in KIF21A(OMIM 608283). A simplex proband with CFEOM3 from a consanguineous Iraqi family harbored a de novo heterozygous KIF21A c.2860C>T variant(p.R954W); this variant accounts for the majority of reported KIF21A mutations but is typically implicated in CFEOM1. A Lebanese father with CFEOM3 and his son with CFEOM1 segregated a heterozygous KIF21A c.2830G>C variant (p.E944Q), previously reported in an individual with CFEOM1. CONCLUSIONS: These results support prior reports of KIF21A mutations as a rare cause of CFEOM3. These families are Middle Eastern or Chinese, supporting a genetic modifier in these populations.

Summary Background A cruise ship is a closed-off environment that simulates the basic functioning of a city in terms of living conditions and interpersonal interactions. Thus, the Diamond Princess cruise ship, which was quarantined because of an onboard outbreak of COVID-19 in February, 2020, provides an opportunity to define the shedding pattern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patient antibody responses before and after the onset of symptoms. Methods We recruited adult (≥18 years) passengers from Hong Kong who had been on board the Diamond Princess cruise ship docked in Yokohama, Japan in February, 2020. All participants had been found to be negative for SARS-CoV-2 by RT-PCR 4 days before disembarking and were transferred to further quarantine in a public estate in Hong Kong, where they were recruited. Participants were prospectively screened by quantitative RT-PCR (RT-qPCR) of nasopharyngeal and throat swabs, and serum IgG and IgM against internal nucleoprotein and the surface spike receptor-binding protein (RBD) of SARS-CoV-2 at baseline (upon entering quarantine) and on days 4, 8, and 12 of quarantine. Findings On Feb 22, 2020, 215 adults were recruited, of whom nine (4%; 95% CI 2–8) were positive for SARS-CoV-2 by RT-qPCR or serology and were hospitalised. Of these nine patients, nasopharyngeal swab RT-qPCR was positive in eight patients (89%; 57–99) at baseline. All nine patients were positive for anti-RBD IgG by day 8. Eight (89%; 57–99) were simultaneously positive for nasopharyngeal swab RT-PCR and anti-RBD IgG. One patient who was positive for anti-RBD IgG and had a negative viral load had multifocal peripheral ground-glass changes on high-resolution CT that were typical of COVID-19. Five patients (56%; 27–81) with ground-glass changes on high-resolution CT were found to have higher anti-nucleoprotein-IgG OD values on day 8 and 12 and anti-RBD IgG OD value on day 12 than patients without ground-glass changes. Six (67%; 35–88) patients remained asymptomatic throughout the 14-day quarantine period. Interpretation Patients with COVID-19 can develop asymptomatic lung infection with viral shedding and those with evidence of pneumonia on imaging tend to have an increased antibody response. Positive IgG or IgM confirmed infection of COVID-19 in both symptomatic and asymptomatic patients. A combination of RT-PCR and serology should be implemented for case finding and contact tracing to facilitate early diagnosis, prompt isolation, and treatment. Funding Shaw Foundation Hong Kong; Sanming-Project of Medicine (Shenzhen); High Level-Hospital Program (Guangdong Health Commission).

Background Strict infection control measures in response to the current COVID‐19 pandemic are expected to remain for an extended period. In aesthetic clinics, most procedures are provided on one to one basis by the physician or therapist. In such a scenario, guidelines detailing the infection control measures for aesthetic clinics are of particular importance. Methods An online meeting of an international group of experts in the field of aesthetic medicine, with experience in administration of an aesthetic clinic, was convened. The meeting aimed to provide a set of consensus guidelines to protect clinic staff and patients from SARS‐CoV‐2 infection. Results Consensus guidelines for ‘preferred practices' were provided for scheduling of patients, patient evaluation and triaging, and for safety precautions about the different procedures. Procedures were categorized into low‐risk, moderate risk, and high‐risk based on the likelihood of transmission of SARS‐CoV‐2 virus from the patient to the treating physician or therapist. Conclusions While not intended to be complete or exhaustive, these guidelines provide sound infection control measures for aesthetic practices. Since guidelines regarding safety measures and use of PPEs may vary from country to country, the local guidelines should also be followed to prevent COVID‐19 infection in aesthetic clinics. This article is protected by copyright. All rights reserved.

