Lirong Liang

Clinical Features of the Initial Cases of 2009 Pandemic Influenza A (H1N1) Virus Infection in China

BACKGROUND The first case of 2009 pandemic influenza A (H1N1) virus infection in China was documented on May 10. Subsequently, persons with suspected cases of infection and contacts of those with suspected infection were tested. Persons in whom infection was confirmed were hospitalized and quarantined, and some of them were closely observed for the purpose of investigating the nature and duration of the disease. METHODS During May and June 2009, we observed 426 persons infected with the 2009 pandemic influenza A (H1N1) virus who were quarantined in 61 hospitals in 20 provinces. Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm infection, the clinical features of the disease were closely monitored, and 254 patients were treated with oseltamivir within 48 hours after the onset of disease. RESULTS The mean age of the 426 patients was 23.4 years, and 53.8% were male. The diagnosis was made at ports of entry (in 32.9% of the patients), during quarantine (20.2%), and in the hospital (46.9%). The median incubation period of the virus was 2 days (range, 1 to 7). The most common symptoms were fever (in 67.4% of the patients) and cough (69.5%). The incidence of diarrhea was 2.8%, and the incidence of nausea and vomiting was 1.9%. Lymphopenia, which was common in both adults (68.1%) and children (92.3%), typically occurred on day 2 (range, 1 to 3) and resolved by day 7 (range, 6 to 9). Hypokalemia was observed in 25.4% of the patients. Duration of fever was typically 3 days (range, 1 to 11). The median length of time during which patients had positive real-time RT-PCR test results was 6 days (range, 1 to 17). Independent risk factors for prolonged real-time RT-PCR positivity included an age of less than 14 years, male sex, and a delay from the onset of symptoms to treatment with oseltamivir of more than 48 hours. CONCLUSIONS Surveillance of the 2009 H1N1 virus in China shows that the majority of those infected have a mild illness. The typical period during which the virus can be detected with the use of real-time RT-PCR is 6 days (whether or not fever is present). The duration of infection may be shortened if oseltamivir is administered.

Efficacy and Safety of Low Dose Recombinant Tissue-Type Plasminogen Activator for the Treatment of Acute Pulmonary Thromboembolism: A Randomized, Multicenter, Controlled Trial

Background Optimal dosing of the recombinant tissue-type plasminogen activator (rt-PA) is important in treating pulmonary thromboembolism (PTE). The aim of this study was to compare the efficacy and safety of a 50 mg/2 h rt-PA regimen with a 100 mg/2 h rt-PA regimen in patients with acute PTE. Methods A prospective, randomized, multicenter trial was conducted in which 118 patients with acute PTE and either hemodynamic instability or massive pulmonary artery obstruction were randomly assigned to receive a treatment regiment of either rt-PA at 50 mg/2 h (n = 65) or 100 mg/2 h (n = 53). The efficacy was determined by observing the improvements of right ventricular dysfunctions (RVDs) on echocardiograms, lung perfusion defects on ventilation perfusion lung scans, and pulmonary artery obstructions on CT angiograms. The adverse events, including death, bleeding, and PTE recurrence, were also evaluated. Results Progressive improvements in RVDs, lung perfusion defects, and pulmonary artery obstructions were found to be similarly significant in both treatment groups. This is true for patients with either hemodynamic instability or massive pulmonary artery obstruction. Three (6%) patients in the rt-PA 100 mg/2 h group and one (2%) in the rt-PA 50 mg/2 h group died as the result of either PTE or bleeding. Importantly, the 50 mg/2 h rt-PA regimen resulted in less bleeding tendency than the 100 mg/2 h regimen (3% vs 10%), especially in patients with a body weight < 65 kg (14.8% vs 41.2%, P = .049). No fatal recurrent PTE was found in either group. Conclusions Compared with the 100 mg/2 h regimen, the 50 mg/2 h rt-PA regimen exhibits similar efficacy and perhaps better safety in patients with acute PTE. These findings support the notion that optimizing rt-PA dosing is worthwhile when treating patients with PTE. Trial registration clinicaltrials.gov; Identifier: NCT00781378

Oseltamivir Compared With the Chinese Traditional Therapy Maxingshigan–Yinqiaosan in the Treatment of H1N1 Influenza: A Randomized Trial

