PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (1208512)

Clipboard (0)
None

Related Articles

1.  Meticillin-resistant Staphylococcus aureus and meticillin-susceptible S. aureus pneumonia: comparison of clinical and thin-section CT findings 
The British Journal of Radiology  2012;85(1014):e168-e175.
Objectives
The purpose of this study was to compare the clinical and thin-section CT findings in patients with meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-susceptible S. aureus (MSSA).
Methods
We retrospectively identified 201 patients with acute MRSA pneumonia and 164 patients with acute MSSA pneumonia who had undergone chest thin-section CT examinations between January 2004 and March 2009. Patients with concurrent infectious disease were excluded from our study. Consequently, our study group comprised 68 patients with MRSA pneumonia (37 male, 31 female) and 83 patients with MSSA pneumonia (32 male, 51 female). Clinical findings in the patients were assessed. Parenchymal abnormalities, lymph node enlargement and pleural effusion were assessed.
Results
Underlying diseases such as cardiovascular were significantly more frequent in the patients with MRSA pneumonia than in those with MSSA pneumonia. CT findings of centrilobular nodules, centrilobular nodules with a tree-in-bud pattern, and bronchial wall thickening were significantly more frequent in the patients with MSSA pneumonia than those with MRSA pneumonia (p=0.038, p=0.007 and p=0.039, respectively). In the group with MRSA, parenchymal abnormalities were observed to be mainly peripherally distributed and the frequency was significantly higher than in the MSSA group (p=0.028). Pleural effusion was significantly more frequent in the patients with MRSA pneumonia than those with MSSA pneumonia (p=0.002).
Conclusions
Findings from the evaluation of thin-section CT manifestations of pneumonia may be useful to distinguish between patients with acute MRSA pneumonia and those with MSSA pneumonia.
doi:10.1259/bjr/65538472
PMCID: PMC3474104  PMID: 21750126
2.  Thin-section CT findings of patients with acute Streptococcus pneumoniae pneumonia with and without concurrent infection 
The British Journal of Radiology  2012;85(1016):e357-e364.
Objectives
The aim of this study was to compare the pulmonary thin-section CT findings of patients with acute Streptococcus pneumoniae pneumonia with and without concurrent infection.
Methods
The study group comprised 86 patients with acute S. pneumoniae pneumonia, 36 patients with S. pneumoniae pneumonia combined with Haemophilus influenzae infection, 26 patients with S. pneumoniae pneumonia combined with Pseudomonas aeruginosa infection and 22 patients with S. pneumoniae pneumonia combined with methicillin-susceptible Staphylococcus aureus (MSSA) infection. We compared the thin-section CT findings among the groups.
Results
Centrilobular nodules and bronchial wall thickening were significantly more frequent in patients with pneumonia caused by concurrent infection (H. influenzae: p<0.001 and p<0.001, P. aeruginosa: p<0.001 and p<0.001, MSSA: p<0.001 and p<0.001, respectively) than in those infected with S. pneumoniae alone. Cavity and bilateral pleural effusions were significantly more frequent in cases of S. pneumoniae pneumonia with concurrent P. aeruginosa infection than in cases of S. pneumoniae pneumonia alone (p<0.001 and p<0.001, respectively) or with concurrent H. influenzae (p<0.05 and p<0.001, respectively) or MSSA infection (p<0.05 and p<0.05, respectively).
Conclusions
When a patient with S. pneumoniae pneumonia has centrilobular nodules, bronchial wall thickening, cavity or bilateral pleural effusions on CT images, concurrent infection should be considered.
doi:10.1259/bjr/18544730
PMCID: PMC3587092  PMID: 22215884
3.  Pulmonary thin-section CT findings in acute Moraxella catarrhalis pulmonary infection 
The British Journal of Radiology  2011;84(1008):1109-1114.
Objective
Moraxella catarrhalis is an important pathogen in the exacerbation of chronic obstructive pulmonary disease. The aim of this study was to assess the clinical and pulmonary thin-section CT findings in patients with acute M. catarrhalis pulmonary infection.
Methods
Thin-section CT scans obtained between January 2004 and March 2009 from 292 patients with acute M. catarrhalis pulmonary infection were retrospectively evaluated. Clinical and pulmonary CT findings in the patients were assessed. Patients with concurrent infection including Streptococcus pneumoniae (n = 72), Haemophilus influenzae (n = 61) or multiple pathogens were excluded from this study.
Results
The study group comprised 109 patients (66 male, 43 female; age range 28–102 years; mean age 74.9 years). Among the 109 patients, 34 had community-acquired and 75 had nosocomial infections. Underlying diseases included pulmonary emphysema (n = 74), cardiovascular disease (n = 44) or malignant disease (n = 41). Abnormal findings were seen on CT scans in all patients and included ground-glass opacity (n = 99), bronchial wall thickening (n = 85) and centrilobular nodules (n = 79). These abnormalities were predominantly seen in the peripheral lung parenchyma (n = 99). Pleural effusion was found in eight patients. No patients had mediastinal and/or hilar lymph node enlargement.
Conclusions
M. catarrhalis pulmonary infection was observed in elderly patients, often in combination with pulmonary emphysema. CT manifestations of infection were mainly ground-glass opacity, bronchial wall thickening and centilobular nodules.
doi:10.1259/bjr/42762966
PMCID: PMC3473838  PMID: 21123308
4.  Characterization of Extended-Host-Range Pseudo-T-Even Bacteriophage Kpp95 Isolated on Klebsiella pneumoniae▿  
Kpp95, isolated on Klebsiella pneumoniae, is a bacteriophage with the morphology of T4-type phages and is capable of rapid lysis of host cells. Its double-stranded genomic DNA (ca. 175 kb, estimated by pulsed-field gel electrophoresis) can be cut only by restriction endonucleases with a cleavage site flanked either by A and T or by T, as tested, suggesting that it contains the modified derivative(s) of G and/or C. Over 26 protein bands were visualized upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the virion proteins. N-terminal sequencing indicated that the most abundant band (46 kDa) is the major coat protein (gp23) which has been cleaved from a signal peptide likely with a length similar to that of T4. Phylogenetic analyses based on the sequences of the central region (263 amino acid residues) of gp23 and the full length of gp18 and gp19 placed Kpp95 among the pseudo-T-even subgroup, most closely related to the coliphage JS98. In addition to being able to lyse many extended-spectrum β-lactamase strains of K. pneumoniae, Kpp95 can lyse Klebsiella oxytoca, Enterobacter agglomerans, and Serratia marcescens cells. Thus, Kpp95 deserves further studies for development as a component of a therapeutic cocktail, owing to its high efficiencies of host lysis plus extended host range.
doi:10.1128/AEM.02113-06
PMCID: PMC1855606  PMID: 17337566
5.  Pseudomonas aeruginosa Keratitis in Mice: Effects of Topical Bacteriophage KPP12 Administration 
PLoS ONE  2012;7(10):e47742.
The therapeutic effects of bacteriophage (phage) KPP12 in Pseudomonas aeruginosa keratitis were investigated in mice. Morphological analysis showed that phage KPP12 is a member of the family Myoviridae, morphotype A1, and DNA sequence analysis revealed that phage KPP12 is similar to PB1-like viruses. Analysis of the phage KPP12 genome did not identify any genes related to drug resistance, pathogenicity or lysogenicity, and so phage KPP12 may be a good candidate for therapeutic. KPP12 showed a broad host range for P. aeruginosa strains isolated from clinical ophthalmic infections. Inoculation of the scarified cornea with P. aeruginosa caused severe keratitis and eventual corneal perforation. Subsequent single-dose administration of KPP12 eye-drops significantly improved disease outcome, and preserved the structural integrity and transparency of the infected cornea. KPP12 treatment resulted in the suppression of neutrophil infiltration and greatly enhanced bacterial clearance in the infected cornea. These results indicate that bacteriophage eye-drops may be a novel adjunctive or alternative therapeutic agent for the treatment of infectious keratitis secondary to antibiotic-resistant bacteria.
doi:10.1371/journal.pone.0047742
PMCID: PMC3474789  PMID: 23082205
6.  Thin-section CT findings in Pseudomonas aeruginosa pulmonary infection 
The British Journal of Radiology  2012;85(1020):1533-1538.
