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Objectives : We aim to study the viral kinetics and host inflammatory response of RSV infection in older adults, and their correlation with disease severity. Methods : We performed a prospective observational study in adults with RSV infection. We serially collected nasal-throat swabs for quantification of RSV-A and RSV-B viral load, and peripheral blood samples for measurement of cytokine/chemokine concentrations. The study endpoints were (i) requiring supplemental oxygen therapy, and (ii) non-invasive ventilation, intensive care, or died within 30 days of admission. We performed multivariable logistic regression models to identify independent variables for severe disease. Results : We enrolled 71 hospitalized patients and 10 outpatients treated for RSV infection (median age 75 years, 51% male, and 74% with comorbidities). Among hospitalized patients, 61% required supplemental oxygen therapy, and 18% had severe disease requiring non-invasive ventilation or intensive care, or died within 30 days. Inflammatory cytokine/chemokines IL-6, CXCL8/IL-8, CXCL9/MIG and CXCL10/IP-10 increased significantly during the acute phase of illness. IL-6 concentration was independently associated with severe disease after adjusting for confounding factors. RSV viral load was not associated with disease severity throughout the course of illness. Conclusion : Host inflammatory response is a major marker of severe disease in older adults with RSV infection.

Background: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. Methods: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin

Aim To review international guidelines and to share our infection control experience during the coronavirus disease 2019 (COVID-19) pandemic at a tertiary eye centre in Hong Kong. Methods Infection control guidelines and recommendations from international ophthalmological bodies are reviewed and discussed. The measures at our hospital were drawn up as per international and local health authorities' guidelines and implemented with the collaboration of doctors, nurses and administrative staff. Results The aims of our infection control measures are to 1) minimize cross-infection within the hospital; 2) protect and support hospital staff; 3) ensure environmental control. To minimize the risk of cross-infection, outpatient attendance and elective surgery have been reduced by 40%, and general anesthesia procedures were reduced by 90%. Patients entering the hospital are screened for fever, travel history, contact and cluster history, and COVID-19 related symptoms. To protect and support hospital staff, we ensure provision of adequate personal protective equipment (PPE) and provide clear guidelines on the level of PPE needed, depending on the clinical situation. Other protective measures include provision of work uniforms, easy access to alcohol-based hand rub, opening new lunch areas, implementation of self-monitoring and self-reporting systems, and communication via online education and updates. Finally, environmental control is achieved by ensuring regular disinfection of the hospital premise, enhancing ventilation, and usage of disposable ophthalmic instruments. Conclusion Our multi-pronged approach to infection control is, so far, successful in minimizing infection risks, while allowing the maintenance of essential ophthalmic services.

Background An obstacle in influenza therapeutics development is the lack of clinical endpoints, especially in hospitalized patients. A single time-point binary outcome measure is limited by patients’ diverse clinical trajectories and low event rates. Methods A 6-point ordinal scale with ascending clinical status severity (scoring: discharged; subacute care; acute care without/with respiratory failure; intensive care unit [ICU]; death) was proposed to study outcomes of adults hospitalized with influenza. Individual patient data from 2 active surveillance cohorts’ datasets (2015/2016−2017/2018; Edmonton, Hong Kong) was used for evaluation. The impact of neuraminidase inhibitor (NAI) treatment on longitudinal ordinal outcome changes over 30 days was analyzed using mixed-effects ordinal logistic regression and group-based trajectory models. Results Patient (n = 1226) baseline characteristics included age (mean 68.0 years), virus-type (A 78.1%, B 21.9%), respiratory failure (57.2%), ICU admittance (14.4%), and NAI treatment within 5 days of illness (69.2%). Outcomes at 30 days included discharged (75.2%), subacute care (13.7%), acute care (4.5%), and death (6.6%). Two main clinical trajectories were identified, predictive by baseline scoring (mean ± SD, 4.3 ± 0.6 vs 3.5 ± 0.6, P Conclusions The ordinal outcome scale is a potentially useful clinical endpoint for influenza therapeutic trials, which could account for the diverse clinical trajectories of hospitalized patients, warranting further development.

Financial markets are noisy learning environments. We propose an approach that regularizes the Temporal Convolutional Network using a supervised autoencoder, which we term the Supervised Temporal Autoencoder (STAE). We show that the addition of the auxiliary reconstruction task is beneficial to the primary supervised learning task in the context of stock return time-series forecasting. We also show that STAE is able to learn features directly from transformed price series, alleviating the need for handcrafted features. The autoencoder also improves interpretability as users can observe output of the decoder and inspect features retained by the network.

Highlights • Many SARS-CoV-2 diagnostic tests are available for patient use with incomplete evidence as to their diagnostic accuracy. • Current publications on SARS-CoV-2 diagnostic accuracy have imperfect study design, heterogeneous methods, and a high risk for bias., Summary Objectives To assess the methodologies used in the estimation of diagnostic accuracy of SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) and other nucleic acid amplification tests (NAATs) and to evaluate the quality and reliability of the studies employing those methods. Methods We conducted a systematic search of English-language articles published December 31, 2019-June 19, 2020. Studies of any design that performed tests on ≥10 patients and reported or inferred correlative statistics were included. Studies were evaluated using elements of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Results We conducted a narrative and tabular synthesis of studies organized by their reference standard strategy or comparative agreement method, resulting in six categorizations. Critical study details were frequently unreported, including the mechanism for patient/sample selection and researcher blinding to results, which lead to concern for bias. Conclusions Current studies estimating test performance characteristics have imperfect study design and statistical methods for the estimation of test performance characteristics of SARS-CoV-2 tests. The included studies employ heterogeneous methods and overall have an increased risk of bias. Employing standardized guidelines for study designs and statistical methods will improve the process for developing and validating rRT-PCR and NAAT for the diagnosis of COVID-19.

Background: Deep throat saliva (DTS) and pooled nasopharyngeal swab and throat swab (NPSTS) are utilized for viral detection. DTS is challenging for children. Swabbing the respiratory mucosa requires trained personnel and may trigger sneezing and coughing, which generate droplets. A reliable, simple and safe sampling method applicable to a wide age range is required for community-based surveillance. Methods: We introduced nasal strip as an easy and low-risk collection method. Asymptomatic and symptomatic SARS-CoV-2 infected patients (n = 38) were recruited. Nasal epithelial lining fluid (NELF) (n = 43) strip paired with nasal swab (n = 13) were collected by a healthcare worker to compare with NPSTS (n = 21) or DTS (n =22) collected within 24 hours as reference. All samples were subjected to viral RNA quantitation by real-time PCR targeting the nucleoprotein gene. Results: Comparable Ct values were observed between paired nasal strip and nasal swab samples. The agreement between nasal strip samples and NPSTS was 94.44% and 100% for NPSTS positive and negative samples. Higher viral RNA concentration was detected in nasal strips than DTS samples. False-negative results were recorded in six DTS specimens, of which four were from children. Storage at room temperature up to 72 (n = 3) hours did not affect diagnostic yield of nasal strips. Conclusions: Nasal strip is a reliable and non-invasive sampling method for SARS-CoV-2 detection, and viral detection remains stable for at least 72 hours. It can be used as an alternative tool for community-based surveillance. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was supported by the HMRF-commissioned grant (Ref: COVID190112 to RWYC, COVID190103 to MHTW and COVID190107 to PKSC) and Hong Kong Institute of Allergy Research Grant 2020 to RWYC. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Joint Chinese University of Hong Kong, New Territories East Cluster Clinical Research Ethics Committee (CREC: 2020.076 and 2020.442) All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Not applicable

