Staphylococcal Pneumonia and Empyema in Infants and Children

One hundred and seventy-six cases of staphylococcal pneumonia and 35 cases of empyema in infants and children have been studied. There were seven deaths, five in patients with empyema and two in patients without this complication. Early diagnosis on the basis of clinical symptoms and signs and institution of therapy without awaiting radiological or bacteriological confirmation are necessary to prevent development of empyema and to reduce the mortality rate. Chloramphenicol and erythromycin, administered systemically, were generally effective. In severely toxic subjects antitoxin appeared to be of value. Blood transfusion was used to correct the rapidly progressive anemia. A chest radiograph was essential to diagnose empyema. Treatment of this condition by closed intercostal catheter drainage was effective. Pneumatoceles were encountered, but resolved spontaneously. Although there has been no significant decrease in the number of cases of pneumonia encountered, there have been no deaths since 1958 on the treatment outlined.     

Lipoid Pneumonia in Infants and Children in South India

Oil-aspiration pneumonia is a common cause of mortality and morbidity in infants and young children in South India. The high incidence of this condition results from the local custom of giving oil baths to infants and of cleansing the mouth, throat, and nose with oil. The clinical findings in 12 cases, 10 of them in babies aged under 8 months, are described. The signs range from an acute segmental collapse of the lung, clearing in a few days, to a chronic picture mimicking pulmonary tuberculosis or mucoviscoidosis. Mothers in South India should be advised to abandon the practice of cleansing their baby''s mouth and nose with oil.     

Association between Respiratory Syncytial Virus Activity and Pneumococcal Disease in Infants: A Time Series Analysis of US Hospitalization Data

BackgroundThe importance of bacterial infections following respiratory syncytial virus (RSV) remains unclear. We evaluated whether variations in RSV epidemic timing and magnitude are associated with variations in pneumococcal disease epidemics and whether changes in pneumococcal disease following the introduction of seven-valent pneumococcal conjugate vaccine (PCV7) were associated with changes in the rate of hospitalizations coded as RSV.ConclusionsThese analyses provide evidence for an interaction between RSV and pneumococcal pneumonia. Future work should evaluate whether treatment for secondary bacterial infections could be considered for pneumonia cases even if a child tests positive for RSV.Please see later in the article for the Editors'' Summary     

Rotavirus Seasonality and Age Effects in a Birth Cohort Study of Southern India

Introduction

Understanding the temporal patterns in disease occurrence is valuable for formulating effective disease preventive programs. Cohort studies present a unique opportunity to explore complex interactions associated with emergence of seasonal patterns of infectious diseases.

Methods

We used data from 452 children participating in a birth cohort study to assess the seasonal patterns of rotavirus diarrhea by creating a weekly time series of rotavirus incidence and fitting a Poisson harmonic regression with biannual peaks. Age and cohort effects were adjusted for by including the weekly counts of number of children in the study and the median age of cohort in a given week. Weekly average temperature, humidity and an interaction term to reflect the joint effect of temperature and humidity were included to consider the effects of meteorological variables.

Results

In the overall rotavirus time series, two significant peaks within a single year were observed – one in winter and the other in summer. The effect of age was found to be the most significant contributor for rotavirus incidence, showing a strong negative association. Seasonality remained a significant factor, even after adjusting for meteorological parameters, and the age and cohort effects.

Conclusions

The methodology for assessing seasonality in cohort studies is not yet developed. This is the first attempt to explore seasonal patterns in a cohort study with a dynamic denominator and rapidly changing immune response on individual and group levels, and provides a highly promising approach for a better understanding of the seasonal patterns of infectious diseases, tracking emergence of pathogenic strains and evaluating the efficacy of intervention programs.     

Pneumonia in Indian and Eskimo Infants and Children: Part I. A Clinical Study

Ninety-seven Indian and Eskimo infants and children who suffered 112 episodes of pneumonia were the subjects of a prospective study carried out at the Charles Camsell Hospital, Edmonton, Alberta, from August 1963 until August 1964. Investigation included viral studies and an evaluation 10 days after admission. The patients were divided into four diagnostic categories and a comparison was made between cases of bacterial and viral origin. The frequency of right-sided disease, particularly of the upper lobe and/or dependent segment involvement, is described. An evaluation of physical signs is attempted. The problem of recurrent pneumonia and the differential diagnosis of tuberculosis in Indian and Eskimo children with pneumonia is discussed.     