Objective
The aim of this study was to assess clinical and pulmonary thin-section CT findings in patients with acute Pseudomonas aeruginosa (PA) pulmonary infection.
Methods
We retrospectively identified 44 patients with acute PA pneumonia who had undergone chest thin-section CT examinations between January 2004 and December 2010. We excluded nine patients with concurrent infections. The final study group comprised 35 patients (21 males, 14 females; age range 30–89 years, mean age 66.9 years) with PA pneumonia. The patients' clinical findings were assessed. Parenchymal abnormalities, enlarged lymph nodes and pleural effusion were evaluated on thin-section CT.
Results
Underlying diseases included malignancy (n=13), a smoking habit (n=11) and cardiac disease (n=8). CT scans of all patients revealed abnormal findings, including ground-glass opacity (n=34), bronchial wall thickening (n=31), consolidation (n=23) and cavities (n=5). Pleural effusion was found in 15 patients.
Conclusion
PA pulmonary infection was observed in patients with underlying diseases such as malignancy or a smoking habit. The CT findings in patients with PA consisted mainly of ground-glass attenuation and bronchial wall thickening.
Advances in knowledge
The CT findings consisted mainly of ground-glass attenuation, bronchial wall thickening and cavities. These findings in patients with an underlying disease such as malignancy or a smoking habit may be suggestive of pneumonia caused by PA infection.
doi:10.1259/bjr/54468236
PMCID: PMC3611710  PMID: 22844034
7.  Radiological findings in acute Haemophilus influenzae pulmonary infection 
The British Journal of Radiology  2012;85(1010):121-126.
Objective
The aim of this study was to assess pulmonary thin-section CT findings in patients with acute Haemophilus influenzae pulmonary infection.
Methods
Thin-section CT scans obtained between January 2004 and March 2009 from 434 patients with acute H. influenzae pulmonary infection were retrospectively evaluated. Patients with concurrent infection diseases, including Streptococcus pneumoniae (n=76), Staphylococcus aureus (n=58) or multiple pathogens (n=89) were excluded from this study. Thus, our study group comprised 211 patients (106 men, 105 women; age range, 16–91 years, mean, 63.9 years). Underlying diseases included cardiac disease (n=35), pulmonary emphysema (n=23), post-operative status for malignancy (n=20) and bronchial asthma (n=15). Frequencies of CT patterns and disease distribution of parenchymal abnormalities, lymph node enlargement and pleural effusion were assessed by thin-section CT.
Results
The CT findings in patients with H. influenzae pulmonary infection consisted mainly of ground-glass opacity (n=185), bronchial wall thickening (n=181), centrilobular nodules (n=137) and consolidation (n=112). These abnormalities were predominantly seen in the peripheral lung parenchyma (n=108). Pleural effusion was found in 22 patients. Two patients had mediastinal lymph node enlargement.
Conclusion
These findings in elderly patients with smoking habits or cardiac disease may be characteristic CT findings of H. influenzae pulmonary infection.
doi:10.1259/bjr/48077494
PMCID: PMC3473957  PMID: 21224303
8.  Na+,K+-pump stimulation improves contractility in isolated muscles of mice with hyperkalemic periodic paralysis 
The Journal of General Physiology  2011;138(1):117-130.
In patients with hyperkalemic periodic paralysis (HyperKPP), attacks of muscle weakness or paralysis are triggered by K+ ingestion or rest after exercise. Force can be restored by muscle work or treatment with β2-adrenoceptor agonists. A missense substitution corresponding to a mutation in the skeletal muscle voltage-gated Na+ channel (Nav1.4, Met1592Val) causing human HyperKPP was targeted into the mouse SCN4A gene (mutants). In soleus muscles prepared from these mutant mice, twitch, tetanic force, and endurance were markedly reduced compared with soleus from wild type (WT), reflecting impaired excitability. In mutant soleus, contractility was considerably more sensitive than WT soleus to inhibition by elevated [K+]o. In resting mutant soleus, tetrodotoxin (TTX)-suppressible 22Na uptake and [Na+]i were increased by 470 and 58%, respectively, and membrane potential was depolarized (by 16 mV, P < 0.0001) and repolarized by TTX. Na+,K+ pump–mediated 86Rb uptake was 83% larger than in WT. Salbutamol stimulated 86Rb uptake and reduced [Na+]i both in mutant and WT soleus. Stimulating Na+,K+ pumps with salbutamol restored force in mutant soleus and extensor digitorum longus (EDL). Increasing [Na+]i with monensin also restored force in soleus. In soleus, EDL, and tibialis anterior muscles of mutant mice, the content of Na+,K+ pumps was 28, 62, and 33% higher than in WT, respectively, possibly reflecting the stimulating effect of elevated [Na+]i on the synthesis of Na+,K+ pumps. The results confirm that the functional disorders of skeletal muscles in HyperKPP are secondary to increased Na+ influx and show that contractility can be restored by acute stimulation of the Na+,K+ pumps. Calcitonin gene-related peptide (CGRP) restored force in mutant soleus but caused no detectable increase in 86Rb uptake. Repeated excitation and capsaicin also restored contractility, possibly because of the release of endogenous CGRP from nerve endings in the isolated muscles. These observations may explain how mild exercise helps locally to prevent severe weakness during an attack of HyperKPP.
doi:10.1085/jgp.201010586
PMCID: PMC3135321  PMID: 21708955
9.  A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation 
Journal of Clinical Investigation  2000;106(3):431-438.
Hyperkalemic periodic paralysis (HyperKPP) is an autosomal dominant skeletal muscle disorder caused by single mutations in the SCN4A gene, encoding the human skeletal muscle voltage-gated Na+ channel. We have now identified one allele with two novel mutations occurring simultaneously in the SCN4A gene. These mutations are found in two distinct families that had symptoms of periodic paralysis and malignant hyperthermia susceptibility. The two nucleotide transitions predict phenylalanine 1490→leucine and methionine 1493→isoleucine changes located in the transmembrane segment S5 in the fourth repeat of the α-subunit Na+ channel. Surprisingly, this mutation did not affect fast inactivation parameters. The only defect produced by the double mutant (F1490L-M1493I, expressed in human embryonic kidney 293 cells) is an enhancement of slow inactivation, a unique behavior not seen in the 24 other disease-causing mutations. The behavior observed in these mutant channels demonstrates that manifestation of HyperKPP does not necessarily require disruption of slow inactivation. Our findings may also shed light on the molecular determinants and mechanism of Na+ channel slow inactivation and help clarify the relationship between Na+ channel defects and the long-term paralytic attacks experienced by patients with HyperKPP.
PMCID: PMC314328  PMID: 10930446
10.  Predominance of HLA-Restricted Cytotoxic T-Lymphocyte Responses to Serotype-Cross-Reactive Epitopes on Nonstructural Proteins following Natural Secondary Dengue Virus Infection 
Journal of Virology  1998;72(5):3999-4004.
We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA B57 restricted, and the CD8+ NS3-specific lines from patient KPP94-024 were HLA B7 restricted. The CD4+ CTL lines from patient KPP94-037 were HLA DR7 restricted. A majority of the CD8+ CTLs isolated from patient KPP94-024 were found to recognize amino acids 221 to 232 on NS3. These results demonstrate that in Thai patients after symptomatic secondary natural dengue infections, CTLs are mainly directed against nonstructural proteins and are broadly cross-reactive.
PMCID: PMC109627  PMID: 9557687
11.  White light endoscopy, narrow band imaging and chromoendoscopy with magnification in diagnosing colorectal neoplasia 
AIM: To evaluate the sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of 3 different techniques: high resolution white light endoscopy (WLE), Narrow Band Imaging (NBI) and Chromoendoscopy (CHR), all with magnification in differentiating adenocarcinomas, adenomatous and hyperplastic colorectal polyps.