Microcirculatory insufficiency has been hypothesized in glaucoma pathogenesis. There is a scarcity of data to comprehensively examine the changes in retinal microvasculature and its role in normal tension glaucoma (NTG). We conducted a cross-sectional case–control study and included 168 eyes from 100 NTG patients and 68 healthy subjects. Quantitative retinal arteriolar and venular metrics were measured from retinal photographs using a computer-assisted program. Radial peripapillary capillary network was imaged with OCT-A and quantitative capillary metrics (circumpapillary vessel density (cpVD) and circumpapillary fractal dimension (cpFD)) were measured with a customized MATLAB program. We found that NTG was associated with decreased arteriolar and venular tortuosity, arteriolar branching angle, cpVD and cpFD. Decreased venular caliber, arteriolar and venular branching angles, cpVD and cpFD were associated with thinner average RNFL thickness. Decreased arteriolar and venular branching angles, cpVD and cpFD were also associated with worse standard automated perimetry measurements (mean deviation and visual field index). Compared with retinal arteriolar and venular metrics, regression models based on OCT-A capillary metrics consistently showed stronger associations with NTG and structural and functional measurements in NTG. We concluded that NTG eyes showed generalized microvascular attenuations, in which OCT-A capillary metrics attenuations were more prominent and strongly associated with NTG.

Background: Cervical cancer is one of the most common cancers in women and about 90% of cervical cancer can be reduced by regular screening. The Pap smear has been well in place as a primary cervical screening method since 1950s, however, coverage is still not optimal. This study explored the feasibility of HPV self-sampling in two under-screened population groups in Hong Kong (HK): never screened and not regularly screened females, to estimate the uptake rate and preference rate in the future. Materials and Methods: This was a cross-sectional study to explore the acceptability and feasibility of HPV self-sampling in two age groups: aged 25&ndash, 35 and aged &ge, 45, which were reported as the highest proportion of the under-screened population in HK between 2017 and 2018. The study invited eligible women from an HPV study cohort to perform HPV self-sampling at home by themselves. The number of specimens returned from participants was recorded and used to determine the feasibility of HPV self-sampling in the community. The participants were asked to fill in the questionnaires before and after HPV self-sampling to indicate their attitudes, acceptability, and future preference for HPV self-sampling as an acceptable alternative primary cervical cancer screening method. Results: A total of 177 subjects participated in the present study and have achieved a good overall uptake rate of 73% (129/177) who returned the self-collected cervicovaginal sample for HPV testing. Among the under-screened population, there was a higher response rate in aged &ge, 45 than those aged 25&ndash, 35. The findings also revealed that women who were under-screened, including those who have never been screened, were more likely to prefer HPV self-sampling than those who had regular screening. This study found that the acceptability of HPV self-sampling was fairly positive among the respondents. The findings also indicated that HPV self-sampling was not only beneficial to enhance their health awareness but also to promote the cervical cancer screening uptake rate, especially among the under-screened or never screened populations. Conclusions: HPV self-sampling would be a solution to overcome the perceived barriers in clinician-based screening. The findings also indicated that it could be feasible to use as an alternative primary cervical cancer screening.

Background Understanding local epidemiology and etiologies of community-acquired pneumonia in hospitalized patients is crucial for determining the appropriateness of treatment guidelines. We aim to determine the etiologies, severity, and outcomes in adults hospitalized for community-acquired pneumonia and to study the impact of empirical antibiotic therapy on patient outcomes. Methods We performed a prospective observational cohort study involving adults hospitalized for community-acquired pneumonia in Hong Kong. Sputum, nasopharyngeal aspirate, blood, and urine were collected for bacterial culture, molecular tests for detection of viruses and atypical pathogens, and antigen tests. Multivariable logistic regression model and Cox proportional hazard models were performed to determine independent factors associated with prolonged hospitalization and mortality. Results From February 2017 to July 2018, 258 patients were enrolled. The median age was 73 (interquartile range, 61–80) years, 66% were male, 57% had underlying chronic illnesses, 13% had CURB-65 score ≥3, and 10% had higher 1-year mortality. Pathogens were identified in 45% of patients; 20% had viral, 15% had bacterial, and 9% had polymicrobial pneumonia. Streptococcus pneumoniae (12%), influenza virus (12%), and Mycoplasma pneumoniae (1.2%) were the most common bacterial, viral, and atypical pathogens, respectively. Nonadherence to local empirical antibiotic treatment guidelines (primarily recommending beta-lactam and doxycycline) was observed in 25% and was independently associated with prolonged hospitalization (≥7 days) and higher mortality, after adjustment for age, underlying chronic illness, and disease severity. Conclusions Adherence to treatment guidelines was associated with shorter hospitalization and improved survival. We provided evidence for the use of doxycycline for coverage of atypical pathogens in nonsevere pneumonia., In this prospective study involving adults hospitalized with community-acquired pneumonia, adherence to treatment guidelines was independently associated with shorter hospitalization and improved survival. Our findings provided evidence for atypical pathogen coverage with doxycycline, which was less evaluated in other cohorts.

Background The magnitude and risk factors of progression of atherosclerosis in Asian HIV-infected individuals were unknown. This study aimed to evaluate: (1) the rate of progression of atherosclerosis in HIV-infected individuals, and (2) metabolic and inflammatory parameters that may predict atherosclerosis progression in HIV-infected individuals in an Asian cohort. Setting A prospective, longitudinal study was performed among adults attending an HIV Metabolic clinic in Hong Kong. Methods Carotid intima media thickness (cIMT) was measured at baseline and 24 months. Body composition, metabolic, and inflammatory biomarkers [including homeostasis model assessment of insulin resistance, LDL (low-density lipoprotein) cholesterol particle size, high-sensitive C reactive protein, adiponectin] associated with cIMT change were analyzed; their predictive performances were estimated using receiver operating characteristic analyses. Results Sixty-one HIV-infected individuals (mean ± SD age 49.8 ± 11.4 years, 89% men, 97% Chinese, diabetes 39%, hypertension 30%, and dyslipidemia 85%) were recruited. Annual rate of change of cIMT was +0.0075 (0.0000-0.0163) mm/yr, and 19% developed new plaque at 24 months. Two patients died during the study period, 1 because of sudden cardiac death. Using receiver operating characteristic analyses, combination of lower limb fat percentage, LDL cholesterol subclass pattern B, and lower adiponectin level, but not Framingham score, predicted greater cIMT progression in HIV-infected individuals. Conclusions Asian HIV-infected individuals had atherosclerosis progression. Limb fat percentage, LDL cholesterol particle size, and adiponectin level may identify at-risk Asian HIV-infected individuals for early intervention.