Poor Survival in Rheumatoid Arthritis Associated with Bronchiectasis: A Family-Based Cohort Study

Background

Diffuse bronchiectasis (DB) may occur in rheumatoid arthritis (RA). CFTR (cystic fibrosis transmembrane conductance regulator) mutations predispose RA patients to DB, but the prognosis of RA-associated DB (RA-DB) is unclear.

Methods

We report long-term mortality data from a nationwide family-based association study of patients with RA only, DB only or RA-DB. We assessed mortality as a function of clinical characteristics and CF/CFTR-RD (CFTR-related disorders) mutations in 137 subjects from 24 kindreds. Potential risk factors were investigated by Cox proportional-hazard analysis with shared Gaussian random effects to account for within-family correlations.

Results

During a median follow-up of 11 years after inclusion, 18 patients died, mostly from cardiorespiratory causes. Survival was significantly lower for RA-DB patients than for unaffected relatives and for patients with RA or DB only. RA patients with DB had also a poorer prognosis in terms of survival after RA diagnosis (HR, 8.6; 95% CI, 1.5–48.2; P = 0.014) and from birth (HR, 9.6; 95% CI, 1.1–81.7; P = 0.039). Early onset of DB (HR, 15.4; 95% CI, 2.1–113.2; P = 0.007) and CF/CFTR-RD mutation (HR, 7.2; 95% CI, 1.4–37.1; P = 0.018) were associated with poorer survival in patients with RA-DB. Thus, CF/CFTR-RD mutations in RA patients with early-onset DB defined a subgroup of high-risk patients with higher mortality rates (log-rank test P = 1.28×10⁻⁵).

Conclusion

DB is associated with poorer survival in patients with RA. Early-onset DB and CFTR mutations are two markers that identify RA patients at a high risk of death, for whom future therapeutic interventions should be designed and evaluated.     

Gestational Age and Neonatal Brain Microstructure in Term Born Infants: A Birth Cohort Study

Objective

Understanding healthy brain development in utero is crucial in order to detect abnormal developmental trajectories due to developmental disorders. However, in most studies neuroimaging was done after a significant postnatal period, and in those studies that performed neuroimaging on fetuses, the quality of data has been affected due to complications of scanning during pregnancy. To understand healthy brain development between 37–41 weeks of gestational age, our study assessed the in utero growth of the brain in healthy term born babies with DTI scanning soon after birth.

Methods

A cohort of 93 infants recruited from maternity hospitals in Singapore underwent diffusion tensor imaging between 5 to 17 days after birth. We did a cross-sectional examination of white matter microstructure of the brain among healthy term infants as a function of gestational age via voxel-based analysis on fractional anisotropy.

Results

Greater gestational age at birth in term infants was associated with larger fractional anisotropy values in early developing brain regions, when corrected for age at scan. Specifically, it was associated with a cluster located at the corpus callosum (corrected p<0.001), as well as another cluster spanning areas of the anterior corona radiata, anterior limb of internal capsule, and external capsule (corrected p<0.001).

Conclusions

Our findings show variation in brain maturation associated with gestational age amongst ‘term’ infants, with increased brain maturation when born with a relatively higher gestational age in comparison to those infants born with a relatively younger gestational age. Future studies should explore if these differences in brain maturation between 37 and 41 weeks of gestational age will persist over time due to development outside the womb.     

Dying for Growth: Global Inequality and the Health of the Poor

Dying for Growth: Global Inequality and the Health of the Poor. Jim Young Kim. Joyce V. Millen. Alec Irwin. and John Gershaman. eds. Monroe, ME: Common Courage Press, 2000. xix. 584 pp.     

Dying for Growth: Global Inequality and the Health of the Poor

Dying for Growth: Global Inequality and the Health of the Poor. Jim Yong Kim. Joyce V. Millen. Alec Irwin. and John Gershman. eds. Monroe, ME: Common Courage Press, 2000. 604 pp.     