METHODS: Each polyp was sequentially assessed first by WLE, followed by NBI and finally by CHR. Digital images of each polyp with each modality were taken and stored. Biopsies or polypectomies were then performed followed by blinded histopathological analysis. Each image was blindly graded based on the Kudo’s pit pattern (KPP). In the assessment with NBI, the mesh brown capillary network pattern (MBCN) of each polyp was also described. The Sn, Sp, PPV and NPV of differentiating hyperplastic (Type I & II-KPP, Type I-MBCN) adenomatous (Types III, IV-KPP, Type II-MBCN) and carcinomatous polyps (Type V-KPP, Type III-MCBN) was then compared with reference to the final histopathological diagnosis.
RESULTS: A total of 50 colorectal polyps (5 adenocarcinomas, 38 adenomas, 7 hyperplastic) were assessed. CHR and NBI [KPP, MBCN or the combined classification (KPP & MBCN)] were superior to WLE in the prediction of polyp histology (P < 0.001, P = 0.002, P = 0.001 and P < 0.001, respectively). NBI, using the MBCN pattern or the combined classification showed higher numerical accuracies compared to CHR, but this was not statistically significant (P = 0.625, 0.250).
CONCLUSION: This feasibility study demonstrated that this combined classification with NBI could potentially be useful in routine clinical practice, allowing the endoscopist to predict histology with higher accuracies using a less cumbersome and technically less challenging method.
doi:10.4253/wjge.v1.i1.45
PMCID: PMC2999075  PMID: 21160650
High-resolution magnification endoscopy; Narrow band imaging with magnification; Chromoendoscopy with magnification; Colorectal polyp; Colorectal neoplasia
12.  Comparison of pulmonary thin section CT findings and serum KL-6 levels in patients with sarcoidosis 
The British Journal of Radiology  2011;84(999):229-235.
Objective
This study aimed to compare thin-section CT images from sarcoidosis patients who had either normal or elevated serum KL-6 levels.
Methods
101 patients with sarcoidosis who underwent thin-section CT examinations of the chest and serum KL-6 measurements between December 2003 and November 2008 were retrospectively identified. The study group comprised 75 sarcoidosis patients (23 male, 52 female; aged 19–82 years, mean 54.1 years) with normal KL-6 levels (152–499 U ml–1, mean 305.7 U ml–1) and 26 sarcoidosis patients (7 male, 19 female; aged 19–75 years, mean 54.3 years) with elevated KL-6 levels (541–2940 U ml–1, mean 802.4 U ml–1). Two chest radiologists, unaware of KL-6 levels, retrospectively and independently interpreted CT images for parenchymal abnormalities, enlarged lymph nodes and pleural effusion.
Results
CT findings in sarcoidosis patients consisted mainly of lymph node enlargement (70/75 with normal KL-6 levels and 21/26 with elevated KL-6 levels), followed by nodules (50 and 25 with normal and elevated levels, respectively) and bronchial wall thickening (25 and 21 with normal and elevated levels, respectively). Ground-glass opacity, nodules, interlobular septal thickening, traction bronchiectasis, architectural distortion and bronchial wall thickening were significantly more frequent in patients with elevated KL-6 levels than those with normal levels (p<0.001, p<0.005, p<0.001, p<0.001, p<0.001 and p<0.001, respectively). By comparison, there was no significant difference in frequency of lymph node enlargement between the two groups.
Conclusion
These results suggest that serum KL-6 levels may be a useful marker for indicating the severity of parenchymal sarcoidosis.
doi:10.1259/bjr/65287605
PMCID: PMC3473878  PMID: 21045068
13.  Mutations in Potassium Channel Kir2.6 Cause Susceptibility to Thyrotoxic Hypokalemic Periodic Paralysis 
Cell  2010;140(1):88-98.
SUMMARY
Thyrotoxic hypokalemic periodic paralysis (TPP) is characterized by acute attacks of weakness, hypokalemia, and thyrotoxicosis of various etiologies. These transient attacks resemble those of patients with familial hypokalemic periodic paralysis (hypoKPP) and resolve with treatment of the underlying hyperthyroidism. Because of the phenotypic similarity of these conditions, we hypothesized that TPP might also be a channelopathy. While sequencing candidate genes, we identified a previously unreported gene (not present in human sequence databases) that encodes an inwardly rectifying potassium (Kir) channel, Kir2.6. This channel, nearly identical to Kir2.2, is expressed in skeletal muscle and is transcriptionally regulated by thyroid hormone. Expression of Kir2.6 in mammalian cells revealed normal Kir currents in whole-cell and single-channel recordings. Kir2.6 mutations were present in up to 33% of the unrelated TPP patients in our collection. Some of these mutations clearly alter a variety of Kir2.6 properties, all altering muscle membrane excitability leading to paralysis.
doi:10.1016/j.cell.2009.12.024
PMCID: PMC2885139  PMID: 20074522
14.  Carriage of Mycoplasma pneumoniae in the Upper Respiratory Tract of Symptomatic and Asymptomatic Children: An Observational Study 
PLoS Medicine  2013;10(5):e1001444.
In order to determine the possible asymptomatic carriage of Mycoplasma pneumoniae in the upper respiratory tracts of children, Emiel Spuesens and colleagues investigate the prevalence of M. pneumoniae in symptomatic and asymptomatic children at a hospital in The Netherlands.
Please see later in the article for the Editors' Summary
Background
Mycoplasma pneumoniae is thought to be a common cause of respiratory tract infections (RTIs) in children. The diagnosis of M. pneumoniae RTIs currently relies on serological methods and/or the detection of bacterial DNA in the upper respiratory tract (URT). It is conceivable, however, that these diagnostic methods also yield positive results if M. pneumoniae is carried asymptomatically in the URT. Positive results from these tests may therefore not always be indicative of a symptomatic infection. The existence of asymptomatic carriage of M. pneumoniae has not been established. We hypothesized that asymptomatic carriage in children exists and investigated whether colonization and symptomatic infection could be differentiated by current diagnostic methods.
Methods and Findings
This study was conducted at the Erasmus MC–Sophia Children's Hospital and the after-hours General Practitioners Cooperative in Rotterdam, The Netherlands. Asymptomatic children (n = 405) and children with RTI symptoms (n = 321) aged 3 mo to 16 y were enrolled in a cross-sectional study from July 1, 2008, to November 30, 2011. Clinical data, pharyngeal and nasopharyngeal specimens, and serum samples were collected. The primary objective was to differentiate between colonization and symptomatic infection with M. pneumoniae by current diagnostic methods, especially real-time PCR. M. pneumoniae DNA was detected in 21.2% (95% CI 17.2%–25.2%) of the asymptomatic children and in 16.2% (95% CI 12.2%–20.2%) of the symptomatic children (p = 0.11). Neither serology nor quantitative PCR nor culture differentiated asymptomatic carriage from infection. A total of 202 children were tested for the presence of other bacterial and viral pathogens. Two or more pathogens were found in 56% (63/112) of the asymptomatic children and in 55.5% (50/90) of the symptomatic children. Finally, longitudinal sampling showed persistence of M. pneumoniae in the URT for up to 4 mo. Fifteen of the 21 asymptomatic children with M. pneumoniae and 19 of the 22 symptomatic children with M. pneumoniae in this longitudinal follow-up tested negative after 1 mo.
