Objective Since acute otitis media (AOM) is the most prevalent bacterial infection in young children, the reliable exclusion of AOM by nurses might save physicians' time for other duties. The study ...aim was to determine whether nurses without otoscopic experience can reliably use tympanometry or spectral gradient acoustic reflectometry (SG-AR) to exclude AOM.
Design Three nurses were trained, who performed examinations with tympanometry and SG-AR. Pneumatic otoscopy by the study physician served as the diagnostic standard.
Setting Study clinic at primary health care level.
Patients. 281 children 6-35 months of age.
Main outcome measures Predictive values (with 95% confidence interval) for tympanometry and SG-AR, and the clinical usefulness, i.e. the proportion of visits where nurses obtained the exclusive test result from both ears of the child.
Results At 459 visits, the negative predictive value of type A and C1 tympanograms (tympanometric peak pressure >-200 daPa) was 94% (91-97%). Based on type A and C1 tympanograms, the nurse could exclude AOM at 94/459 (20%) of visits. The negative predictive value of SG-AR level 1 result (>95°) was 94% (89-97%). Based on the SG-AR level 1 result, the nurse could exclude AOM at 36/459 (8%) of visits.
Conclusion Type A and C1 tympanograms and SG-AR level 1 results obtained by nurses are reliable test results in excluding AOM. However, the clinical usefulness of these test results is limited by their rarity. Type A and C1 tympanograms were obtained by nurses from both ears of the child only at one-fifth of the symptomatic visits.
Key Points
Acute otitis media (AOM) is the most prevalent bacterial infection in young children. Nurses' role in excluding AOM is unknown.
Type A and C1 tympanograms (tympanometric peak pressure >-200 daPa) obtained by nurses are reliable test results in excluding AOM.
With type A and C1 tympanograms, nurses could exclude AOM only at one-fifth of the symptomatic visits.
The clinical usefulness of the exclusion of AOM performed by nurses seems to be limited.
Objective. Scandinavian guidelines recommend controlling middle-ear effusion (MEE) after acute otitis media. The study aim was to determine whether nurses without otoscopic experience can reliably ...exclude MEE with tympanometry or spectral gradient acoustic reflectometry (SG-AR) at asymptomatic visits. Design. Three nurses were taught to perform examinations with tympanometry and SG-AR. Pneumatic otoscopy by the study physician served as the diagnostic standard. Setting. Study clinic at primary health care level. Patients. A total of 156 children aged 6-35 months. Main outcome measures. Predictive values (with 95% confidence interval) for tympanometry and SG-AR, and the clinical usefulness, i.e. the proportion of visits where nurses obtained the exclusive test result from both ears of the child. Results. At 196 visits, the negative predictive value of type A and C1 tympanograms (tympanometric peak pressure > −200 daPa) was 95% (91-97%). Based on type A and C1 tympanograms, the nurse could exclude MEE at 81/196 (41%) of visits. The negative predictive value of SG-AR level 1 result was 86% (79-91%). Based on SG-AR level 1 results, the nurse could exclude MEE at 29/196 (15%) of visits. Conclusion. Tympanograms with tympanometric peak pressure > −200 daPa (types A and C1) obtained by nurses are reliable test results in excluding MEE. However, these test results were obtained at less than half of the asymptomatic visits and, thus, the usefulness of excluding MEE by nurses depends on the clinical setting.
Rhinovirus is the most common virus causing respiratory tract illnesses in children. Rhinoviruses are classified into species A, B and C. We examined the associations between different rhinovirus ...species and respiratory illness severity.
This is a retrospective observational cohort study on confirmed rhinovirus infections in 134 children 3-23 months of age, who were enrolled in 2 prospective studies on bronchiolitis and acute otitis media, respectively, conducted simultaneously in Turku University Hospital, Turku, Finland, between September 2007 and December 2008.
Rhinovirus C is the most prevalent species in our study, and it was associated with severe wheezing and febrile illness. We also noted that history of atopic eczema was associated with wheezing.
Our understanding of rhinovirus C as the most pathogenic rhinovirus species was fortified. Existing research supports the idea that atopic characteristics are associated with the severity of the rhinovirus C-induced illness.
•Resistance to nitrofurantoin, fosfomycin and mecillinam was <10% for E. coli isolates.•Viable first-line treatments were not always available.•Trimethoprim and Trim/sulfa recommended as first-line ...despite high resistance.•Over-the-counter sales of furazidin could explain higher resistance to nitrofurantoin.•Russian patients had a higher risk of outpatient UTI caused by resistant E. coli.
In the Northern Dimension Antibiotic Resistance Study (NoDARS), Finland, Germany, Latvia, Poland, Russia and Sweden collected urine samples from outpatient women (aged 18–65years) with symptoms of uncomplicated urinary tract infection (UTI) to investigate the levels of antimicrobial resistance (AMR) among Escherichia coli isolates.
A total of 775 E. coli isolates from 1280 clinical urine samples were collected from October 2015 to January 2017. Antimicrobial susceptibility testing was performed and the results were interpreted according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria.
Overall AMR rates to the commonly used antibiotics nitrofurantoin, fosfomycin and mecillinam (except for Germany that was missing a result for mecillinam) were 1.2%, 1.3% and 4.1%, respectively. The highest overall resistance rates were determined for ampicillin (39.6%), trimethoprim (23.8%), trimethoprim/sulfamethoxazole (22.4%), amoxicillin/clavulanic acid (16.7%) and ciprofloxacin (15.1%), varying significantly between countries. The rate of extended-spectrum β-lactamase (ESBL) production was 8.7%. None of the isolates showed resistance to meropenem.
