RESUMO
To provide comprehensive information on the epidemiology and burden of respiratory syncytial virus hospitalisation (RSVH) in preterm infants, a pooled analysis was undertaken of seven multicentre, prospective, observational studies from across the Northern Hemisphere (2000-2014). Data from all 320-356 weeks' gestational age (wGA) infants without comorbidity were analysed. RSVH occurred in 534/14 504 (3.7%) infants; equating to a rate of 5.65 per 100 patient-seasons, with the rate in individual wGA groups dependent upon exposure time (P = 0.032). Most RSVHs (60.1%) occurred in December-January. Median age at RSVH was 88 days (interquartile range (IQR): 54-159). Respiratory support was required by 82.0% of infants: oxygen in 70.4% (median 4 (IQR: 2-6) days); non-invasive ventilation in 19.3% (median 3 (IQR: 2-5) days); and mechanical ventilation in 10.2% (median 5 (IQR: 3-7) days). Intensive care unit admission was required by 17.9% of infants (median 6 days (IQR: 2-8) days). Median overall hospital length of stay (LOS) was 5 (IQR: 3-8) days. Hospital resource use was similar across wGA groups except for overall LOS, which was shortest in those born 35 wGA (median 3 vs. 4-6 days for 32-34 wGA; P < 0.001). Strategies to reduce the burden of RSVH in otherwise healthy 32-35 wGA infants are indicated.
Assuntos
Hospitalização/estatística & dados numéricos , Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sincicial Respiratório Humano , Antivirais/uso terapêutico , Estudos de Coortes , Idade Gestacional , Humanos , Lactente , Tempo de Internação , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/terapiaRESUMO
RATIONALE: New methods to enhance the electrospray ionization (ESI) signals are essential for low-level analysis of oligonucleotides. We report a systematic evaluation comparing 13 ion-pairing agents with and without hexafluoroisopropanol to understand their effect on the ion abundance of hetero-oligonucleotides. METHODS: A Waters Synapt G2 HDMS quadrupole time-of-flight instrument was used to compare oligonucleotide signal intensity with 13 alkylamine ion-pairing agents at varying concentrations. The alkylamines that yielded the highest signal intensity were further evaluated with hexafluoroisopropanol at concentrations between 5 and 100 mM. The chemical properties of the solution components and analytes were evaluated to identify key factors in predicting optimal mobile phase conditions for different classes of oligonucleotides. RESULTS: We identified a series of optimized mobile phase systems using diisopropylamine, tripropylamine, dimethylbutylamine, methyldibutylamine, and dimethylhexylamine along with 25 to 50 mM hexafluoroisopropanol that yielded significantly higher MS signal intensity for both siRNA and DNA compared with the traditionally used triethlyamine/hexafluoroisopropanol system. We explored charge state reduction, adduct formation and ESI mechanisms and identify the Henry's Law constant k aq/g as a key chemical property in predicting alkylamines that will increase oligonucleotide ion intensity. We also find that the hydrophobicity of the oligonucleotide plays a major role in choosing ion-pairing agents that will increase ion abundance. CONCLUSIONS: This comprehensive and systematic optimization finds that the hydrophobicity of the oligonucleotide was a key factor in choosing alkylamine ion-pairing agents to increase ESI abundance. We identified that diisopropylamine and tripropylamine combined with lower concentrations of hexafluoroisopropanol yielded the highest signal intensity for these oligonucleotides.
Assuntos
DNA/química , Oligonucleotídeos/química , RNA Interferente Pequeno/química , Espectrometria de Massas por Ionização por Electrospray/instrumentação , Propanóis/química , Espectrometria de Massas por Ionização por Electrospray/métodosAssuntos
Glândulas Suprarrenais/fisiologia , Tonsila do Cerebelo/fisiologia , Comportamento Animal , Ventrículos Cerebrais/fisiologia , Sistema Límbico/fisiologia , Hipófise/fisiologia , Testículo/fisiologia , Adrenalectomia , Agressão , Animais , Castração , Comportamento Exploratório , Humanos , Hipofisectomia , Masculino , RatosRESUMO
This paper examines the role of market research in the decision process used to invest in continuing care retirement centers (CCRCs). Given changing demographics and the availability of financing, there has been a rapid increase in the number of CCRCs that are being developed. However, a large number of these centers have either failed or are experiencing financial difficulty. Some industry participants have blamed poor or inadequate market research as a factor contributing to the failure of many centers to meet expectations. This paper discusses how the process used to invest in centers and how the motivations of the different actors in the investment decision can influence the role and use of market research. Recommendations are suggested for how industry investors can better understand and use market research in the decision to invest in a retirement center.