Timothy H. Rainer

Viral Loads and Duration of Viral Shedding in Adult Patients Hospitalized with Influenza

Abstract 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<.05) and viral RNA clearance at 1 week (odds ratio, 0.10 [95% confidence interval, 0.03–0.35] and 0.30 [0.10–0.90] for patients treated on day 1–2 and day 3–4, respectively). Conversely, major comorbidities and systemic corticosteroid use for asthma or chronic obstructive pulmonary disease exacerbations were associated with slower viral clearance. Viral RNA clearance was associated with a shorter hospital stay (7.0 vs 13.5 days; P=.001) ConclusionPatients hospitalized with severe influenza have more active and prolonged viral replication. Weakened host defenses slow viral clearance, whereas antivirals started within the first 4 days of illness enhance viral clearance

International perspectives on emergency department crowding.

The maturation of emergency medicine (EM) as a specialty has coincided with dramatic increases in emergency department (ED) visit rates, both in the United States and around the world. ED crowding has become a public health problem where periodic supply and demand mismatches in ED and hospital resources cause long waiting times and delays in critical treatments. ED crowding has been associated with several negative clinical outcomes, including higher complication rates and mortality. This article describes emergency care systems and the extent of crowding across 15 countries outside of the United States: Australia, Canada, Denmark, Finland, France, Germany, Hong Kong, India, Iran, Italy, The Netherlands, Saudi Arabia, Catalonia (Spain), Sweden, and the United Kingdom. The authors are local emergency care leaders with knowledge of emergency care in their particular countries. Where available, data are provided about visit patterns in each country; however, for many of these countries, no national data are available on ED visits rates or crowding. For most of the countries included, there is both objective evidence of increases in ED visit rates and ED crowding and also subjective assessments of trends toward higher crowding in the ED. ED crowding appears to be worsening in many countries despite the presence of universal health coverage. Scandinavian countries with robust systems to manage acute care outside the ED do not report crowding is a major problem. The main cause for crowding identified by many authors is the boarding of admitted patients, similar to the United States. Many hospitals in these countries have implemented operational interventions to mitigate crowding in the ED, and some countries have imposed strict limits on ED length of stay (LOS), while others have no clear plan to mitigate crowding. An understanding of the causes and potential solutions implemented in these countries can provide a lens into how to mitigate ED crowding in the United States through health policy interventions and hospital operational changes.

Prospective comparison of three predictive rules for assessing severity of community-acquired pneumonia in Hong Kong

Background: Community-acquired pneumonia (CAP) is a leading infectious cause of death throughout the world, including Hong Kong. Aim: To compare the ability of three validated prediction rules for CAP to predict mortality in Hong Kong: the 20 variable Pneumonia Severity Index (PSI), the 6-point CURB65 scale adopted by the British Thoracic Society and the simpler CRB65. Methods: A prospective observational study of 1016 consecutive inpatients with CAP (583 men, mean (SD) age 72 (17) years) was performed in a university hospital in the New Territories of Hong Kong in 2004. The patients were classified into three risk groups (low, intermediate and high) according to each rule. The ability of the three rules to predict 30 day mortality was compared. Results: The overall mortality and intensive care unit (ICU) admission rates were 8.6% and 4.0%, respectively. PSI, CURB65 and CRB65 performed similarly, and the areas under the receiver operating characteristic (ROC) curve were 0.736 (95% CI 0.687 to 0.736), 0.733 (95% CI 0.679 to 0.787) and 0.694 (95% CI 0.634 to 0.753), respectively. All three rules had high negative predictive values but relatively low positive predictive values at all cut-off points. Larger proportions of patients were identified as low risk by PSI (47.2%) and CURB65 (43.3%) than by CRB65 (12.6%). Conclusion: All three predictive rules have a similar performance in predicting the severity of CAP, but CURB65 is more suitable than the other two for use in the emergency department because of its simplicity of application and ability to identify low-risk patients.

Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys

Objective To assess the acceptability of pre-pandemic influenza vaccination among healthcare workers in public hospitals in Hong Kong and the effect of escalation in the World Health Organization’s alert level for an influenza pandemic. Design Repeated cross sectional studies using self administered, anonymous questionnaires Setting Surveys at 31 hospital departments of internal medicine, paediatrics, and emergency medicine under the Hong Kong Hospital Authority from January to March 2009 and in May 2009 Participants 2255 healthcare workers completed the questionnaires in the two studies. They were doctors, nurses, or allied health professionals working in the public hospital system. Main outcome measures Stated willingness to accept pre-pandemic influenza vaccination (influenza A subtypes H5N1 or H1N1) and its associating factors. Results The overall willingness to accept pre-pandemic H5N1 vaccine was only 28.4% in the first survey, conducted at WHO influenza pandemic alert phase 3. No significant changes in the level of willingness to accept pre-pandemic H5N1 vaccine were observed despite the escalation to alert phase 5. The willingness to accept pre-pandemic H1N1 vaccine was 47.9% among healthcare workers when the WHO alert level was at phase 5. The most common reasons for an intention to accept were “wish to be protected” and “following health authority’s advice.” The major barriers identified were fear of side effects and doubts about efficacy. More than half of the respondents thought nurses should be the first priority group to receive the vaccines. The strongest positive associating factors were history of seasonal influenza vaccination and perceived risk of contracting the infection. Conclusions The willingness to accept pre-pandemic influenza vaccination was low, and no significant effect was observed with the change in WHO alert level. Further studies are required to elucidate the root cause of the low intention to accept pre-pandemic vaccination.

