Ipratropium bromide in acute asthma: small beneficial effects?
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Publications and source records attributed to C Rodrigo.
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OBJECTIVE: To review the literature to determine the benefits of corticosteroids (CCSs) (oral, IM, IV, or inhaled) in the treatment of adult patients with acute asthma presenting at an acute-care setting. SEARCH STRATEGY: A MEDLINE search was conducted using the following terms: (1) Asthma OR Wheez, AND (2) Glucocorticoids OR Steroids, AND (3) Acute OR Emerg. Other sources were the CURRENT CONTENTS database, review articles, reference sections of located studies, and a manual search of the top 15 journals for respiratory and emergency medicine. SELECTION CRITERIA: Patients were selected for the study by the following criteria: (1) English language; (2) adult patients with asthma whose acute exacerbations were the primary reason for assessment; (3) involvement in randomized, controlled trials conducted in an emergency care setting; (4) patients had participated in a study investigating a primary research question involving treatment with CCSs; and (5) outcomes based on results of pulmonary function tests and on hospital admission rates. RESULTS: At the 3-h assessment, only high doses of inhaled CCSs significantly improved pulmonary function compared with placebo (effect size [ES], 0.56; 95% confidence interval [CI], 0.15 to 0.97). On the other hand, after receiving IV CCSs, patients required at least 6 to 24 h to show moderate but nonsignificant improvements of pulmonary function (6-h ES, 0.44 [95% CI, -0.01 to 0.89]; 12-h ES, 0.54 [95% CI, -0.08 to 1.17]; and 24-h ES, 0.53 [95% CI, -0.39 to 1.45]). The data from the six studies that we used to pool information on admission rate outcome showed a 32% reduction in favor of the use of IV CCSs (relative risk [RR], 0.68 [95% CI, 0.47 to 0.99]; number needed to treat, 12.5 [95% CI, 7.1 to 50]). However, the pooled effect of the three high-quality studies showed no difference between groups (RR, 1.21; 95% CI, 0.67 to 2.18). Oral CCSs provided a similarly beneficial effect on pulmonary function when compared with parenteral administration (ES, -0.14; 95% CI, -0.82 to 0.31. Finally, the results showed a nonsignificant favorable trend toward improved outcome with medium or high doses of CCSs. CONCLUSIONS: This evidence-based evaluation suggests that the administration of parenteral CCSs to the patient on arrival at the emergency department (ED) neither improves airflow obstruction nor reduces the need for hospitalization. Parenteral CCSs probably require >6 to 24 h to begin to act. Comprehensible conclusions about admission rates in the ED setting are difficult to make. At the 3-h assessment, only high doses of inhaled CCSs (in one study) significantly improved pulmonary function compared with placebo. IV and oral CCSs appear to have equivalent effects, and there is a tendency toward improvement in pulmonary function with medium or high doses.
A systematic study of the inactivation kinetics of Bacillus stearothermophilus spores was carried out in nonisothermic heating conditions using a linear temperature increase program and analyzing the experimental data by means of a one-step nonlinear regression. The D and z values estimated are close to those obtained in isothermic conditions and estimated by using a two-step model, first D values are calculated, and then in the second step a z value is deduced (D(121 degrees C) = 3.08 and 4.38 min, respectively, and z = 7 and 7.9 degrees C, respectively). No convergence problems were observed when using the one-step nonlinear regression proposed. The results indicated that the methodology applied in this study can be used to obtain kinetic data for bacterial spores, which could mean a significant reduction in the amount of experimental work employed to generate these data.
