To determine the burden of community-acquired pneumonia (CAP) affecting adults in North America, a comprehensive literature review was conducted to examine the incidence, morbidity and mortality, ...etiology, antibiotic resistance, and economic impact of CAP in this population. In the United States, there were approximately 4.2 million ambulatory care visits for pneumonia in 2006. Pneumonia and influenza continue to be a common cause of death in the United States (ranked eighth) and Canada (ranked seventh). In 2005, there were > 60 000 deaths due to pneumonia in persons aged ≥ 15 years in the United States alone. The hospitalization rate for all infectious diseases increased from 1525 hospitalizations per 100 000 persons in 1998 to 1667 per 100 000 persons in 2005. Admission to an intensive care unit was required in 10% to 20% of patients hospitalized with pneumonia. The mean length of stay for pneumonia was ≥ 5 days and the 30-day rehospitalization rate was as high as 20%. Mortality was highest for CAP patients who were hospitalized; the 30-day mortality rate was as high as 23%. All-cause mortality for CAP patients was as high as 28% within 1 year. Streptococcus pneumoniae continues to be the most frequently identified pathogen associated with CAP, and pneumococcal resistance to antimicrobials may make treatment more difficult. The economic burden associated with CAP remains substantial at > $17 billion annually in the United States. Despite the availability and widespread adherence to recommended treatment guidelines, CAP continues to present a significant burden in adults. Furthermore, given the aging population in North America, clinicians can expect to encounter an increasing number of adult patients with CAP. Given the significance of the disease burden, the potential benefit of pneumococcal vaccination in adults is substantial.
Metabolomics is an emerging field providing insight into physiological processes. It is an effective tool to investigate disease diagnosis or conduct toxicological studies by observing changes in ...metabolite concentrations in various biofluids. Multivariate statistical analysis is generally employed with nuclear magnetic resonance (NMR) or mass spectrometry (MS) data to determine differences between groups (for instance diseased vs healthy). Characteristic predictive models may be built based on a set of training data, and these models are subsequently used to predict whether new test data falls under a specific class. In this study, metabolomic data is obtained by doing a 1H NMR spectroscopy on urine samples obtained from healthy subjects (male and female) and patients suffering from Streptococcus pneumoniae. We compare the performance of traditional PLS-DA multivariate analysis to support vector machines (SVMs), a technique widely used in genome studies on two case studies: (1) a case where nearly complete distinction may be seen (healthy versus pneumonia) and (2) a case where distinction is more ambiguous (male versus female). We show that SVMs are superior to PLS-DA in both cases in terms of predictive accuracy with the least number of features. With fewer number of features, SVMs are able to give better predictive model when compared to that of PLS-DA.
Metabolomics may have the capacity to revolutionize disease diagnosis through the identification of scores of metabolites that vary during environmental, pathogenic, or toxicological insult. NMR ...spectroscopy has become one of the main tools for measuring these changes since an NMR spectrum can accurately identify metabolites and their concentrations. The predominant approach in analyzing NMR data has been through the technique of spectral binning. However, identification of spectral areas in an NMR spectrum is insufficient for diagnostic evaluation, since it is unknown whether areas of interest are strictly caused by metabolic changes or are simply artifacts. In this paper, we explore differences in gender, diurnal variation, and age in a human population. We use the example of gender differences to compare traditional spectral binning techniques (NMR spectral areas) to novel targeted profiling techniques (metabolites and their concentrations). We show that targeted profiling produces robust models, generates accurate metabolite concentration data, and provides data that can be used to help understand metabolic differences in a healthy population. Metabolites relating to mitochondrial energy metabolism were found to differentiate gender and age. Dietary components and some metabolites related to circadian rhythms were found to differentiate time of day urine collection. The mechanisms by which these differences arise will be key to the discovery of new diagnostic tests and new understandings of the mechanism of disease.
The relationship between increased short-term mortality rates after invasive pneumococcal disease (IPD) has been frequently studied. However, the relationship between IPD and long-term mortality ...rates is unknown. IPD patients in Alberta, Canada, had clinical data collected that were linked to administrative databases. We used Cox proportional hazards modeling, and the primary outcome was time to all-cause deaths. First IPD events were identified in 4,522 patients, who had a median follow-up of 3.2 years (interquartile range 0.8‒9.1 years). Overall all-cause mortality rates were consistently higher among cases than controls at 30 days (adjusted hazard ratio aHR 3.75, 95% CI 3.29–4.28), 30‒90 days (aHR 1.56, 95% CI 1.27‒1.93), and >90 days (aHR 1.43, 95% CI 1.33–1.54). IPD increases risk for short, intermediate, and long-term mortality rates regardless of age, sex, or concurrent conditions. These findings can help clinicians focus on postdischarge patient plans to limit long-term effects after acute IPD infection.
Information on the long-term prognosis after community-acquired pneumonia (CAP) is limited.
