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The BIOFIRE SPOTFIRE Respiratory (R) Panel is a novel, in vitro diagnostic PCR assay with 15 pathogen targets. The runtime is about 15 min which is the shortest among similar panels in the market. We evaluated the performance of the SPOTFIRE R Panel with 151 specimens, including 133 collected from the upper respiratory tract (URT), 13 from the lower respiratory tract (LRT) and 5 external quality assessment program (EQAP) samples. The respiratory specimens were enrolled throughout the first two post-COVID-19 influenza seasons in Hong Kong (March to December 2023). For URT specimens, full concordance was observed between the SPOTFIRE R Panel and the standard-of-care FilmArray Respiratory 2.1 plus Panel (RP2.1 plus ) for 109 specimens (109/133, 81.95%). After discrepant analysis, the SPOTFIRE R Panel identified more pathogens than the RP2.1 plus in 15 specimens and vice versa in 3 specimens. The per-target negative and positive percentage agreement (NPA and PPA) were 92.86-100% except the PPA of adenovirus (88.24%). For LRT and EQAP samples, all results were fully concordant. To conclude, the performance of the SPOTFIRE R Panel was comparable to the RP2.1 plus .

As the COVID-19 pandemic progresses, there is an increasing need for rapid, accessible assays for SARS-CoV-2 detection. We present a clinical evaluation and real-world implementation of the INDICAID COVID-19 rapid antigen test (INDICAID rapid test). A multisite clinical evaluation of the INDICAID rapid test using prospectively collected nasal (bilateral anterior) swab samples from symptomatic subjects was performed. The INDICAID rapid test demonstrated a positive percent agreement (PPA) and negative percent agreement (NPA) of 85.3% (95% confidence interval [95% CI], 75.6% to 91.6%) and 94.9% (95% CI, 91.6% to 96.9%), respectively, compared to laboratory-based reverse transcriptase PCR (RT-PCR) using nasal specimens. The INDICAID rapid test was then implemented at COVID-19 outbreak screening centers in Hong Kong as part of a testing algorithm (termed "dual-track") to screen asymptomatic individuals for prioritization for confirmatory RT-PCR testing. In one approach, preliminary positive INDICAID rapid test results triggered expedited processing for laboratory-based RT-PCR, reducing the average time to confirmatory result from 10.85 h to 7.0 h. In a second approach, preliminary positive results triggered subsequent testing with an onsite rapid RT-PCR, reducing the average time to confirmatory result to 0.84 h. In 22,994 asymptomatic patients, the INDICAID rapid test demonstrated a PPA of 84.2% (95% CI, 69.6% to 92.6%) and an NPA of 99.9% (95% CI, 99.9% to 100%) compared to laboratory-based RT-PCR using combined nasal/oropharyngeal specimens. The INDICAID rapid test has excellent performance compared to laboratory-based RT-PCR testing and, when used in tandem with RT-PCR, reduces the time to confirmatory positive result. IMPORTANCE Laboratory-based RT-PCR, the current gold standard for COVID-19 testing, can require a turnaround time of 24 to 48 h from sample collection to result. The delayed time to result limits the effectiveness of centralized RT-PCR testing to reduce transmission and stem potential outbreaks. To address this, we conducted a thorough evaluation of the INDICAID COVID-19 rapid antigen test, a 20-minute rapid antigen test, in both symptomatic and asymptomatic populations. The INDICAID rapid test demonstrated high sensitivity and specificity with RT-PCR as the comparator method. A dual-track testing algorithm was also evaluated utilizing the INDICAID rapid test to screen for preliminary positive patients, whose samples were then prioritized for RT-PCR testing. The dual-track method demonstrated significant improvements in expediting the reporting of positive RT-PCR test results compared to standard RT-PCR testing without prioritization, offering an improved strategy for community testing and controlling SARS-CoV-2 outbreaks.