Summary IFITM3 and TLR3 SNPs are associated with fatal clinical outcome of Chinese patients with avian (H7N9) or pandemic (H1N1pdm09) influenza virus infections, and the risks are cumulative. Our findings pose important public health and clinical implications in the at-risk populations., Background. We examined associations between single-nucleotide polymorphisms (SNPs) of IFITM3, TLR3, and CD55 genes and influenza clinical outcomes in Chinese. Methods. A multicenter study was conducted on 275 adult cases of avian (H7N9) and pandemic (H1N1pdm09) influenza. Host DNA was extracted from diagnostic respiratory samples; IFITM3 rs12252, TLR3 rs5743313, CD55 rs2564978, and TLR4 rs4986790/4986791 were targeted for genotyping (Sanger sequencing). The primary outcome analyzed was death. Results. IFITM3 and TLR3 SNPs were in Hardy–Weinberg equilibrium; their allele frequencies (IFITM3/C-allele 0.56, TLR3/C-allele 0.88) were comparable to 1000 Genomes Han Chinese data. We found over-representation of homozygous IFITM3 CC (54.5% vs 33.2%; P = .02) and TLR3 CC (93.3% vs 76.9%; P = .04) genotypes among fatal cases. Recessive genetic models showed their significant independent associations with higher death risks (adjusted hazard ratio [aHR] 2.78, 95% confidence interval [CI] 1.29–6.02, and aHR 4.85, 95% CI 1.11−21.06, respectively). Cumulative effects were found (aHR 3.53, 95% CI 1.64−7.59 per risk genotype; aHR 9.99, 95% CI 1.27−78.59 with both). Results were consistent for each influenza subtype and other severity indicators. The CD55 TT genotype was linked to severity. TLR4 was nonpolymorphic. Conclusions. Host genetic factors may influence clinical outcomes of avian and pandemic influenza infections. Such findings have important implications on disease burden and patient care in at-risk populations.

Australia was previously believed to be free of enzootic swine influenza viruses due strict quarantine practices and use of biosecure breeding facilities. The first proven Australian outbreak of swine influenza occurred in Western Australian in 2012, revealing an unrecognized zoonotic risk, and a potential future pandemic threat. A public health investigation was undertaken to determine whether zoonotic infections had occurred and to reduce the risk of further transmission between humans and swine. A program of monitoring, testing, treatment, and vaccination was commenced, and a serosurvey of workers was also undertaken. No acute infections with the swine influenza viruses were detected. Serosurvey results were difficult to interpret due to previous influenza infections and past and current vaccinations. However, several workers had elevated haemagglutination inhibition (HI) antibody levels to the swine influenza viruses that could not be attributed to vaccination or infection with contemporaneous seasonal influenza A viruses. However, we lacked a suitable control population, so this was inconclusive. The experience was valuable in developing better protocols for managing outbreaks at the human–animal interface. Strict adherence to biosecurity practices, and ongoing monitoring of swine and their human contacts is important to mitigate pandemic risk. Strain specific serological assays would greatly assist in identifying zoonotic transmission.

Background Chronic hepatitis B virus (HBV) infection increases the risk of liver injury in patients who undergo antituberculosis treatment. It is uncertain whether antiviral treatment for HBV at the time of tuberculosis diagnosis would reduce the risk of liver injury. Methods We performed a population-level, retrospective, cohort study that involved all patients with tuberculosis-HBV coinfection treated in public hospitals in Hong Kong over a 16-year period. Patients who received antiviral treatment at the time of tuberculosis diagnosis were considered "patients on antiviral therapy." A multivariable Cox proportional hazards model was used to determine the adjusted hazard ratio of hospitalization due to drug-induced liver injury within 1 year in patients on antiviral therapy, adjusting for the propensity score. Results Of 3698 patients with tuberculosis-HBV coinfection, 488 (13.2%) were patients on antiviral therapy. Of the remaining 3210 patients, 446 (13.9%) started antiviral therapy within 1 year of tuberculosis diagnosis. Adjusting for the propensity score, patients on antiviral therapy had a lower risk of hospitalization due to drug-induced liver injury compared with those not on treatment (adjusted hazard ratio, 0.44; 95% confidence interval .26-.72). Compared with patients who started antiviral therapy within 1 year of tuberculosis diagnosis, patients on antiviral therapy also had a lower risk of hospitalization due to drug-induced liver injury and a lower risk of liver-related mortality. Conclusions We show that antiviral treatment for HBV given at the time of tuberculosis diagnosis reduced the risk of liver injury in tuberculosis-HBV coinfected patients.

A prospective study among adults hospitalized for polymerase chain reaction–confirmed respiratory syncytial virus infections (n = 123) showed frequent occurrence of lower respiratory-tract complications causing respiratory insufficiency (52.8%), requirement for assisted ventilation (16.3%), and intensive care unit admission/death (12.2%). High viral RNA concentration was detected at time of hospitalization, including in patients who presented later than 2 days of illness (day 1–2, 7.29 ± 1.47; day 3–4, 7.28 ± 1.41; day 5–8, 6.66 ± 1.87 log10 copies/mL). RNA concentration was independently associated with risk of complications and respiratory insufficiency (adjusted odds ratio 1.40 per log10 copies/mL increase, 95% confidence interval, 1.03–1.90; P = .034). Our data indicate the need and provide a basis for clinical research on antiviral therapy in this population.

The mortality rate in patients with haemodynamically unstable pelvic fractures is as high as 40–60%. Despite the new advances in trauma care which are in phase in trauma centres in Hong Kong, the management of haemodynamically unstable pelvic fracture is still heterogeneous. The aim of this study is to review the results of management of haemodynamically unstable pelvic fracture patients in Hong Kong over a five year period. This is a retrospective multi-centred cohort study of patients with haemodynamic and mechanically unstable pelvic fractures from 1 January 2010 to 31 December 2014. The primary outcome investigated is mortality of patients (including overall, 30-day, 7-day and 24-hour mortalities). Implementation of three-in-one pelvic damage control protocol was identified to be a significant independent predictive factor for overall, 30-day, seven-day and 24-hour mortalities. The overall in-hospital and 30-day mortality rates for patients managed with three-in-one protocol was 12.5%, while it was 11% for seven day mortality and 6% for 24 hour mortality. There were no significant differences in demographic characteristics, physiological measurements, types of pelvic fracture, severity and mechanism of injury between patients managed with or without three-in-one protocol. Implementation of the multidisciplinary three-in-one pelvic damage control protocol reduces mortality and therefore should be highly recommended. The results are convincing as it has eliminated the limitations of our previous single-centred trial.

Background An international valuation protocol exists for obtaining societal values for each of the 3125 health states of the five-level EuroQol-five dimensions (EQ-5D-5L) questionnaire. A feedback module (FM) that can be related to theoretical models used in behavioral economics was recently included in this protocol. Objectives Our objective was to assess the impact of using an FM to estimate an EQ-5D-5L value set in Hong Kong. Methods EQ-5D-5L health states were elicited using a composite time trade-off (C-TTO) and a discrete-choice (DC) experiment. Use of the FM according to participant characteristics and the impact of the FM on the number of inconsistent C-TTO responses were assessed. We employed a main-effects hybrid model that combined data from both elicitation techniques. Results In total, 1014 individuals completed the survey. The sample was representative of the general Chinese Hong Kong population in terms of sex, educational attainment, marital status, and most age groups but not for employment status. The use of the FM reduced the number of C-TTO inconsistencies. Participant characteristics differed significantly between those who used and did not use the FM. The model without a constant resulted in logical consistent coefficients and was therefore selected as the model to produce the value set. The predicted EQ-5D-5L values ranged from −0.864 to 1. Conclusions The use of an FM to allow participants to exclude C-TTO responses reduced the number of inconsistent responses and improved the quality of the data when estimating an EQ-5D-5L value set in Hong Kong. Electronic supplementary material The online version of this article (doi:10.1007/s40271-017-0278-0) contains supplementary material, which is available to authorized users.