Background The coronavirus disease 2019 (COVID-19) pandemic has put tremendous pressure on the healthcare system worldwide. Diagnostic testing remained one of the limiting factors for early identification and isolation of infected patients. This study aimed to evaluate posterior oropharyngeal saliva (POPS) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection among patients with confirmed or suspected COVID-19. Methods The laboratory information system was searched retrospectively for all respiratory specimens and POPS requested for SARS-CoV-2 RNA detection between 1 February 2020 and 15 April 2020. The agreement and diagnostic performance of POPS against NPsp were evaluated. Results A total of 13772 specimens were identified during the study period, including 2130 POPS and 8438 nasopharyngeal specimens (NPsp). Two hundred and twenty-nine same-day POPS-NPsp paired were identified with POPS and NPsp positivity of 61.5% (95% confidence interval [CI] 55.1–67.6%) and 53.3% (95% CI 46.8–59.6%). The overall, negative and positive percent agreement were 76.0% (95% CI 70.2–80.9%), 65.4% (95% CI 55.5–74.2%), 85.2% (95% CI 77.4–90.8%). Better positive percent agreement was observed in POPS-NPsp obtained within 7 days (96.6%, 95% CI 87.3–99.4%) compared with after 7 days of symptom onset (75.0%, 95% CI 61.4–85.2%). Among the 104 positive pairs, the mean difference in Cp value was 0.26 (range: 12.63 to −14.74), with an overall higher Cp value in NPsp (Pearson coefficient 0.579). No significant temporal variation was noted between the 2 specimen types. Conclusions POPS is an acceptable alternative specimen to nasopharyngeal specimen for the detection of SARS-CoV-2.

Rapid advances in information and sensor technology have led to the development of tools and methods for personalized health monitoring. These techniques support timely and efficient healthcare services by tracking the vital signs, detecting physiological changes and predicting health risks. In this paper, we propose an integrated system to monitor the wellness condition of elderly. This system is conceptualized to provide a computer-aided decision support for clinicians and community nurses, by means of which they can easily monitor and analyze an elderly's overall activity and vital signs using a wearable wellness tracker and an all-in-one satiation-based monitoring device, offering an efficient solution with a reduction in time cost and human error. We design a data-preparing scheme for acquiring data and processing data from multiple monitoring devices, and propose a personalized scheme for forecasting the elderly's one-day-ahead wellness condition via data integration and statistical learning. We conduct a pilot study at a nursing home in Hong Kong to demonstrate the implementation of the proposed system. The proposed forecasting scheme is validated by the collected data.

Motor, sensory, and integrative activities of the brain are coordinated by a series of midline-bridging neuronal commissures whose development is tightly regulated. Here we report a new human syndrome in which these commissures are widely disrupted, thus causing clinical manifestations of horizontal gaze palsy, scoliosis, and intellectual disability. Affected individuals were found to possess biallelic loss-of-function mutations in the gene encoding the axon-guidance receptor 'deleted in colorectal carcinoma' (DCC), which has been implicated in congenital mirror movements when it is mutated in the heterozygous state but whose biallelic loss-of-function human phenotype has not been reported. Structural MRI and diffusion tractography demonstrated broad disorganization of white-matter tracts throughout the human central nervous system (CNS), including loss of all commissural tracts at multiple levels of the neuraxis. Combined with data from animal models, these findings show that DCC is a master regulator of midline crossing and development of white-matter projections throughout the human CNS.

Hong Kong has been implementing a policy of assessment for learning to counter-balance the strong, high-stakes, summative, and examination-oriented practices of the territory. While the purposes teachers have for various classroom assessment tasks are devoted to this learning premise, their views are bounded by the social expectations of assessment for accountability. This paper reports on a study of the types of assessment tasks used by four primary school curriculum leaders, the nature of assessment for learning in Hong Kong primary school context, and their views of how the tasks could support learning improvement in the accountability era. Results indicate that, consistent with official policy, “improvement” was the dominant reason for using the eight assessment tasks discussed in interviews. However, these tasks also met the functions of “accountability,” consistent with the dominant use of assessment in the Chinese context. It appears that assessment for learning in Hong Kong practice is still bounded by the need to demonstrating school quality through the preparation of students for examinations, which raises questions about the policy’s validity. This paper concludes with factors that hinder a formative learning practice and recommends some follow-up strategies under this improvement-accountability tension.