Background: Human fecal carriage of Enterobacteriaceae possessing mobilized colistin resistance genes (mcr-1 and mcr-2) remains obscure in Hong Kong. As part of routine surveillance on emerging antibiotic resistance, we conducted a prospective study on this topic in a regional hospital in Hong Kong., Methods: From October 31 to November 25, 2016, all fecal specimens submitted for routine analysis were included in this surveillance study. These comprised 672 consecutive routine fecal specimens collected from 616 individuals. Fecal specimens were screened for colistin-resistant Enterobacteriaceae by culture-based method, and the presence of mcr-1 and mcr-2 genes in resistant isolates was identified by polymerase chain reaction and Sanger sequencing. Whole genome sequencing (WGS) of mcr-1-possessing Escherichia coli strains was facilitated using Illumina® MiSeq® followed by sequence analysis with appropriate bioinformatics tools., Results: Fourteen mcr-1-positive E. coli strains were isolated from 14 separate individuals (2.08% of total fecal specimens), with 9 of them being asymptomatic, healthy clients coming for health assessment. No mcr-2-possessing Enterobacteriaceae was identified. Colistin minimum inhibitory concentrations of these mcr-1-positive isolates ranged from 2 to 4 μg/mL. All these isolates were susceptible to carbapenems with 2 being extended spectrum β-lactamase producers. WGS data revealed that these isolates belonged to at least 12 different sequence types (STs) and possessed diversified plasmid replicons, virulence and acquired antibiotic resistance genes. Further study on an E. coli ST201 strain (Pasteur scheme) revealed coexistence of 47,818-bp IncP-1 and 33,309-bp IncX4 types of mcr-1 plasmids, which was a combination of stability and high transmissibility., Conclusions: To the best of our knowledge, this is the first study on human fecal carriage of Enterobacteriaceae possessing mcr-1 and mcr-2 genes in Hong Kong. Our data further revealed asymptomatic carriage of mcr-1-possessing Enterobacteriaceae by both patients and healthy individuals. This is alarming considering wide diversity and high transmissibility of mcr-1 plasmids, which potentially facilitate emergence of pan-drug-resistant bacteria in future infection. This also highlights the importance of surveillance on emerging antibiotic resistance, especially for patients under intensive care.

This report presents the latest estimates of Hong Kong domestic health spending for financial years 1989/90 to 2011/12, cross-stratified and categorized by financing source, provider, and function. Total expenditure on health (TEH) was HK$101 985 million in financial year 2011/12, which represents an increase of HK$8580 million or 9.2% over the preceding year. TEH grew faster relative to gross domestic product (GDP) leading to a rise in TEH as a percentage of GDP from 5.1% in 2010/11 to 5.2% in 2011/12. During the period 1989/90 to 2011/12, total health spending per capita (at constant 2012 prices) grew at an average annual rate of 4.8%, which was faster than the average annual growth rate of per capita GDP by 1.8 percentage points. In 2011/12, public and private expenditure on health increased by 8.3% and 10.0% when compared with 2010/11, reaching HK$49,262 million and HK$52,723 million respectively. Consequently, public share of total health expenditure dropped slightly from 48.7% to 48.3% over the year. Of private spending, the most important source of health financing was out-of-pocket payments by households (34.9% of TEH), followed by employer-provided group medical benefits (7.5%) and private insurance (7.4%). It is worth noting that private insurance will likely take over employers as the second largest private payer if the insurance market continues to expand at the current rate. Of the HK$101,985 million total health expenditure in 2011/12, current expenditure comprised HK$96,572 million (94.7%), whereas HK$5413 million (5.3%) was for capital expenses (ie investment in medical facilities). Analysed by health care function, services of curative care accounted for the largest share of total health spending (65.2%), which was made up of ambulatory services (33.6%), in-patient curative care (26.9%), day patient hospital services (4.1%), and home care (0.5%). Notwithstanding its small share, the total spending for day patient hospital services shows an increasing trend over the period 1989/90 to 2011/12, likely as a result of policy directives to shift the emphasis from in-patient to day patient care. Hospitals accounted for an increasing share of total spending, from 28.2% in 1989/90 to 46.8% in 2002/03 and then dropped slightly to 42% to 44% during the period 2005/06 to 2011/12, which was primarily driven by reduced expenditure of Hospital Authority. As a result of the epidemics which are of public health importance (eg avian flu, SARS, swine flu) and the expansion of private health insurance market in the last two decades, spending on provision and administration of public health programmes, and general health administration and insurance accounted for increasing, though less significant, shares of total health spending over the period. Without taking into account capital expenses (ie investment in medical facilities), public current expenditure on health amounted to HK$45,321 million (46.9% of total current expenditure) in 2011/12 with the remaining HK$51,251 million made up of private sources of funds. Public current expenditure was mostly incurred at hospitals (74.1%), whereas private current expenditure was mostly incurred at providers of ambulatory health care (51.2%). Although both public and private spending were mostly expended on personal health care services and goods (91.1% of total current spending), the distributional patterns among functional categories differed. Public expenditure was targeted at in-patient care (47.3%) and substantially less on out-patient care (27.4%). In comparison, private spending was mostly concentrated on out-patient care (42.7%), whereas in-patient care (24.7%) and medical goods outside the patient care setting (19.9%) comprised the majority of the remaining share. Compared to the Organisation for Economic Co-operation and Development countries, Hong Kong has devoted a relatively low percentage of GDP to health care in the last decade. As a share of total spending, public funding (either general government revenue or social security funds) was also lower than those in most economies with comparable economic development and public revenue collection base. Nonetheless, Hong Kong health care system achieved service quality and health outcome that fared well by global standards, indicating cost efficiency and effectiveness.