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The objectives of this study were to compare the efficacy of salbutamol delivered by either metered-dose inhaler plus spacer (MDI-spacer) or by wet nebulization (NEB), and to determine the relationships between physiologic responses and plasma salbutamol concentrations. Asthmatic patients presenting to the emergency department (ED) with acute severe asthma (forced expiratory volume in the first second [FEV1] less than 50% of predicted) were enrolled in a randomized, double-blind, parallel-group study. The MDI-spacer group received salbutamol, delivered via MDI into a spacer device, in four puffs actuated in rapid succession at 10-minute intervals (2.4 mg/h). The NEB group was treated with nebulized salbutamol, 1.5 mg, via nebulizer at 15-minute intervals (6 mg/h). Doses were calculated on the basis of the percentage of total dose that reaches the lower airway with both methods. The protocol involved 3 hours of this treatment. Mean peak expiratory flow rate (PEFR) and FEV1 improved significantly over baseline values for both groups (P=.01). However, there were no significant differences between both groups for PEFR and FEV1 at any point studied. The examination of the relationships between cumulative dose of salbutamol and change in FEV1 showed a significant linear relationship (P=.01) for both methods (MDI r=.97; NEB r=.97). The regression equations showed that for every 1 mg of salbutamol by MDI-spacer, 2.5 mg are needed from nebulization to have equal therapeutic response. At the end of treatment, the salbutamol plasma levels were 10.1+/-1.6 ng/ml for the MDI-spacer group and 14.4+/-2.3 ng/ml for the NEB group (P=.0003). Both groups showed a nonsignificant heart rate decrease. A significant group-by-time interaction means that differences between groups increased with time (P=.04). Additionally, the NEB group presented a higher incidence of tremor (P=.03) and anxiety (P=.04), reflecting larger systemic absorption of salbutamol. These data indicate that when doses used are calculated on the basis of the percentage of total drug that reaches the lower airway, there was equivalent bronchodilatation after salbutamol administered by either MDI-spacer or nebulization in patients with acute severe asthma. However, nebulizer therapy produced greater side effects related to the increase in salbutamol absorption and higher plasma level.
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The Meridian ImmunoCard Mycoplasma kit, a 10-min card-based enzyme-linked immunosorbent assay (ELISA) designed to detect immunoglobulin M (IgM) antibodies to Mycoplasma pneumoniae was evaluated. We compared the ImmunoCard with the Fujirebio Serodia Myco II particle agglutination test, as well as with the complement fixation (CF) test to detect M. pneumoniae antibodies in paediatric patients. The ImmunoCard test and Serodia Myco II test agreed in 93.95%, and ImmunoCard test and CF test agreed in 83.51% of the 182 specimens tested. Nine specimens gave negative particle agglutination titres in the acute phase sample, and 28 specimens gave negative CF titres in the acute phase sample, although in the ImmunoCard test they were positive. These results may indicate that the ImmunoCard assay detects lower IgM levels of antibodies than the Serodia Myco II and CF test. The ImmunoCard appears to be a good screening assay test for M. pneumoniae IgM in children in whom M. pneumoniae IgM is found frequently.
This randomized, double-blind trial was designed to determine the benefit of high and cumulative doses of flunisolide added to salbutamol in patients with acute asthma in the emergency room (ER). Ninety-four patients who presented to an ER for treatment of an acute exacerbation of asthma were assigned in a randomized, double-blind fashion to receive salbutamol and placebo (n = 47) or salbutamol combined with flunisolide (n = 47). Both drugs were administered successively through a metered-dose inhaler and spacer at 10-min intervals for 3 h (400 microg of salbutamol and 1 mg of flunisolide every 10 min). In both groups, FEV1 and peak expiratory flow rate (PEFR) improved significantly over baseline values (p < 0.01). Results in the flunisolide group were significantly different from those in the placebo group at 90, 120, 150, and 180 min. Data analyzed separately in accord with the duration of the attack before presenting at the ER (< 24 or > or = 24 h) showed that the placebo > or = 24 h group produced a significantly lower FEV1 at 120, 150, and 180 min (p = 0.041) than did the remaining groups. Our data support the theory that high and cumulative doses of inhaled flunisolide administered by metered-dose inhaler with spacer and added to salbutamol are an effective therapy for patients with acute asthma and a prolonged duration of symptoms before ER presentation.
