Retrospective review of 27 European cases of fatal elephant endotheliotropic herpesvirus-haemorrhagic disease reveals evidence of disseminated intravascular coagulation.

Elephant endotheliotropic herpesvirus haemorrhagic disease (EEHV-HD) is widely acknowledged as the most common cause of mortality in young Asian elephants (Elephas maximus) in captivity. The objective of the current study was to perform a blinded, retrospective pathology review of European EEHV-HD fatalities, constituting the largest systematic assessment of EEHV-HD pathology to date. Findings between viral genotypes were compared with the aim to investigate if disseminated intravascular coagulation (DIC) could be substantiated as a significant complicating factor, thereby increasing the understanding of disease pathophysiology. Immunohistochemical staining confirmed endothelial cell (EC) damage and the presence of EC intranuclear inclusion bodies, demonstrating a direct viral cytopathic effect. Microthrombi were observed in 63% of cases in several organs, including lungs, which, together with widespread haemorrhage and thrombocytopenia reported in EEHV-HD case reports, supports the presence of overt DIC as a serious haemostatic complication of active EEHV infection. Death was attributed to widespread vascular damage with multi-organ dysfunction, including severe acute myocardial haemorrhage and subsequent cardiac failure. Systemic inflammation observed in the absence of bacterial infection may be caused by cytokine release syndrome. Findings reinforce the necessity to investigate cytokine responses and haemostatic status during symptomatic and asymptomatic EEHV viraemia, to potentially support the use of anti-inflammatory treatment in conjunction with anti-viral therapy and cardiovascular support.

Effectiveness of the 2009 seasonal influenza vaccine against pandemic influenza A(H1N1)2009 in healthcare workers in New Zealand, June-August 2009.

There is uncertainty whether the 2009 seasonal influenza vaccination influences the risk of infection with the 2009 pandemic influenza A(H1N1) virus. This issue was investigated in 548 healthcare workers from Capital and Coast District Health Board, Wellington, New Zealand, presenting with influenza-like illness during the influenza pandemic between June and August 2009. All workers completed an assessment sheet and had a nasopharyngeal swab tested by real-time RT-PCR. The risk of pandemic influenza A(H1N1) infection associated with the 2009 seasonal inactivated trivalent influenza vaccine was determined by logistic regression, with adjustment for potential confounding variables. In 96 workers pandemic influenza A(H1N1) RNA was detected and 452 tested negative. The multivariate analysis did not show any effect of vaccination on PCR-confirmed influenza A(H1N1)2009 infection (odds ratio 1.2, 95% confidence interval 0.7­1.9, p=0.48). We conclude that 2009 seasonal influenza vaccination had no protective effect against influenza A(H1N1)2009 infection amongst healthcare workers. To protect against further waves of the current pandemic influenza or future pandemics in which the influenza virus is antigenically distinct from contemporary seasonal influenza viruses, it would be necessary to vaccinate with a specific pandemic influenza vaccine, or a seasonal influenza vaccine that includes the pandemic influenza serotype.

Assessing PaCO2 in acute respiratory disease: accuracy of a transcutaneous carbon dioxide device.

BACKGROUND: Pulse oximetry non-invasively assesses the arterial oxygen saturation of patients with acute respiratory disease; however, measurement of the arterial partial pressure of carbon dioxide (PaCO(2)) requires an arterial blood gas. The transcutaneous partial pressure of carbon dioxide (PtCO(2) ) has been used in other settings with variable accuracy. We investigated the accuracy of a PtCO(2) device in the assessment of PaCO(2) in patients with asthma and suspected pneumonia attending the emergency department. METHODS: Patients with severe asthma (FEV(1) < 50% predicted) or suspected pneumonia (fever, cough and respiratory rate >18/min) were enrolled. Subjects were excluded if they had a history of chronic obstructive pulmonary disease or other conditions associated with respiratory failure. Arterial blood gases were taken at the discretion of the investigator according to clinical need, and paired with a simultaneous reading from the PtCO(2) probe. RESULTS: Twenty-five patients were studied with one set of data excluded because of poor PtCO(2) signal quality. The remaining 24 paired samples comprised 12 asthma and 12 pneumonia patients. The range of PaCO(2) was 19-64 mmHg with a median of 36.5 mmHg. Bland-Altman analysis showed a mean (SD) PaCO(2) - PtCO(2) difference of -0.13 (1.9) mmHg with limits of agreement of plus or minus 3.8 mmHg (-3.9 to +3.7). CONCLUSION: A PtCO(2) device was accurate in the assessment of PaCO(2) in patients with acute severe asthma and suspected pneumonia when compared with an arterial blood gas. These bedside monitors have the potential to improve patient care by non-invasively monitoring patients with acute respiratory disease at risk of hypercapnia.