Time Course of Early and Late Changes in Plasma DNA in Trauma Patients

BACKGROUND Cell-free DNA concentrations increase in the circulation of patients after trauma and may have prognostic potential, but little is know concerning the temporal changes or clearance of the DNA or its relationships with posttraumatic complications. We investigated temporal changes in plasma DNA concentrations in patients after trauma with use of real-time quantitative PCR. METHODS Serial plasma samples were taken from two trauma populations. In the first study, samples were collected every 20 min from 25 patients within the first 3 h of trauma. In the second study, samples were collected every day from 36 other trauma patients admitted to the intensive care unit (ICU). RESULTS In the first study, plasma DNA was increased within 20 min of injury and was significantly higher in patients with severe injury and in patients who went on to develop organ failure. In patients with less severe injuries, plasma DNA concentrations decreased toward reference values within 3 h. In the second study, plasma DNA concentrations were higher in patients who developed multiple organ dysfunction syndrome between the second and fourth days of admission than in patients who did not develop the syndrome. In patients who remained in the ICU with continuing organ dysfunction, plasma DNA remained higher than in healthy controls even at 28 days after injury. Most survivors with multiple organ dysfunction syndrome showed an initial very high peak followed by a prolonged smaller increase. CONCLUSIONS Plasma DNA concentrations increase early after injury and are higher in patients with severe injuries and in those who develop organ failure. Increased plasma DNA persists for days after injuries, especially in patients with multiple organ dysfunction syndrome.

Evaluation of WHO criteria for identifying patients with severe acute respiratory syndrome out of hospital: prospective observational study

Abstract Objectives To determine the clinical and radiological features of severe acute respiratory syndrome (SARS) and to evaluate the accuracy of the World Health Organizations guidelines on defining cases of SARS. Design Prospective observational study. Setting A newly set up SARS screening clinic in the emergency department of a university hospital in Hong Kongs New Territories. Participants 556 hospital staff, patients, and relatives who attended the screening clinic and who had had contact with someone with SARS. Main outcome measure Number of confirmed cases of SARS. Results Of the 556 people, 141 were admitted to hospital, and 97 had confirmed SARS. Fever, chills, malaise, myalgia, rigor, loss of appetite, vomiting, diarrhoea, and neck pain but not respiratory tract symptoms were significantly more common among the 97 patients than among the other patients. The overall accuracy of the WHO guidelines for identifying suspected SARS was 83% and their negative predictive value was 86% (95% confidence interval 83% to 89%). They had a sensitivity of 26% (17% to 36%) and a specificity of 96% (93% to 97%). Conclusions Current WHO guidelines for diagnosing suspected SARS may not be sufficiently sensitive in assessing patients before admission to hospital. Daily follow up, evaluation of non-respiratory, systemic symptoms, and chest radiography would be better screening tools.

Comparison of Oral Prednisolone/Paracetamol and Oral Indomethacin/Paracetamol Combination Therapy in the Treatment of Acute Goutlike Arthritis: A Double-Blind, Randomized, Controlled Trial

Study objective We compare the analgesic efficacy and adverse effects of oral prednisolone/acetaminophen and oral indomethacin/acetaminophen combination therapy in the treatment of acute goutlike arthritis in patients presenting to an emergency department (ED). Methods This is a double-blind, randomized, controlled study in a university hospital emergency department (ED) in the New Territories of Hong Kong. Patients older than 17 years and presenting between February 1, 2003, and June 30, 2004, with a clinical diagnosis of goutlike arthritis were randomized to receive either oral prednisolone/acetaminophen or oral indomethacin/acetaminophen combination therapy. Primary outcome measures were pain scores, time to resolution of symptoms and signs, and adverse effects. Secondary outcome measures were the need for additional acetaminophen and relapse rate. Results There were 90 patients randomized: 46 patients to the indomethacin group and 44 patients to the prednisolone group. Baseline characteristics, including pain scores, were similar in the 2 groups. Both treatment groups had a similar decrease in pain score in the ED. The mean rate of decrease in pain score with activity for indomethacin was −1.7±1.6 (SD) mm per day and for prednisolone was −2.9±2.0 (SD) mm per day (mean difference 1.2 mm/day; 95% confidence interval 0.4 to 2.0 mm/day; P=.0026). Although these differences were statistically significant, at no time was the difference in mean pain score greater than 13 mm. Therefore, it is unclear whether these differences are clinically significant. The mean total dose of acetaminophen consumed by the prednisolone group was significantly more than in the indomethacin group (mean 10.3 g, range 1 to 21 g versus mean 6.4 g, range 1 to 21 g). Twenty-nine patients in the indomethacin group and 12 patients in the prednisolone group experienced adverse effects (P<.05). The commonest adverse effects in the indomethacin group were nausea, indigestion, epigastric pain, dizziness, and gastrointestinal bleeding (N=5; 11%). None of the patients in the prednisolone group developed gastrointestinal bleeding. The relapse rate for both groups was similar. Conclusion In the treatment of acute goutlike arthritis, oral prednisolone/acetaminophen combination is as effective as oral indomethacin/acetaminophen combination in relieving pain but is associated with fewer adverse effects.