STUDY OBJECTIVES: To examine the main therapeutic response patterns to high doses of salbutamol and to determine the factors that contribute to outcome in acute severe asthma. SETTING: The emergency department (ED) of a large, urban hospital with primary and referral care responsibilities. PATIENTS AND DESIGN: One hundred sixteen consecutive patients with acute exacerbations of asthma were enrolled in the trial, using a prospective sequential design. INTERVENTIONS: All patients were treated with salbutamol delivered with a metered-dose inhaler into a spacer device in four puffs (400 microg) at 10-min intervals. The protocol involved 3 h of this treatment (1,200 microg each 30 min). MEASURES AND RESULTS: A dose-response increase in pulmonary function was found, but only 70% improved sufficiently to be discharged. Of these, almost 70% required < or =2.4 mg of the drug within 1 h to reach the discharge threshold, whereas the remainder 30% need > or =3.6 mg. In 30% of subjects, salbutamol was ineffective. These patients were characterized by a more severe disease as judged by previous beta2-agonist use, larger duration of attack before ED visit, and a more severe obstruction at presentation. However, the most important predictors of outcome were peak expiratory flow rate (PEFR) as percent of predicted, PEFR as liters per minute, and PEFR variation over baseline value, all at 30 min. CONCLUSIONS: This study described two different therapeutic response patterns to salbutamol. Almost 70% of patients were sensitive to salbutamol (good response pattern), and in this group, 2.4 to 3.6 mg represents optimal treatment. In the remainder 30% of patients (poor response pattern), salbutamol in high doses had little effect. However, the outcome was not determined by the intensity of the initial symptoms or by the value of the presenting PEFR, but rather by the early (30 min) short-term response to treatment.
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STUDY OBJECTIVES: The aim of this study was to develop an acute asthma index for utilization in the early differentiation between patients with poor and good therapeutic response in the emergency department (ED) setting. SETTING: The ED of a large tertiary-care hospital in Montevideo, Uruguay. PATIENTS AND DESIGN: The study included 145 consecutive adult patients (mean age [+/- SEM], 33.4+/-0.97) who presented to an ED (analysis sample). The inclusion criteria were: (1) age between 18 and 50 years; (2) a peak expiratory flow rate (PEFR) or FEV1 below 35% of predicted; and (3) no history of chronic cough or cardiac, hepatic, renal, or other medical disease. INTERVENTIONS: All patients were treated with salbutamol delivered by metered-dose inhaler into a spacer device in four puffs actuated at 10-min intervals. The protocol involved 3 h of this treatment. After that time, patients with poor response received hydrocortisone, 500 mg IV. The outcome was defined as the FEV1 after 3 h of treatment in a dichotomized form: < or =45% of predicted = poor response, and >45% of predicted = good response. RESULTS: Biserial correlations between different variables and the outcome showed that PEFR as percent of predicted and PEFR variation over baseline, both measured at 30 min, were the most important predictors of a good or poor response after 3 h of treatment. Next, we developed an acute asthma index using these predictive measures. A comparison of index sensitivity, specificity, predictive values, and the area under the receiver operating characteristic (ROC) curve across different cutoff scores indicates that a score of 4 results in the least error of classification (sensitivity = 0.79; specificity = 0.96; area under the ROC curve = 0.87; positive predictive value = 0.94; and negative predictive value = 0.86). To validate the developed index, we prospectively studied a second sample of 77 consecutive patients (mean age 32.6+/-1.22 years) who presented for treatment of acute asthma (validation sample). The area under the ROC for the analysis sample was not greater than the validation sample area (p = 0.24). Thus, the validation sample showed similar levels of sensitivity and specificity, positive and negative predictive values, and area under the ROC curve (0.80, 0.88, 0.85, 0.84, and 0.89, respectively), indicating the stability of the model. CONCLUSIONS: The study suggested the predictive accuracy of a two-item bedside index. This acute asthma index provides a tool for assessing acute asthma severity using objective criteria easily accessible to the ED physician.
The effect of heating on ascorbic acid in green asparagus during a simulated retort operation was investigated. The asparagus was heated in trays of ethylene-vinyl alcohol copolymer for selected time intervals at four temperatures ranging from 110 to 125 degrees C. It was found that the rate of degradation followed first-order kinetics. Kinetic parameters were obtained by using two least squares methods. The activation energy and z value were 35 kcal/mol and 20 degrees C, respectively.