BACKGROUND Observational studies from Asia suggest that maxingshigan-yinqiaosan may be effective in the treatment of acute H1N1 influenza. OBJECTIVE To compare the efficacy and safety of oseltamivir and maxingshigan-yinqiaosan in treating uncomplicated H1N1 influenza. DESIGN Prospective, nonblinded, randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00935194) SETTING Eleven hospitals from 4 provinces in China. PATIENTS 410 persons [corrected] aged 15 to 69 [corrected] years with laboratory-confirmed H1N1 influenza. INTERVENTION Oseltamivir, 75 mg twice daily; maxingshigan-yinqiaosan decoction (composed of 12 Chinese herbal medicines, including honey-fried Herba Ephedrae), 200 mL 4 times daily; oseltamivir plus maxingshigan-yinqiaosan; or no intervention (control). Interventions and control were given for 5 days. MEASUREMENTS Primary outcome was time to fever resolution. Secondary outcomes included symptom scores and viral shedding determined by using real-time reverse transcriptase polymerase chain reaction. RESULTS Significant reductions in the estimated median time to fever resolution compared with the control group (26.0 hours [95% CI, 24.0 to 33.0 hours]) were seen with oseltamivir (34% [95% CI, 20% to 46%]; P < 0.001), maxingshigan-yinqiaosan (37% [CI, 23% to 49%]; P < 0.001), and oseltamivir plus maxingshigan-yinqiaosan (47% [CI, 35% to 56%]; P < 0.001). Time to fever resolution was reduced by 19% (CI, 0.3% to 34%; P = 0.05) with oseltamivir plus maxingshigan-yinqiaosan compared with oseltamivir. The interventions and control did not differ in terms of decrease in symptom scores (P = 0.38). Two patients who received maxingshigan-yinqiaosan reported nausea and vomiting. LIMITATIONS Participants were young and had mild H1N1 influenza virus infection. Missing viral data precluded definitive conclusions about viral shedding. CONCLUSION Oseltamivir and maxingshigan-yinqiaosan, alone and in combination, reduced time to fever resolution in patients with H1N1 influenza virus infection. These data suggest that maxingshigan-yinqiaosan may be used as an alternative treatment of H1N1 influenza virus infection. PRIMARY FUNDING SOURCE Beijing Science and Technology Project and Beijing Nova Program.

Pulmonary Embolism Incidence and Fatality Trends in Chinese Hospitals from 1997 to 2008: A Multicenter Registration Study

Background There has not been sufficient evidence to support the Asians being less susceptible to pulmonary embolism (PE) than other ethnicities, because the prevalence of PE/deep venous thrombosis (DVT) in different racial and ethnic groups has not been carefully studied until recently except in Caucasians. To test the hypothesis that the Chinese population has a lower risk for PE, this study comprehensively assessed the hospital-based incidence and case fatality rates for PE during the 1997–2008 in China. Methods A registration study of patients with suspected PE syndromes admitted to 60 level-3 hospitals involved in the National Cooperative Project for the Prevention and Treatment of Venous Thromboembolism (NCPPT) was conducted from January 1997 to December 2008. The only exclusion criterion was an age of less than 18 years. Helical computed tomography scan, ventilation-perfusion lung scintigraphy or pulmonary angiography was carried out before or after hospitalization. All images were reviewed and evaluated independently by two specialists. Results A total of 18,206 patients were confirmed with PE from 16,972,182 hospital admissions. The annual incidence was 0.1% (95% CI: 0.1% to 0.2%). The overall incidence of PE in male patients (0.2%, 95% CI: 0.1% to 0.3%) was higher than that in female patients (0.1% and 95% CI: 0.0% to 0.1%). An increasing incidence gradient for PE was noticed from Southern to Northern China. In addition, the case fatality rate was apparently decreasing: 25.1% (95% CI: 16.2% to 36.9%) in 1997 to 8.7% (95% CI: 3.5% to 15.8%) in 2008. Conclusions Our findings suggest the relatively stable PE incidence and decreasing fatality trends in Chinese hospitals may be partially attributable to the implementation of the NCCPT and suggest the government should reevaluate the severity of PE so that health resources for the prevention, diagnosis and treatment of PE could be used to their fullest.

Clinical Features of Pneumonia Caused by 2009 Influenza A(H1N1) Virus in Beijing, China