Conclusions
Although our study has limitations, such as a single study site and limited sample size, our data indicate that the presence of M. pneumoniae in the URT is common in asymptomatic children. The current diagnostic tests for M. pneumoniae are unable to differentiate between asymptomatic carriage and symptomatic infection.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Pneumonia (a form of acute respiratory infection) is the single largest cause of death in children worldwide, killing an estimated 1.2 million children aged five and under every year, particularly in South Asia and sub-Saharan Africa. In these settings, bacterial infections with Streptococcus pneumoniae and Haemophilus influenzae are the most common causes of bacterial pneumonia. However, in high-income settings, bacterial infection with Mycoplasma pneumoniae is a major cause of upper and lower respiratory tract infections in children: over one-third of childhood cases of community-acquired pneumonia that require admission to a hospital are caused by M. pneumoniae. Currently, diagnosis of M. pneumoniae infections relies on the detection of antibodies against M. pneumoniae in the blood or detection of bacterial DNA in samples from the upper respiratory tract through polymerase chain reaction (PCR) tests.
Why Was This Study Done?
Other bacteria, such as Streptococcus pneumoniae, are commonly present in children without causing infection, a situation known as asymptomatic carriage. However, to date, it is unknown whether M. pneumoniae is also commonly carried in the upper respiratory tract of children without causing symptoms or leading to infection. The possibility of asymptomatic carriage of M. pneumoniae could have major implications for the interpretation of the results of diagnostic tests and also for clinical management. So in this study conducted in The Netherlands, the researchers investigated whether asymptomatic carriage of M. pneumoniae exists and also whether symptomatic infection could be differentiated from asymptomatic carriage by current diagnostic methods.
What Did the Researchers Do and Find?
Between 2008 and 2011, the researchers recruited children aged between three months and 16 years attending a hospital in Rotterdam for an elective surgical procedure (asymptomatic group) or admitted with a respiratory tract infection (symptomatic group). All children had blood tests and respiratory samples (nasopharyngeal swab) taken on admission and were tested for other pathogens. The researchers invited children who tested positive for M. pneumoniae by PCR to attend for further follow-up and tested them monthly for the presence of M. pneumoniae DNA in the upper respiratory tract until the test was negative on two occasions. Using these methods, the researchers recruited 726 children over the study period—405 in the asymptomatic group and 321 in the symptomatic group. The researchers found that the prevalence of M. pneumoniae did not differ between the asymptomatic group and the symptomatic group, with prevalences of 21.2% and 16.2%, respectively (the prevalence of M. pneumoniae also did not differ significantly between those with lower versus upper respiratory infection). There were also no differences in prevalence in the asymptomatic and symptomatic groups when diagnosed using blood tests. The researchers found a high rate of multiple, coexisting bacterial and viral pathogens in both asymptomatic and symptomatic children: two or more pathogens were found in 56% (63/112) of the asymptomatic children and in 55.5% (50/90) of the symptomatic children. Furthermore, season and the year of enrollment affected the prevalence of M. pneumoniae in the asymptomatic group, ranging from 3% during the spring of 2009 to 58% during the summer of 2010. Finally, of the 21 children from the asymptomatic group who participated in the follow-up study, 15 (71%) tested negative within one month, and in the symptomatic group, 19 of 22 children (86%) tested negative after the first visit.
What Do These Findings Mean?
These findings show that M. pneumoniae is carried at high rates in the upper respiratory tracts of healthy children, and that this asymptomatic carriage cannot be differentiated from symptomatic respiratory tract infection by diagnostic tests (serology or PCR). As the prevalence of M. pneumoniae varied between year and season, carriage of M. pneumoniae may follow a cyclic epidemic pattern. This study is from a single study site in one city in The Netherlands, with a relatively small number of children, and so these findings may not be generalizable to other populations. However, as this study suggests that current diagnostic tests do not discriminate between carriage and infection, clinicians may need to reconsider the clinical significance of a positive test result. Future studies are needed to address this diagnostic challenge and also to investigate possible factors that may affect the progression of asymptomatic carriage of M. pneumoniae to symptomatic infection.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001444.
MicrobeWiki has more information on M. pneumoniae
Lab Tests Online explains current tests for M. pneumoniae
doi:10.1371/journal.pmed.1001444
PMCID: PMC3653782  PMID: 23690754
15.  Measuring Coverage in MNCH: A Prospective Validation Study in Pakistan and Bangladesh on Measuring Correct Treatment of Childhood Pneumonia 
PLoS Medicine  2013;10(5):e1001422.
Background
Antibiotic treatment for pneumonia as measured by Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) is a key indicator for tracking progress in achieving Millennium Development Goal 4. Concerns about the validity of this indicator led us to perform an evaluation in urban and rural settings in Pakistan and Bangladesh.
Methods and Findings
Caregivers of 950 children under 5 y with pneumonia and 980 with “no pneumonia” were identified in urban and rural settings and allocated for DHS/MICS questions 2 or 4 wk later. Study physicians assigned a diagnosis of pneumonia as reference standard; the predictive ability of DHS/MICS questions and additional measurement tools to identify pneumonia versus non-pneumonia cases was evaluated.
Results at both sites showed suboptimal discriminative power, with no difference between 2- or 4-wk recall. Individual patterns of sensitivity and specificity varied substantially across study sites (sensitivity 66.9% and 45.5%, and specificity 68.8% and 69.5%, for DHS in Pakistan and Bangladesh, respectively). Prescribed antibiotics for pneumonia were correctly recalled by about two-thirds of caregivers using DHS questions, increasing to 72% and 82% in Pakistan and Bangladesh, respectively, using a drug chart and detailed enquiry.
Conclusions
Monitoring antibiotic treatment of pneumonia is essential for national and global programs. Current (DHS/MICS questions) and proposed new (video and pneumonia score) methods of identifying pneumonia based on maternal recall discriminate poorly between pneumonia and children with cough. Furthermore, these methods have a low yield to identify children who have true pneumonia. Reported antibiotic treatment rates among these children are therefore not a valid proxy indicator of pneumonia treatment rates. These results have important implications for program monitoring and suggest that data in its current format from DHS/MICS surveys should not be used for the purpose of monitoring antibiotic treatment rates in children with pneumonia at the present time.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Pneumonia is a major cause of death in children younger than five years across the globe, with approximately 1.2 million children younger than five years dying from pneumonia every year. Pneumonia can be caused by bacteria, fungi, or viruses. It is possible to effectively treat bacterial pneumonia with appropriate antibiotics; however, only about 30% of children receive the antibiotic treatment they need. The Millennium Development Goals (MDGs) are eight international development goals that were established in 2000. The fourth goal (MDG 4) aims to reduce child mortality, specifically, to reduce the under-five mortality rate by two-thirds, between 1990 and 2015. Given that approximately 18% of all deaths in children under five are caused by pneumonia, providing universal coverage with effective treatments for pneumonia is an important part of MDG 4.
To ensure that MDG 4 targets are met, it is important to measure progress in providing effective treatments. For pneumonia, one of the key indicators for measuring progress is the proportion of children with pneumonia in a population who receive antibiotic treatment, also known as the antibiotic treatment rate. The antibiotic treatment rate is often measured using surveys, such as the Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS), which collect nationally representative data about populations and health in developing countries.
Why Was This Study Done?
Concerns have been raised about whether information collected from DHS and MICS is able to accurately identify cases of pneumonia. In a clinical setting, pneumonia is typically diagnosed based on a combination of physical symptoms, including coughing, rapid breathing, or difficulty breathing, and a chest X-ray. The surveys rely on information collected from interviews of mothers and primary caregivers using structured questions about whether the child has experienced physical symptoms in the past two weeks and whether these were chest-related. The DHS survey labels this condition as “symptoms of acute respiratory infection,” while the MICS survey uses the term “suspected pneumonia.” Thus, these surveys provide a proxy measure for pneumonia that is limited by the reliance on the recall of symptoms by the mother or caregiver. Here the researchers have evaluated the use of these surveys to discriminate physician-diagnosed pneumonia and to provide accurate recall of antibiotic treatment in urban and rural settings in Pakistan and Bangladesh.
What Did the Researchers Do and Find?