CONTEXT: Meningococcal disease is associated with significant morbidity and mortality. Development of a prognostic model based on clinical findings may be useful for identification and management of patients with meningococcal infection. OBJECTIVES: To construct and validate a bedside model and scoring system for prognosis in meningococcal disease. DESIGN: Prospective, population-based study. SETTING: Twenty-four hospitals in the metropolitan area of Barcelona, Spain. PATIENTS: A total of 907 patients with microbiologically proven meningococcal disease. Patients diagnosed with meningococcal disease from 1987 through 1990 were used to develop the prognostic model, and those diagnosed in 1991 and 1992 were used to validate it. OUTCOME MEASURES: Clinical independent prognostic factors for mortality in meningococcal disease. The association between outcome and independent prognostic factors was determined by logistic regression analysis. A scoring system was constructed and tested using receiver operating characteristic curves. RESULTS: Among 624 patients in the derivation set, 287 (46%) were male, the mean age was 12.4 years, and 34 patients (5.4%) died. Among 283 patients in the validation set, 124 (43.8%) were male, the mean age was 12.7 years, and 17 patients (6.0%) died. In multivariate analysis, independent predictors of death were hemorrhagic diathesis (odds ratio [OR], 101; 95% confidence interval [CI], 30-333), focal neurologic signs (OR, 25; 95% CI, 7-83), and age 60 years or older (OR, 10; 95% CI, 3-34), whereas receipt of adequate antibiotic therapy prior to admission was associated with reduced likelihood of death (OR, 0.09; 95% CI, 0.02-0.4). Hemorrhagic diathesis was scored with 2 points, presence of focal neurologic signs with 1 point, age of 60 years or older with 1 point, and preadmission antibiotic therapy was scored as -1. The clinical scores of -1, 0, 1, 2, and 3 or more points were associated with a probability of death of 0%, 2.3%, 27.3%, 73.3%, and 100%, respectively. CONCLUSIONS: Hemorrhagic diathesis, focal neurologic signs, and age of 60 years or older were independent predictors of death in meningococcal disease, whereas receipt of adequate antibiotic therapy was associated with a more favorable prognosis. The scoring system presented is simple, is based on findings readily available at the bedside, and may be useful to help guide aggressive therapy.
Data from studies using the factor analysis technique have shown that asthma appears to be multidimensional and that most of the subjective and objective measures utilized in the assessment of asthma patients represent a much smaller number of underlying dimensions. Additionally, several investigators have emphasized that evaluation of acute asthma is an ongoing process, as the degree and time course of the response to therapy vary considerably between patients. The aim of this study was to examine the usefulness of the most common clinical and objective measures in the evaluation of acute asthma in the emergency department (ED) for predicting the outcome of acute episodes in adults. In an effort to identify variables that can predict the outcome of patients with acute asthma, 184 adults (age 32.4 +/- 11.6 [mean +/- SD]) (analysis sample) who presented to an ED were studied. The inclusion criteria were: (1) age between 18 and 50 years; (2) a peak expiratory flow rate (PEFR) or forced expiratory volume in the first second (FEV1) below 50% of predicted; and (3) no history of chronic cough or cardiac, hepatic, renal, or other medical disease. All patients were treated with salbutamol delivered with metered-dose inhaler (MDI) into a spacer device in 4 puffs actuated at 10-minute intervals and 500 mg of intravenous hydrocortisone. The multivariate statistical technique of discriminant analysis was utilized to develop the index, and after this, a new sample (n = 91), the validation sample, was studied to validate the index. In the analysis sample 163 patients (89%) were discharged (relapse rate within 7 days = 10%) and 21 (11%) were hospitalized (mean duration of hospital stay = 5.75 +/- 2.81 days). The discriminant analysis identified three independent variables that make the greatest contribution in discriminating between the two groups studied: PEFR variation over baseline, PEFR as percent of predicted, and accessory muscle use, all measured at 30 minutes after the beginning of treatment. A multifactorial index using these three variables presented a sensitivity of 0.86, a specificity of 0.96, a positive predictive value of 0.75, and a negative predictive value of 0.98. The validation sample index sensitivity, specificity, and positive and negative predictive values were 0.83, 0.97, 0.83, and 0.97, respectively. In conclusion, a predictive index has been developed for evaluating patients with asthma who present to an ED. This simple and brief three-item index can facilitate an early decision (30 minutes of treatment) to hospitalize patients with severe asthma.