Background: The efficacy of seasonal influenza vaccination against 2009 pandemic influenza A(H1N1) remains unclear., Methods: One child aged 6-17 years in each of 796 households was randomized to receive 2009-2010 seasonal trivalent inactivated influenza vaccine (TIV) or saline placebo between August 2009 and February 2010. Households were followed up with serology, symptom diaries, and collection of respiratory specimens during illnesses. The primary outcomes were influenza infection confirmed by reverse-transcription polymerase chain reaction (RT-PCR) or a ≥4-fold rise in serum antibody titer measured by hemagglutination inhibition assay., Results: Receipt of TIV led to 8-13-fold mean geometric rises in antibody titers against seasonal A and B viruses, but only 1.5-fold mean geometric rises against the pandemic A(H1N1) virus that was not included in the vaccine. Children who received TIV had a reduced risk of seasonal influenza B confirmed by RT-PCR, with a vaccine efficacy estimate of 66% (95% confidence interval [CI], 31%-83%). Children who received TIV also a had reduced risk of pandemic influenza A(H1N1) indicated by serology, with a vaccine efficacy estimate of 47% (95% CI, 15%-67%)., Conclusions: Seasonal TIV prevented pandemic influenza A(H1N1) and influenza B infections in children. Pandemic A(H1N1) circulated at the time of vaccination and for a short time afterward with no substantial seasonal influenza activity during that period. The potential mechanism for seasonal TIV to provide protection, possibly short lived, for children against pandemic A(H1N1) infection despite poor cross-reactive serologic response deserves further investigation. Clinical Trials Registration. NCT00792051.