The researchers identified caregivers of 950 children under five years with pneumonia and 980 who had a cough or cold but did not have pneumonia from urban and rural settings in Pakistan and Bangladesh. Cases of pneumonia were identified based on a physician diagnosis using World Health Organization guidelines. They randomly assigned caregivers to be interviewed using DHS and MICS questions with either a two- or four-week recall period. They then assessed how well the DHS and MICS questions were able to accurately diagnose pneumonia and accurately recall antibiotic use. In addition, they asked caregivers to complete a pneumonia score questionnaire and showed them a video tool showing children with and without pneumonia, as well as a medication drug chart, to determine if these alternative measures improved the accuracy of pneumonia diagnosis or recall of antibiotic use. They found that both surveys, the pneumonia score, and the video tool had poor ability to discriminate between children with and without physician-diagnosed pneumonia, and there were no differences between using two- or four-week recall. The sensitivity (proportion of pneumonia cases that were correctly identified) ranged from 23% to 72%, and the specificity (the proportion of “no pneumonia” cases that were correctly identified) ranged from 53% to 83%, depending on the setting. They also observed that prescribed antibiotics for pneumonia were correctly recalled by about two-thirds of caregivers using DHS questions, and this increased to about three-quarters of caregivers when using a drug chart and detailed enquiry.
What Do These Findings Mean?
The findings of this study suggest that the current use of questions from DHS and MICS based on mother or caregiver recall are not sufficient for accurately identifying pneumonia and antibiotic use in children. Because these surveys have poor ability to identify children who have true pneumonia, reported antibiotic treatment rates for children with pneumonia based on data from these surveys may not be accurate, and these surveys should not be used to monitor treatment rates. These findings should be interpreted cautiously, given the relatively high rate of loss to follow-up and delayed follow-up in some of the children and because some of the settings in this study may not be similar to other low-income settings.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001422.
More information is available on the United Nations goal to reduce child mortality (MDG 4)
The World Health Organization provides information on pneumonia, its impact on children, and the global action plan for prevention and control of pneumonia
More information is available on Demographic and Health Surveys and Multiple Indicator Cluster Surveys
KidsHealth, a resource maintained by the Nemours Foundation (a not-for-profit organization for children's health) provides information for parents on pneumonia (in English and Spanish)
MedlinePlus provides links to additional information on pneumonia (in English and Spanish)
doi:10.1371/journal.pmed.1001422
PMCID: PMC3646205  PMID: 23667339
16.  Bleomycin in the treatment of 50 cases with malignant pleural effusion  
Background: Patients with symptomatic malignant pleural effusion (MPE) may gain profit from pleurodesis for relief of dyspnea and in preventing the accumulation of fluid or air in the pleural space. Pleurodesis methods are palliative and regard the patient's symptoms and underlying disease condition that are different. The purpose of this study was to assess the efficacy of bleomycin in the treatment of malignant pleural effusion.
Methods: From March 2003 to August 2009, 50 cases of malignant pleural effusion referred for chemical pleurodesis. Malignant pleural effusion was diagnosed by cytotogical examination of pleural fluid after thoracosynthesis. Pleurodesis was done by pleural fluid instillation of bleomycin. The severity of effusion with response to treatment was compared.
Results: Nineteen (38%) cases were males and 31 (62%) were females. The mean age of these patients was 60.3±15.8 years (range=31 to 85 years). The majority of patients had breast cancer and lung adenocarcinoma. The mean volume of pleural fluid drained was 2282±848.69cc (range 800-4500 cc). Pleural effusion was mild in 2 (4%) patients, moderate in 25 (50%) and severe in 23 (46%). There was no statistically significant difference between the response to treatment and the amount of effusion (p=.087). Complete response was seen in 33 (66%) patients, partial response in 11 (22%) and failure to treatment in 6 (12%). There was no relationship between the response to treatment and tumor type. There was not any complication in 33 (66%) patients, but fever was seen in 2 (4%) and chest pain in 7 (14%) and both of them in 8 (16%).
Conclusion: The results show that pleurodesis with bleomycin has improved the symptoms of 88 percent of patients without causing any significant complications. Although pleurodesis does not have any effect on patients' survival, it has positive impact on their lives continuously by enhancing the quality of life.
PMCID: PMC3770504  PMID: 24049586
Pleural effusion; Malignancy; Pleurodesis; Bleomycin.
17.  Pleural effusions in patients with AIDS 
Sexually Transmitted Infections  2000;76(2):122-125.
Objective: To describe the range of pathology causing pleural effusions in HIV infected patients with acute respiratory episodes and to attempt to identify whether any associated radiological abnormalities enabled aetiological discrimination.
Methods: Prospective study of chest radiographs of 58 consecutive HIV infected patients with pleural effusion and their microbiological, cytological, and histopathological diagnoses.
Results: A specific diagnosis was made in all cases. Diagnoses were Kaposi's sarcoma, 19 patients; parapneumonic effusion, 16 patients; tuberculosis, eight patients; Pneumocystis carinii pneumonia, six patients; lymphoma, four patients; pulmonary embolus, two patients; and heart failure, aspergillus/leishmaniasis, and Cryptococcus neoformans, one case each. Most effusions (50/58) were small. Bilateral effusions were commoner in Kaposi's sarcoma (12/19) and lymphoma (3/4) than in parapneumonic effusion (3/16). Concomitant interstitial parenchymal shadowing did not aid discrimination. A combination of bilateral effusions, focal air space consolidation, intrapulmonary nodules, and/or hilar lymphadenopathy suggests Kaposi's sarcoma. Unilateral effusion with focal air space consolidation suggests parapneumonic effusion if intrapulmonary nodules are absent: if miliary nodules and/or mediastinal lymphadenopathy are detected, this suggests tuberculosis.
Conclusions: A wide variety of infectious and malignant conditions cause pleural effusions in HIV infected patients, the most common cause in this group was Kaposi's sarcoma. The presence of additional radiological abnormalities such as focal air space consolidation, intrapulmonary nodules, and mediastinal lymphadenopathy aids aetiological discrimination.
Key Words: pleural effusion; Kaposi's sarcoma; bacterial pneumonia; chest radiograph
doi:10.1136/sti.76.2.122
PMCID: PMC1758298  PMID: 10858714
18.  Serum Vascular Endothelial Growth Factor in Pediatric Patients with Community-Acquired Pneumonia and Pleural Effusion 
Journal of Korean Medical Science  2006;21(4):608-613.
This study investigated the serum vascular endothelial growth factor (VEGF) levels in children with community-acquired pneumonia. Serum VEGF levels were measured in patients with pneumonia (n=29) and in control subjects (n=27) by a sandwich enzyme-linked immunosorbent assay. The pneumonia group was classified into bronchopneumonia with pleural effusion (n=1), bronchopneumonia without pleural effusion (n=15), lobar pneumonia with pleural effusion (n=4), and lobar pneumonia without pleural effusion (n=9) groups based on the findings of chest radiographs. We also measured serum IL-6 levels and the other acute inflammatory parameters. Serum levels of VEGF in children with pneumonia were significantly higher than those in control subjects (p<0.01). Children with lobar pneumonia with or without effusion showed significantly higher levels of serum VEGF than children with bronchopneumonia. For lobar pneumonia, children with pleural effusion showed higher levels of VEGF than those without pleural effusion. Children with a positive urinary S. pneumonia antigen test also showed higher levels of VEGF than those with a negative result. Serum IL-6 levels did not show significant differences between children with pneumonia and control subjects. Serum levels of VEGF showed a positive correlation with the erythrocyte sedimentation rate in the children with pneumonia. In conclusion, VEGF may be one of the key mediators that lead to lobar pneumonia and parapneumonic effusion.
doi:10.3346/jkms.2006.21.4.608
PMCID: PMC2729879  PMID: 16891801
Vascular Endothelial Growth Factor A; Interleukin-6; Pleural Effusion; Community-Acquired Infections; Pneumonia
19.  Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness 
The Journal of Clinical Investigation  2008;118(4):1437-1449.