Oculomotor synkinesis is the involuntary movement of the eyes or eyelids with a voluntary attempt at a different movement. The chemokine receptor CXCR4 and its ligand CXCL12 regulate oculomotor nerve development; mice with loss of either molecule have oculomotor synkinesis. In a consanguineous family with congenital ptosis and elevation of the ptotic eyelid with ipsilateral abduction, we identified a co-segregating homozygous missense variant (c.772G>A) in ACKR3, which encodes an atypical chemokine receptor that binds CXCL12 and functions as a scavenger receptor, regulating levels of CXCL12 available for CXCR4 signaling. The mutant protein (p.V258M) is expressed and traffics to the cell surface but has a lower binding affinity for CXCL12. Mice with loss of Ackr3 have variable phenotypes that include misrouting of the oculomotor and abducens nerves. All embryos show oculomotor nerve misrouting, ranging from complete misprojection in the midbrain, to aberrant peripheral branching, to a thin nerve, which aberrantly innervates the lateral rectus (as seen in Duane syndrome). The abducens nerve phenotype ranges from complete absence, to aberrant projections within the orbit, to a normal trajectory. Loss of ACKR3 in the midbrain leads to downregulation of CXCR4 protein, consistent with reports that excess CXCL12 causes ligand-induced degradation of CXCR4. Correspondingly, excess CXCL12 applied to ex vivo oculomotor slices causes axon misrouting, similar to inhibition of CXCR4. Thus, ACKR3, through its regulation of CXCL12 levels, is an important regulator of axon guidance in the oculomotor system; complete loss causes oculomotor synkinesis in mice, while reduced function causes oculomotor synkinesis in humans.

Background The genetic basis of monocular elevation deficiency (MED) is unclear. It has previously been considered to arise due to a supranuclear abnormality. Methods Two brothers with MED were referred to Leicester Royal Infirmary, UK from the local opticians. Their father had bilateral ptosis and was unable to elevate both eyes, consistent with the diagnosis of congenital fibrosis of extraocular muscles (CFEOM). Candidate sequencing was performed in all family members. Results Both affected siblings (aged 7 and 12 years) were unable to elevate the right eye. Their father had bilateral ptosis, left esotropia and bilateral limitation of elevation. Chin up head posture was present in the older sibling and the father. Bell’s phenomenon and vertical rotational vestibulo-ocular reflex were absent in the right eye for both children. Mild bilateral facial nerve palsy was present in the older sibling and the father. Both siblings had slight difficulty with tandem gait. MRI revealed hypoplastic oculomotor nerve. Left anterior insular focal cortical dysplasia was seen in the older sibling. Sequencing of TUBB3 revealed a novel heterozygous variant (c.1263G>C, p.E421D) segregating with the phenotype. This residue is in the C-terminal H12 α-helix of β-tubulin and is one of three putative kinesin binding sites. Conclusion We show that familial MED can arise from a TUBB3 variant and could be considered a limited form of CFEOM. Neurological features such as mild facial palsy and cortical malformations can be present in patients with MED. Thus, in individuals with congenital MED, consideration may be made for TUBB3 mutation screening.

Background Superior performance of surgical treatment over medical treatment for primary aldosteronism (PA) has been reported in small-scale clinical studies with diverse clinical outcomes, but no solid conclusion has been drawn as results of large randomized trials are lacking. Methods: We performed a search of PubMed, MEDLINE, Embase and Cochrane Library for randomized or observational studies that investigated cardiovascular outcomes in patients with primary aldosteronism undergoing medical versus surgical treatment. - Composite outcomes including persistence of hypertension (HT) and incidence of significant clinical events (e.g. major adverse cardiovascular events [MACE] and all-cause mortality) after treatment was considered. Meta-analyses of both composite and individual outcomes were conducted. Risks of bias of the included studies were assessed with Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) checklist. Findings: A total of 368 related citations were reviewed and 11 studies that fulfilled the inclusion criteria, with altogether 5,994 PA patients, were included in the meta-analysis. Evaluation showed that there were low-moderate risks of bias in (63.64%) 7 of the included studies. The results of meta-analyses demonstrated lower incidence of composite outcomes among PA patients who underwent surgical treatment over medical treatment (Odds Ratio (OR): 0.49, 95% CI: 0.29-0.83 in random effects model). Surgical treatment also led to less incidence of persistence of HT (OR of non-cure of HT: 0.31, 95% CI: 0.11-0.85 in random effects model). Fewer major cardiovascular events and mortality events after surgical treatment were observed in the fixed effect model (OR: 0.47, 95% CI: 0.39-0.56), but failed to reach significant statistical levels in random effects model (OR: 0.71, 95% CI: 0.33-1.52) when compared to medical treatment. Interpretation: Superior performance of surgical treatment over medical treatment for PA patients is confirmed with meta-analyses in terms of lower incidences of composite outcomes and non-cure of HT. Hence, adrenalectomy could now be concluded as the treatment of choice for lateralized PA. Funding Statement: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Interests: All authors declare no competing interests Ethics Approval Statement: The pre-defined review protocol was registered at the PROSPERO international prospective register of systematic reviews (PROSPERO registration number CRD42019119175). The protocol for this trial and supporting CONSORT checklist are available as supporting information.