Pre-hospital oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: High concentration oxygen is commonly administered during acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this study was to determine the association between oxygen, severity markers and poor outcomes in AECOPD. METHODS: In an audit of patients with AECOPD arriving by ambulance to the Emergency Department of Wellington Hospital, details of oxygen administration, clinical outcomes and severity markers were documented. The main outcome measure was a composite of death, assisted ventilation, or respiratory failure. Associations between oxygen therapy, severity markers and poor clinical outcomes were assessed by logistic regression. RESULTS: Of 250 patients 77 (31%) died, required assisted ventilation or were in respiratory failure. Increased oxygen flow was associated with increasing risk of death, assisted ventilation or respiratory failure with an odds ratio (OR) of 1.2 (95% CI 1.0-1.4) per 1 L/min oxygen flow. Increasing PaO(2) was associated with a greater risk of a poor outcome with an OR of 1.1 (95% CI 1.0-1.3) per 10 mmHg higher PaO(2). Home oxygen (OR 2.8, 95% CI 1.5-5.1), previous respiratory failure (OR 2.6, 95% CI 1.5-4.6), previous ventilation (OR 3.2, 95% CI 1.7-5.9) and home nebulizer use (OR 2.4, 95% CI 1.4-4.3) were associated with an increased risk of a poor outcome. CONCLUSION: In AECOPD high flow oxygen in the ambulance is associated with poor clinical outcomes. A number of easily identified markers of chronic disease severity indicate an increased risk of a poor clinical outcome.

Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy.

BACKGROUND: There is concern that long-acting beta agonist (LABA) drugs may increase the risk of asthma mortality. METHODS: A meta-analysis was conducted of asthma deaths in randomised controlled clinical trials from the GlaxoSmithKline database that compared salmeterol with a non-LABA comparator treatment in asthma. The Peto one-step method was used to determine the risk overall (all studies) and in derived datasets based on inhaled corticosteroid (ICS) use. RESULTS: There were 35 asthma deaths in 215 studies with 106,575 subjects. Two studies (SMART and SNS) contributed 30/35 (86%) asthma deaths, the overall findings largely reflecting the characteristics of these studies. The odds ratio for risk of asthma mortality with salmeterol was 2.7 (95% CI 1.4 to 5.3). In 54 placebo controlled studies the risk of death from asthma in patients not prescribed ICS was 7.3 (95% CI 1.8 to 29.4). In 127 studies in which patients were prescribed ICS, the risk of asthma death was 2.1 (95% CI 0.6 to 7.9). In 63 studies in which patients were randomised to receive the combination salmeterol/fluticasone propionate inhaler or ICS, there were no asthma deaths among 22,600 patients. CONCLUSIONS: Salmeterol monotherapy in asthma increases the risk of asthma mortality and this risk is reduced with concomitant ICS therapy. There is no evidence that combination salmeterol/fluticasone propionate therapy is associated with an increased risk of asthma mortality, although this interpretation is limited by the low statistical power of available studies.

Risk of mortality associated with formoterol: a systematic review and meta-analysis.

