The role of intrinsic efficacy in determining response to a β2-agonist in acute severe asthma

SummaryBackgroundCurrent guidelines recommend repeated doses of albuterol for the emergency treatment of acute asthma. However, approximately one-third of patients show little or no initial response to this partial β2-agonist.MethodsWe conducted a randomized, double-blind, proof-of-concept study to investigate whether a full β2-agonist, isoproterenol, offers a therapeutic advantage in adults presenting with acute severe asthma (FEV1<50%) who fail to respond to an initial treatment of the partial β2-agonist, albuterol. Study subjects were randomized to receive a 2-h continuous nebulization of either albuterol (7.5mg/h) (n=10, mean FEV1=37% predicted) or isoproterenol (7.5mg/h) (n=9, mean FEV1=33% predicted). Respiratory symptoms, vital signs and pulmonary function measures were collected.ResultsSubjects from both treatment groups had similar baseline characteristics. The percent improvements from baseline FEV1 at 60 and 120min were significantly higher in subjects receiving isoproterenol than those receiving albuterol (44 vs. 17% and 63 vs. 24%, respectively, P<0.05). The change in symptoms measured by the modified Borg score was also significantly greater in subjects receiving isoproterenol (P<0.01). Both treatments were well tolerated, though the mean increase in pulse rate at 60 and 120min (21 vs. 1 and 23 vs. 6beats/min, respectively, P<0.05) and the mean change in serum potassium at 120min (−0.52 vs. −0.07meq/L, P<0.05) from baseline were significantly greater in the isoproterenol group.ConclusionsOur data suggest that in subjects presenting with acute severe asthma who fail to show an initial response to albuterol, the use of a β2-agonist of higher intrinsic efficacy can be more effective in improving lung function and symptoms

Barriers and facilitators to COVID-19 vaccine uptake among Australian health professional students during the pandemic: a nationwide study

Using a cross-sectional online survey we investigated knowledge, attitudes, and risk perception about COVID-19 vaccination and identified factors influencing vaccine uptake among Australian health professional students from October 2021 to January 2022. We analysed data from 1114 health professional students from 17 Australian universities. Most participants were enrolled in nursing programs (n = 958, 86.8%), and 91.6% (n = 858) of the participants received COVID-19 vaccination. Approximately 27% believed COVID-19 was no more serious than seasonal influenza and that they had a low risk of acquiring COVID-19. Nearly 20% disagreed that COVID-19 vaccines in Australia were safe and perceived they were at higher-risk of acquiring COVID infection than the general population. Higher-risk perception viewing vaccination as their professional responsibility, and vaccine mandate strongly predicted vaccination behaviour. Participants consider COVID-19 information from health professionals, government websites, and World Health Organization as the most trusted information sources. The findings highlight that healthcare decision-makers and university administrators need to monitor students’ hesitancy with vaccination to improve students’ promotion of the vaccination to the general population

Triphasic waveforms are superior to biphasic waveforms for transthoracic defibrillation Experimental studies

AbstractObjectivesOur objective was to evaluate the efficacy of triphasic waveforms for transthoracic defibrillation in a swine model.BackgroundTriphasic shocks have been found to cause less post-shock dysfunction than biphasic shocks in chick embryo studies.MethodsAfter 30 s of electrically induced ventricular fibrillation (VF), each pig in part I (n = 32) received truncated exponential biphasic (7.2/7.2 ms) and triphasic (4.8/4.8/4.8 ms) transthoracic shocks. Each pig in part II (n = 14) received biphasic (5/5 ms) and triphasic shocks (5/5/5 ms). Three selected energy levels (50, 100, and 150 J) were tested for parts I and II. Pigs in part III (n = 13) received biphasic (5/5 ms) and triphasic (5/5/5 ms) shocks at a higher energy (200 and 300 J). Although the individual pulse durations of these shocks were equal, the energy of each pulse varied. Nine pigs in part I also received shocks where each individual pulse contained equal energy but was of a different duration (biphasic 3.3/11.1 ms; triphasic 2.0/3.2/9.2 ms).ResultsTriphasic shocks of equal duration pulses achieved higher success than biphasic shocks at delivered low energies: <40 J: 38 ± 5% triphasic vs. 19 ± 4% biphasic (p < 0.01); 40 to <50 J: 66 ± 7% vs. 42 ± 7% (p < 0.01); and 50 to <65 J: 78 ± 4% vs. 54 ± 5% (p < 0.05). Shocks of equal energy but different duration pulses achieved relatively poor success for both triphasic and biphasic waveforms. Shock-induced ventricular tachycardia (VT) and asystole occurred less often after triphasic shocks.ConclusionsTriphasic transthoracic shocks composed of equal duration pulses were superior to biphasic shocks for VF termination at low energies and caused less VT and asystole