One set of missense mutations in the neuron specific beta tubulin isotype 3 (TUBB3) has been reported to cause malformations of cortical development (MCD), while a second set has been reported to cause isolated or syndromic Congenital Fibrosis of the Extraocular Muscles type 3 (CFEOM3). Because TUBB3 mutations reported to cause CFEOM had not been associated with cortical malformations, while mutations reported to cause MCD had not been associated with CFEOM or other forms of paralytic strabismus, it was hypothesized that each set of mutations might alter microtubule function differently. Here, however, we report two novel de novo heterozygous TUBB3 amino acid substitutions, G71R and G98S, in four patients with both MCD and syndromic CFEOM3. These patients present with moderately severe CFEOM3, nystagmus, torticollis, and developmental delay, and have intellectual and social disabilities. Neuroimaging reveals defective cortical gyration, as well as hypoplasia or agenesis of the corpus callosum and anterior commissure, malformations of hippocampi, thalami, basal ganglia and cerebella, and brainstem and cranial nerve hypoplasia. These new TUBB3 substitutions meld the two previously distinct TUBB3-associated phenotypes, and implicate similar microtubule dysfunction underlying both.

Purpose: To determine whether rare copy number variants (CNVs) increase risk for comitant esotropia. Methods: CNVs were identified in 1614 Caucasian individuals with comitant esotropia and 3922 Caucasian controls from Illumina SNP genotyping using two Hidden Markov model (HMM) algorithms, PennCNV and QuantiSNP, which call CNVs based on logR ratio and B allele frequency. Deletions and duplications greater than 10 kb were included. Common CNVs were excluded. Association testing was performed with 1 million permutations in PLINK. Significant CNVs were confirmed with digital droplet polymerase chain reaction (ddPCR). Whole genome sequencing was performed to determine insertion location and breakpoints. Results: Esotropia patients have similar rates and proportions of CNVs compared with controls but greater total length and average size of both deletions and duplications. Three recurrent rare duplications significantly (P = 1 × 10-6) increase the risk of esotropia: chromosome 2p11.2 (hg19, 2:87428677-87965359), spanning one long noncoding RNA (lncRNA) and two microRNAs (OR 14.16; 95% confidence interval [CI] 5.4-38.1); chromosome 4p15.2 (hg19, 4:25554332-25577184), spanning one lncRNA (OR 11.1; 95% CI 4.6-25.2); chromosome 10q11.22 (hg19, 10:47049547-47703870) spanning seven protein-coding genes, one lncRNA, and four pseudogenes (OR 8.96; 95% CI 5.4-14.9). Overall, 114 cases (7%) and only 28 controls (0.7%) had one of the three rare duplications. No case nor control had more than one of these three duplications. Conclusions: Rare CNVs are a source of genetic variation that contribute to the genetic risk for comitant esotropia, which is likely polygenic. Future research into the functional consequences of these recurrent duplications may shed light on the pathophysiology of esotropia.

Seven unrelated individuals (four pediatric, three adults) with the TUBB3 E410K syndrome, harboring identical de novo heterozygous TUBB3 c.1228 G>A mutations, underwent neuropsychological testing and neuroimaging. Despite the absence of cortical malformations, they have intellectual and social disabilities. To search for potential etiologies for these deficits, we compared their brain's structural and white matter organization to 22 controls using structural and diffusion magnetic resonance imaging. Diffusion images were processed to calculate fractional anisotropy (FA) and perform tract reconstructions. Cortical parcellation-based network analysis and gyral topology-based FA analyses were performed. Major interhemispheric, projection and intrahemispheric tracts were manually segmented. Subjects had decreased corpus callosum volume and decreased network efficiency. While only pediatric subjects had diffuse decreases in FA predominantly affecting mid- and long-range tracts, only adult subjects had white matter volume loss associated with decreased cortical surface area. All subjects showed aberrant corticospinal tract trajectory and bilateral absence of the dorsal language network long segment. Furthermore, pediatric subjects had more tracts with decreased FA compared with controls than did adult subjects. These findings define a TUBB3 E410K neuroimaging endophenotype and lead to the hypothesis that the age-related changes are due to microscopic intrahemispheric misguided axons that are pruned during maturation.