AIMS: The aim of the study was to test the immunomodulating capacity of Anapsos, Polypodium leucotomos extract, in vitro in an attempt to explore how this extract acts from an immunological point of view and thus to identify a common link capable of explaining most of its effects. METHODS: Polypodium leucotomos rhizomes were harvested in Guatemala and the extract, Anapsos, obtained. Mononuclear cells were obtained by density gradient centrifugation from healthy donors, and stimulated with phytohemagglutinin or Pokeweed with and without Anapsos and with Anapsos alone. Cell proliferation was determined by thymidine incorporation. Cells were also stimulated and the following cytokines determined by ELISA at 0, 12, 24, 48, 72, and 96 h: IL-1 beta, TNF-alpha, IL-2, INF-8, IL-4 and IL-10. RESULTS: Anapsos, Polypodium leucotomos extract, has a modulating effect on the in vitro production and release of cytokines by peripheral blood mononuclear cells of healthy subjects. At doses effective in vivo, Anapsos can stimulate PBMNc proliferation, delay IL-1 beta secretion and at the same time increase that of IL-2, IL-10, and INF-gamma. CONCLUSIONS: Anapsos may have an antagonistic effect on some of the cytokines released on cell stimulation with LPS and/or PHA, which suggests that this product has a pleiotropic effect on different populations in the immune system.
The Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (AMTDT) was adapted for the detection of Mycobacterium tuberculosis complex in 224 nonrespiratory specimens from 188 patients. The sensitivity and specificity of the AMTDT for such specimens, after resolution of discrepant results, were 85.7 and 100%, respectively. Pretreatment of nonrespiratory specimens with sodium dodecyl (lauryl) sulfate is mandatory to obtain consistent and reproducible AMTDT results. The use of 500 microliters of decontaminated specimen improves the sensitivity of the test. Because the AMTDT detects stable rRNA from noncultivable bacilli, it is not useful for monitoring patients receiving treatment.
Five hundred twenty processed respiratory specimens from 326 patients received for the diagnosis of tuberculosis or other mycobacterial infections were tested by means of the LCx Mycobacterium tuberculosis Assay from Abbott Laboratories, which uses ligase chain reaction technology for the direct detection of M. tuberculosis complex in respiratory specimens. The results of the LCx M. tuberculosis Assay were compared with the results of culture and staining techniques. After a combination of culture results and the patient's clinical data, a total of 195 specimens were collected from 110 patients who were positively diagnosed as having pulmonary tuberculosis. Twenty-three of these 195 specimens which corresponded to 10 patients with a history of pulmonary tuberculosis (TB) and anti-TB treatment ranging from 1 to 6 months were culture negative. The other 172 specimens were culture positive for M. tuberculosis. With an overall positivity rate of 37.5% (195 of 520 specimens), the sensitivity, specificity, and positive and negative predictive values were 90.8, 100, 100, and 94.7%, respectively, for the LCx M. tuberculosis Assay; 88.2, 100, 100, and 93.4%, respectively, for culture; and 82.6, 92, 72.9, and 97.6%, respectively, for acid-fast staining. For 161 specimens (82.6%) from patients smear positive for the disease and 34 specimens (17.4%) from patients smear negative for the disease, the sensitivity values for the LCx M. tuberculosis Assay were 98.8 and 53%, respectively. There were no statistically significant differences in the sensitivities and specificities between the LCx M. tuberculosis Assay and culture (P > 0.05). Conclusively, the LCx M. tuberculosis Assay has proved to have an acceptable sensitivity and a high specificity in detecting M. tuberculosis and has the potential of reducing the diagnosis time to an 8-h working day.