Research-Based Web Design & Usability Guidelines [2006 edition]

The new edition of the U.S. Department of Health and Human Services’ (HHS) Research-Based Web Design and Usability Guidelines. These guidelines reflect HHS’ commitment to identifying innovative, research-based approaches that result in highly responsive and easy-to-use Web sites for the public. These guidelines help move us in that direction by providing practical, yet authoritative, guidance on a broad range of Web design and communication issues. Having access to the best available research helps to ensure we make the right decisions the first time around and reduces the possibility of errors and costly mistakes

Differentiated thyroid carcinoma in children and adolescents

From 1936 to 1990, 89 children and adolescents (72 girls and 17 boys) were treated for differentiated thyroid carcinoma at the University of Michigan Medical Center; 58 of these patients were first reported in 1971. Thirty (34%) patients had previously received external irradiation to the head and neck, although only 1 (3%) patient of the last 33 patients seen had this history. Patients first presenting from 1971 to 1990 had less advanced disease than those seen earlier. Also, during this time period, the rate of initial palpable cervical adenopathy fell from 63% to 36%, local infiltration of primary cancer from 31% to 6%, and initial pulmonary metastases from 19% to 6%. The incidence of cervical nodal metastases has remained 88% for 54 years. Papillary or the follicular variant of papillary carcinoma was found in 93% of all patients. Seventy-nine (89%) patients had total or completion total thyroidectomy. Surgical management of lymphatic metastases varied from regional excision of nodes to radical neck dissection. The overall rate of permanent accidental recurrent laryngeal nerve palsy and hypoparathyroidism was 4.5%, although neither has occurred in a child or adolescent undergoing surgery at the center in the past 25 years. The most recent 33 patients had a low rate of local/regional persistence or recurrence. Cervical nodal persistence occurred in 21%; there were no thyroid recurrences. Eighty-two percent of patients received 131 I. The long-term mortality rate was 2.2%. We continue to advocate total thyroidectomy, cervical lymph node dissection, and postoperative 131 I therapy as the most conservative treatment regimen for children with differentiated thyroid carcinoma. Entre 1936 et 1990, 89 enfants et adolescents (72 filles et 17 garons) ont été traités pour cancer différencie de la thyroïde au Centre Médical de l'Université de Michigan. Cinquante huit d'entre eux ont fait l'objet d'une publication en 1971. Trente de ces patients (34%) avaient eu une radiothérapie externe au niveau de la tête et/ou du cou, mais ce facteur n'a été retrouvé que chez un des 33 derniers patients (3%). Les patients vus entre 1971 et 1990 avaient une maladie moins avancée. Pendant cette période, le taux d'adénopathies cervicales palpables est passée de 63 à 36%; le pourcentage de patients ayant une infiltration locale, de 31 à 6%, et celui de métastases pulmonaires de 19 à 6%. L'incidence des métastases ganglionnaires cervicales, par contre, est restée de 88% depuis 54 ans. Le cancer était papillaire ou folliculaire dans 93% des cas. Soixante-neuf patients (89%) ont eu une thyroïdectomie totale, soit d'embl%ee soit secondairement. La thérapeutique des métastases ganglionnaires a varié depuis l'exérèse régionale et le curage ganglionnaire cervical. Le taux global de paralysie récurrentielle et de l'hypoparathyroïde était de 4.5%, mais aucune de ces deux complications n'a été observée pour les enfants opérés dans notre centre au cours des 25 dernières années. Parmi les 33 derniers patients, le taux de tissu résiduel ou de récidive était bas. Dans 21% des cas, il persistait du tissu néoplasique après chirurgie, sans récidive. Quatre-vingt pour cent de ces patients ont eu un traitement par l'iode 131. La mortalité à distance était de 2.2%. Nous continuous de recommander une thyroïdectomie totale, une lymphadénectomie cervicale et une iodothérapie post-opératoire par l'iode 131 comme le traitement les plus conservateurs du cancer différencié de la thyroïde chez l'enfant. Ochenta y nueve niños y adolescentes (72 de sexo femenino y 17 de sexo masculino) fuiron tratados por carcinoma tiroideo diferenciado en el Centro Médico de la Universidad de Michigan; 58 de estos pacientes fueron reportados por primera vez en 1971. Treinta pacientes (34%) tenían historia de irradiación a la cabeza y el cuello; sin embargo, solamente uno de los últimos 33 (3%) presentó tal historia. Los pacientes vistos entre 1971 y 1990 exhibían enfermedad menos avanzada que aquellos vistos previamente. Así mismo, la incidencia de adenopatías cervicales palpables descendió de 63% a 36%, la de infiltración local por cáncer primario de 31% a 6% y la de metástasis pulmonares iniciales de 19% a 6%. La incidencia de metástasis ganglionares cervicales se ha mantenido en 88% por 54 años. La variante papilar o folicular del carcinoma papilar se encontró en 93% de los pacientes de la serie. Setenta y nueve pacientes (89%) fueron sometidos a toroidectomía total o a reoperación para completar la tiroidectomía total. El manejo quirúrgico de las metástasis linfáticas varió desde la resección regional de los ganglios hasta la disección radical del cuello. La tasa global de lesión accidental, permanente o temporal, del nervio recurrente laríngeo y de hopoparatiroidismo fue 4.5%, aunque ninguna de estas complicaciones ha ocurrido en un niño o en un adolescente sometido a cirugía en nuestro centro médico en los últimos 25 años. Los últimos 33 pacientes exhibieron una tasa reducida de persistencia o de recurrencia local/regional. La persistencia ganglionar cervical se presentó en 21% de los casos; no hubo recurrencias tiroideas. Ochenta y dos por ciento de los pacientes recibió 131 I. La tassa de mortalidad a largo plazo fui 2.2%. Nuestro grupo continúa preconizando tiroidectomía total, disección ganglionar cervical y terapia postoperatoria con 131 I como la modalidad terapéutica más conservadora en carcinoma diferenciado de la glándula tiroidea en la niñez.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41290/1/268_2005_Article_BF02067317.pd

Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication.

RationaleWe recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest.ObjectivesWe now validate a clinical test for urinary [TIMP-2]·[IGFBP7] at a high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse population of critically ill patients.MethodsWe conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary [TIMP-2]·[IGFBP7] to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were masked to the results of the test.Measurements and main resultsUrinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. The primary endpoint was reached in 17% of patients. For a single urinary [TIMP-2]·[IGFBP7] test, sensitivity at the prespecified high-sensitivity cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval [CI], 85-98%) with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill patients with urinary [TIMP-2]·[IGFBP7] greater than 0.3 had seven times the risk for AKI (95% CI, 4-22) compared with critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary [TIMP-2]·[IGFBP7] remained statistically significant and a strong predictor of AKI (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs. area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus [TIMP-2]·[IGFBP7]).ConclusionsUrinary [TIMP-2]·[IGFBP7] greater than 0.3 (ng/ml)(2)/1,000 identifies patients at risk for imminent AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 01573962)

Simultaneous determination of trimethoprim and sulfamethoxazole in dried plasma and urine spots

Trimethoprim-sulfamethoxazole (TMP-SMX) is an antimicrobial drug combination commonly prescribed in children and adults. The study objectives were to validate and apply an HPLC–MS/MS method to quantify TMP-SMX in dried plasma spots (DPS) and dried urine spots (DUS), and perform a comparability analysis with liquid matrices

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

SCOPUS: ar.jinfo:eu-repo/semantics/publishe