Clare D. Ramsey

Critically Ill Patients With 2009 Influenza A(H1N1) Infection in Canada

CONTEXT Between March and July 2009, the largest number of confirmed cases of 2009 influenza A(H1N1) infection occurred in North America. OBJECTIVE To describe characteristics, treatment, and outcomes of critically ill patients in Canada with 2009 influenza A(H1N1) infection. DESIGN, SETTING, AND PATIENTS A prospective observational study of 168 critically ill patients with 2009 influenza A(H1N1) infection in 38 adult and pediatric intensive care units (ICUs) in Canada between April 16 and August 12, 2009. MAIN OUTCOME MEASURES The primary outcome measures were 28-day and 90-day mortality. Secondary outcomes included frequency and duration of mechanical ventilation and duration of ICU stay. RESULTS Critical illness occurred in 215 patients with confirmed (n = 162), probable (n = 6), or suspected (n = 47) community-acquired 2009 influenza A(H1N1) infection. Among the 168 patients with confirmed or probable 2009 influenza A(H1N1), the mean (SD) age was 32.3 (21.4) years; 113 were female (67.3%) and 50 were children (29.8%). Overall mortality among critically ill patients at 28 days was 14.3% (95% confidence interval, 9.5%-20.7%). There were 43 patients who were aboriginal Canadians (25.6%). The median time from symptom onset to hospital admission was 4 days (interquartile range [IQR], 2-7 days) and from hospitalization to ICU admission was 1 day (IQR, 0-2 days). Shock and nonpulmonary acute organ dysfunction was common (Sequential Organ Failure Assessment mean [SD] score of 6.8 [3.6] on day 1). Neuraminidase inhibitors were administered to 152 patients (90.5%). All patients were severely hypoxemic (mean [SD] ratio of Pao(2) to fraction of inspired oxygen [Fio(2)] of 147 [128] mm Hg) at ICU admission. Mechanical ventilation was received by 136 patients (81.0%). The median duration of ventilation was 12 days (IQR, 6-20 days) and ICU stay was 12 days (IQR, 5-20 days). Lung rescue therapies included neuromuscular blockade (28% of patients), inhaled nitric oxide (13.7%), high-frequency oscillatory ventilation (11.9%), extracorporeal membrane oxygenation (4.2%), and prone positioning ventilation (3.0%). Overall mortality among critically ill patients at 90 days was 17.3% (95% confidence interval, 12.0%-24.0%; n = 29). CONCLUSION Critical illness due to 2009 influenza A(H1N1) in Canada occurred rapidly after hospital admission, often in young adults, and was associated with severe hypoxemia, multisystem organ failure, a requirement for prolonged mechanical ventilation, and the frequent use of rescue therapies.

Probiotic supplementation during pregnancy or infancy for the prevention of asthma and wheeze: systematic review and meta-analysis

Objective To evaluate the association of probiotic supplementation during pregnancy or infancy with childhood asthma and wheeze. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, and Central (Cochrane Library) databases from inception to August 2013, plus the World Health Organization’s international clinical trials registry platform and relevant conference proceedings for the preceding five years. Included trials and relevant reviews were forward searched in Web of Science. Review methods Two reviewers independently identified randomised controlled trials evaluating probiotics administered to mothers during pregnancy or to infants during the first year of life. The primary outcome was doctor diagnosed asthma; secondary outcomes included wheeze and lower respiratory tract infection. Results We identified 20 eligible trials including 4866 children. Trials were heterogeneous in the type and duration of probiotic supplementation, and duration of follow-up. Only five trials conducted follow-up beyond participants’ age of 6 years (median 24 months), and none were powered to detect asthma as the primary outcome. The overall rate of doctor diagnosed asthma was 10.7%; overall rates of incident wheeze and lower respiratory tract infection were 33.3% and 13.9%, respectively. Among 3257 infants enrolled in nine trials contributing asthma data, the risk ratio of doctor diagnosed asthma in participants randomised to receive probiotics was 0.99 (95% confidence interval 0.81 to 1.21, I2=0%). The risk ratio of incident wheeze was 0.97 (0.87 to 1.09, I2=0%, 9 trials, 1949 infants). Among 1364 infants enrolled in six trials, the risk ratio of lower respiratory tract infection after probiotic supplementation was 1.26 (0.99 to 1.61, I2=0%). We adjudicated most trials to be of high (ten trials) or unclear (nine trials) risk of bias, mainly due to attrition. Conclusions We found no evidence to support a protective association between perinatal use of probiotics and doctor diagnosed asthma or childhood wheeze. Randomised controlled trials to date have not yielded sufficient evidence to recommend probiotics for the primary prevention of these disorders. Extended follow-up of existing trials, along with further clinical and basic research, are needed to accurately define the role of probiotics in the prevention of childhood asthma. Systematic review registration PROSPERO (CRD42013004385).

A matched cohort study of postoperative outcomes in obstructive sleep apnea: could preoperative diagnosis and treatment prevent complications?

