Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.

Awareness of fertility preservation among Chinese medical students.

INTRODUCTION: The fertility preservation (FP) services offered in Hong Kong are underutilised. There have been no previous studies on Chinese medical students to investigate the underlying reasons for this underutilisation in terms of awareness, knowledge, and attitudes towards FP and age-related fertility. METHODS: This was a cross-sectional survey among Chinese medical students in Hong Kong. RESULTS: The majority of participants (77.8%) were not familiar with any clinics or specialists who provide FP services. The vast majority (88.1%) underestimated female infertility at age 45 years, and 89.8% overestimated the age of male fertility decline. The students' FP knowledge was mainly acquired from electronic media (58.4%) and medical school (57.6%). Medical students showed overwhelming support towards FP for medical reasons (97.9%) but had mixed responses about FP for elective reasons related to career development in women (58.8%). Of the participants, 80.2% agreed that the government should subsidise FP services for patients with medical reasons. CONCLUSION: This study highlights the limited awareness and knowledge of FP among Chinese medical students. There is a strong worldwide need to increase education about and exposure to FP in the medical curriculum and improve medical students' knowledge.

Preliminary evidence for the features of non-reducible discogenic low back pain: survey of an international physiotherapy expert panel with the Delphi technique.

OBJECTIVES: The lumbar intervertebral disc is a known source of low back pain (LBP). Various clinical features of discogenic pain have been proposed, but none have been validated. Several subgroups of discogenic pain have been hypothesised, with non-reducible discogenic pain (NRDP) proposed as a relevant clinical subgroup. The objectives of this study were to obtain consensus from an expert panel on the features of discogenic low back pain, the existence of subgroups of discogenic LBP, particularly NRDP, and the associated features of NRDP. DESIGN: Three-round Delphi survey. PARTICIPANTS: Twenty-one international physiotherapists with expertise in LBP. METHODS: Panellists listed and ranked features that they believed to be indicative of discogenic pain and NRDP. On completion of Round 3, features with ≥50% agreement between panellists were deemed to have reached consensus. RESULTS: After three rounds, 10 features of discogenic LBP were identified. Nineteen of the panellists believed that NRDP was a subgroup of discogenic LBP, and nine features of NRDP were identified. CONCLUSION: This study provides preliminary validation for the features associated with discogenic LBP. It also provides evidence supporting the existence and features of NRDP as a separate clinical subgroup of discogenic LBP.

Rapid and specific determination of DNA adducts for clinical diagnosis of poisoning and disease associated with aristolochic acid.

1. A liquid chromatography-mass spectrometry method was developed to detect and characterise aristocholic acid-DNA adducts in biological samples. 2. The detection of DNA adducts in plasma, urine or the cells found in urine may be useful to support the diagnosis and monitoring of aristocholic acid-associated poisoning and disease. 3. Efforts should be made to improve the sensitivity and specificity of this approach for the detection and characterisation of exposure to other mutagens/carcinogens.

Parental attitudes on expanded newborn screening in Hong Kong.

OBJECTIVES: Classical inborn errors of metabolism (IEM) affect about 1 in 4000 in Hong Kong. Despite the widespread implementation of expanded newborn screening in most countries, Hong Kong only screen for three conditions and the awareness of public has not been evaluated. This is the first study to examine the parental knowledge and attitudes towards expanded newborn screening in Hong Kong. METHODS: A cross-sectional survey was conducted in the Princess Margaret Hospital. Parents with babies born from 1st July to 31st October 2010 were randomly recruited. Fifteen questions relating to the knowledge of newborn screening and biochemical genetic disorders, preferences about the features of newborn screening, the economic values, and attitudes toward false positive results were asked. RESULTS: In total, 172 subjects were interviewed by phone (overall response rate 97.2%). There were 87.8% parents who had never heard of expanded newborn screening; 99.4% demanded more parental education; 83.5% thought the programme should be implemented immediately; 97.7% supported population screening, even though the diseases are incurable; 93.9% accepted the possibility of false positive and false negative results; 70.4% preferred a voluntary basis; 83.2% believed that the programme should be fully government funded as basic primary care; 98.8% agreed that Hong Kong should follow mainland China's policy on expanded newborn screening; 98.2% required pre-test counseling; and 96.4% required an explicit parental consent before blood sampling. CONCLUSIONS: The response from parents overwhelmingly favoured having expanded newborn screening in Hong Kong. Parental tolerance was high. Parents valued the parental autonomy with informed consent and pre-test counseling the most. The success of any screening programme requires the public participation and this study is the first to prove the parental call for an expanded newborn screening in Hong Kong.