Quantitative Analysis of Circulating Mitochondrial DNA in Plasma

BACKGROUND Recent studies have demonstrated the existence of circulating mitochondrial DNA in plasma and serum, but the concentrations and physical characteristics of circulating mitochondrial DNA are unknown. The aim of this study was to develop an assay to quantify mitochondrial DNA in the plasma of healthy individuals. METHODS We adopted a real-time quantitative PCR approach and evaluated the specificity of the assay for detecting mitochondrial DNA with a cell line (rho(0)) devoid of mitochondria. The concentrations and physical characteristics of circulating mitochondrial DNA were investigated by experiments conducted in three modules. In module 1, we evaluated the concentrations of mitochondrial DNA in plasma aliquots derived from four blood-processing protocols. In module 2, we investigated the existence of both particle-associated and free forms of mitochondrial DNA in plasma by subjecting plasma to filtration and ultracentrifugation. In module 3, we used filters with different pore sizes to investigate the size characteristics of the particle-associated fraction of circulating mitochondrial DNA. RESULTS The mitochondrial DNA-specific, real-time quantitative PCR had a dynamic range of five orders of magnitude and a sensitivity that enabled detection of one copy of mitochondrial DNA in plasma. In module 1, we found significant differences in the amounts of circulating mitochondrial DNA among plasma aliquots processed by different methods. Data from module 2 revealed that a significant fraction of mitochondrial DNA in plasma was filterable or pelletable by ultracentrifugation. Module 3 demonstrated that filters with different pore sizes removed mitochondrial DNA from plasma to different degrees. CONCLUSIONS Both particle-associated and free mitochondrial DNA are present in plasma, and their respective concentrations are affected by the process used to harvest plasma from whole blood. These results may have implications in the design of future studies on circulating mitochondrial DNA measured in different disease conditions.

Prevalence of survivor bias in observational studies on fresh frozen plasma: erythrocyte ratios in trauma requiring massive transfusion

Observational studies on transfusion in trauma comparing high versus low plasma:erythrocyte ratio were prone to survivor bias because plasma administration typically started later than erythrocytes. Therefore, early deaths were categorized in the low plasma:erythrocyte group, whereas early survivors had a higher chance of receiving a higher ratio. When early deaths were excluded, however, a bias against higher ratio can be created. Survivor bias could be reduced by performing before-and-after studies or treating the plasma:erythrocyte ratio as a time-dependent covariate. We reviewed 26 studies on blood ratios in trauma. Fifteen of the studies were survivor bias-unlikely or biased against higher ratio; among them, 10 showed an association between higher ratio and improved survival, and five did not. Eleven studies that were judged survivor bias-prone favoring higher ratio suggested that a higher ratio was superior. Without randomized controlled trials controlling for survivor bias, the current available evidence supporting higher plasma:erythrocyte resuscitation is inconclusive.

Early risk stratification of patients with major trauma requiring massive blood transfusion

BACKGROUND There is limited evidence to guide the recognition of patients with massive, uncontrolled hemorrhage who require initiation of a massive transfusion (MT) protocol. OBJECTIVE To risk stratify patients with major trauma and to predict need for MT. DESIGNS Retrospective analysis of an administrative trauma database of major trauma patients. A REGIONAL TRAUMA CENTRE: A regional trauma centres in Hong Kong. PATIENTS Patients with Injury Severity Score ≥ 9 and age ≥ 12 years were included. Burn patients, patients with known severe anemia and renal failure, or died within 24h were excluded. MAIN OUTCOME MEASURES Delivery of ≥ 10 units of packed red blood cells (RBC) within 24h. RESULTS Between 01/01/2001 and 30/06/2009, 1891 patients met the inclusion criteria. 92 patients required ≥ 10 units RBC within 24h. Seven variables which were easy to be measured in the ED and significantly predicted the need for MT are heart rate ≥ 120/min; systolic blood pressure ≤ 90 mm Hg; Glasgow coma scale ≤ 8; displaced pelvic fracture; CT scan or FAST positive for fluid; base deficit >5 mmol/L; hemoglobin ≤ 7 g/dL; and hemoglobin 7.1-10 g/dL. At a cut off of ≥ 6, the overall correct classification for predicting need for MT was 96.9%, with a sensitivity of 31.5% and specificity of 99.7%, and an incidence of MT of 82.9%. The area under the curve was 0.889. CONCLUSION A prediction rule for determining an increased likelihood for the need for massive transfusion has been derived. This needs validation in an independent data set.