During the first wave of an influenza pandemic prior to the availability of an effective vaccine, healthcare workers (HCWs) may be at particular risk of infection with the novel influenza strain. We conducted a cross-sectional study of the prevalence of antibody to pandemic influenza A (H1N1) 2009 (pH1N1) among HCWs in Hong Kong in February-March 2010 following the first pandemic wave. Sera collected from HCWs were tested for antibody to pH1N1 influenza virus by viral neutralisation (VN). We assessed factors associated with higher antibody titres, and we compared antibody titres in HCWs with those in a separate community study. In total we enrolled 703 HCWs. Among 599 HCWs who did not report receipt of pH1N1 vaccine, 12% had antibody titre ≥1:40 by VN. There were no significant differences in the age-specific proportions of unvaccinated HCWs with antibody titre ≥1:40 compared with the general community following the first wave of pH1N1. Under good adherence to infection control guidelines, potential occupational exposures in the hospital setting did not appear to be associated with any substantial excess risk of pH1N1 infection in HCWs. Most HCWs had low antibody titres following the first pandemic wave., (Copyright © 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: While patterns of incidence of clinical influenza have been well described, much uncertainty remains over patterns of incidence of infection. The 2009 pandemic provided both the motivation and opportunity to investigate patterns of mild and asymptomatic infection using serological techniques. However, to date, only broad epidemiological patterns have been defined, based on largely cross-sectional study designs with convenience sampling frameworks., Methods and Findings: We conducted a paired serological survey of a cohort of households in Hong Kong, recruited using random digit dialing, and gathered data on severe confirmed cases from the public hospital system (>90% inpatient days). Paired sera were obtained from 770 individuals, aged 3 to 103, along with detailed individual-level and household-level risk factors for infection. Also, we extrapolated beyond the period of our study using time series of severe cases and we simulated alternate study designs using epidemiological parameters obtained from our data. Rates of infection during the period of our study decreased substantially with age: for 3-19 years, the attack rate was 39% (31%-49%); 20-39 years, 8.9% (5.3%-14.7%); 40-59 years, 5.3% (3.5%-8.0%); and 60 years or older, 0.77% (0.18%-4.2%). We estimated parameters for a parsimonious model of infection in which a linear age term and the presence of a child in the household were used to predict the log odds of infection. Patterns of symptom reporting suggested that children experienced symptoms more often than adults. The overall rate of confirmed pandemic (H1N1) 2009 influenza (H1N1pdm) deaths was 7.6 (6.2-9.5) per 100,000 infections. However, there was substantial and progressive increase in deaths per 100,000 infections with increasing age from 0.66 (0.65-0.86) for 3-19 years up to 220 (50-4,000) for 60 years and older. Extrapolating beyond the period of our study using rates of severe disease, we estimated that 56% (43%-69%) of 3-19 year olds and 16% (13%-18%) of people overall were infected by the pandemic strain up to the end of January 2010. Using simulation, we found that, during 2009, larger cohorts with shorter follow-up times could have rapidly provided similar data to those presented here., Conclusions: Should H1N1pdm evolve to be more infectious in older adults, average rates of severe disease per infection could be higher in future waves: measuring such changes in severity requires studies similar to that described here. The benefit of effective vaccination against H1N1pdm infection is likely to be substantial for older individuals. Revised pandemic influenza preparedness plans should include prospective serological cohort studies. Many individuals, of all ages, remained susceptible to H1N1pdm after the main 2009 wave in Hong Kong. Please see later in the article for the Editors' Summary.

Fetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese β-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5%; that resulting from the BCL11A polymorphism is 6.4%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations.

Background: Healthcare workers in many countries are recommended to receive influenza vaccine to protect themselves as well as patients. A monovalent H1N1 vaccine became available in Hong Kong in December 2009 and around 10% of local healthcare workers had received the vaccine by February 2010., Methods: We conducted a cross-sectional study of the prevalence of antibody to pandemic (H1N1) 2009 among HCWs in Hong Kong in February-March 2010 following the first pandemic wave and the pH1N1 vaccination campaign. In this study we focus on the subset of healthcare workers who reported receipt of non-adjuvanted monovalent 2009 H1N1 vaccine (Panenza, Sanofi Pasteur). Sera collected from HCWs were tested for antibody against the pH1N1 virus by hemagglutination inhibition (HI) and viral neutralization (VN) assays., Results: We enrolled 703 HCWs. Among 104 HCWs who reported receipt of pH1N1 vaccine, 54% (95% confidence interval (CI): 44%-63%) had antibody titer ≥1∶40 by HI and 42% (95% CI: 33%-52%) had antibody titer ≥1∶40 by VN. The proportion of HCWs with antibody titer ≥1∶40 by HI and VN significantly decreased with age, and the proportion with antibody titer ≥1∶40 by VN was marginally significantly lower among HCWs who reported prior receipt of 2007-08 seasonal influenza vaccine (odds ratio: 0.43; 95% CI: 0.19-1.00). After adjustment for age, the effect of prior seasonal vaccine receipt was not statistically significant., Conclusions: Our findings suggest that monovalent H1N1 vaccine may have had suboptimal immunogenicity in HCWs in Hong Kong. Larger studies are required to confirm whether influenza vaccine maintains high efficacy and effectiveness in HCWs.