In search of the diagnosis, and the patient: transient galactosemia demystified after 14 years.

Infantile galactosemia can be caused by inborn errors of galactose metabolism or other rare causes like Fanconi-Bickel syndrome, congenital porto-systemic shunting and multiple hepatic arterio-venous malformations. All these disease entities are however not commonly seen. We report a case of transient infantile galactosemia who first presented in the 1990s, for which no underlying pathology could be identified despite extensive investigations. The diagnosis had not been apparent until after more than a decade, at that time the patient was lost to contact. Considering the potential diagnosis an important and significant one, efforts were made by the case pathologists and clinicians to search for the patient. Ethical dilemmas were encountered during the search of the patient, which involved issues of patient confidentiality and autonomy, and the doctors' duty-to-care. Modern biochemical and molecular testing confirmed the diagnosis after the patient was finally found. The case illustrates the power of molecular testing to retrospectively diagnose an inherited metabolic disease when biochemical abnormalities have subsided, the value of an accurate and precise diagnosis, and the importance of appropriate genetic counselling in an apparently asymptomatic patient in the era of personalized medicine.

Prevalence of vertebral fracture in Asian men and women: comparison between Hong Kong, Thailand, Indonesia and Japan.

OBJECTIVES: Little is known about the prevalence of vertebral fracture among Asians. This study investigated the prevalence of radiographically defined vertebral fracture, and identified associated risk factors in the aged population of four Asian countries. STUDY DESIGN: In total, 1588 males and females aged ≥ 65 years were recruited from Hong Kong, Thailand, Indonesia and Japan. METHODS: Standard X-rays for the spine were taken and vertebral heights were measured. Vertebral fracture was defined as a reduction of >3 standard deviations in vertebral height ratio. Bone mineral density (BMD) of the hip was measured by dual energy X-ray absorptiometry, and anthropometric measurements were taken in Hong Kong and Japan. Other relevant data were entered in a standard questionnaire. RESULTS: The prevalence of vertebral fracture for both males and females was highest in Japan for younger (65-74 years) and older (≥ 75 years) age groups (36.6% and 37.6% for males; 18.8% and 28.7% for females). Lower hip BMD was associated with vertebral fracture in both sexes. Older age, lower quality of life score on Short Form-12 (physical), past longest occupation as a farmer, and history of cataract were significantly associated with vertebral fracture in females. However, smoking did not appear to be an important risk factor for vertebral fracture. CONCLUSIONS: Radiographic assessments for vertebral fracture were performed in all four Asian countries. The prevalence of vertebral fracture was highest in Japan. Lower hip BMD, poorer physical condition and past longest occupation as a farmer were associated with vertebral fracture.

BAG3-related myofibrillar myopathy in a Chinese family.

In contrast to the usual slow disease progression in myofibrillar myopathies, patients with Bag3opathy often have a rapidly progressive and more severe phenotype with a worse prognosis. We describe a Chinese patient, born to non-consanguineous parents, who first presented at age 6 with clumsy walking and difficult climbing staircase. With a history of restrictive lung disease previously diagnosed as asthma, she progressed rapidly with proximal myopathy, rigid spine and bilateral tightening of the Achilles tendons requiring surgical elongation. Hypertrophic cardiomyopathy with restrictive physiology was shown by echocardiogram. Moreover, prolonged QT interval was also noted in the patient. Family history was unremarkable yet her father was incidentally found to have prolonged QT interval. Mutation analysis with genomic DNA of the proband showed heterozygous de novo known mutation c.626C>T (p.Pro209Leu) and a germline variation c.772C>T (p.Arg258Trp) in BAG3. Her father was found to be a carrier of c.772C>T. Muscle biopsy findings were suggestive of myofibrillar myopathy on light microscopy and ultrastructural studies. To our knowledge, this is the first Chinese case of Bag3opathy so far reported.

Using the Theory of Planned Behaviour and implementation intentions to predict and facilitate upward family communication about mammography.

Regular mammography facilitates early detection of breast cancer, and thus increases the chances of survival from this disease. Daughter-initiated (i.e. upward) communication about mammography within mother-daughter dyads may promote mammography to women of screening age. The current study examined this communication behaviour within the context of the Theory of Planned Behaviour (TPB), and aimed to bridge the intention-behaviour gap by trialling an implementation intention (II) intervention that aimed to facilitate upward family communication about mammography. Young women aged 18-39 (N=116) were assigned to either a control or experimental condition, and the latter group formed IIs about initiating a conversation with an older female family member about mammography. Overall, those who formed IIs were more likely to engage in the target communication behaviour, however the intervention was most effective for those who reported low levels of intention at baseline. Perceived behavioural control emerged as the most important variable in predicting the target behaviour. The altruistic nature of this behaviour, and the fact that it is not wholly under volitional control, may have contributed to this finding. Future studies that systematically explore the relative roles of intention and perceived behavioural control in behaviours of this nature are warranted.

