Safety concerns have been raised regarding the regular use of long-acting beta(2)-adrenergic agonists (LABAs) alone or with inhaled corticosteroids (ICSs). The purpose of this study was to examine ...the long-term safety of budesonide/formoterol pressurized metered-dose inhaler (pMDI). This 52-week, double-blind study (SD-039-0728; n=708) included patients >or=12 years of age with moderate to severe persistent asthma previously receiving ICSs. After 2 weeks on budesonide pMDI 320 microg twice daily (b.i.d.), patients were randomized 3:1:1 overall to budesonide/formoterol pMDI 640/18 microg b.i.d., budesonide/formoterol pMDI 320/9 microg b.i.d., or budesonide pMDI 640 microg b.i.d. The incidence of adverse events (AEs) was similar across the groups. Drug-related AEs (>or=2% overall) were oral candidiasis, tremor, and pharyngolaryngeal pain. No clinically meaningful differences in laboratory, electrocardiogram, or Holter monitor variables were observed. The percentage of patients with >or=1 asthma exacerbation was significantly lower (p=0.006) with budesonide/formoterol 640/18 (12.2%) and numerically lower with budesonide/formoterol 320/9 (14.4%) versus budesonide (21.8%). The number of asthma exacerbations per patient-treatment year was lower with budesonide/formoterol 640/18 (0.174; p=0.004) and budesonide/formoterol 320/9 (0.185; p=0.049) versus budesonide (0.315). Improvements in forced expiratory volume in 1 second and diary variables were significantly greater (p<0.001) with both budesonide/formoterol doses versus budesonide. Budesonide/formoterol 640/18 and 320/9 microg b.i.d. showed an acceptable safety profile relative to budesonide, with no significant or unexpected patterns of abnormalities observed by adding a LABA to budesonide for up to 1 year in this patient population. Improvements in asthma control were shown with both doses of budesonide/formoterol versus budesonide.
COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. ...PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to inhibit coronavirus family 3CL protease activity with selectivity over human host protease targets. Furthermore, we show that PF-00835231 has additive/synergistic activity in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of PF-07304814 as a potential COVID-19 treatment.
Diameter, height, crown shape and crown area were measured on 23-42 trees ranging in size from saplings to large adults for each of eight common dicotyledonous tree species in a neotropical forest on ...Barro Colorado Island, Panama.
Background. The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of ...causality of pneumonia, we compared viral load in the URT of children with World Health Organization–defined severe and very severe pneumonia and age-matched community controls. Methods. In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted. Results. The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of <0.80 for all viruses, suggesting poor to fair discrimination between cases and controls. Fatal and very severe pneumonia cases did not have higher viral load than less severe cases for most viruses. Conclusions. Although we found higher viral loads among pneumonia cases than controls for some viruses, the utility in using viral load of URT specimens to define viral pneumonia was equivocal. Our analysis was limited by lack of a gold standard for viral pneumonia.
Management of Crohn's disease in adults Lichtenstein, Gary R; Hanauer, Stephen B; Sandborn, William J
The American journal of gastroenterology,
02/2009, Letnik:
104, Številka:
2
Journal Article
Recenzirano
Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research, derived ...from extensive review of published literature. When data that will withstand objective scrutiny are not available, a recommendation may be made based on a consensus of experts. Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty. Guidelines are intended to be flexible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are inflexible and rarely violated. Given the wide range of choices in any health-care problem, the physician should select the course best suited to the individual patient and the clinical situation presented. These guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee. Expert opinion is solicited from the outset for the document. The quality of evidence upon which a specific recommendation is based is as follows: Grade A: Homogeneous evidence from multiple well-designed randomized (therapeutic) or cohort (descriptive) controlled trials, each involving a number of participants to be of sufficient statistical power. Grade B: Evidence from at least one large well-designed clinical trial with or without randomization, from cohort or case-control analytic studies, or well-designed meta-analysis. Grade C: Evidence based on clinical experience, descriptive studies, or reports of expert committees. The Committee reviews guidelines in depth, with participation from experienced clinicians and others in related fields. The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments at a later time.
ECG Interpretation Proficiency of Healthcare Professionals Kashou, Anthony H.; Noseworthy, Peter A.; Beckman, Thomas J. ...
Current problems in cardiology,
October 2023, 2023-Oct, 2023-10-00, 20231001, Letnik:
48, Številka:
10
Journal Article
Recenzirano
ECG interpretation is essential in modern medicine, yet achieving and maintaining competency can be challenging for healthcare professionals. Quantifying proficiency gaps can inform educational ...interventions for addressing these challenges. Medical professionals from diverse disciplines and training levels interpreted 30 12-lead ECGs with common urgent and nonurgent findings. Average accuracy (percentage of correctly identified findings), interpretation time per ECG, and self-reported confidence (rated on a scale of 0 not confident, 1 somewhat confident, or 2 confident) were evaluated. Among the 1206 participants, there were 72 (6%) primary care physicians (PCPs), 146 (12%) cardiology fellows-in-training (FITs), 353 (29%) resident physicians, 182 (15%) medical students, 84 (7%) advanced practice providers (APPs), 120 (10%) nurses, and 249 (21%) allied health professionals (AHPs). Overall, participants achieved an average overall accuracy of 56.4% ± 17.2%, interpretation time of 142 ± 67 seconds, and confidence of 0.83 ± 0.53. Cardiology FITs demonstrated superior performance across all metrics. PCPs had a higher accuracy compared to nurses and APPs (58.1% vs 46.8% and 50.6%; P < 0.01), but a lower accuracy than resident physicians (58.1% vs 59.7%; P < 0.01). AHPs outperformed nurses and APPs in every metric and showed comparable performance to resident physicians and PCPs. Our findings highlight significant gaps in the ECG interpretation proficiency among healthcare professionals.
Since
Escherichia coli O157:H7 first emerged as a food borne pathogen in the mid 1980s, it has been linked to many cases of food poisoning across the world. While multiple sources and routes of ...transmission for this pathogen are now recognised, beef and beef products remain an important vehicle of the pathogen and continue to be linked to outbreaks across the developed world. Much research has been directed at
E. coli O157:H7 transmission, survival and control in the beef chain and this paper presents an overview of current knowledge on this pathogen in the beef chain from primary production through slaughter, processing, distribution, final preparation and cooking. In order to strategically manage
E. coli O157:H7 and to devise approaches to reduce the public health risk posed, many national and international groups have applied quantitative risk assessment techniques to model the risk posed by
E. coli O157:H7 in beef, particularly in ground/minced beef which is most often linked with infection. This paper reviews these quantitative risk assessments and their application in managing the risk posed by
E. coli O157:H7 in beef.
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