To determine if CAP increases adverse long-term outcomes relative to a control population.
Between 2000 and ...2002, 6,078 adults with CAP from six hospitals and seven emergency departments in Edmonton (AB, Canada) were prospectively recruited and matched on age, sex, and site of treatment with five control subjects without pneumonia (n = 29,402). Mortality, hospitalizations, and emergency department admissions through 2012 were evaluated using multivariable Cox proportional hazards analyses adjusted for socioeconomic status and comorbidities.
Average age was 59 years (2,682 44% ≥ 65 yr), 3,214 (53%) were men, and 3,425 (56%) were managed as outpatients. Over a median of 9.8 years, 2,858 patients with CAP died compared with 9,399 control subjects (absolute risk difference, 30 per 1,000 patient years py; adjusted hazard ratio aHR, 1.65; 95% confidence interval, 1.57-1.73; P < 0.001). Patients with CAP who were younger than 25 years old had the lowest absolute rate difference for mortality (4 per 1,000 py; aHR, 2.40), and patients older than 80 years old had the highest absolute rate difference (92 per 1,000 py; aHR, 1.42). Absolute rates of all-cause hospitalization, emergency department visits, and CAP-related visits were all significantly higher in patients with CAP compared with control subjects (P < 0.001 for all comparisons).
Our results indicate that an episode of CAP confers a high risk of long-term adverse events compared with the general population who have not experienced CAP, and this is irrespective of age.
Some studies suggest better outcomes with macrolide therapy for critically ill patients with community-acquired pneumonia. To further explore this, we performed a systematic review of studies with ...mortality endpoints that compared macrolide therapy with other regimens in critically ill patients with community-acquired pneumonia.
Studies were identified via electronic databases, grey literature, and conference proceedings through May 2013.
Using prespecified criteria, two reviewers selected studies; studies of outpatients and hospitalized noncritically ill patients were excluded.
Two reviewers extracted data and evaluated bias using the Newcastle-Ottawa Scale. Random effects models were used to generate pooled risk ratios and evaluate heterogeneity (I).
Twenty-eight observational studies (no randomized control trials) were included. Average age ranged from 58 to 78 years and 14-49% were women. In our primary analysis of 9,850 patients, macrolide use was associated with statistically significant lower mortality compared with nonmacrolides (21% 846 of 4,036 patients vs 24% 1,369 of 5,814; risk ratio, 0.82; 95% CI, 0.70-0.97; p = 0.02; I = 63%). When macrolide monotherapy was excluded, the macrolide mortality benefit was maintained (21% 737 of 3,447 patients vs 23% 1,245 of 5,425; risk ratio, 0.84; 95% CI, 0.71-1.00; p = 0.05; I = 60%). When broadly guideline-concordant regimens were compared, there was a trend to improved mortality and heterogeneity was reduced (20% 511 of 2,561 patients mortality with beta-lactam/macrolide therapy vs 23% 386 of 1,680 with beta-lactam/fluoroquinolone; risk ratio, 0.83; 95% CI, 0.67-1.03; p = 0.09; I = 25%). When adjusted risk estimates were pooled from eight studies, macrolide therapy was still associated with a significant reduction in mortality (risk ratio, 0.75; 95% CI, 0.58-0.96; p = 0.02; I = 57%).
In observational studies of almost 10,000 critically ill patients with community-acquired pneumonia, macrolide use was associated with a significant 18% relative (3% absolute) reduction in mortality compared with nonmacrolide therapies. After pooling data from studies that provided adjusted risk estimates, an even larger mortality reduction was observed. These results suggest that macrolides be considered first-line combination treatment in critically ill patients with community-acquired pneumonia and support current guidelines.
AbstractObjectiveTo determine the attributable risk of community acquired pneumonia on incidence of heart failure throughout the age range of affected patients and severity of the ...infection.DesignCohort study.SettingSix hospitals and seven emergency departments in Edmonton, Alberta, Canada, 2000-02.Participants4988 adults with community acquired pneumonia and no history of heart failure were prospectively recruited and matched on age, sex, and setting of treatment (inpatient or outpatient) with up to five adults without pneumonia (controls) or prevalent heart failure (n=23 060).Main outcome measuresRisk of hospital admission for incident heart failure or a combined endpoint of heart failure or death up to 2012, evaluated using multivariable Cox proportional hazards analyses.ResultsThe average age of participants was 55 years, 2649 (53.1%) were men, and 63.4% were managed as outpatients. Over a median of 9.9 years (interquartile range 5.9-10.6), 11.9% (n=592) of patients with pneumonia had incident heart failure compared with 7.4% (n=1712) of controls (adjusted hazard ratio 1.61, 95% confidence interval 1.44 to 1.81). Patients with pneumonia aged 65 or less had the lowest absolute increase (but greatest relative risk) of heart failure compared with controls (4.8% v 2.2%; adjusted hazard ratio 1.98, 95% confidence interval 1.5 to 2.53), whereas patients with pneumonia aged more than 65 years had the highest absolute increase (but lowest relative risk) of heart failure (24.8% v 18.9%; adjusted hazard ratio 1.55, 1.36 to 1.77). Results were consistent in the short term (90 days) and intermediate term (one year) and whether patients were treated in hospital or as outpatients.ConclusionOur results show that community acquired pneumonia substantially increases the risk of heart failure across the age and severity range of cases. This should be considered when formulating post-discharge care plans and preventive strategies, and assessing downstream episodes of dyspnoea.