Introduction − Macrolides can ameliorate inflammation in respiratory diseases, providing clinical benefits. Data in influenza is lacking. Method − A randomized, open-label, multicenter trial among adults hospitalized for laboratory-confirmed influenza was conducted. Study treatments of oseltamivir and azithromycin (500 mg/day), or oseltamivir alone, both for 5 days, were allocated at 1:1 ratio. The primary outcome was plasma cytokine/chemokine concentration change over time (Day 0–10); secondary outcomes were viral load and symptom score changes. Generalized Estimating Equation (GEE) models were used to analyze longitudinal data. Results − Fifty patients were randomized to the oseltamivir-azithromycin or oseltamivir groups, with comparable baseline characteristics (age, 57 ± 18 years; A/H3N2, 70%), complications (72%), and viral load. Pro-inflammatory cytokines IL-6 (GEE: β −0.037, 95%CI-0.067,-0.007, P = 0.016; reduction from baseline −83.4% vs −59.5%), CXCL8/IL-8 (β −0.018, 95%CI-0.037,0.000, P = 0.056; −80.5% vs −58.0%), IL-17 (β −0.064, 95%CI-0.117,-0.012, P = 0.015; −74.0% vs −34.3%), CXCL9/MIG (β −0.010, 95%CI-0.020,0.000, P = 0.043; −71.3% vs −56.0%), sTNFR-1, IL-18, and CRP declined faster in the oseltamivir-azithromycin group. There was a trend toward faster symptom resolution (β −0.463, 95%CI-1.297,0.371). Viral RNA decline (P = 0.777) and culture-negativity rates were unaffected. Additional ex vivo studies confirmed reduced induction of IL-6 (P = 0.017) and CXCL8/IL-8 (P = 0.005) with azithromycin. Conclusion − We found significant anti-inflammatory effects with adjunctive macrolide treatment in adults with severe influenza infections. Virus control was unimpaired. Clinical benefits of a macrolide-containing regimen deserve further study. [ClinicalTrials.gov NCT01779570]

The outbreak of highly pathogenic H5N1 avian influenza, with its international spread, confirmed that emerging infectious disease control must be underpinned by effective laboratory services. Laboratory results are the essential data underpinning effective surveillance, case diagnosis, or monitoring of responses. Importantly, laboratories are best managed within national and international networks of technological support rather than in isolation. A well planned laboratory network can deliver both a geographical spread of testing capacity and also a cost effective hierarchy of capability. Hence in the international context regional networks can be particularly effective. Laboratories are an integral part of a country's veterinary services and their role and function should be clearly defined in the national animal health strategy and supporting government policies. Not every laboratory should be expected to deliver every possible service, and integration into regional and broader international networks should be a part of the overall strategy. The outputs required of each laboratory should be defined and then ensured through accredited quality assurance. The political and scientific environment in which laboratories operate changes continuously, not only through evolving national and regional animal health priorities but also through new test technologies and enhancements to existing technologies. Active networks help individual laboratories to monitor, evaluate, and respond to such challenges and opportunities. The end result is enhanced emerging infectious disease preparedness across the region.

Introduction Myocardial fibrosis is dysrhythmogenic and may contribute to the high incidence of cardiac death in stroke survivors, especially if they have long QTc. We tested the hypothesis that procollagen-1-carboxy terminal peptide (P1CP), a biomarker of myocardial fibrosis, might be improved following treatment with spironolactone or amiloride in stroke survivors. We also tested the hypothesis that both drugs would shorten QTc. Methods Study design: randomised, double-blinded, placebo-controlled, cross-over trial (spironolactone vs. amiloride vs. placebo). Duration of Study: 3months (1month per drug). Primary endpoints: P1CP, QTc Results 11 stroke survivors (5 female), aged 71+4, BP 139/81mmHg+20/11mmHg, completed the study. Both spironolactone and amiloride significantly reduced P1CP [Spironolactone–Placebo=−24 ug/L, 95% CI=−40 to −6.9; Amiloride–Placebo=−28 ug/L, 95% CI=−44 to −11]. Spironolactone and amiloride both shortened QTc [Spironolactone vs. Placebo=−18ms 1/2 , 95% CI=−36 to −0.55; Amiloride vs Placebo=−25ms 1/2 , 95% CI=−42 to −7.5]. Conclusions Procollagen-1-carboxy terminal peptide was reduced following treatment with spironolactone within a month. Further, this is the first study demonstrating amiloride could also improve myocardial fibrosis. The beneficial effects of both drugs on myocardial fibrosis, coupled with their effects on raising potassium translated to a shortening of QTc. Future studies should test the hypothesis that these drugs might reduce the risk of sudden cardiac death in stroke survivors.

Background It is unclear if higher-dose oseltamivir provides benefit beyond the standard dose in influenza patients who require hospitalization. Methods A prospective intervention study was performed in 2 acute care general hospitals in Hong Kong over 4 seasonal peaks (2010-2012). Adults (≥18 years) with laboratory-confirmed influenza (85 A/H3N2, 34 A/H1N1pdm09, 36 B) infections who presented within 96 hours were recruited. Study regimen of either 150 mg or 75 mg oseltamivir twice daily for 5 days was allocated by site, which was switched after 2 seasons. Subjects with preexisting renal impairment (creatinine clearance, 40-60 mL/minute) received 75 mg oseltamivir twice daily. Viral clearance by day 5 and clinical responses were compared between groups. Plasma steady-state trough oseltamivir carboxylate (OC) concentration was measured by high-performance liquid chromatography-tandem mass spectrometry. Results Altogether, 41 and 114 patients received 150 mg and 75 mg twice-daily oseltamivir, respectively; their enrollment characteristics (mean age, 61 ± 18 vs 66 ± 16 years) and illness severity were comparable. Trough OC levels were higher in the 150-mg group (501.0 ± 237.0 vs 342.6 ± 192.7 ng/mL). There were no significant differences in day 5 viral RNA (44.7% vs 40.2%) or culture negativity (100.0% vs 98.1%), RNA decline rate, and durations of fever, oxygen supplementation, and hospitalization. Results were similar when analyzed by study arm (all cases and among those without renal impairment). Subanalysis of influenza B patients showed faster RNA decline rate (analysis of variance, F = 4.14; P = .05) and clearance (day 5, 80.0% vs 57.1%) with higher-dose treatment. No oseltamivir resistance was found. Treatments were generally well tolerated. Conclusions We found no additional benefit of higher-dose oseltamivir treatment in adults hospitalized with influenza A, but an improved virologic response in influenza B. Clinical trials registration ClinicalTrials.gov, NCT01052961.