Uncovering clinical research trends allows us to understand the direction of healthcare services and is essential for longer-term healthcare planning. The Hospital Authority Convention is a mainstream annual healthcare conference that gathers up-to-date Hong Kong medical research. We propose to use state-of-the-art medical document mining and topic modelling methods to uncover latent themes and structures in the publications. We collected 742 articles from HA Convention from the year 2013 to 2016 and selected 56 publications from the category of "Clinical Safety and Quality Service" for further analysis. Applying natural language processing and Latent Dirichlet Allocation (LDA) methods, we identified 7 potential topics, namely: surgical operation, hospital discharge, medical error, nursing procedure, service performance assessment, patient and staff engagement, and admission algorithm and standardisation. This exploratory study demonstrates that key themes exist in the annual HA Convention and we observe potential changes in healthcare services focus over the years in the selected category.

The current incidence and prevalence of noncommunicable diseases (NCDs) is currently a cause for great concern on a global scale; future projections are no less disconcerting. Unhealthy lifestyle patterns are at the core of the NCD crisis; physical inactivity, excess body mass, poor nutrition and tobacco use are the primary lifestyle factors that substantially increase the risk of developing one or more NCDs. We have now come to recognize that healthy lifestyle interventions are a medical necessity that should be prescribed to all individuals. Perhaps the most well-established model for healthy lifestyle interventions in the current healthcare model is cardiac rehabilitation. To have any hope of improving the outlook for NCDs on a global scale, what is currently known as cardiac rehabilitation must transform into broad-based healthy lifestyle programing, with a shifted focus on primordial and primary prevention.

Background A limited number of studies on long-term effects of particulate matter with aerodynamic diameter < 2.5 μm (PM2.5) on health suggest it can be an important cause of morbidity and mortality. In Asia where air quality is poor and deteriorating, local data on long-term effects of PM2.5 to support policy on air quality management are scarce. Objectives We assessed long-term effects of PM2.5 on the mortality in a single Asian city. Methods For 10–13 years, we followed up a cohort of 66,820 participants ≥ 65 years of age who were enrolled and interviewed in all 18 Elderly Health Centres of the Department of Health, Hong Kong, in 1998–2001. Their residential addresses were geocoded into x- and y-coordinates, and their proxy exposures to PM2.5 at their addresses in 1 × 1 km grids were estimated from the U.S. National Aeronautics and Space Administration (NASA) satellite data. We used Cox regression models to calculate hazard ratios (HRs) of mortality associated with PM2.5. Results Mortality HRs per 10-μg/m3 increase in PM2.5 were 1.14 (95% CI: 1.07, 1.22) for all natural causes, 1.22 (95% CI: 1.08, 1.39) for cardiovascular causes, 1.42 (95% CI: 1.16, 1.73) for ischemic heart disease, 1.24 (95% CI: 1.00, 1.53) for cerebrovascular disease, and 1.05 (95% CI: 0.90, 1.22) for respiratory causes. Conclusions Our methods in using NASA satellite data provide a readily accessible and affordable approach to estimation of a sufficient range of individual PM2.5 exposures in a single city. This approach can expand the capacity to conduct environmental accountability studies in areas with few measurements of fine particles. Citation Wong CM, Lai HK, Tsang H, Thach TQ, Thomas GN, Lam KB, Chan KP, Yang L, Lau AK, Ayres JG, Lee SY, Chan WM, Hedley AJ, Lam TH. 2015. Satellite-based estimates of long-term exposure to fine particles and association with mortality in elderly Hong Kong residents. Environ Health Perspect 123:1167–1172; http://dx.doi.org/10.1289/ehp.1408264

Auction is a common competitive business-to-business (B2B) procurement procedure for supplying products and services, which are solicited, received, and evaluated. Currently, most auction portals support only forward auctions with interactive Web portals, while large companies usually construct their own reverse auction Websites. To provide a unified and more comprehensive solution, the authors develop an E-Auction System (EAS) to provide both forward and reverse auction support in a Web services environment. Buyer and sellers can post their requests via automated Web services for better Enterprise Information System (EIS) integration. Alternatively, they can manually browse the portal with a browser to post requests or submit their bid prices. Their EAS also provides an auction-matching function that automatically matches forward and reverse auction records to help completing business processes effectively. Further, their EAS's CRM system can capture and analyze user bidding behavior and posting to provide personalized Webpages. Besides, alert services provide notification of auction and bid statuses to customers for efficiency.