Skin Barrier Function and Staphylococcus aureus Colonization in Vestibulum Nasi and Fauces in Healthy Infants and Infants with Eczema: A Population-Based Cohort Study

Atopic eczema (AE) is associated with Staphylococcus aureus (S. aureus) colonization and skin barrier dysfunction, often measured by increased transepidermal water loss (TEWL). In the present study, the primary aim was to see whether S. aureus colonization in the vestibulum nasi and/or fauces was associated with increased TEWL in infants with healthy skin and infants with eczema. Secondarily, we aimed to investigate whether TEWL measurements on non-lesional skin on the lateral upper arm is equivalent to volar forearm in infants. In 167 of 240 infants, recruited from the general population, TEWL measurements on the lateral upper arm and volar forearm, using a DermaLab USB, fulfilled our environmental requirements. The mean of three TEWL measurements from each site was used for analysis. The infants were diagnosed with no eczema (n = 110), possible AE (n = 28) or AE (n = 29). DNA samples were analysed for mutations in the filaggrin gene (FLG). Bacterial cultures were reported positive with the identification of at least one culture with S. aureus from vestibulum nasi and/or fauces. S. aureus colonization, found in 89 infants (53%), was not associated with increased TEWL (i.e. TEWL in the upper quartile), neither on the lateral upper arm or volar forearm (p = 0.08 and p = 0.98, respectively), nor with AE (p = 0.10) or FLG mutation (p = 0.17). TEWL was significantly higher on both measuring sites in infants with AE compared to infants with possible AE and no eczema. FLG mutation was significantly associated with increased TEWL, with a 47% difference in TEWL. We conclude that S. aureus in vestibulum nasi and/or fauces was not associated with TEWL, whereas TEWL measurements on the lateral upper arm and volar forearm appear equally appropriate in infants.     

Incidence of Dengue Virus Infection in Adults and Children in a Prospective Longitudinal Cohort in the Philippines

Background

The mean age of dengue has been increasing in some but not all countries. We sought to determine the incidence of dengue virus (DENV) infection in adults and children in a prospective cohort study in the Philippines where dengue is hyperendemic.

Methodology/Principal Findings

A prospective cohort of subjects ≥6 months old in Cebu City, Philippines, underwent active community-based surveillance for acute febrile illnesses by weekly contact. Fever history within the prior seven days was evaluated with an acute illness visit followed by 2, 5, and 8-day, and 3-week convalescent visits. Blood was collected at the acute and 3-week visits. Scheduled visits took place at enrolment and 12 months that included blood collections. Acute samples were tested by DENV PCR and acute/convalescent samples by DENV IgM/IgG ELISA to identify symptomatic infections. Enrolment and 12-month samples were tested by DENV hemagglutination inhibition (HAI) assay to identify subclinical infections. Of 1,008 enrolled subjects, 854 completed all study activities at 12 months per-protocol undergoing 868 person-years of surveillance. The incidence of symptomatic and subclinical infections was 1.62 and 7.03 per 100 person-years, respectively. However, in subjects >15 years old, only one symptomatic infection occurred whereas 27 subclinical infections were identified. DENV HAI seroprevalence increased sharply with age with baseline multitypic HAIs associated with fewer symptomatic infections. Using a catalytic model, the historical infection rate among dengue naïve individuals was estimated to be high at 11–22%/year.

Conclusions/Significance

In this hyperendemic area with high seroprevalence of multitypic DENV HAIs in adults, symptomatic dengue rarely occurred in individuals older than 15 years. Our findings demonstrate that dengue is primarily a pediatric disease in areas with high force of infection. However, the average age of dengue could increase if force of infection decreases over time, as is occurring in some hyperendemic countries such as Thailand.     

Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study

Background

Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance.

Methods

We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis.

Results

Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5–98.8), 80.8% specificity (72.6–87.1), positive likelihood ratio 4.9 (3.4–7.1), negative likelihood ratio 0.083 (0.022–0.32), and misclassification rate 0.20 (standard error 0.038).

Conclusions

In Tanzanian children with WHO-defined clinical pneumonia, combinations of host biomarkers distinguished between end-point pneumonia, other infiltrates, and normal chest x-ray, whereas clinical variables did not. These findings generate pathophysiological hypotheses and may have potential research and clinical utility.     