RYR1-related central core myopathy in a Chinese adolescent boy.

Central core myopathy is a rare, inherited neuromuscular disorder with a wide spectrum of phenotypic presentations. It is also considered an allelic disease of malignant hyperthermia. We report a case of central core myopathy in a Chinese adolescent boy presenting with atypical clinical features and a moderately elevated serum creatine kinase level. The diagnosis was made from the histopathological findings of central cores on muscle biopsy, and confirmed by the molecular genetic testing for the RYR1 gene mutation. This is the first case of central core myopathy confirmed by molecular study in our locality.

Refractory bulbar and respiratory dysfunction in a young Chinese woman with seronegative, muscle-specific tyrosine kinase antibody-positive myasthenia gravis: response to cyclophosphamide and rituximab treatment.

The use of cyclophosphamide and rituximab for patients with refractory myasthenia gravis has shown promising results. We report on a 31-year-old Chinese woman with acetylcholine receptor antibody-negative and muscle-specific tyrosine kinase antibody-positive generalised myasthenia gravis who had refractory bulbar dysfunction and respiratory failure despite immunosuppressive therapy and thymectomy, and partial and sustained responses to cyclophosphamide and rituximab treatment, respectively. Myasthenia crisis was diagnosed when she presented in the third trimester of pregnancy with dysphagia, bilateral ptosis, prominent fatigability, and respiratory failure. She required prolonged intensive care and non-invasive ventilatory support despite several courses of intravenous immunoglobulins and plasmapheresis. Pulse cyclophosphamide 500 mg/m(2) was given monthly for 4 consecutive months with a partial response. Rituximab 500 mg weekly was subsequently given for 4 weeks with a dramatic and sustained response. She remained symptom-free and assumed full maternal care at 1 year. To the authors' knowledge, this is the first report of a Chinese patient with refractory myasthenia gravis who responded to cyclophosphamide and rituximab.

An expedited stroke triage pathway: the key to shortening the door-to-needle time in delivery of thrombolysis.

OBJECTIVES: To assess time management of stroke thrombolysis triage and functional outcomes in patients receiving recombinant tissue plasminogen activator for hyperacute stroke, and identify bottlenecks in delivery of the treatment. DESIGN: Prospective study. SETTING: A university teaching hospital in Hong Kong. PATIENTS: Patients with suspected hyperacute stroke referred to the stroke thrombolysis team during October 2008 to September 2009. MAIN OUTCOME MEASURES: Time performance records including door-to-stroke team, door-to-needle, and onset-to-thrombolysis times. Functional outcomes by modified Rankin Scale score at 3 months, and thrombolysis-related complications including haemorrhagic transformations and mortality. RESULTS: During the 12-month period, 95 thrombolysis calls were received; recombinant tissue plasminogen activator was given intravenously to 17 (18%) of the patients and intra-arterially to 11 (12%). The mean (standard deviation) door-to-stroke team and the door-to-needle times for intravenous recombinant tissue plasminogen activator patients were 33 (25) and 80 (25) minutes, respectively; both were about 20 minutes longer than that recommended by the National Institute of Neurological Disorders and Stroke. The mean National Institute of Health Stroke Scale score for patients received intravenous recombinant tissue plasminogen activator was 16 (standard deviation, 7). The mean (standard deviation) onset-to-treatment time was 144 (42) minutes. Nine (53%) patients who received intravenous recombinant tissue plasminogen activator achieved favourable outcomes at 3 months, with a modified Rankin Scale score of 0 to 1. Symptomatic haemorrhage and mortality occurred in one (6%) patient. CONCLUSION: A dedicated stroke triage pathway is essential to ensure efficient and safe delivery of thrombolysis therapy. Improvements in door-to-stroke team time through integration with emergency medicine staff and neuroradiologists may improve thrombolysis eligibility.

Detection and characterisation of beta-globin gene cluster deletions in Chinese using multiplex ligation-dependent probe amplification.