Background. Better understanding of complications and outcomes of adults hospitalized with respiratory syn-cytial virus (RSV) infection is necessary.Methods. A retrospective cohort study was conducted on all adults (≥18 years) admitted to 3 acute care generalhospitals in Hong Kong with virologically confirmed RSV infection during 2009–2011 (N=607). Adults hospital-ized forseasonal influenza during the period wereused forcomparison (n=547). Both infections were prospectivelydiagnosed following a standard protocol. Independent reviews of chest radiographs were performed by radiologists.Main outcome measures were all-cause death, respiratory failure requiring ventilatory support, and hospitalizationduration. Cox proportional hazards models were used foranalyses.Results. Themeanage ofRSV patients was75 (SD,16) years; 87% hadunderlyingconditions. Lower respiratoryand cardiovascularcomplications were diagnosed in 71.9% (pneumonia, 42.3%; acute bronchitis, 21.9%; chronic ob-structive pulmonary disease/asthma exacerbation, 27.3%) and 14.3% of patients, respectively; 12.5% had bacterialsuperinfections. Supplemental oxygen and ventilatory support were required in 67.9% and 11.1%, respectively.Crude all-cause mortality was 9.1% and 11.9% within 30days and 60 days, respectively; mean length ofstayof survi-vors was 12 (SD, 13) days. Advanced age, radiographic pneumonia, requirement for ventilation, bacterial superin-fection, and elevated urea level and white blood cell count were independently associated with poorer survival.Systemic corticosteroid use was associated with longer hospitalization and secondary infections. The overall out-comes of survival and length of stay were not significantly different from those in influenza.Conclusions. RSV can cause severe lower respiratory complications in older adults, resulting in respiratoryfailure, prolonged hospitalization, and high mortality similar to seasonal influenza. Corticosteroids did not seem toimprove outcomes. The unmet need forantiviral therapy and vaccination against RSV in adults should be promptlyaddressed.Keywords. RSV; hospitalization; respiratory failure; lower respiratory tract infection; adults.Respiratory syncytial virus (RSV) is known to be animportant cause of lower respiratory tract infection ininfants and young children, leading to hospitalizationsand deaths [1]. Its impact in adults, however, has onlybeen appreciated in recent years. It has been estimatedthat RSV infects 3%–10% of adults annually; althoughmost infections are mild, increasing evidence suggeststhat severe lower respiratory tract infections can occur,especially among older adults and those with underlyingconditions [2–4].RSV may have accounted for 5%–15%of community-acquired pneumonia, 9%–10% of hospi-tal admissions for acute cardiorespiratory diseases, andexcessive deaths duringseasonalpeaks [3,4].Thedisease

BackgroundTo describe direct medical costs of influenza in hospitalized elderly, with and without intensive care unit (ICU) admission, during the 2014–2015 season in Hong Kong.MethodsA retrospective study was conducted in 110 inpatients aged ≥65 years with laboratory-confirmed influenza treated by antiviral therapy during season 2014–2015 in a tertiary hospital. Resource utilization of influenza-related diagnostic and laboratory tests, medications for influenza treatment, usage of general medical ward and ICU during the influenza-related length of hospital stay (IR-LOS) were collected.ResultsThere were 18 (16.4%) and 92 (83.4%) cases with and without ICU admission, respectively. The difference in influenza-related mortality rates between patients with (11.1%) and without ICU admission (2.2%) was not statistically significant ( P=0.064). Patients with ICU admission reported longer IR-LOS (12.7 ±6.0 days versus 5.5 ±2.7 days; PConclusionsHospitalization cost in elderly for seasonal influenza was substantial in Hong Kong. The cost in patients with ICU admission was significantly higher than those without ICU care. Respiratory complications and male gender predicted ICU admission. Influenza B infection predicted high-cost hospitalization in non-ICU survivors.

Summary Background Little is known about the importance of liver fibrosis and fatty liver in HIV-monoinfected individuals without hepatitis virus co-infection, particularly among the Asian population. Aim To evaluate prevalence and risk factors for liver fibrosis and fatty liver in Asian HIV-monoinfected individuals. Methods Eighty asymptomatic HIV-monoinfected individuals (tested negative for HBV/HCV) were compared with 160 matched HIV-uninfected healthy controls. Transient elastography and proton-magnetic resonance spectroscopy (1H-MRS) were performed to measure liver stiffness and hepatic steatosis respectively. Blood samples were analysed for metabolic profiles and markers of steatohepatitis (e.g. cytokeratin-18). Results All HIV-infected individuals (mean ± s.d. age 54 ± 11 years, male 93%, Chinese 94%; diagnosis median duration 8 (IQR 4–13 years) were stable on anti-retrovirals (PI-based 58.7%, NNRTI-based 25.0% integrase-inhibitors 16.3%); diabetes, dyslipidaemia, and metabolic syndrome were common. Fatty liver disease was detected in 28.7%. There was significantly higher degree of liver stiffness [4.9 (IQR 4.1–6.2) kPa vs. 4.2 (IQR 3.6–5.0) kPa, P < 0.001], and greater proportions developed significant fibrosis (7.0 kPa, 14.3% vs. 3.1%, P = 0.001) and cirrhosis (10.3 kPa, 5.2% vs. 0.6%, P = 0.040) compared with controls. HIV infection was an independent risk factor for significant fibrosis (adjusted OR 4.00, 95% CI 1.29–12.41, P = 0.016). HIV-infected individuals with fatty liver had excessive liver stiffness and fibrosis. Two cases of asymptomatic hepatocellular carcinoma were detected. Conclusions HIV-monoinfected patients are at risk for liver fibrosis and cirrhosis. HIV-related mechanisms and fatty liver disease may play important roles. Screening and intervention to prevent severe outcomes should be considered.

An open-label trial on intravenous peramivir was conducted among adult patients hospitalised for influenza-associated lower respiratory tract complications (LRTCs). Virus culture and quantitative reverse transcription PCR (qRT-PCR) were performed serially until Day 10. Peramivir treatment was associated with viral RNA decline as well as culture and RNA negativity, which occurred at rates comparable with those of oseltamivir: by Day 5, viral load decline -2.5 log10 copies/mL [βinteraction -0.071, standard error (SE) 0.121, 95% confidence interval (CI) -0.309 to 0.167]; culture-negative, 94% (vs. 95%); and RNA-negative, 44% (vs. 36%). Extended treatment of >5 days was required in 69% of cases because of slow clinical resolution and viral clearance in LRTCs. Peramivir was well tolerated. These data are useful for future trial design in this unique population.

In an observational cohort study, we found that adults hospitalized for oseltamivir-resistant (H275Y) seasonal H1N1 influenza (n = 46) were older than those infected with oseltamivir-susceptible strains (n = 31) [74(IQR 59–83) versus 64(IQR 48–76) years; P = 0·045], and most had major comorbidities (78% versus 65%). Disease severity and clinical outcomes were comparable between the two groups: radiographic pneumonia 40–42%, supplemental oxygen use 47–48%, critical illness 11–13%, median duration of hospitalization 5–6 days, death rate 6–9%. Failure to receive effective antiviral therapy was associated with progression to critical illness (23% versus 0%, P = 0·016) and death (20% versus 0%, P = 0·033) in hospitalized patients with seasonal H1N1 influenza.

