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

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)

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

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

Supplementary_appendix - Analysis of Rothman Index Data to Predict Postdischarge Adverse Events in a Medical Intensive Care Unit

<p>Supplementary_appendix for Analysis of Rothman Index Data to Predict Postdischarge Adverse Events in a Medical Intensive Care Unit by Deepa Bangalore Gotur, Faisal Masud, Jaya Paranilam, and Janice L. Zimmerman in Journal of Intensive Care Medicine</p

Women in Intensive Care study: a preliminary assessment of international data on female representation in the ICU physician workforce, leadership and academic positions

Abstract Background Despite increasing female enrolment into medical schools, persistent gender gaps exist in the physician workforce. There are limited published data on female representation in the critical care medicine workforce. Methods To obtain a global perspective, societies (n = 84; 79,834 members (40,363 physicians, 39,471 non-physicians)) registered with the World Federation of Societies of Intensive and Critical Care Medicine were surveyed. Longitudinal data on female trainee and specialist positions between 2006-2017 were obtained from Australia and New Zealand. Data regarding leadership and academic faculty representation were also collected from national training bodies and other organisations of critical care medicine. Results Of the 84 societies, 23 had a registered membership of greater than 500 members. Responses were received from 27 societies (n = 55,996), mainly high-income countries, covering 70.1% of the membership. Amongst the physician workforce, the gender distribution was available from six (22%) participating societies—mean proportion of females 37 ± 11% (range 26–50%). Longitudinal data from Australia and New Zealand between 2006 and 2017 demonstrate rising proportions of female trainees and specialists. Female trainee and specialist numbers increased from 26 to 37% and from 13 to 22% respectively. Globally, female representation in leadership positions was presidencies of critical care organisations (0–41%), representation on critical care medicine boards and councils (8–50%) and faculty representation at symposia (7–34%). Significant gaps in knowledge exist: data from low and middle-income countries, the age distribution and the time taken to enter and complete training. Conclusions Despite limited information globally, available data suggest that females are under-represented in training programmes, specialist positions, academic faculty and leadership roles in intensive care. There are significant gaps in data on female participation in the critical care workforce. Further data from intensive care organisations worldwide are required to understand the demographics, challenges and barriers to their professional progress