Hyperkalemic periodic paralysis (HyperKPP) produces myotonia and attacks of muscle weakness triggered by rest after exercise or by K+ ingestion. We introduced a missense substitution corresponding to a human familial HyperKPP mutation (Met1592Val) into the mouse gene encoding the skeletal muscle voltage-gated Na+ channel NaV1.4. Mice heterozygous for this mutation exhibited prominent myotonia at rest and muscle fiber-type switching to a more oxidative phenotype compared with controls. Isolated mutant extensor digitorum longus muscles were abnormally sensitive to the Na+/K+ pump inhibitor ouabain and exhibited age-dependent changes, including delayed relaxation and altered generation of tetanic force. Moreover, rapid and sustained weakness of isolated mutant muscles was induced when the extracellular K+ concentration was increased from 4 mM to 10 mM, a level observed in the muscle interstitium of humans during exercise. Mutant muscle recovered from stimulation-induced fatigue more slowly than did control muscle, and the extent of recovery was decreased in the presence of high extracellular K+ levels. These findings demonstrate that expression of the Met1592Val Na+ channel in mouse muscle is sufficient to produce important features of HyperKPP, including myotonia, K+-sensitive paralysis, and susceptibility to delayed weakness during recovery from fatigue.
doi:10.1172/JCI32638
PMCID: PMC2260907  PMID: 18317596
20.  Radiographic features of Mycoplasma pneumoniae pneumonia: differential diagnosis and performance timing 
Background
The Japanese Respiratory Society guidelines propose a differential diagnosis for atypical pneumonia and bacterial pneumonia using a scoring system for the selection of appropriate antibiotic. In order to improve this scoring system, the guidelines are seeking new specific parameter. The purpose of this study was to clarify the pattern of abnormalities with Mycoplasma pneumoniae pneumonia on chest computed tomography (CT) and whether the radiographic findings could distinguish M. pneumoniae pneumonia from Streptococcus pneumoniae pneumonia.
Methods
A retrospective review was performed of the CT findings of 64 cases and 68 cases where M. pneumoniae and S. pneumoniae, respectively, were the only pathogen identified by the panel of diagnostic tests used.
Results
Of the 64 patients with M. pneumoniae pneumonia, bronchial wall thickening was observed most frequently (81%), followed by centrilobular nodules (78%), ground-glass attenuation (78%), and consolidation (61%). Bronchial wall thickening and centrilobular nodules were observed more often in M. pneumoniae patients than in S. pneumoniae patients (p < 0.0001). The presence of bilateral bronchial wall thickening or centrilobular nodules was only seen in patients with M. pneumoniae pneumonia. Using the scoring system of the Japanese Respiratory Society guidelines and chest CT findings, 97% of M. pneumoniae patients were suspected to be M. pneumoniae pneumonia without serology. When comparing the CT findings between early stage and progressed stage in the same patients with severe pneumonia, the radiographic features of early stage M. pneumoniae pneumonia were not observed clearly in the progressed stage.
Conclusion
The present results indicate that the diagnosis of M. pneumoniae pneumonia would appear to be reliable when found with a combination of bronchial wall thickening and centrilobular nodules in the CT findings. However, these CT findings are not observed in progressed severe M. pneumoniae pneumonia patients.
doi:10.1186/1471-2342-9-7
PMCID: PMC2680832  PMID: 19400968
21.  Community acquired pneumonia in adults: a study comparing clinical features and outcome in Africa (Republic of Guinea) and Europe (France). 
Thorax  1996;51(4):385-388.
BACKGROUND: Community acquired pneumonia is the most common cause of death from infectious disease both in western and developing countries. A study was carried out in Conakry, Republic of Guinea and Tours, France in order to compare signs, symptoms, severity of illness, risk factors, and clinical outcome of community acquired pneumonia in adult patients admitted to hospital. METHODS: The study was performed in the cities of Conakry and Tours over the same one year period. Patients with nosocomial pneumonia, tuberculosis, and those who were HIV positive were excluded. Data were recorded on the same forms in both centres. A severity score was calculated according to American Thoracic Society criteria. Follow up was evaluated at days 2, 7 and 15. RESULTS: A total of 333 patients (218 from Conakry, 115 from Tours) were included in the study with a diagnosis of community acquired pneumonia, with or without lung abscess or pleural effusion. Mean age was higher and pre-existing illness rate, dehydration, agitation, and stupor were more frequent in patients in Tours. Respiration rates of > 30 breaths/min and the incidence of crackles were identical in the two centres. Fever above 39 degrees C, initial shock, chest pain, and herpes were significantly more frequent in Conakry. Initial chest radiographic abnormalities were similar in the two groups, ranging from unilateral pleuropulmonary involvement (89% and 83% in Conakry and Tours, respectively) to diffuse patchy parenchymal disease. Parapneumonic effusion was present in 17% and 16% of the patients of Conakry and Tours, respectively. Pneumonia was considered to be severe in 33% and 42% of the patients, respectively. In Conakry first line antibiotic therapy was penicillin alone (2 million units a day) for 197 patients (90%) and second line antibiotic therapy was prescribed for 25 patients (12%). In Tours first line therapy consisted of a single antibiotic (amoxicillin, third generation cephalosporins) for 65 patients (57%) and second line antibiotic therapy was prescribed for 55 patients (48%). The clinical outcome was similar in Conakry and Tours: 88% and 85% of patients, respectively, were afebrile or clinically cured at day 15. The mortality rate was similar (6% and 8%, respectively). CONCLUSIONS: The problems encountered in the management of community acquired pneumonia are quite different in western and developing countries. This study shows that low doses of penicillin can cure 90% of African patients with pneumonia as effectively as more aggregative treatments in European patients who are both older and have greater comorbidity. Although pneumococci with reduced penicillin sensitivity occur in western countries, this does not seem to be the case in black Africa. For these reasons, low doses of penicillin or amoxicillin remain good first line treatment.
PMCID: PMC1090673  PMID: 8733490
22.  Community Case Management of Fever Due to Malaria and Pneumonia in Children Under Five in Zambia: A Cluster Randomized Controlled Trial 
PLoS Medicine  2010;7(9):e1000340.
In a cluster randomized trial, Kojo Yeboah-Antwi and colleagues find that integrated management of malaria and pneumonia in children under five by community health workers is both feasible and effective.
Background
Pneumonia and malaria, two of the leading causes of morbidity and mortality among children under five in Zambia, often have overlapping clinical manifestations. Zambia is piloting the use of artemether-lumefantrine (AL) by community health workers (CHWs) to treat uncomplicated malaria. Valid concerns about potential overuse of AL could be addressed by the use of malaria rapid diagnostics employed at the community level. Currently, CHWs in Zambia evaluate and treat children with suspected malaria in rural areas, but they refer children with suspected pneumonia to the nearest health facility. This study was designed to assess the effectiveness and feasibility of using CHWs to manage nonsevere pneumonia and uncomplicated malaria with the aid of rapid diagnostic tests (RDTs).
Methods and Findings
Community health posts staffed by CHWs were matched and randomly allocated to intervention and control arms. Children between the ages of 6 months and 5 years were managed according to the study protocol, as follows. Intervention CHWs performed RDTs, treated test-positive children with AL, and treated those with nonsevere pneumonia (increased respiratory rate) with amoxicillin. Control CHWs did not perform RDTs, treated all febrile children with AL, and referred those with signs of pneumonia to the health facility, as per Ministry of Health policy. The primary outcomes were the use of AL in children with fever and early and appropriate treatment with antibiotics for nonsevere pneumonia. A total of 3,125 children with fever and/or difficult/fast breathing were managed over a 12-month period. In the intervention arm, 27.5% (265/963) of children with fever received AL compared to 99.1% (2066/2084) of control children (risk ratio 0.23, 95% confidence interval 0.14–0.38). For children classified with nonsevere pneumonia, 68.2% (247/362) in the intervention arm and 13.3% (22/203) in the control arm received early and appropriate treatment (risk ratio 5.32, 95% confidence interval 2.19–8.94). There were two deaths in the intervention and one in the control arm.