Treatment of vitamin D deficiency for 3 months with oral cholecalciferol 5,000 IU daily was more effective than 2,000 IU daily in achieving optimal serum 25-hydroxyvitamin D (25OHD) concentrations. Optimal 25OHD serum level calculated to be 63.8 nmol/L. All parameters of muscle strength improved following administration of cholecalciferol for 3 months. The aim of this study was to determine the optimal dose of cholecalciferol required to achieve target serum 25OHD level ≥75 nmol/L and its relationship to both bone turnover and muscle strength. Thirty deficient patients (serum 25OHD ≤50 nmol/L) were randomly assigned into two groups—i.e. 2,000 and 5,000 IU/day. Data were collected at baseline, at 2 and 3 months post-therapy: (a) clinical demographics, (b) dietary calcium recall, (c) physical tests of muscle function and (d) biochemistry. Statistical analysis used paired student t test and analysis of variance. Regression analysis was used to determine relationship between serum 25OHD and parathyroid hormone (PTH). Twenty-six (87%) patients completed 3 months of therapy. The percent increase in serum 25OHD (compared to baseline) was 82.7% in 2,000-IU group and 219.5% in 5,000-IU group. All participants (100%) achieved a serum 25OHD concentration >50 nmol/L; only 5 subjects (45.4%) in 2,000-IU group compared to 14 subjects (93.3%) in 5,000-IU group achieved final 25OHD concentration ≥75 nmol/L (p

The work in this paper, as continuation of previous research, improves the previous robot configuration and focuses on the mechatronic design and implementation of the robotic hanger system for garment inspection. In this improved 3‐DOF smart hanger, three groups of linkages, body, shoulder, and sleeve links (joints), instead of the four‐link robot consisting of three revolute joints and one prismatic joint in the previous design, can freely move in the 2D plane. In comparison with the previous design, the prismatic joint was removed. Link 2 and link 3 are replaced by the body link, and an extra shoulder link is added. Furthermore, the body link always keeps vertical status during motion, and the shoulder and sleeve links provide the convenience for holding the garment. Through these three pairs of improved links, the robotic hanger extends the garment effectively through several motion processes with position and force control where the force control was not considered in the previous design. Due to the ...

In this paper, the dynamics of single and two electrically coupled map-based neurons under external electrical stimulation is studied. In order to realize the synchronization of two chaotic spiking neurons, a controller based on the idea of feedback linearization is proposed. The simulation results demonstrate the effectiveness of this developed control method. An important feature of the feedback control is that the amplitude of control signal tends to zero as soon as the synchronization is achieved.

The controlled smart hanger is an indispensable component in the automatic system for garment inspection. Fuzzy logic is chosen for the smart hanger manipulator since it can describe the human behavior remarkably well. In this paper, the dynamic model of the manipulator governing the contact force with garment fabric is first developed. An adaptive fuzzy logic PID control scheme is successfully formulated for the contact force control. Simulation results indicate that the fuzzy PID controller can yield a faster response without overshoot and a smaller error performance as compared to the traditional method based on PID. The stability of the fuzzy PID controller is also demonstrated by computer simulations.

It is unclear whether pandemic 2009 influenza A (pH1N1) infection caused more significant disease among hospitalized adults than seasonal influenza.A prospective, observational study was conducted in adults hospitalized with polymerase chain reaction-confirmed pH1N1 infection in 2 acute-care general hospitals from June 2009 to May 2010 (n = 382). Complications and outcomes were described and compared with those in a seasonal influenza cohort (2007-2008, same hospitals; n = 754).Hospitalized patients with pH1N1 influenza were younger than those with seasonal influenza (mean age ± standard deviation, 47 ± 20 vs 70 ± 19 years) and fewer had comorbid conditions (48% vs 64%). The rate of positive immunofluorescence assay results was low (54% vs 84%), and antiviral use was frequent (96% vs 52%). Most patients in both cohorts developed complicated illnesses (67.8% vs 77.1%), but patients with pH1N1 influenza had higher rates of extrapulmonary complications (23% vs 16%; P = .004) and intensive care unit admission and/or death (patient age35 years, 2.3% vs 0%; 35-65 years, 12.4% vs 3.2%;65 years, 13.5% vs 8.5%; adjusted odds ratio [OR] 2.13; 95% confidence interval [CI], 1.25-3.62; P = .005). Patients who received antiviral treatment within 96 h after onset had better survival (log-rank test, P.001). However, without timely treatment, the mortality risk was higher with pH1N1 infection (9.0% vs 5.8% for seasonal influenza; adjusted OR, 6.85; 95% CI, 1.64-28.65; P = .008]. Bacterial superinfection worsened outcomes.Adults hospitalized for pH1N1 influenza had significant complications and mortality despite being younger than patients with seasonal influenza. Antiviral treatment within 96 h may improve survival.

Model-based fault diagnosis using artificial intelligence techniques often deals with uncertain knowledge and incomplete information. Probability reasoning is a method to deal with uncertain or incomplete information, and Bayesian network is a tool that brings it into the real world application. A novel approach for constructing the Bayesian network structure on the basis of a bond graph model is proposed. Specification of prior and conditional probability distributions (CPDs) for the Bayesian network can be completed by expert knowledge and learning from historical data. The resulting Bayesian network is then applied for diagnosing faulty components from physical systems. The performance of the proposed fault diagnosis scheme based on bond graph derived Bayesian network is demonstrated through simulation studies.

BackgroundThe goal of this study was to characterize viral loads and factors affecting viral clearance in persons with severe influenza MethodsThis was a 1-year prospective, observational study involving consecutive adults hospitalized with influenza. Nasal and throat swabs were collected at presentation, then daily until 1 week after symptom onset. Real-time reverse-transcriptase polymerase chain reaction to determine viral RNA concentration and virus isolation were performed. Viral RNA concentration was analyzed using multiple linear or logistic regressions or mixed-effect models ResultsOne hundred forty-seven inpatients with influenza A (H3N2) infection were studied (mean age ± standard deviation, 72±16 years). Viral RNA concentration at presentation positively correlated with symptom scores and was significantly higher than that among time-matched outpatients (control subjects). Patients with major comorbidities had high viral RNA concentration even when presenting >2 days after symptom onset (mean ± standard deviation, 5.06±1.85 vs 3.62±2.13 log10 copies/mL; P=.005; β, +0.86 [95% confidence interval, +0.03 to +1.68]). Viral RNA concentration demonstrated a nonlinear decrease with time; 26% of oseltamivir-treated and 57% of untreated patients had RNA detected at 1 week after symptom onset. Oseltamivir started on or before symptom day 4 was independently associated with an accelerated decrease in viral RNA concentration (mean β [standard error], −1.19 [0.43] and −0.68 [0.33] log10 copies/mL for patients treated on day 1 and days 2–3, respectively; P

In this paper, both off-line architecture optimization and on-line adaptation have been developed for a dynamic neural network (DNN) in nonlinear system identification. In the off-line architecture optimization, a new effective encoding scheme-Direct Matrix Mapping Encoding (DMME) method is proposed to represent the structure of neural network by establishing connection matrices. A series of GA operations are applied to the connection matrices to find the optimal number of neurons on each hidden layer and interconnection between two neighboring layers of DNN. The hybrid training is adopted to evolve the architecture, and to tune the weights and input delays of DNN by combining GA with the modified adaptation laws. The modified adaptation laws are subsequently used to tune the input time delays, weights and linear parameters in the optimized DNN-based model in on-line nonlinear system identification. The effectiveness of the architecture optimization and adaptation is extensively tested by means of two nonlinear system identification examples.

Objective: To investigate the effects of patellar taping on the electromyographic onset of vastus medialis obliquus and vastus lateralis, and their magnitudes of reflex contraction before and after quadriceps muscle fatigue in subjects with patellofemoral pain. Methods: Sixteen adults (5 males) diagnosed with patellofemoral pain were studied. The timing of surface electromyography onset and magnitude of vastus medialis obliquus and vastus lateralis contractions were measured during a postero-anterior knee perturbation test. The tests were conducted in random order under three conditions of real taping, placebo taping and no taping. Afterwards, the subjects performed knee extension exercises until fatigue and the above tests were repeated, so as to examine the effects of patellar taping in a muscle fatigued condition. Results: There was no significant difference in electromyographic onset timing of vastus medialis obliquus and vastus lateralis or in the amplitude of vastus lateralis contraction among the different testing conditions. For vastus medialis obliquus amplitude, however, it was significantly higher in the no taping than the real taping condition regardless of the state of fatigue (P = 0.013). Conclusions: The present study suggests that patellar taping might not enhance the temporal activation of vastus medialis obliquus in subjects with patellofemoral pain before and after muscle fatigue. Furthermore, vastus medialis obliquus contraction might be inhibited by patellar taping.