Background Data on symptoms and radiographic changes in patients with pandemic 2009 influenza A(H1N1) (A[H1N1]) pneumonia during convalescence have not been reported. Methods During October 26, 2009, and January 23, 2010, adult patients with pneumonia with laboratory-confirmed or clinically suspected A(H1N1) infections were observed for clinical characteristics, high-resolution chest CT scan, and lung function test changes during acute and 3-month convalescent phases. Results Of the 65 case subjects, the median age was 41 (interquartile range [IQR], 28-57) years, 60.0% were men, and 55.4% had at least one underlying medical condition. Sixty-two patients started oseltamivir therapy within a median of 5 (IQR, 4-6) days from the onset of illness, and 31 received IV corticosteroids. ARDS developed in 33 patients, and 24 were treated initially with noninvasive positive pressure ventilation (NPPV). In this group, NPPV was successful in 13 patients (54.2%). Nine patients died at a median of 16 (IQR, 10-24) days after onset of illness. Multivariate Cox regression identified two independent risk factors for death: progressive dyspnea after resolution of fever (relative risk, 5.852; 95% CI, 1.395-24.541; P = .016) and a higher APACHE (Acute Physiology and Chronic Health Evaluation) II score on presentation (relative risk for each point, 1.312; 95% CI, 1.140-1.511; P < .001). At 3-month follow-up of survivors with A(H1N1), ground-glass opacities were still present, although diminished, in 85.7%, and diffusing capacity for carbon monoxide was mildly reduced in 61.5%. Conclusions Ground-glass opacities and decreased diffusing capacity were the main abnormalities observed at 3-month follow-up of survivors of A(H1N1).

Efficacy and safety of 2-hour urokinase regime in acute pulmonary embolism: a randomized controlled trial

BackgroundsUrokinase (UK) 2 200 U/kg·h for 12 hours infusion(UK-12 h)is an ACCP recommended regimen in treating acute pulmonary embolism (PE). It is unclear whether this dose and time can be reduced further. We compared the efficacy and safety of 20, 000 U/kg for 2 hours (UK-2 h) with the UK-12 h regime in selected PE patients.MethodsA randomized trial involving 129 patients was conducted. Patients with acute PE were randomly assigned to receive either UK-12 h (n = 70), or UK-2 h (n = 59). The efficacy was determined by the improvement of right heart dysfunction and perfusion defect at 24 h and 14 d post UK treatment. The bleeding incidence, death rate and PE recurrence were also evaluated.ResultsSimilarly significant improvements in right heart dysfunction and lung perfusion defects were observed in both groups. Overall bleeding incidents were low in both groups. Major bleeding directly associated with UK infusion occurred in one patient in the UK-2 h group and one in the UK-12 h group. Mortality rates were low, with one reported fatal recurrent in the UK-12 h group and none in the UK-2 h group. When the rate of bleeding, death and PE recurrence were compared separately in the hemodynamic instability and the massive anatomic obstruction subgroups, no significant difference was found.ConclusionsThe UK-2 h regimen exhibits similar efficacy and safety as the UK-12 h regimen for acute PE.Trial RegistrationClinical trial registered with http://clinicaltrials.gov/ct2/show/NCT00799968 (Identifier: NCT 00799968)

Prevalence and Associations of VTE in Patients With Newly Diagnosed Lung Cancer

BACKGROUND The risk of VTE before anticancer therapy in patients with lung cancer is not well defined. METHODS A total of 673 hospitalized patients with newly diagnosed lung cancer were examined for VTE within 1 week after admission at five hospitals between January 2009 and January 2011. Additionally, VTE diagnoses within the last 3 months were reviewed. All VTE events were confirmed with imaging studies. Blood cell count and serum carcinoembryonic antigen (CEA) levels were measured before initial treatment. RESULTS VTE events occurred in 89 of the 673 patients (13.2%) enrolled in this study. Forty-two patients (6.2%) developed lower extremity DVT alone, 33 patients (4.9%) developed pulmonary embolism (PE) alone, and 14 patients (2.1%) developed both DVT and PE. By multivariate logistic regression analysis, distant metastasis (OR, 2.2; 95% CI, 1.2-3.9) and leukocytosis (OR, 2.8; 95% CI, 1.5-5.4) were significantly associated with DVT, adenocarcinoma (OR, 2.1; 95% CI, 1.1-4.4) and anemia (OR, 4.6; 95% CI, 1.4-14.5) were significantly associated with PE, and an elevated CEA level in tertiles was linearly associated with PE (P for trend = .06). The area under the receiver operating characteristic curve for the prognostic or diagnostic CEA values was 0.68 (95% CI, 0.59-0.76; P < .001). CONCLUSIONS The prevalence of VTE was high in patients with newly diagnosed lung cancer. In patients with lung cancer, the factors associated with DVT might be different from those associated with PE. An elevated CEA level might facilitate the identification of patients at a higher risk of developing PE.