Conclusions
The potential for CHWs to use RDTs, AL, and amoxicillin to manage both malaria and pneumonia at the community level is promising and might reduce overuse of AL, as well as provide early and appropriate treatment to children with nonsevere pneumonia.
Trial registration
ClinicalTrials.gov NCT00513500
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, about 11 million children die before their fifth birthday. Most of these deaths are in developing countries and most are due to a handful of causes—pneumonia (lung inflammation usually caused by an infection), malaria (a parasitic disease spread by mosquitoes), measles, diarrhea, and birth-related problems. In sub-Saharan Africa, pneumonia and malaria alone are responsible for nearly a third of deaths in young children. Both these diseases can be treated if caught early—pneumonia with antibiotics such as amoxicillin and malaria with artemisinin-based combination therapy (ACT), a treatment that contains several powerful antimalarial drugs. Unfortunately, parents in rural areas in sub-Saharan Africa rarely have easy access to health facilities and sick children are often treated at home by community health workers (CHWs, individuals with some medical training who provide basic health care to their communities), drug sellers, and traditional healers. This situation means that ongoing global efforts to reduce child mortality will require innovative community level interventions if they are to succeed.
Why Was This Study Done?
One community level intervention that the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) recently recommended is integrated management of malaria and pneumonia in countries where these diseases are major childhood killers. One such country is Zambia. In rural areas of Zambia, CHWs treat suspected cases of uncomplicated (mild) malaria with artemether-lumefantrine (AL, an ACT) or with sulfadoxine-pyrimethamine (a non-ACT antimalarial drug combination) and refer children with suspected pneumonia to the nearest health facility. However, because uncomplicated malaria and pneumonia both cause fever, many children are treated inappropriately. This misdiagnosis is worrying because giving antimalarial drugs to children with pneumonia delays their treatment with more appropriate drugs and increases the risk of drug-resistant malaria emerging. The use of rapid diagnostic tests (RDTs) for malaria might be one way to improve the treatment of malaria and pneumonia by CHWs in Zambia. Here, the researchers investigate the feasibility and effectiveness of this approach in a cluster randomized controlled trial, a study that compares the outcomes of groups (clusters) of patients randomly allocated to different interventions.
What Did the Researchers Do and Find?
The researchers randomly allocated 31 community health posts (fixed locations where CHWs provide medical services to several villages) to the study's intervention and control arms. CHWs in the intervention arm did RDTs for malaria on all the children under 5 years old who presented with fever and/or difficult or fast breathing (symptoms of pneumonia), treated test-positive children with AL, and treated those with nonsevere pneumonia (an increased breathing rate) with amoxicillin. CHWs in the control arm did not use RDTs but treated all children with fever with AL and referred those with signs of pneumonia to the nearest health facility. About 3,000 children with fever were treated during the 12-month study. 99.1% of the children in the control arm received AL compared with 27.5% of the children in the intervention arm, a 4-fold reduction in treatment for malaria. Importantly, the CHWs in the intervention arm adhered to treatment guidelines and did not give AL to children with negative RDT results. Of the children classified with nonsevere pneumonia, 13.3% of those in the control arm received early and appropriate treatment with amoxicillin compared to 68.2% of those in the intervention arm, a 5-fold increase in the timely treatment for pneumonia.
What Do These Findings Mean?
These findings indicate that CHWs in Zambia are capable of using RDTs, AL, and amoxicillin to manage malaria and pneumonia. They show that the intervention tested in this study has the potential to reduce the overuse of AL and to provide early and appropriate treatment for nonsevere pneumonia. Although this approach needs to be tested in other settings, these findings suggest that the use of CHWs might be a feasible and effective way to provide integrated management of pneumonia and malaria at the community level in developing countries. Importantly, these results also support the evaluation of the treatment by CHWs of other major childhood diseases and raise the possibility of saving the lives of many children in sub-Saharan Africa and other developing regions of the world through community level interventions.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000340.
WHO provides information on malaria, on rapid diagnostic tests for malaria, on artemisinin-combination therapy, and on global child mortality and efforts to reduce it (in several languages); WHO also provides a country health profile for Zambia
The US Centers for Disease Control and Prevention provide information on malaria (in English and Spanish)
Kidshealth, a resource maintained by the not-for-profit Nemours Foundation (a not-for-profit organization for children's health), provides information for parents on pneumonia (in English and Spanish)
MedlinePlus provides links to additional information on malaria and on pneumonia (in English and Spanish)
More information about the Zambia Integrated Management of Malaria and Pneumonia Study is available
doi:10.1371/journal.pmed.1000340
PMCID: PMC2943441  PMID: 20877714
23.  Readmissions after Hospitalization for Heart Failure, Acute Myocardial Infarction, or Pneumonia among Young and Middle-Aged Adults: A Retrospective Observational Cohort Study 
PLoS Medicine  2014;11(9):e1001737.
Isuru Ranasinghe and colleagues compare readmissions after hospitalization for heart failure, acute myocardial infarction, or pneumonia in adults aged 18 to 64 years with readmissions in those aged 65 and older.
Please see later in the article for the Editors' Summary
Background
Patients aged ≥65 years are vulnerable to readmissions due to a transient period of generalized risk after hospitalization. However, whether young and middle-aged adults share a similar risk pattern is uncertain. We compared the rate, timing, and readmission diagnoses following hospitalization for heart failure (HF), acute myocardial infarction (AMI), and pneumonia among patients aged 18–64 years with patients aged ≥65 years.
Methods and Findings
We used an all-payer administrative dataset from California consisting of all hospitalizations for HF (n = 206,141), AMI (n = 107,256), and pneumonia (n = 199,620) from 2007–2009. The primary outcomes were unplanned 30-day readmission rate, timing of readmission, and readmission diagnoses. Our findings show that the readmission rate among patients aged 18–64 years exceeded the readmission rate in patients aged ≥65 years in the HF cohort (23.4% vs. 22.0%, p<0.001), but was lower in the AMI (11.2% vs. 17.5%, p<0.001) and pneumonia (14.4% vs. 17.3%, p<0.001) cohorts. When adjusted for sex, race, comorbidities, and payer status, the 30-day readmission risk in patients aged 18–64 years was similar to patients ≥65 years in the HF (HR 0.99; 95%CI 0.97–1.02) and pneumonia (HR 0.97; 95%CI 0.94–1.01) cohorts and was marginally lower in the AMI cohort (HR 0.92; 95%CI 0.87–0.96). For all cohorts, the timing of readmission was similar; readmission risks were highest between days 2 and 5 and declined thereafter across all age groups. Diagnoses other than the index admission diagnosis accounted for a substantial proportion of readmissions among age groups <65 years; a non-cardiac diagnosis represented 39–44% of readmissions in the HF cohort and 37–45% of readmissions in the AMI cohort, while a non-pulmonary diagnosis represented 61–64% of patients in the pneumonia cohort.
Conclusion
When adjusted for differences in patient characteristics, young and middle-aged adults have 30-day readmission rates that are similar to elderly patients for HF, AMI, and pneumonia. A generalized risk after hospitalization is present regardless of age.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Many elderly people who are admitted to hospital, successfully treated, and discharged are readmitted soon after, often for an unrelated illness. In the US, for example, nearly a fifth of Medicare beneficiaries are readmitted to hospital within 30 days of discharge (Medicare is a national insurance program that primarily pays for health care services for Americans aged 65 and older). Experts have recently coined the term “post-hospital syndrome” for the transient period of increased susceptibility to a range of adverse health events that elderly patients seem to experience and have suggested that exposure to stress during hospital stays may underlie the syndrome. For example, hospital patients frequently have their sleep disrupted because of hospital routines, they are often in pain, they may have insufficient food intake (sometimes because they are waiting for an operation), and they may lose physical conditioning because they are confined to bed. These and other stressors can reduce individuals' natural reserves and increase their vulnerability to a range of illnesses and conditions.
Why Was This Study Done?