PurposeThe purpose of this paper is to show how to design effective and practical controllers that satisfy multiple simultaneous specifications (MSS) criteria concurrently.Design/methodology/approachIn automatic flight control system or autopilots, MSS such as good holding (small static altitude holding error), fast response, smooth transition (less oscillation, overshoot) are needed to be satisfied concurrently. So how to design the MSS controller effectively and practically is a very significant and challenging job. An MSS controller design method is proposed. The paper further applies the method together with the fine‐tuning technique to the 6 DoF non‐linear F‐16 fighter longitudinal control channel. Simulation results show its applicability to non‐linear flight control system.FindingsIt was found that the simulation results demonstrate that the MSS design method with controller fine‐tuning can be applied to the nonlinear F‐16 fighter longitudinal control system.Research limitations/implicationsThe practical implementation of this research work needs further investigation.Practical implicationsThe simplicity of the design algorithm facilitates the application of the design to other aircrafts by use of Matlab.Originality/valueThe simulation results presented demonstrate that the proposed MSS apply well to non‐linear F‐16 fighters.

Detecting fault before it deteriorates the system performance is crucial for the reliability and safety of many engineering systems. This paper develops an intelligent technique based on fuzzy-genetic algorithm (FGA) for automatically detecting faults on HVAC system. Many researchers have proposed only using fuzzy systems to effect fault detection and diagnosis. Other applications of the FGA are mainly focused on the synthesis of fuzzy control rules. The proposed automatic fault detection system (AFD) monitors the HVAC system states continuously by fuzzy system. The optimization capability of genetic algorithms allows the generation of optimal fuzzy rules. Faults are represented as different fault levels in the AFD system and are distinguished by fuzzy system after tuning its rule table. Simulation studies are conducted to verify the proposed AFD system for the single zone air handler system.

Stroke survivors are most likely to die of cardiac death, yet few undergo comprehensive cardiac assessment to look for reversible causes. Myocardial fibrosis (MF) is not only the hallmark of cardiomyopathy, but also a substrate for sudden cardiac death, ventricular tachyarrhythmia and heart failure. Procollagen carboxyl-terminal telopeptide (PICP) was found to be a marker of MF. The relationship between PICP and cardiac abnormalities in stroke survivors is unknown. We recently showed that MF in stroke survivors can be treated by spironolactone and amiloride in a randomised placebo-controlled cross-over study with reduction in PICP levels and QTc [1].

We explored the feasibility and efficacy of an exercise programme for elderly people with knee pain conducted via videoconferencing. Twenty-two community-dwelling subjects aged 60 years or above with knee pain were recruited from two community centres in Hong Kong. A 12-week exercise programme, including strengthening and balance training, was given via videoconferencing to subjects at both centres, in conjunction with a home-based exercise programme. The outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), quadriceps muscle strength, Berg's Balance Scale (BBS) and subjects' degree of acceptance of videoconferencing. Twenty subjects completed the 12-week programme and significant improvements occurred in all domains of the WOMAC score (P

There are inevitable variations in the signature patterns written by the same person. The variations can occur in the shape or in the relative positions of the characteristic features. In this paper, two methods are proposed to track the variations. Given the set of training signature samples, the first method measures the positional variations of the one-dimensional projection profiles of the signature patterns; and the second method determines the variations in relative stroke positions in the two-dimension signature patterns. The statistics on these variations are determined from the training set. Given a signature to be verified, the positional displacements are determined and the authenticity is decided based on the statistics of the training samples. For the purpose of comparison, two existing methods proposed by other researchers were implemented and tested on the same database. Furthermore, two volunteers were recruited to perform the same verification task. Results show that the proposed system compares favorably with other methods and outperforms the volunteers.

It is difficult for beginners to learn Japanese by self-learning because there is no teacher can give any guidance and feedback to them for improvement. Besides, most of the beginners may not have any basic knowledge of Japanese language, for example, Japanese alphabets or phonology, they don’t have any idea how to get start with and what should be learnt at the beginning. This paper introduces an Android mobile application for the beginners to acquire fundamental knowledge of Japanese language so as to gain the self-learning proficiency in Japanese. This application provides learning materials, auto-generated exercises, handwriting practice tool, voice recording and recognition tool for beginners to learn Japanese. Besides, this application proposes an adaptive learning system to users, which aims to provide different supplementary exercises or learning approaches to learner based on the current performance of an individual learner.

Aims To test the hypothesis that urate predicts cardiac death after stroke independent of conventional risk factors of atherosclerosis, creatinine and diuretic use. Methods and Results Serum urate concentration was measured in an unselected cohort of 354 stroke survivors who were followed-up for a median of 2·8 years. Cardiac death was the primary end-point. Urate was associated with a statistically significant threefold increase in relative risk of cardiac death even after adjustment for other conventional risk factors. In the subgroup of patients who were not on diuretics, raised urate was associated with a 12-fold significant increase in relative risk of cardiac death after adjusting for renal function and other conventional risk factors. A urate concentration of greater than 0·31mmol.l−1 was 78% sensitive at predicting cardiac death within 5 years after stroke, but was only 54% specific. If urate exceeded 0·38mmol.l−1, specificity of predicting cardiac death within 5 years after stroke was 88%. Conclusions Elevated serum urate concentration may be used to stratify risk of future cardiac death after stroke. This appeared to be true even in stroke survivors who were not on diuretic therapy.