Background: The relationship between seasonal influenza vaccine and susceptibility to 2009 pandemic A/H1N1 virus infection is not fully understood., Methods: One child 6-15 years of age from each of 119 households was randomized to receive 1 dose of inactivated trivalent seasonal influenza vaccine (TIV) or saline placebo in November 2008. Serum samples were collected from study subjects and their household contacts before and 1 month after vaccination (December 2008), after winter (April 2009) and summer influenza (September-October 2009) seasons. Seasonal and pandemic influenza were confirmed by serum hemagglutinination inhibition, viral neutralization titers, and reverse-transcription polymerase chain reaction performed on nasal and throat swab samples collected during illness episodes., Results: TIV recipients had lower rates of serologically confirmed seasonal A/H1N1 infection (TIV group, 8%; placebo group, 21%; P=.10) and A/H3N2 infection (7% vs 12%; P=A9), but higher rates of pandemic A/H1N1 infection (32% vs 17%; [Formula: see text]). In multivariable analysis, those infected with seasonal influenza A during the study had a lower risk of laboratory-confirmed pandemic A/H1N1 infection (adjusted odds ratio [OR], 0.35; 95% confidence interval [CI], 0.14-0.87), and receipt of seasonal TIV was unassociated with risk of pandemic A/H1N1 infection (adjusted OR, 1.11; 95% CI, 0.54-2.26)., Conclusions: TIV protected against strain-matched infection in children. Seasonal influenza infection appeared to confer cross-protection against pandemic influenza. Whether prior seasonal influenza vaccination affects the risk of infection with the pandemic strain requires additional study., Clinical Trials Registration: ClinicalTrials.gov number NCT00792051 .

Background: Serial cross-sectional data on antibody levels to the 2009 pandemic H1N1 influenza A virus from a population can be used to estimate the infection attack rates and immunity against future infection in the community., Methods: From April through December 2009, we obtained 12,217 serum specimens from blood donors (aged 16-59 years), 2520 specimens from hospital outpatients (aged 5-59 years), and 917 specimens from subjects involved in a community pediatric cohort study (aged 5-14 years). We estimated infection attack rates by comparing the proportions of specimens with antibody titers ≥ 1:40 by viral microneutralization before and after the first wave of the pandemic. Estimates were validated using paired serum samples from 324 individuals that spanned the first wave. Combining these estimates with epidemiologic surveillance data, we calculated the proportion of infections that led to hospitalization, admission to the intensive care unit (ICU), and death., Results: We found that 3.3% and 14% of persons aged 5-59 years had antibody titers ≥ 1:40 before and after the first wave, respectively. The overall attack rate was 10.7%, with age stratification as follows: 43.4% in persons aged 5-14 years, 15.8% in persons aged 15-19 years, 11.8% in persons aged 20-29 years, and 4%-4.6% in persons aged 30-59 years. Case-hospitalization rates were 0.47%-0.87% among persons aged 5-59 years. Case-ICU rates were 7.9 cases per 100,000 infections in persons aged 5-14 years and 75 cases per 100,000 infections in persons aged 50-59 years, respectively. Case-fatality rates were 0.4 cases per 100,000 infections in persons aged 5-14 years and 26.5 cases per 100,000 infections in persons aged 50-59 years, respectively., Conclusions: Almost half of all school-aged children in Hong Kong were infected during the first wave. Compared with school children aged 5-14 years, older adults aged 50-59 years had 9.5 and 66 times higher risks of ICU admission and death if infected, respectively.