There is concern long-acting beta-agonist (LABA) drugs may increase the risk of asthma mortality. We undertook a systematic review which included the AstraZeneca Formoterol Clinical Trial Safety Database and Novartis Food and Drug Administration Formoterol Briefing Document. Randomised controlled clinical trials of duration > or = 4 weeks that compared formoterol with a non-LABA comparator treatment in asthma were included in a meta-analysis of the risk of all-cause mortality and asthma death. Simple contingency tables, Peto's one-step method and a Bayesian analysis were used. There were 42 deaths (nine from asthma) recorded in 62 studies with 49,327 subjects. The simple contingency table odds ratio for risk of all-cause mortality with formoterol was 1.1 (95% CI 0.6-2.2) and for asthma death was 2.7 (95% CI 0.5-26.7). Analyses by the other methods using both "as randomised" and "as exposed" classifications of treatment gave similar risk estimates with wide confidence and credible intervals. We conclude that there was insufficient power to determine whether formoterol increases the risk of mortality. However, the point estimates of a 2.0- to 3.2-fold increased risk of asthma death are not reassuring and add weight to evidence that LABA use in certain circumstances may increase the risk of asthma mortality.

Routine use of oxygen in the treatment of myocardial infarction: systematic review.

CONTEXT: International guidelines recommend the routine use of oxygen therapy in the treatment of myocardial infarction (MI). OBJECTIVE: To undertake a systematic review and meta-analysis of randomised placebo-controlled trials of oxygen therapy in MI. DATA SOURCES: Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, EMBASE and CINHAL. STUDY SELECTION: Randomised placebo-controlled trials of oxygen therapy in MI. DATA EXTRACTION: The primary clinical outcome was mortality. RESULTS: Two of 51 potential studies met the inclusion criteria. The one study with substantive clinical outcome data reported that in uncomplicated MI, high-flow oxygen was associated with a non-significant increased risk of death (risk ratio 2.9, 95% CI 0.8 to 10.3, p = 0.08) and a greater serum aspartate aminotransferase level (difference 19.2 IU/ml, 95% CI 0 to 38.4, p = 0.05) than room air. CONCLUSION: The limited evidence that does exist suggests that the routine use of high-flow oxygen in uncomplicated MI may result in a greater infarct size and possibly increase the risk of mortality.

The risk of asthma mortality with inhaled long acting beta-agonists.

This article reviews the available evidence as to whether inhaled long acting beta-agonists (LABA) increase the risk of asthma mortality and considers the implications for the use of this treatment in the management of asthma. Randomised controlled trials suggest that LABAs prescribed as monotherapy may increase the risk of asthma death in certain circumstances, such as the unsupervised "off-label" use without concomitant inhaled corticosteroid (ICS) treatment in patients with unstable asthma. However, there is also evidence that the use of LABAs in conjunction with ICS treatment in adult asthma as recommended in current guidelines is not associated with an increased risk of asthma mortality. The only way in which a prescriber can ensure that a patient with asthma takes LABA treatment in conjunction with ICS is through a combination ICS/LABA product, an approach which may have additional therapeutic advantages. We propose that in the management of asthma, a case can now be made to limit the availability of LABAs to combination LABA/ICS therapy.

Dose-response relationship for risk of non-vertebral fracture with inhaled corticosteroids.

OBJECTIVE: To determine the strength of association between the dose of inhaled corticosteroids (ICS) and risk of non-vertebral fracture in adults. METHODS: A systematic review and meta-analysis of case-control studies of non-vertebral fractures in adults, in which at least two doses of ICS were reported as the dose of beclomethasone dipropionate (BDP) or equivalent. RESULTS: Five case-control studies were identified, with a total of 43 783 cases and 259 936 controls. There was an association between the risk of non-vertebral fracture and increasing dose of BDP. The random-effects odds ratio of relative risk for a non-vertebral fracture was 1.12 (95% confidence interval 1.00-1.26) per 1000 microg increase in the daily dose of BDP or equivalent. CONCLUSION: In older adults, the relative risk of non-vertebral fractures increases by about 12% for each 1000 microg/day increase in the dose of BDP or equivalent. The magnitude of this risk was considerably less than other common risk factors for fracture in the older adult.

Prolonged seated immobility at work is a common risk factor for venous thromboembolism leading to hospital admission.

The role of seated immobility at work in the pathogenesis of venous thromboembolism (VTE) is uncertain. In this case series, 61 patients aged <65 years with a recent admission for deep venous thrombosis and/or pulmonary embolism completed an interviewer-administered questionnaire to obtain information regarding risk factors. Prolonged seated immobility at work in the 4 weeks before the VTE event was defined as being seated at least 8 h in a 24-h period and at least 3 h at a time without getting up, at least 10 h in a 24-h period and at least 2 h at a time without getting up or at least 12 h in a 24-h period and at least 1 h at a time without getting up. The most commonly identified risk factors were family history of VTE (21 of 61, 34%), seated immobility at work (21 of 61, 34%) and a thrombophilic state (19 of 61, 31%). We conclude that prolonged seated immobility at work may represent a common and important risk factor for VTE.