The Time Factor in Studies of Growth Inhibition in Excised Organ Sections

1. Apprehension over the adequncy of current techniques stimulateda detailed study of the time factor in the arsenate inhibitionof growth and respiration in excised stem and root sectionsof Pisum sativum.
2. Growth inhibition by arsenate sets in veryslowly, its rateof onset being related to the molar concentration(C) of arsenateate by the relation where T₅₀ is the time taken in hours to reduce the growthrateto 50 per cent of the control and K is a constant. An explanationof the physiological basis of this relationship is attempted.
3. Estimates were made of the final steady growth rate (relativeto control) in various arsenate concentrations. The inhibitionscalculated from this rate are held to approximate to the truearsenate effect and are shown to be very different from thosecalculated from ‘total growth’ measures.
4. Respirationof growing stem sections is not inhibited by thelow arsenateconcentrations that inhibit growth. Some inhibitionis indicatedat high concentrations (3 ? 10^–4M. and over)but onlyafter 15-20 hours of exposure.
5. Two per cent sucrose has noeffect on the arsenate inhibiitionof stem growth. Sucrose,however, markedly stimulates respirationin stem sections, butthis stimulation is prevented by arsenate.
6. The misinterpretationswhich may arise as a result of ignoringthe time factor in inhibitionstudies in excised organ sectionsare discussed and the desirabilityof constructing completegrowth curves in all such studies isstressed.

     

Classification of Time Series Gene Expression in Clinical Studies via Integration of Biological Network

The increasing availability of time series expression datasets, although promising, raises a number of new computational challenges. Accordingly, the development of suitable classification methods to make reliable and sound predictions is becoming a pressing issue. We propose, here, a new method to classify time series gene expression via integration of biological networks. We evaluated our approach on 2 different datasets and showed that the use of a hidden Markov model/Gaussian mixture models hybrid explores the time-dependence of the expression data, thereby leading to better prediction results. We demonstrated that the biclustering procedure identifies function-related genes as a whole, giving rise to high accordance in prognosis prediction across independent time series datasets. In addition, we showed that integration of biological networks into our method significantly improves prediction performance. Moreover, we compared our approach with several state-of–the-art algorithms and found that our method outperformed previous approaches with regard to various criteria. Finally, our approach achieved better prediction results on early-stage data, implying the potential of our method for practical prediction.     

Material Flow Accounts and Driving Factors of Economic Growth in the Philippines

This study looks into material flow trends in the Philippines from 1985 to 2010 by utilizing the methodology of economy‐wide material flow analysis. Using domestic data sources, this study presents disaggregated annual material flow trends in terms of four major material categories, namely: biomass; fossil energy carriers; ores and industrial minerals; and construction minerals. The results describe in detail the growth of material flows in a high‐density country at the onset of its development and reveal the shift of material consumption from dominance of renewable materials in 1985 to nonrenewable materials in 2010. IPAT analysis shows that the increase in material consumption was driven by population growth from 1985 to 1998 and by growth in affluence from 1999 to 2010. However, high inequalities amidst the growing economy suggest that a small group of wealthy people have influenced the acceleration of material consumption in the Philippines. The results of this research are intended to provide a thorough analysis of the processes occurring in Philippine economic growth in order to assist in tackling implications for the important issue of sustainable resource management.     

Clinical Outcomes and Microbiological Characteristics of Severe Pneumonia in Cancer Patients: A Prospective Cohort Study

Introduction

Pneumonia is the most frequent type of infection in cancer patients and a frequent cause of ICU admission. The primary aims of this study were to describe the clinical and microbiological characteristics and outcomes in critically ill cancer patients with severe pneumonia.

Methods

Prospective cohort study in 325 adult cancer patients admitted to three ICUs with severe pneumonia not acquired in the hospital setting. Demographic, clinical and microbiological data were collected.

Results

There were 229 (71%) patients with solid tumors and 96 (29%) patients with hematological malignancies. 75% of all patients were in septic shock and 81% needed invasive mechanical ventilation. ICU and hospital mortality rates were 45.8% and 64.9%. Microbiological confirmation was present in 169 (52%) with a predominance of Gram negative bacteria [99 (58.6%)]. The most frequent pathogens were methicillin-sensitive S. aureus [42 (24.9%)], P. aeruginosa [41(24.3%)] and S. pneumonia [21 (12.4%)]. A relatively low incidence of MR [23 (13.6%)] was observed. Adequate antibiotics were prescribed for most patients [136 (80.5%)]. In multivariate analysis, septic shock at ICU admission [OR 5.52 (1.92–15.84)], the use of invasive MV [OR 12.74 (3.60–45.07)] and poor Performance Status [OR 3.00 (1.07–8.42)] were associated with increased hospital mortality.

Conclusions

Severe pneumonia is associated with high mortality rates in cancer patients. A relatively low rate of MR pathogens is observed and severity of illness and organ dysfunction seems to be the best predictors of outcome in this population.