Enhanced fetal hemoglobin (Hb F) production can partially compensate for the lack of adult hemoglobin (Hb A) in patients with beta-thalassemia major or intermedia, and ameliorate the clinical severity of these diseases. To further elucidate factors governing Hb F levels, we evaluated demographic, clinical, laboratory, and genetic characteristics in 241 unrelated adult beta-thalassemia carriers in Hong Kong. They had wide variations in Hb F and F-cell numbers skewing toward higher levels. Individuals who coinherited the Xmn IT-allele in the (G)gamma-globin gene promoter had higher Hb F and more F-cells compared with those lacking the Xmn I T-allele. However, both groups exhibited a similarly wide spread of Hb F and F-cells. The correlation of Hb F and F-cells corresponded well to both linear and exponential models, suggesting multiple mechanisms for Hb F augmentation. The heritabilities of Hb F and F-cells were calculated in 66 families (111 parents who were beta-thalassemia carriers and 82 asymptomatic offspring) to be 0.7 to 0.9. The Xmn I polymorphism accounted for 9% of the Hb F and 13% of the F-cell heritabilities. These results suggest that these family members are well suited for genome wide association studies that will identify genetic loci regulating Hb F production, and likely novel pharmacological targets for reactivating Hb F production in adults., (Copyright 2008 Wiley-Liss, Inc.)

Background: The thalassaemias are the commonest blood disorders worldwide, with South East Asia and southern China as areas of high prevalence. Accurate diagnosis of these disorders helps in clinical management with improved outcome., Methods: The alpha-globin genotypes of 100 Chinese patients in Hong Kong with haemoglobin H (Hb H) disease were characterised. Single-tube multiplex gap-PCR was used to detect --(SEA), -alpha(3.7) and -alpha(4.2), while Hb CS, Hb QS and codon 30 (DeltaGAG) were identified by single-tube multiplex amplification refractory mutation system (ARMS). Automated direct nucleotide sequencing of the amplified alpha2- and alpha1-globin genes was performed to characterise other non-deletional alpha-thalassaemia determinants., Results: In the 100 cases studied, 99 cases had --(SEA) in combination with deletional alpha(+)-thalassaemia or non-deletional alpha-globin gene mutation involving the alpha2-globin gene. In 70 cases of the deletional form, 43 cases showed the genotype of (--(SEA)/-alpha(3.7)) and 27 cases of (--(SEA)/-alpha(4.2)). Three of the 27 cases of (--(SEA)/-alpha(4.2)) were found to have Hb Q-Thailand linked in-cis with -alpha(4.2). The remaining 30 cases were of non-deletional form with the following genotypes: 11 cases of (--(SEA)/alpha(HbCS)alpha), 9 cases of (--(SEA)/alpha(HbQS)alpha), 3 cases of (--(SEA)/alpha(cd30 (DeltaGAG))alpha), 3 cases of (--(SEA)/alpha(cd31)alpha), 2 cases of (--(SEA)/alpha(poly-A)alpha), 1 case of (--(SEA)/alpha(HbWestmead)alpha) and 1 case of (--(non-SEA)/alpha(HbQS)alpha)., Conclusions: Based on two rapid diagnostic tests, multiplex gap-PCR and multiplex ARMS, more than 90% of the cases were genetically characterised. This laboratory strategy should be widely applicable for genetic diagnosis of alpha-thalassaemia.

In this report we examine the (AC)n(AT)xTy motif residing -530 bp 5' upstream of the beta-globin gene in Chinese thalassaemic patients. This motif is a putative binding site for a repressor protein, termed beta protein 1 (BP1) (Berg et al., Nucleic Acids Res 1989;17:8833-8852). Variations in the (AC)n(AT)xTy repeats affect the binding affinity of BP1, thereby altering the expression of the beta-globin gene. Eight different configurations of this repeat motif are identified in our population of Chinese beta-thalassaemia patients. A (AC)3(AT)7T5 motif was identified among these thalassaemia patients and its influence in beta-globin gene expression was studied using stable transfection assay in murine erythroleukemia (MEL) cells. Our data demonstrated that the (AC)3(AT)7T5 motif has a moderately strong repressor effect on the expression of the cis-linked beta-globin gene. The high affinity of BP1 for this motif may result in the suppression of the transcription of the beta-globin gene (Berg et al., Am J Hematol 1991;36:42-47). We postulate that silencer elements in the beta-globin promoter play an important role in modifying the clinical presentation of the disease., ((c) 2006 Wiley-Liss, Inc.)