BACKGROUND: Deletions in the beta-globin cluster causing thalassaemia and hereditary persistence of fetal haemoglobin (HPFH) are uncommon and difficult to detect. Data in Chinese are very scarce. AIMS: To use a recently available technique to investigate the frequencies and nature of beta-globin cluster deletions in Chinese. METHODS: 106 subjects with phenotypes of thalassaemia or HPFH and suspected to have deletions in the beta-globin cluster were studied. A commercially available kit employing multiplex ligation-dependent probe amplification (MLPA) was used to screen for deletions. Gap PCR and direct nucleotide sequencing were used to characterise deletions detected. RESULTS: 17 deletions in the beta-globin cluster were found in 17 patients: 8 of Chinese ((A)gammadeltabeta)(0) thalassaemia, 7 of Southeast Asian (Vietnamese) deletion and 2 of Thai ((A)gammadeltabeta)(0) thalassaemia. The only type of deletion detected in deltabeta-thalassaemia was Chinese ((A)gammadeltabeta)(0) thalassaemia. The deletional form of HPFH was rarely seen in only 1 case of Thai ((A)gammadeltabeta)(0) thalassaemia. Deletions presenting as beta-thalassaemia trait and raised HbF were all of the Southeast Asian (Vietnamese) deletion type. When these deletions were co-inherited with classical beta-thalassaemia mutations in compound heterozygous states, the phenotypes could be very variable. CONCLUSIONS: In the Chinese population, there are only relatively few types of deletions seen in the beta-globin cluster. MLPA is a fast and effective way of screening for these deletions. Characterisation of these deletions allows the development of simpler and more specific PCR-based tests for routine diagnostic use. Accurate prediction of phenotype is not always feasible. The molecular defects in many cases of HPFH still await discovery.

The HBS1L-MYB intergenic region on chromosome 6q23 is a quantitative trait locus controlling fetal haemoglobin level in carriers of beta-thalassaemia.

BACKGROUND: Fetal haemoglobin (HbF) level modifies the clinical severity of HBB disorders. Intergenic variants of HBS1L-MYB on chromosome 6q23 have recently been shown to be a major quantitative trait locus (QTL) influencing HbF levels in normal Caucasian adults. METHODS: A unique and well-characterised cohort of 238 Chinese subjects with beta-thalassaemia trait was used to conduct a single-nucleotide polymorphism (SNP) association study for HbF level. RESULTS: Within this locus, 29 trait-associated SNPs in a non-coding 56 kb segment were identified. They were divided into five linkage disequilibrium (LD) blocks in the Chinese participants. CONCLUSIONS: The data independently validate for the first time the significance of the HBS1L-MYB intergenic region in regulating HbF expression in a separate ethnic group that has a high prevalence of beta-thalassaemia. Functional studies to unravel the biological significance of this region in regulating HbF production is clearly indicated, which may lead to new strategies to modify the disease course of severe HBB disorders.

Aconite poisoning in camouflage.

The Toxicology Reference Laboratory has confirmed 10 cases of aconite poisoning from March 2004 to May 2006. In four of these 10 cases, the aconite herb was not listed in the written prescription. We report these four cases to highlight the problem of 'hidden' aconite poisoning.

Drug-induced hypoglycaemia--new insight into an old problem.

OBJECTIVE: To review the causes of drug-induced hypoglycaemia in patients not taking hypoglycaemic medications. DESIGN: Retrospective study. SETTING: Regional hospitals in Hong Kong. PATIENTS: Patients with suspected drug-induced hypoglycaemia without a known history of exposure to hypoglycaemic agents, referred to the Hospital Authority Toxicology Reference Laboratory from June 2005 to March 2006 inclusive. MAIN OUTCOME MEASURES: Rate of positive cases, laboratory findings, possible causes, age distribution, and final outcomes. RESULTS: A total of 51 such patients were referred, in whom the presence of oral hypoglycaemic agents was detected (or inferred) in 23 (45%). In 12 of the 23 patients, oral hypoglycaemic agents could only be detected by target analysis, not through broad-spectrum screening. Gliclazide and glibenclamide were detected in 14 and eight patients respectively, whereas glimepiride, nateglinide and rosiglitazone were detected in the remaining patient. Possible sources of oral hypoglycaemic agents included drug administration errors in residential care homes for the elderly (n=9), mistakenly taking medication of a family member or employer (n=6), taking stock medication by mistake (n=2), taking Chinese proprietary medicine adulterated with oral hypoglycaemic agents (n=1), taking unknown pills bought from a retail pharmacy (n=1), and unknown (n=4). Regarding these 23 patients, 17 (74%) were aged 70 years or above and 21 (91%) recovered uneventfully. CONCLUSION: Hypoglycaemia due to inadvertent use of oral hypoglycaemic agents is a recognised problem, particularly in cases where family members living in the same household are taking similar medications. Possible drug administration errors in residential care homes for the elderly should be investigated, and procedures rectified if confirmed. Health care providers should be vigilant to such potential errors, especially in cases of unexplained hypoglycaemia.