Abstract Q fever is a worldwide zoonosis due to Coxiella burnetii, responsible for endocarditis and endovascular infections. Since the 1990s, the combination hydroxychloroquine + doxycycline has ...constituted the curative and prophylactic treatment in persistent focalized Q fever. This combination appears to have significantly reduced the treatment’s duration (from 60 to 26 months), yet substantial evidence of effectiveness remains lacking. Data are mostly based on in vitro and observational studies. We conducted a literature review to assess the effectiveness of this therapy, along with potential alternatives. The proposed in vitro mechanism of action describes the inhibition of Coxiella replication by doxycycline through the restoration of its bactericidal activity (inhibited in acidic environment) by alkalinization of phagolysosome-like vacuoles with hydroxychloroquine. So far, the rarity and heterogeneous presentation of cases have made it challenging to design prospective studies with statistical power. The main studies supporting this treatment are retrospective cohorts, dating back to the 1990s–2000s. Retrospective studies from the large Dutch outbreak of Q fever (>4000 cases between 2007 and 2010) did not corroborate a clear benefit of this combination, notably in comparison with other regimens. Thus, there is still no consensus among the medical community on this issue. However insufficient the evidence, today the doxycycline + hydroxychloroquine combination remains the regimen with the largest clinical experience in the treatment of ‘chronic’ Q fever. Reinforcing the guidelines’ level of evidence is critical. We herein propose the creation of an extensive international registry, followed by a prospective cohort or ideally a randomized controlled trial.
Background. There is debate surrounding the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV). We determined whether PPV was associated with reduced mortality or additional ...hospitalization for vaccine-preventable infections in patients previously hospitalized for community-acquired pneumonia (CAP). Methods. From 2000 through 2002, adults with CAP admitted to the hospital in Edmonton, Alberta, Canada, were enrolled in a population-based cohort. Postdischarge outcomes during 5 years were ascertained using administrative databases. The primary outcome was the composite of all-cause mortality or additional hospitalization for vaccine-preventable infections. Proportional hazards analysis was used to determine the association between PPV use and outcomes. Results. A total of 2950 patients were followed up for a median of 3.8 years. The mean patient age was 68 years; 52% were male. One-third (n=956) received PPV: 667 (70%) before and 289 (30%) during hospitalization. After discharge, 1404 patients (48%) died, 504 (17%) were admitted with vaccine-preventable infections, and 1626 (55%) reached the composite outcome of death or infection. PPV was not associated with reduced risk of the composite outcome (589 62% vs 1037 52% for those unvaccinated; adjusted hazard ratio HR, 0.91; 95% confidence interval CI, 0.79–1.04). Results were not altered in sensitivity analyses using propensity scores (adjusted HR, 0.91; 95% CI, 0.79–1.04), restricting the sample to patients 65 years or older (adjusted HR, 0.90; 95% CI, 0.77–1.04), or considering only those who received PPV at discharge (adjusted HR, 0.84; 95% CI, 0.71–1.00). Conclusions. One-half of patients discharged from the hospital after pneumonia die or are subsequently hospitalized with a vaccine-preventable infection within 5 years. PPV was not associated with a reduced risk of death or hospitalization. Better pneumococcal vaccination strategies are urgently needed.
Pneumonia in the elderly is a common and serious problem with a clinical presentation that can differ from that in younger patients. Older patients with pneumonia complain of significantly fewer ...symptoms than do younger patients, and delirium commonly occurs. Indeed, delirium may be the only manifestation of pneumonia in this group of patients. Alcoholism, asthma, immunosuppression, and age >70 years are risk factors for community-acquired pneumonia in the elderly. Among nursing home residents, the following are risk factors for pneumonia: advanced age, male sex, difficulty in swallowing, inability to take oral medications, profound disability, bedridden state, and urinary incontinence. Streptococcus pneumoniae is the most common cause of pneumonia among the elderly. Aspiration pneumonia is underdiagnosed in this group of patients, and tuberculosis always should be considered. In this population an etiologic diagnosis is rarely available when antimicrobial therapy must be instituted. Use of the guidelines for treatment of pneumonia issued by the Infectious Diseases Society of America, with modification for treatment in the nursing home setting, is recommended.
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