Although stress is one possible determinant of the post-hospital syndrome, the underlying causes and patterns of hospital readmission are generally poorly understood. In particular, it is not known whether the post-hospital syndrome affects young and middle-aged patients as well as elderly patients. Importantly, a better understanding of the post-hospital syndrome is needed before effective strategies to reduce hospital readmissions can be developed. In this retrospective observational cohort study, the researchers compare readmission rates, timing, and diagnoses after hospitalization for heart failure (HF), acute myocardial infarction (AMI; heart attack), and pneumonia among patients aged 18–64 years living in California with readmission rates, timing, and diagnoses among patients aged 65 years or older hospitalized for the same conditions. A retrospective observational cohort study analyzes data that has been already been collected for a group (cohort) of people. Readmission is common among people of all ages who are admitted to hospital for HF, AMI, and pneumonia, and readmissions after hospitalization for these conditions among elderly Medicare patients are used in the US as a measure of hospital quality; hospitals with high readmission rates are subject to a Medicare reimbursement penalty.
What Did the Researchers Do and Find?
The researchers used the Healthcare Cost and Utilization Project inpatient dataset for California to identify all the hospitalizations for HF, AMI, and pneumonia in California in 2007–2009 and to obtain data on the 30-day unplanned rehospitalization rate, timing of readmission, and readmission diagnoses for the identified patients (more than half a million patients). Nearly 30% of all hospital readmissions after hospitalization for HF, AMI, and pneumonia in California occurred among patients aged 18–64. After hospitalization for AMI, pneumonia, and HF, 11.2%, 14.4%, and 23.4%, respectively, of young and middle-aged patients were readmitted. Notably, the 30-day readmission rate among patients aged 18–64 admitted for HF exceeded the readmission rate among elderly patients admitted for the same condition. After allowing for other factors likely to affect the risk of readmission such as other illnesses, the 30-day readmission risk in patients aged 18–64 was similar to that in patients aged 65 years or older admitted for HF and pneumonia and only marginally lower among patients admitted for AMI. Finally, the timing of readmission was similar in both age groups and diagnoses other than the index admission diagnosis accounted for a substantial proportion of readmissions in both age groups.
What Do These Findings Mean?
This study shows that after adjusting for differences in patient characteristics, the 30-day hospital readmission rates among young and middle-aged patients after hospitalization for HF, AMI, and pneumonia were similar to those among elderly patients. Moreover, the timing of readmission and the reasons for readmission among young and middle-aged patients were similar to those among elderly patients. These findings may not apply to other US states or to other countries and may not reflect the pattern of hospital readmissions following conditions other than HF, AMI, and pneumonia. Nevertheless, these findings suggest that the post-hospital syndrome affects young and middle-aged as well as elderly patients. Hospital readmission should therefore be considered as a potential problem for people of all ages and broad-based, multidisciplinary strategies that target patients of all ages should be developed to mitigate the risk of hospital readmissions.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001737.
The Institute for Healthcare Improvement provides information about reducing avoidable hospital readmissions
Information about the US Centers for Medicare & Medicaid Services readmissions reduction program is available
An article written by one of the study authors about the post-hospital syndrome is available
doi:10.1371/journal.pmed.1001737
PMCID: PMC4181962  PMID: 25268126
24.  Silicosis due to Denim Sandblasting in Young People: MDCT Findings 
Objective:
Occupational lung disease due to silica dust is one of the most common work-related injuries. In denim sandblasting, workers are exposed to silica that may cause immediate mortality, especially in young people. The aim of this study was to assess the multidetector computed tomography (MDCT) findings of silicosis in denim sandblasters and to better define the role of MDCT in the early detection of silicosis.
Materials and Methods:
The study included 12 consecutive male patients who were admitted to a pulmonary outpatient clinic between April 2009 and December 2009. All patients had been working as sandblasters for at least one year. All patients underwent chest CT examinations for suspected silicosis. Two radiologists independently assessed the images for the presence and distribution of airspace consolidation, ground-glass opacity, nodules, interlobular septal thickening, parenchymal bands, fibrosis, masses, traction bronchiectasis, honeycombing, lobular low-attenuation areas, emphysema, pleural effusion or thickening, and mediastinal or hilar adenopathy.
Results:
MDCT detected parenchymal abnormalities in the lungs in eight (67%) of the twelve patients. The most common MDCT finding was ground glass opacity (58%). Other common findings were parencyhmal nodules and interlobular septal thickening, predominantly in the upper zones. Nodules were detected in six (50%) of the twelve patients. In four cases (67%), the nodules were numerous (>10), were predominantly smaller than 10 mm, and were centrilobular in distribution. In five (42%) of the 12 patients, interlobular septal thickening was detected. Only one (8%) patient presented with airspace consolidation; this was bilateral in the upper zones and associated with air bronchograms. In one (8%) patient there were several traction bronchiectases in the upper zones. None of the patients presented with pleural effusion, thickening, or honeycombing. Enlarged mediastinal nodes were identified in half of the patients, predominantly in the precarinal, paratracheal, and prevascular regions. No egg-shell calcification was detected. One (8%) patient presented with punctate calcification in the hilar region.
Conclusions:
Early detection of silicosis is important because it may cause immediate mortality, especially in young people. Enlarged mediastinal lymph nodes, centrilobular nodules, interlobular septal thickening, and patchy ground glass opacity may be early MDCT findings of silicosis. Thus, MDCT plays an important role in the early detection of silicosis in denim sandblasters.
doi:10.5152/eajm.2010.07
PMCID: PMC4261307  PMID: 25610113
Denim sandblaster; Multidedector computed tomography; Silicosis
25.  Tomographic findings of acute pulmonary toxoplasmosis in immunocompetent patients 
BMC Pulmonary Medicine  2014;14(1):185.
Background
Toxoplasmosis is one of the most common human zoonosis, and is generally benign in most of the individuals. Pulmonary involvement is common in immunocompromised subjects, but very rare in immunocompetents and there are scarce reports of tomographic findings in the literature. The aim of the study is to describe three immunocompetent patients diagnosed with acute pulmonary toxoplasmosis and their respective thoracic tomographic findings. Acute toxoplasmosis was diagnosed according to the results of serological tests suggestive of recent primary infection and the absence of an alternative etiology.
Case presentation
From 2009 to 2013, three patients were diagnosed with acute respiratory failure secondary to acute toxoplasmosis. The patients were two female and one male, and were 38, 56 and 36 years old. Similarly they presented a two-week febrile illness and progressive dyspnea before admission. Laboratory tests demonstrated lymphocytosis, slight changes in liver enzymes and high inflammatory markers. Tomographic findings were bilateral smooth septal and peribronchovascular thickening (100%), ground-glass opacities (100%), atelectasis (33%), random nodules (33%), lymph node enlargement (33%) and pleural effusion (66%). All the patients improved their symptoms after treatment, and complete resolution of tomographic findings were found in the followup.
Conclusion
These cases provide a unique description of the presentation and evolution of pulmonary tomographic manifestations of toxoplasmosis in immunocompetent patients. Toxoplasma pneumonia manifests with fever, dyspnea and a non-productive cough that may result in respiratory failure. In animal models, changes were described as interstitial pneumonitis with focal infiltrates of neutrophils that can finally evolve into a pattern of diffuse alveolar damage with focal necrosis. The tomographic findings are characterized as ground glass opacities, smooth septal and marked peribronchovascular thickening; and may mimic pulmonary congestion, lymphangitis, atypical pneumonia and pneumocystosis. This is the largest series of CT findings of acute toxoplasmosis in immunocompetent hosts, and the diagnosis should be considered as patients that present with acute respiratory failure in the context of a subacute febrile illness with bilateral and diffuse interstitial infiltrates with marked peribronchovascular thickening. If promptly treated, pulmonary toxoplasmosis can result in complete clinical and radiological recovery in immunocompetent hosts.
doi:10.1186/1471-2466-14-185
PMCID: PMC4254211  PMID: 25420956
Pulmonary toxoplasmosis; Chest; Toxoplasmosis

Results 1-25 (1208512)