Context: A heterozygous de novo c.1228G>A mutation (E410K) in the TUBB3 gene encoding the neuronal-specific β-tubulin isotype 3 (TUBB3) causes the TUBB3 E410K syndrome characterized by congenital fibrosis of the extraocular muscles (CFEOM), facial weakness, intellectual and social disabilities, and Kallmann syndrome (anosmia with hypogonadotropic hypogonadism). All TUBB3 E410K subjects reported to date are sporadic cases. Objective: This study aimed to report the clinical, genetic, and molecular features of a familial presentation of the TUBB3 E410K syndrome. Design: Case report of a mother and three affected children with clinical features of the TUBB3 E410K syndrome. Setting: Academic Medical Center. Main Outcome Measures: Genetic analysis of the TUBB3 gene and clinical evaluation of endocrine and nonendocrine phenotypes. Results: A de novo TUBB3 c.1228G>A mutation arose in a female proband who displayed CFEOM, facial weakness, intellectual and social disabilities, and anosmia. However, she underwent normal sexual development at puberty and had three spontaneous pregnancies with subsequent autosomal-dominant inheritance of the mutation by her three boys. All sons displayed nonendocrine features of the TUBB3 E410K syndrome similar to their mother but, in addition, had variable features suggestive of additional endocrine abnormalities. Conclusions: This first report of an autosomal-dominant inheritance of the TUBB3 c.1228G>A mutation in a family provides new insights into the spectrum and variability of endocrine phenotypes associated with the TUBB3 E410K syndrome. These observations emphasize the need for appropriate clinical evaluation and complicate genetic counseling of patients and families with this syndrome.

Background. Obesity was first noted as a risk factor for severe illness associated with pandemic H1N1 infection in 2009, but the relationship between obesity and seasonal influenza remains unclear. Methods. We used datafrom a population-based cohort comprising 66 820 older (≥65 years) participants with a follow-up period from 1998 to 2012. The impact of influenza activity on respiratory mortality rates was estimated using a Cox proportional hazards model adjusted for comorbidities, meteorological factors, and other co-circulating respiratory viruses. We also tested whether the association of influenza with respiratory mortality varied with obesity and/or health status. As a control outcome, we similarly assessed the association of influenza with deaths from external causes, because these deaths should be unrelated to influenza. Results. Seasonal influenza activity was associated with higher respiratory mortality (hazard ratio [HR], 1.13 for influenza activity in the influenza season vs noninfluenza season; 95% confidence interval [CI], 1.05–1.22). The effect of seasonal influenza was 19% greater in obese individuals than normal-weight individuals (HR, 1.19; 95% CI, 1.01– 1.42). The marginally significant and greater effect modification of obesity status on the association between seasonal influenza and respiratory mortality was also observed among older people in good health (HR, 1.35; 95% CI, .97– 1.87). No such relations were observed for death from external causes. Conclusions. Obesity aggravates the effect of seasonal influenza on respiratory mortality. Priority for influenza vaccine should be considered for obese older people to decrease the burden of influenza.

MYF5 is member of the Myc-like basic helix-loop-helix transcription factor family and, in cooperation with other myogenic regulatory factors MYOD and MYF5, is a key regulator of early stages of myogenesis. Here, we report three consanguineous families with biallelic homozygous loss-of-function mutations in MYF5 who define a clinical disorder characterized by congenital ophthalmoplegia with scoliosis and vertebral and rib anomalies. The clinical phenotype overlaps strikingly with that reported in several Myf5 knockout mouse models. Affected members of two families share a haploidentical region that contains a homozygous 10 by frameshift mutation in exon 1 of MYF5 (c.23_32delAGTTCTCACC [p.GIn8Leufs*86]) predicted to undergo nonsense-mediated decay. Affected members of the third family harbor a homozygous missense change in exon 1 of MYF5 (c.283C>T [p.Arg95Cys]). Using in vitro assays, we show that this missense mutation acts as a loss-of-function allele by impairing MYF5 DNA binding and nuclear localization. We performed whole-genome sequencing in one affected individual with the frameshift mutation and did not identify additional rare variants in the haploidentical region that might account for differences in severity among the families. These data support the direct role of MYF5 in rib, spine, and extraocular muscle formation in humans.