Background Influenza virus infections are causing substantial morbidity and mortality, despite availability of antiviral treatments. Macrolides have been shown to ameliorate inflammation in respiratory diseases and provide clinical benefits. Data in influenza, however, are scarce. We aimed to assess the anti-inflammatory effects of macrolide treatment in patients with influenza, and its effects on viral clearance and symptom resolution. Methods In this open-label, multicentre, randomised controlled trial, we recruited adults admitted to hospital for laboratory-confirmed influenza in Hong Kong. Key inclusion criteria were age 18 years or older, influenza A and B virus infections confirmed by PCR or immunofluorescence assays, and presentation within 4 days from illness onset. Patients were randomly assigned (1:1) using a computer-generated sequence to oseltamivir (75 mg twice daily) plus azithromycin (500 mg per day) or oseltamivir (75mg twice daily) alone, both given orally for 5 days. The primary outcome was change in plasma cytokine and chemokine concentration over time (day 0–10), analysed by intention to treat. Generalised estimating equation (GEE) models were used to analyse longitudinal data, and were adjusted for potential confounders. Ethics approvals were obtained from the institutional review bodies of all participating institutes. All patients provided written informed consent. This trial is registered with ClinicalTrials.gov, number NCT01779570. Findings During the influenza seasons beginning from 2013–14 through to 2015–16, 50 patients were randomly assigned to the oseltamivir-azithromycin (n=25) or oseltamivir (n=25) groups, with similar baseline characteristics (mean age 54·7 years [SD 18·5] in the oseltamivir-azithromycin group vs 58·6 years [18·1] in the oseltamivir group; 16 [64%] of 25 patients in the oseltamivir-azithromycin group were men vs 15 [60%] of 25 in the oseltamivir group). Three key pro-inflammatory cytokines declined faster in the oseltamivir-azithromycin group than in the oseltamivir group: interleukin (IL)-6 (GEE β=–0·037 [95% CI −0·067 to −0·007], p=0·016; change from baseline −83·4% vs −59·5%), IL-17 (β=–0·064 [–0·117 to −0·012], p=0·015; −74·0% vs −34·3%), and CXCL9 (β=–0·010 [–0·020 to 0·000], p=0·043; −71·3% vs −56·0%). Non-significant differences in the following cytokines were observed between treatment groups: CXCL8 (β=–0·018 [–0·037 to 0·000], p=0·056; −80·5% vs −58·0%), sTNFR-1 (β=–0·003 [–0·006 to 0·000], p=0·084; −40·1% vs −24·8%), IL-18 (β=–0·006 [–0·015 to 0·003], p=0·197; −29·1% vs 30·2%), and C-reactive protein (β=–0·033 [–0·088 to 0·022], p>0·10; −77·5% vs −48·2%). Two serious adverse events (SAEs) occurred in the oseltamivir-azithromycin group (Pseudomonas aeruginosa pneumonia, post-influenza vestibular neuronitis onset after stopping treatment for 1 week) versus one SAE in the oseltamivir group (increased ascites; p>0·99); all SAEs were considered unrelated to treatment. Other common adverse events were gastrointestinal or hepatic symptoms (five [20%] of 25 in the oseltamivir-azithromycin group vs four [16%] of 25 in the oseltamivir group; p>0.99) and dizziness or hearing symptoms (two [8%] vs two [8%]; p>0·99). All events were transient and reversible, and no participants died in this study. Interpretation We found significant anti-inflammatory effects with adjunctive macrolide treatment in adults with severe influenza infection. The clinical benefits of a macrolide-containing regimen deserve further study. Funding Research Grant Council of the Government of the Hong Kong Special Administrative Region, China (468112).

Background Whether host genetic factors determine clinical severity of influenza virus infections is unclear. This study examined the effects of single nucleotide polymorphisms (SNPs) of IFITM3, TLR3, CD55 , and TLR4 genes on outcomes of avian influenza A (H7N9) and pandemic influenza A (H1N1) pdm09 in Chinese patients. Methods This multicentre cohort study took place in four centres in Hong Kong, Beijing, Guangdong, and Shanghai and included adults prospectively diagnosed with H7N9 and H1N1 pdm09 infections during three respective seasonal outbreaks (H7N9, 2013–15; H1N1 pdm09 , 2011–14). The inclusion criteria were PCR-confirmed H7N9 or H1N1 pdm09 virus infection, age 18 years or older, and Chinese ethnicity. Host DNA was extracted from diagnostic respiratory samples, and IFITM3 (rs12252), TLR3 (rs5743313), CD55 (rs2564978), and TLR4 (rs4986790/4986791) were genotyped by Sanger sequencing. The data were tested to see whether they deviated from the Hardy-Weinberg equilibrium, and were compared with the 1000 Genomes data. The primary outcome for analysis was mortality. The effects of the SNPs were examined under different genetic models (recessive, additive, and dominant). The joint effect of significant loci was tested by computing the genetic risk score. All identifying patient information was removed from the dataset, and only anonymous data were used for analysis; individual consent was not required. Ethics approvals were obtained from the institutional review boards of all participating institutes. Findings Our cohort consisted of 275 adults with H7N9 and H1N1 pdm09 infections, of whom 33 died. In patients who died, we found over-representation of the homozygous IFITM3 CC genotype (18 [54%] of 33 patients with available data who died vs 70 [33%] of 211 with available data who survived; p=0·017) and the TLR3 CC genotype (28 [93%] of 30 vs 160 [77%] of 208; p=0·039). Recessive genetic models, adjusted for age, comorbidity, and antiviral treatment, showed that these genotypes had a significant association with increased risk of death ( IFITM3 CC genotype, adjusted hazard ratio [HR] 2·78 [95% CI 1·29–6·02]; and TLR3 CC genotype, adjusted HR 4·85 [1·11–21·06]). Cumulative effects were found (adjusted HR 3·53 [95% CI 1·64–7·59] per risk genotype; adjusted HR 9·99 [1·27–78·59] with both genotypes). The case-fatality rate in patients with a genetic risk score of 2, 1, and 0 was 23%, 11%, and 3%, respectively. Results were similar for each influenza subtype and other severity indicators such as development of acute respiratory failure. The population-attributable risk for mortality was 35·5% (95% CI 9·9–69·8) for IFITM3 CC and 74·6% (21·7–100) for TLR3 CC (combined effect, 83·6% [52·3–100]), owing to their high prevalence among Chinese people. A SNP of CD55 (genotype TT) was linked to severity of influenza as indicated by an increased risk for hospital admission (adjusted odds ratio [OR] 2·77, 95% CI 1·21–6·36; p=0·02); TLR4 was shown to be non-polymorphic in this cohort. Interpretation Host genetic factors might influence clinical outcomes of avian and pandemic influenza. Our findings could have important implications on public health and health-care planning, patient care, and design of clinical trials. Funding Health and Medical Research Fund (RRG-09) of the Hong Kong Special Administrative Region, China.

OBJECTIVE. To investigate the clinical efficacy and safety of irreversible electroporation for ablation of liver tumour in humans. DATA SOURCES. The PubMed and MEDLINE databases were systematically searched. STUDY SELECTION. Clinical research published in English in the last 10 years until October 2013 that address clinical issues related to irreversible electroporation of human liver tumours were selected. "Liver tumor", "local ablative therapy", and "irreversible electroporation" were used as the search terms. DATA EXTRACTION AND SYNTHESIS. The data extracted for this review was analysed by the authors, with a focus on the clinical efficacy and the safety of irreversible electroporation. The complete response rates look promising, ranging from 72% to 100%, except in one study in a subgroup of liver tumours in which the complete response rate was only 50% that was likely due to the inclusion of larger-size tumours. In one study, the local recurrence rate at 12 months was approximately 40%. As for the safety of irreversible electroporation, there were only a few reported complications (cardiac arrhythmia, pneumothorax, and electrolyte disturbance) that were mostly transient and not serious. There was no reported mortality related to the use of irreversible electroporation. CONCLUSION. Irreversible electroporation is a potentially effective liver tumour ablative therapy that gives rise to only mild and transient side-effects. Further studies with better patient selection criteria and longer follow-up are needed to clarify its role as a first-line liver tumour treatment modality.

In this paper, a method is proposed for offline signature verification. It is based on a smoothness criterion. It is observed that the cursive segments of forgery signatures are generally less smooth and less natural than the genuine ones, especially for those signatures that consist of cursive graphic patterns. Two approaches are proposed to extract a smoothness feature: a crossing method and a fractal dimension method. When the proposed smoothness feature is combined with other global shape features for signature verification, satisfactory results are obtained.

Cantonese language rehabilitation in 28 prelingually deaf children who underwent cochlear implantation was evaluated. All patients were implanted with multichannel devices and the operations went smoothly. They all had improved scores on audiological assessments and speech perception tests. The speech evaluation tests included the recognition of sounds, vowels, consonants and tone. Sentence recognition and story comprehension were both improved after training for 2 years. Cochlear implantation is a useful measure for the speech rehabilitation of prelingually profound deaf children when hearing aids are of no benefit. The multichannel implant device is of clinical significance in the rehabilitation of those patients using tonal language.