Clinical features and risk factors for severe and critical pregnant women with 2009 pandemic H1N1 influenza infection in China

Background2009 pandemic H1N1 (pH1N1) influenza posed an increased risk of severe illness among pregnant women. Data on risk factors associated with death of pregnant women and neonates with pH1N1 infections are limited outside of developed countries.MethodsRetrospective observational study in 394 severe or critical pregnant women admitted to a hospital with pH1N1 influenza from Sep. 1, 2009 to Dec. 31, 2009. rRT-PCR testing was used to confirm infection. In-hospital mortality was the primary endpoint of this study. Univariable logistic analysis and multivariate logistic regression analysis were used to investigate the potential factors on admission that might be associated with the maternal and neonatal mortality.Results394 pregnant women were included, 286 were infected with pH1N1 in the third trimester. 351 had pneumonia, and 77 died. A PaO2/FiO2 ≤ 200 (odds ratio (OR), 27.16; 95% confidence interval (CI), 2.64-279.70) and higher BMI (i.e. ≥ 30) on admission (OR, 1.26; 95% CI, 1.09 to 1.47) were independent risk factors for maternal death. Of 211 deliveries, 146 neonates survived. Premature delivery (OR, 4.17; 95% CI, 1.19-14.56) was associated neonatal mortality. Among 186 patients who received mechanical ventilation, 83 patients were treated with non-invasive ventilation (NIV) and 38 were successful with NIV. The death rate was lower among patients who initially received NIV than those who were initially intubated (24/83, 28.9% vs 43/87, 49.4%; p = 0.006). Septic shock was an independent risk factor for failure of NIV.ConclusionsSevere hypoxemia and higher BMI on admission were associated with adverse outcomes for pregnant women. Preterm delivery was a risk factor for neonatal death among pregnant women with pH1N1 influenza infection. NIV may be useful in selected pregnant women without septic shock.

Incidence and risk factors of chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism

BACKGROUND Early identification and treatment of chronic thromboembolic pulmonary hypertension (CTEPH) are critical to prevent disease progression. We determined the incidence and risk factors for CTEPH in patients with a first episode of acute pulmonary embolism (PE). METHODS In this study, consecutive patients with first-episode acute PE were followed for ≤5 years. Pulmonary hypertension (PH) was screened for by echocardiography. Suspected cases were evaluated by right heart catheterization (RHC) and pulmonary angiography (PA). If invasive procedures were not permitted, PH was diagnosed by systolic pulmonary artery pressure (SPAP) >50 mmHg. Diagnosis of CTEPH was confirmed by PA, ventilation/perfusion (V/Q) lung scan, or computed tomography (CT) PA (CTPA). RESULTS Overall, 614 patients with acute PE were included (median follow-up, 3.3 years). Ten patients were diagnosed with CTEPH: cumulative incidence 0.8% [95% confidence interval (CI), 0.0-1.6%] at 1 year, 1.3% (95% CI, 0.3-2.3%) at 2 years, and 1.7% (95% CI, 0.7-2.7%) at 3 years. No cases of CTEPH developed after 3 years. History of lower-limb varicose veins [hazard ratio (HR), 4.3; 95% CI, 1.2-15.4; P=0.024], SPAP >50 mmHg at initial PE episode (HR, 23.5; 95% CI, 2.7-207.6; P=0.005), intermediate-risk PE (HR, 1.2; 95% CI, 1.0-1.4; P=0.030), and CT obstruction index over 30% at 3 months after acute PE (HR, 42.5; 95% CI, 4.4-409.8; P=0.001) were associated with increased risk of CTEPH. CONCLUSIONS CTEPH was not rare after acute PE in this Chinese population, especially within 3 years of diagnosis. Lower-limb varicose veins, intermediate-risk PE with elevated SPAP in the acute phase, and residual emboli during follow-up might increase the risk of CTEPH.

Switchable 3D optofluidic Y-branch waveguides tuned by Dean flows

Optical branch waveguides are one of the most important optical elements and have been widely exploited for optical communication systems. However, prevailing devices are typically solid and have limit in tunability. Liquid optical devices have attracted more interest for the advantage of tunability of liquid media, but their signals suffer serious leakage if the refractive index (RI) of liquid is smaller than that of solid channels. This paper demonstrates the tunable three-dimensional (3D) optofluidic Y-branch waveguides in plannar microchannels by simply introducing Dean flow. This device can reconfigure 3D Y-branch profiles and separate the intensity of light as tunable ratio from 0 to 1 by adjusting the flow rates with low loss. Different from the prevailing 2D liquid counterparts, the 3D configuration offer much more freedom in the selection of liquid media as liquid’s RI can be totally independent to the solid channel structure. The transmission loss through the device is estimated to 0.97 db when the splitting angle is 10°, which shows the light is confined better in the 3D liquid structures than traditional 2D liquid counterparts. The Y-branch waveguides show potential in applications of integrated optofluidic devices.