Anti-Lepore haemoglobins (Hb) are rare betadelta fusion variants that arise from non-homologous crossover during meiosis, resulting in a delta-betadelta-beta configuration. A novel anti-Lepore mutation (anti-Lepore Hong Kong) was found in two Chinese families with raised Hb A(2). Direct sequencing revealed a crossover within a 54-bp region spanning the junction of cap site (CAP) and exon 1, which predicted the production of normal delta-globin. Determination of alpha/beta-mRNA ratios by quantitative real-time polymerase chain reaction demonstrated downregulation of the beta gene in cis due to the interposed betadelta fusion gene. Although heterozygotes have normal red cell indices and are clinically silent, compound heterozygotes with beta(0) mutation in trans produce a mild thalassaemia intermedia phenotype with a markedly raised Hb A(2) level that may mimic clinically mild Hb E-beta(+)-thalassaemia. Awareness of the presence of anti-Lepore Hong Kong will help to resolve diagnostic problems in regions with significant prevalence of globin disorders.

An audit on the turnaround time (TAT) of a hospital phlebotomy service was undertaken to assess whether or not the existing service standards can satisfy the needs and expectations of both the external and internal customers. A job request survey form was designed and implemented in June 2005 to be used by the day shift to record the number of phlebotomy cases and the corresponding TAT. The success rate and complaints related to phlebotomy were also recorded. Phlebotomists provided the data for this study on an honor system basis. Out of 2,118 test requests received by the laboratory, 1,867 (88.1 percent) were phlebotomy requests. Approximately 62 phlebotomy requests were recorded, on average, per day shift. The average time, expressed in mean +/- standard deviation (SD) needed for response, arrival, and job completion was 7.4 +/- 1.5 minutes, 5.6 +/- 1.6 minutes, and 10.4 +/- 2.4 minutes respectively, with an average overall TAT of 23.4 +/- 4.1 minutes per phlebotomy request. The success rate at first phlebotomy attempt was 97 percent, and only one complaint was received during the audit period. This study may help hospital management identify possible bottlenecks that delay phlebotomy TAT, thus improving service standards in this area.

Objectives: To determine the cost effectiveness of a universal prenatal screening program for alpha- and beta-thalassaemia., Methods: We retrospectively reviewed our program from 1998 to 2002, and calculated the direct and indirect costs of various components., Results: 18,936 women were screened at our prenatal clinic and 153 couples were subsequently referred to our Prenatal Diagnostic Centre for counselling and further investigations. In addition, there were 238 tertiary referrals and 157 self-referrals. After investigations, 84 fetuses were at risk of beta-thalassaemia major/beta-E thalassaemia, 19 of them were affected and 18 were aborted. The total expenditure on our program (HK 10.0 million dollars) would be less than the postnatal service costs (HK 40.4 million dollars) for 18beta-thalassaemia major fetuses if they were born. Of 361 women at risk of carrying a homozygous alpha0-thalassaemia fetus, 311 (86.2%) opted for the indirect approach (using serial ultrasound examinations to exclude Hb Bart's disease), and 76 (24.5%) subsequently underwent an invasive test for a definitive diagnosis. The sensitivity and false positive rate of this indirect approach was 100.0% and 2.9% respectively., Conclusion: It is cost effective to run a universal prenatal screening program in an area where both beta-thalassaemia and alpha-thalassaemia are prevalent. The indirect approach can effectively avoid an invasive test in unaffected pregnancies., (Copyright 2004 John Wiley & Sons, Ltd.)

Guidelines for the prevention and management of red cell alloantibodies during pregnancy, related to anti-D in particular, are well established in Caucasian populations. However, because of the racial difference of the blood group distribution, applicability to Chinese is unknown as a result of insufficient data on the prevalence and their outcome. In a retrospective review of 28,303 (21,327 Chinese) antenatal attendances from 1997 to 2001, 213 (0.79%) women were found to have a total of 230 irregular antibodies. About 137 (0.64%) were ethnic Chinese, and a total of 160 irregular antibodies were identified in their blood samples. About 58 of these Chinese women (0.27%) were found to have 66 clinically significant antibodies. There was only one case of anti-D detected in an Rh(D)-negative subject. Our study shows the overall prevalence of clinically significant antibodies in Chinese women, which was not different from that of the Western population. However, the specificities of the antibodies differ with the commonest antibodies encountered; these being anti-Mi (57.6%), anti-E (19.7%), anti-S (10.6%) and anti-c (7.6%). Neonatal jaundice was observed in 37 babies and 10 of them required phototherapy. The findings support the previous recommendation that routine antenatal antibody screening for Chinese women may not be worthwhile except in Rh(D)-negative subjects or those with an antecedent history of haemolytic disease of the newborn (HDN). The relative high incidence of anti-Mi in the present study and the local population, in general, may warrant a large-scale prospective study of pregnancy outcome in these subjects, especially in the light of the previous case reports of HDN because of anti-Mi.