Background:Obstructive sleep apnea (OSA) is associated with increased risk of postoperative complications. The authors investigated whether preoperative diagnosis and prescription of continuous positive airway pressure therapy reduces these risks. Methods:Matched cohort analysis of polysomnography data and Manitoban health administrative data (1987 to 2008). Postoperative outcomes in adult OSA patients up to 5 yr before (undiagnosed OSA, n = 1,571), and any time after (diagnosed OSA, n = 2,640) polysomnography and prescription of continuous positive airway pressure therapy for a new diagnosis of OSA, were compared with controls at low risk of having sleep apnea (n = 16,277). Controls were matched by exact procedure, indication, and approximate date of surgery. Procedures used to treat sleep apnea were excluded. Follow-up was at least 7 postoperative days. Results were reported as odds ratio (95% CI) for OSA or subgroup versus controls. Results:In multivariate analyses, the risk of respiratory complications (2.08 [1.35 to 3.19], P < 0.001) was similarly increased for both undiagnosed and diagnosed OSA. The risk of cardiovascular complications, primarily cardiac arrest and shock, was significantly different (P = 0.009) between undiagnosed OSA (2.20 [1.16 to 4.17], P = 0.02) and diagnosed OSA patients (0.75 [0.43 to 1.28], P = 0.29). For both outcomes, OSA severity, type of surgery, age, and other comorbidities were also important risk modifiers. Conclusions:Diagnosis of OSA and prescription of continuous positive airway pressure therapy were associated with a reduction in postoperative cardiovascular complications. Despite limitations in the data, these results could be used to justify and inform large efficacy trials of perioperative continuous positive airway pressure therapy in OSA patients.

The hygiene hypothesis and asthma.

Purpose of review Reduced exposure to childhood infections may explain the increased prevalence of allergic diseases in industrialized countries (the hygiene hypothesis). This review will examine recent epidemiologic studies of the hygiene hypothesis and asthma. Recent findings Recent studies have confirmed previous findings of an inverse association between increased exposure to other children during childhood and either allergen sensitization or hay fever. However, there is conflicting evidence regarding the relation between exposure to other children and asthma. Although it has been hypothesized that vaccinations may influence the development of asthma, recent findings do not support this association. Serologic evidence of exposure to certain gastrointestinal pathogens (eg, hepatitis A virus) has been inversely associated with either allergen sensitization or asthma in some, but not all, recent studies. Although heavy infestation with certain parasites (eg, helminths) is protective against allergen sensitization, there is conflicting evidence regarding the relation between parasitic infection and asthma. The results of recent studies suggest that the relation between endotoxin exposure and asthma is complex and likely influenced by factors related to the exposure itself, the host, and other covariates. Although it has been postulated that antibiotic use in early life is a risk factor for asthma, this hypothesis is not supported by recent findings. Summary For every exposure studied with regard to the hygiene hypothesis, there are inconsistent findings in relation to asthma. The hygiene hypothesis is not likely to be the sole explanation for the ongoing asthma epidemic in industrialized nations.

Ventilator management for hypoxemic respiratory failure attributable to H1N1 novel swine origin influenza virus.

Novel H1N1 swine origin influenza virus has led to a worldwide pandemic. During the pandemic, a significant number of patients became critically ill primarily because of respiratory failure. Most of these patients required intubation and mechanical ventilation and were treated with conventional modes of mechanical ventilation using a lung-protective strategy with low tidal volumes, plateau pressures <30 to 35 cm H2O, and optimal positive end-expiratory pressure. In some patients with persistent hypoxemia, alternative modes of ventilation, such as high-frequency oscillatory ventilation and airway pressure release ventilation, were used. We review the ventilatory management, recruitment maneuvers, prone positioning, and goals of ventilatory therapy for hypoxemic respiratory failure in general, as well as lessons learned in the management of H1N1-related respiratory failure.

Genome-wide association study of the age of onset of childhood asthma

BACKGROUND Childhood asthma is a complex disease with known heritability and phenotypic diversity. Although an earlier onset has been associated with more severe disease, there has been no genome-wide association study of the age of onset of asthma in children. OBJECTIVE We sought to identify genetic variants associated with earlier onset of childhood asthma. METHODS We conducted the first genome-wide association study of the age of onset of childhood asthma among participants in the Childhood Asthma Management Program (CAMP) and used 3 independent cohorts from North America, Costa Rica, and Sweden for replication. RESULTS Two single nucleotide polymorphisms (SNPs) were associated with earlier onset of asthma in the combined analysis of CAMP and the replication cohorts: rs9815663 (Fisher P= 2.31 × 10(-8)) and rs7927044 (P= 6.54 × 10(-9)). Of these 2 SNPs, rs9815663 was also significantly associated with earlier asthma onset in an analysis including only the replication cohorts. Ten SNPs in linkage disequilibrium with rs9815663 were also associated with earlier asthma onset (2.24 × 10(-7) <P< 8.22 × 10(-6)). Having 1 or more risk alleles of the 2 SNPs of interest (rs9815663 and rs7927044) was associated with lower lung function and higher asthma medication use during 4 years of follow-up in CAMP. CONCLUSIONS We have identified 2 SNPs associated with earlier onset of childhood asthma in 4 independent cohorts.