Use of PCR-targeted mutagenesis to disrupt production of fusaricidin-type antifungal antibiotics in Paenibacillus polymyxa.

Paenibacillus polymyxa (formerly Bacillus polymyxa) PKB1 has been identified as a potential agent for biocontrol of blackleg disease of canola, caused by the pathogenic fungus Leptosphaeria maculans. The factors presumed to contribute to disease suppression by strain PKB1 include the production of fusaricidin-type antifungal metabolites that appear around the onset of bacterial sporulation. The fusaricidins are a family of lipopeptide antibiotics consisting of a beta-hydroxy fatty acid linked to a cyclic hexapeptide. Using a reverse genetic approach based on conserved motifs of nonribosomal peptide synthetases, a DNA fragment that appears to encode the first two modules of the putative fusaricidin synthetase (fusA) was isolated from PKB1. To confirm the involvement of fusA in production of fusaricidins, a modified PCR targeting mutagenesis protocol was developed to create a fusA mutation in PKB1. A DNA fragment internal to fusA was replaced by a gene disruption cassette containing two antibiotic resistance genes for independent selection of apramycin resistance in Escherichia coli and chloramphenicol resistance in P. polymyxa. Inclusion of an oriT site in the disruption cassette allowed efficient transfer of the inactivated fusA allele to P. polymyxa by intergeneric conjugation. Targeted disruption of fusA led to the complete loss of antifungal activity against L. maculans, suggesting that fusA plays an essential role in the nonribosomal synthesis of fusaricidins.

Survey of the Royal Australasian College of Physicians examination candidates: preparation and impact on lifestyle.

Candidates currently view the Royal Australasian College of Physicians' written examination as a major undertaking, knowing that approximately one-third fail on their first attempt. We anonymously surveyed New Zealand registrars who sat the written examination in 2004. We found that the majority of candidates spend long hours preparing over a several months, and that the examination had a detrimental impact on their personal lives. The results of this survey have important implications in the context of efforts to reduce the stress of doctors, and should lead to a change in either the examination itself or an increase in support provided to registrars preparing for it.

Patterns of external chest compression.

We studied the performance of external chest compression by 20 fourth year medical students on 2 study days, separated by 5-7 weeks, 4-8 months after they had been initially trained in cardiopulmonary resuscitation (CPR). Our hypotheses were (1) that a given individual would perform external chest compressions in the same manner each time CPR was performed and (2) that the pattern of performance of chest compressions would be determined, in part, by the anthropometric characteristics of the rescuer. A Laerdal Skillmeter Resusci-Anne CPR manikin chest compression transducer was interfaced with an analogue-to-digital conversion board in a Macintosh LC III computer. Each subject on each study day performed four cycles of 15 compressions and two ventilations twice, once on a table (which raised the surface of the manikin sternum to 95 cm) and once on the floor. For each individual, on each attempt, we calculated the depth and rate of compressions, duty cycle, peak compression velocity, time to peak compression velocity and time to peak compression depth. In addition, we calculated the regression slope of compression depth versus compression number for each cycle of 15 chest compressions and over four cycles of compressions. Statistically significant correlations were observed between the first and second study days in each of the variables of chest compression measured, indicating that the performance of chest compressions was constant over time for a given individual. We observed that the depth of compression, duty cycle, time to peak compression, time to peak velocity and regression slope of depth of compressions versus compression number were significantly related to the height and weight of the rescuer.

Adherence to antiretroviral therapy among HIV-positive children: examination of the role of caregiver health beliefs.