Objective: To determine the incidence of venous thromboembolic disease in children of Chinese origin, and associated predisposing factors. DESIGN. Retrospective case series., Setting: A general, public hospital serving a population of approximately 181,000 children in Hong Kong., Patients and Methods: Hong Kong Chinese children under the age of 15 years who were diagnosed with a symptomatic venous thromboembolic event between 1995 and 2000 were included. Data on clinical features, predisposing factors, treatment, and outcome were obtained from review of hospital medical records., Results: Eight children (five girls and three boys) of mean age 11.5 years (range, 0-14.7 years) were included in the study. They presented with deep vein thrombosis (n=4, with pulmonary embolism in one), superior vena cava thrombosis (n=1), and cerebral venous sinus thrombosis (n=3). Predisposing factors included hereditary protein C deficiency (n=3), protein S deficiency (n=2), anticardiolipin antibodies (n=1), malignancy (n=3), recent neurosurgery (n=2), infection (n=1), with multiple predisposing factors seen in three patients. Anticoagulant therapy was prescribed in five patients, and long-term warfarin therapy was required in two cases. Venous thromboembolic disease resolved in all children, but one patient had a recurrence after cessation of warfarin therapy, and one patient had post-thrombotic syndrome., Conclusion: The rate of venous thromboembolic disease in Hong Kong Chinese children was comparable to that seen in Caucasian children, with an annual incidence of 0.74 per 100,000 children. Predisposing factors, including hereditary prothrombotic conditions, were common.

The establishment of esophageal cancer cell lines can facilitate the search for molecular mechanisms underlying its pathogenesis. Two novel human esophageal squamous cell carcinoma (ESCC) cell lines, HKESC-2 and HKESC-3, were established from a moderately differentiated ESCC of a 46-year-old Chinese woman and a well-differentiated ESCC of a 74-year-old Chinese man, both from Hong Kong. The pathological characteristics (morphological, immunohistochemical, and electron microscopic studies), tumorigenicity in nude mice, cytogenetic features, and DNA ploidy of the two cell lines were investigated. The two cell lines have been maintained in vitro for more than 17 months and passaged over 85 times for HKESC-2 and 58 times for HKESC-3. Both grew as monolayers, with a doubling time of 24 hours for HKESC-2 and 48 h for HKESC-3. Their squamous epithelial nature was authenticated by their strong immunopositivity with the anti-cytokeratin antibodies and the ultrastructural demonstration of tonofilaments and desmosomes. They are tumorigenic in nude mice and had DNA aneuploidy. G-banding cytogenetic analysis showed hyperdiploidy in HKESC-2 and near-tetraploidy in HKESC-3. Frequent breakpoints were noted at 1p22, 1p32, and 9q34 in HKESC-2 and at 1p31, 3p25, 3p14, 6q16, 6q21, 8p21, 9q34, 13q32, and 17q25 in HKESC-3. Comparative genomic hybridization analysis found that chromosomal gains were at 3q24-qter, 5q21-qter, 8q11-qter, 13q21-q31, 17q11-qter, 19, 22q22 for HKESC-2 and at 3q13-qter, 5p, 6p, 9q21-qter, 10q21-q22, 12q15-pter, 14q24-qter, 16, 17q24-qter, 20 for HKESC-3. Chromosomal losses were at 3p13-pter, 18q12-qter for HKESC-3. These two newly established cell lines will be useful tools in the study of the molecular pathogenesis and biological behavior of ESCC cells and for testing new therapeutic reagents for ESCC in the future.