In most cases, low AMR rates were detected against the first-line antibiotics recommended in national UTI treatment guidelines, giving support to their future use. These results also support the European Association of Urology guidelines stating that nitrofurantoin, fosfomycin and mecillinam are viable treatment options for uncomplicated UTI.
Bone marrow mononuclear cells (BMMCs) have been evaluated for their ability to improve cardiac repair and benefit patients with severe ischemic heart disease and heart failure. In our single-center ...trial in 2006-2011 we demonstrated the safety and efficacy of BMMCs injected intramyocardially in conjunction with coronary artery bypass surgery. The effect persisted in the follow-up study 5 years later. In this study, we investigated the efficacy of BMMC therapy beyond 10 years. A total of 18 patients (46%) died during over 10-years follow-up and 21 were contacted for participation. Late gadolinium enhancement cardiac magnetic resonance imaging (CMRI) and clinical evaluation were performed on 14 patients, seven from each group. CMRIs from the study baseline, 1-year and 5-years follow-ups were re-analyzed to enable comparison. The CMRI demonstrated a 2.1-fold larger reduction in the mass of late gadolinium enhancement values between the preoperative and the over 10-years follow-up, suggesting less scar or fibrosis after BMMC treatment (- 15.1%; 95% CI - 23 to - 6.7% vs. - 7.3%; 95% CI - 16 to 4.5%, p = 0.039), compared to placebo. No differences in mortality or morbidity were observed. Intramyocardially injected BMMCs may exert long-term benefits in patients with ischemic heart failure. This deserves further evaluation in patients who have received BMMCs in international clinical studies over two decades.
ABSTRACT
Purpose
Drug delivery to the brain is impeded by the blood-brain barrier (BBB). Here, we attempted to enhance the brain uptake of cationic dopamine by utilizing the large amino acid ...transporter 1 (LAT1) at the BBB by prodrug approach.
Methods
Three amino acid prodrugs of dopamine were synthesized and their prodrug properties were examined
in vitro
. Their LAT1-binding and BBB-permeation were studied using the
in situ
rat brain perfusion technique. The brain uptake after intravenous administration and the dopamine-releasing ability in the rat striatum after intraperitoneal administration were also determined for the most promising prodrug.
Results
All prodrugs underwent adequate cleavage in rat tissue homogenates. The prodrug with phenylalanine derivative as the promoiety had both higher affinity for LAT1 and better brain uptake properties than those with an alkyl amino acid -mimicking promoiety. The phenylalanine prodrug was taken up into the brain after intravenous injection but after intraperitoneal injection the prodrug did not elevate striatal dopamine concentrations above those achieved by corresponding
L
-dopa treatment.
Conclusions
These results indicate that attachment of phenylalanine to a cationic drug via an amide bond from the meta-position of its aromatic ring could be highly applicable in prodrug design for LAT1-mediated CNS-delivery of not only anionic but also cationic polar drugs.
Mitochondria are eukaryotic organelles supporting individual life-style via generation of proton motive force and cellular energy, and indispensable metabolic pathways. As part of genome sequencing ...of the white rot Basidiomycota species Phlebia radiata, we first assembled its mitochondrial genome (mtDNA). So far, the 156 348 bp mtDNA is the second largest described for fungi, and of considerable size among eukaryotes. The P. radiata mtDNA assembled as single circular dsDNA molecule containing genes for the large and small ribosomal RNAs, 28 transfer RNAs, and over 100 open reading frames encoding the 14 fungal conserved protein subunits of the mitochondrial complexes I, III, IV, and V. Two genes (atp6 and tRNA-IleGAU) were duplicated within 6.1 kbp inverted region, which is a unique feature of the genome. The large mtDNA size, however, is explained by the dominance of intronic and intergenic regions (sum 80% of mtDNA sequence). The intergenic DNA stretches harness short (≤ 200 nt) repetitive, dispersed and overlapping sequence elements in abundance. Long self-splicing introns of types I and II interrupt eleven of the conserved genes (cox1,2,3; cob; nad1,2,4,4L,5; rnl; rns). The introns embrace a total of 57 homing endonucleases with LAGLIDADGD and GYI-YIG core motifs, which makes P. radiata mtDNA to one of the largest known reservoirs of intron-homing endonucleases. The inverted duplication, intergenic stretches, and intronic features are indications of dynamics and genetic flexibility of the mtDNA, not fully recognized to this extent in fungal mitochondrial genomes previously, thus giving new insights for the evolution of organelle genomes in eukaryotes.
Uncertainties in the organization, external environment and from single projects may hamper project portfolio performance unless managed properly. This paper introduces a framework on uncertainties ...and their management in project portfolios and pursues increased understanding on how managers can take uncertainty into account better. We explore uncertainties, how managers frame them as opportunities or threats, and the actual practice of managing them across ten R&D project portfolios. The framework on project portfolio uncertainties and their management is further refined based on the empirical results. As key contributions, we show evidence on the balanced existence of three types of uncertainties, the threat bias in their framing, and the dominance of rational, opportunity driven mechanisms of control in uncertainty management. We discuss the context-dependent practice of project portfolio management and the need to complement rational mechanisms with structural and cultural, for project portfolio management to become a dynamic capability.
•Organizational complexity, environment and projects cause portfolio uncertainty.•Managers frame portfolio uncertainties into opportunities, threats and neutral.•Uncertainties can be managed using rational, structural and cultural mechanisms.•Managers perceive portfolio uncertainties more often as threats than opportunities.•The use of rational control mechanisms dominates in uncertainty management.
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