This study examined the association between two components of the Health Belief Model (perceived vulnerability and barriers) and adherence to antiretroviral therapy (ART) among children who are HIV-infected. The parents/caregivers of 30 children (mean age = 5.21, SD = 3.18) who were HIV-infected and who were on active ART were surveyed to assess current methods of adherence assessment and educational efforts within the institution. All participants (except one) were African American and reported low monthly family incomes (M = $869.45, SD = $832.63). Assessment instruments included measures of perceived vulnerability, caregiver-reported adherence and perceived barriers, and objective measures of adherence (clinical pill count; electronic measurement). The results failed to demonstrate a significant relationship between parental perceived vulnerability, perceived barriers and adherence to antiretroviral medications. Methods of assessing adherence provided significantly discrepant estimates of adherence. Results are discussed in terms of implications for patient care and for future research in this area. The addition of behavioural and motivational components to traditional educational approaches may positively impact treatment results.

Educating for community-based occupational therapy practice: a demonstration project.

SUMMARY This paper describes a demonstration program designed by one university Occupational Therapy program to prepare graduates to work in community-based practice settings. Faculty and students are involved in a partnership with designated community agencies to learn to assess needs, plan programs, and evaluate outcomes using a variety of research methodologies. Completion of the project is tied to the completion of a required master's degree research paper. Results of the first year of the project have been largely successful and those involved look forward to continuing the project in the future. The project is described and recommendations for change based on these results are presented.

Health benefits achieved through the Seventh-Day Adventist Wellness Challenge program.

CONTEXT: The Wellness Challenge program introduces the philosophy of the healing power of God and stresses the importance of developing a sense of spirituality in conjunction with the promotion of good health. OBJECTIVE: To employ scientific rigor to the outcome measures of the Seventh-Day Adventist Wellness Challenge program. DESIGN: A 2-tailed, paired sample t test. SETTING: East Pasco Medical Center in Zephyrhills, Fla. PARTICIPANTS: 165 participants. INTERVENTION: Presurvey, 21-day outpatient wellness intervention; postsurvey, 6 weeks after completion of the program. MAIN OUTCOME MEASURES: Changes in behaviors related to cigarette smoking, alcohol use, eating patterns, exercise, water consumption, rest, relaxation, and time spent outdoors, as well as demographic data. RESULTS: Statistically significant differences were found between the pre- and postprogram clinical and laboratory test results for the participants' blood pressure, weight, glucose levels, and cholesterol at .05 alpha. Furthermore, self-health improvements measured by a pre- and postsurvey response confirmed statistically significant improvement in participants' willingness to improve their lifestyle behaviors for a potentially greater quality of life. CONCLUSION: The Wellness Challenge program offers ways to reduce risk factors related to chronic disease while improving the quality of life within an adult population by allowing people to slowly incorporate newly acquired tools into their everyday life.

Responses of seventh grade students to "do you have a partner with whom you would like to have a baby?".

This study investigated differences in demographic data, self-esteem, and coping skills for 225 students in Grade 7 who reported having a partner with whom they wanted to have a baby and 946 students who did not. Data were collected on the Rosenberg Self-esteem Scale, the Family Crisis-oriented Personal Evaluation Scale, and questions related to attitudes towards teen pregnancy and demographic data. The sample included 548 (46.8%) boys and 624 (53.2%) girls whose mean age was 13.2 yr. Students with a partner had significantly lower scores on the curriculum questions, self-esteem, and family coping skills, combined with higher scores in passivity. They indicated a desire to have a greater number of children, beginning by having their first child at a younger age and believed that having a baby improves a couple's relationship. Possible approaches may include effective teaching methods to overcome passivity through boosting self-confidence, goal-setting, and acquiring a purpose in life besides parenting a child.

Continuing education about physically abusive relationships: does education change the perceptions of health care practitioners?

BACKGROUND: The purpose of this study is to determine the effectiveness of mandatory continuing education for domestic violence. METHOD: This study surveyed health care professionals attending the 1993 and 1997 National Perinatal Association Conference in Florida to determine change their awareness and identification of pregnant women involved in physically abusive relationships. RESULTS: Even though in 1993 Florida initiated a mandatory 1-hour continuing education credit on domestic violence, the findings report that there were no statistically significant changes for awareness and identification. However, there was a statistically significant increase in the availability of patient education materials within the 4-year period. CONCLUSION: Both the 1993 and 1997 respondents expressed a desire for more professional education related to domestic violence.