H1n1: viral pneumonia as a cause of acute respiratory distress syndrome

Purpose of reviewTo review the literature on novel swine origin influenza A (H1N1 2009) as a cause of respiratory failure and acute respiratory distress syndrome (ARDS). Recent findingsH1N1 2009 was first recognized as a pathogen in March of 2009, when there was a spike in the number of cases of influenza-like illness leading to severe and at times fatal pneumonia. The etiologic agent was then identified as a novel H1N1 influenza A virus, which subsequent spread rapidly throughout the globe. Most countries reported cases of severe viral pneumonitis requiring intensive care unit (ICU) admission. Severe disease was noted to occur more commonly in younger patients than those typically affected by seasonal influenza and obesity and pregnancy were associated with severe disease. The majority of patients requiring ICU admission met criteria for ARDS and case fatality ratio was estimated at less than 0.5%. Chest radiographs and pathology resembled ARDS and most patients were treated with low tidal volume ventilation, high positive end expiratory pressure and at times, rescue therapies. Available evidence suggests that early antiviral treatment improves outcomes from H1N1 2009. SummaryH1N1 2009 has emerged as an important cause of ARDS in 2009–2010. Prompt recognition and treatment with antivirals improves outcomes.

Rates of readmission and death associated with leaving hospital against medical advice: a population-based study

Background: Leaving hospital against medical advice may have adverse consequences. Previous studies have been limited by evaluating specific types of patients, small sample sizes and incomplete determination of outcomes. We hypothesized that leaving hospital against medical advice would be associated with increases in subsequent readmission and death. Methods: In a population-based analysis involving all adults admitted to hospital and discharged alive in Manitoba from Apr. 1, 1990, to Feb. 28, 2009, we evaluated all-cause 90-day mortality and 30-day hospital readmission. We used multivariable regression, adjusted for age, sex, socioeconomic status, year of hospital admission, patient comorbidities, hospital diagnosis, past frequency of admission to hospital, having previously left hospital against medical advice and data clustering (patients with multiple admissions). For readmission, we assessed both between-person and within-person effects of leaving hospital against medical advice. Results: Leaving against medical advice occurred in 21 417 of 1 916 104 index hospital admissions (1.1%), and was associated with higher adjusted rates of 90-day mortality (odds ratio [OR] 2.51, 95% confidence interval [CI] 2.18–2.89), and 30-day hospital readmission (within-person OR 2.10, CI 1.99–2.21; between-person OR 3.04, CI 2.79–3.30). In our additional analyses, elevated rates of readmission and death associated with leaving against medical advice were manifest within 1 week and persisted for at least 180 days after discharge. Interpretation: Adults who left the hospital against medical advice had higher rates of hospital readmission and death. The persistence of these effects suggests that they are not solely a result of incomplete treatment of acute illness. Interventions aimed at reducing these effects may need to include longitudinal interventions extending beyond admission to hospital.

Health-Care Use Among Puerto Rican and African-American Children With Asthma

STUDY OBJECTIVES To compare the rates of emergency department (ED) visits, hospitalizations, hospital days, and outpatient clinic visits for asthma among children in two ethnic minority groups that are disproportionately affected by asthma (Puerto Ricans and African Americans). STUDY DESIGN This cross-sectional study was part of an asthma intervention program in Hartford, CT, in which 6,554 children were screened for asthma by primary care providers using a parental survey. Medicaid and the supplementary State Childrens Health Insurance Plan data about health-care utilization for asthma were obtained for each child for the 12 months preceding completion of the screening survey. RESULTS Among 2,304 children in whom asthma had been diagnosed, Puerto Ricans had more severe asthma than African Americans. In analyses adjusted for asthma severity and other potential confounders, Puerto Rican children had more clinic visits for asthma (rate ratio [RR], 1.31; 95% confidence interval [CI], 1.12 to 1.53) but spent fewer days in the hospital for asthma (RR, 0.36; 95% CI, 0.24 to 0.53) than African-American children. There were no differences in the rates of ED visits or hospitalizations between the two groups. CONCLUSIONS Puerto Rican children had more severe asthma but were less likely than African-American children to have prolonged hospitalizations for asthma. This finding may be due to the frequent clinic visits for asthma made by Puerto Rican children. Further research is needed to understand the cultural factors that contribute to different approaches to health-care utilization among ethnic minorities.

The Challenge of Asthma in Minority Populations

The burden and disparity of asthma in race/ethnic minorities present a significant challenge. In this review, we will evaluate data on asthma epidemiology in minorities, examine potential reasons for asthma disparities, and discuss strategies of intervention and culturally sensitive care.