Adjunctive treatment of decompression illness with a non-steroidal anti-inflammatory drug (tenoxicam) reduces compression requirement. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Treatment of chronic obstructive pulmonary disease with corticosteroids. Comparison of daily vs alternate-day therapy. Randomized trial of the use of heliox as a driving gas for updraft nebulization of bronchodilators in the emergent treatment of acute exacerbations of chronic obstructive pulmonary disease. Inhaling beta(2)-agonist with heliox-driven in bronchial asthma. Use of heliox-driven nebulizer therapy in the treatment of acute asthma. Significant variability in response to inhaled corticosteroids for persistent asthma. Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity. Treatment of refractory myositis: a randomized crossover study of two new cytotoxic regimens.
We report a randomized trial examining adjunctive administration of the NSAID, tenoxicam, to divers suffering with DCI. 180 subjects were graded for severity on admission and randomized according to a stratified random number schedule. Subjects were recompressed and treatment continued daily until symptom stabilization or complete resolution. Tenoxicam 20 mg or a placebo preparation was administered at the first air break during the initial recompression and continued daily for seven days. The subjects were assessed using a recovery status score at the completion of treatment and at 4-6 weeks. The proportion of patients with mild residual symptoms at discharge and final follow-up was not significantly different (discharge placebo 30% versus tenoxicam 37%, P=0.41; six weeks placebo 20% versus tenoxicam 17%, P=0.58). There was a significant reduction in the number of treatments required to achieve discharge (median treatments placebo 3, tenoxicam 2, P=0.01). 61% of patients in the tenoxicam group required less than 3 compressions, versus 40% in the placebo group (P=0.01, RRR 33 % [95%CI 9%-56%], NNT=5 [95%CI 3-18]). There was no evidence of increased complications of treatment in the tenoxicam group. When given this NSAID, patients with DCI require fewer hyperbaric oxygen (HBO2) sessions to achieve a standard clinical end-point and there is likely to be an associated cost saving. The standard treatment for spinal cord compression caused by metastatic cancer is corticosteroids and radiotherapy. The role of surgery has not been established. We assessed the efficacy of direct decompressive surgery.
                In this randomised, multi-institutional, non-blinded trial, we randomly assigned patients with spinal cord compression caused by metastatic cancer to either surgery followed by radiotherapy (n=50) or radiotherapy alone (n=51). Radiotherapy for both treatment groups was given in ten 3 Gy fractions. The primary endpoint was the ability to walk. Secondary endpoints were urinary continence, muscle strength and functional status, the need for corticosteroids and opioid analgesics, and survival time. All analyses were by intention to treat.
                After an interim analysis the study was stopped because the criterion of a predetermined early stopping rule was met. Thus, 123 patients were assessed for eligibility before the study closed and 101 were randomised. Significantly more patients in the surgery group (42/50, 84%) than in the radiotherapy group (29/51, 57%) were able to walk after treatment (odds ratio 6.2 [95% CI 2.0-19.8] p=0.001). Patients treated with surgery also retained the ability to walk significantly longer than did those with radiotherapy alone (median 122 days vs 13 days, p=0.003). 32 patients entered the study unable to walk; significantly more patients in the surgery group regained the ability to walk than patients in the radiation group (10/16 [62%] vs 3/16 [19%], p=0.01). The need for corticosteroids and opioid analgesics was significantly reduced in the surgical group.
                Direct decompressive surgery plus postoperative radiotherapy is superior to treatment with radiotherapy alone for patients with spinal cord compression caused by metastatic cancer. We compared the efficacy of corticosteroid therapy initiated as an alternate-day regimen to that of a four-times-daily regimen in patients with stable chronic obstructive pulmonary disease. In this double-blind study, 44 patients with moderate to severe COPD (mean FEV1 740 +/- 310 ml) were hospitalized and randomly allocated to receive methylprednisolone, 8 mg qid, 64 mg qod, or placebo for a ten-day period. The mean FEV1 and FVC improved significantly to a comparable degree in both steroid-treated groups, but not in the placebo-treated group. Eight of the 29 steroid-treated patients (28 percent) had improved FEV1 of more than 25 percent compared with only one of the 15 placebo-treated patients. Those in the qod group also had notable improvement in SaO2. Although the correlation between the improvement after the administration of nebulized bronchodilators and that after corticosteroid therapy was significant, some patients had more than a 25 percent improvement in their FEV1 with corticosteroids, but less than a 10 percent improvement after nebulized bronchodilators. We conclude that a substantial proportion of all patients with stable COPD will have a greater than 25 percent improvement in their flow rates with corticosteroid administration. Since the response to a qod regimen is comparable to that of a qid regimen, and since the qod regimen is associated with fewer side effects, we recommend that a qod regimen be tried initially. To determine whether the bronchodilator effects of albuterol and ipratropium bromide are greater if updraft nebulization is driven by 80% helium and 20% oxygen (HELIOX) than if driven by compressed room air (AIR) during the treatment of an acute exacerbations of chronic obstructive pulmonary disease (COPD).
                The emergency department of a 750-bed inner-city community hospital.
                Over a 12-month period, a convenience sample of 50 normoxic patients presenting with signs and symptoms of an acute exacerbation of COPD were prospectively randomized to receive either HELIOX or AIR as the driving gas for updraft nebulization of a mixture of albuterol 2.5 mg and ipratropium bromide 0.5 mg. Additional aerosol treatments with albuterol 2.5 mg were given at 20, 40, and 120 mins after randomization using the assigned gas. Spirometry was obtained while breathing room air before the first treatment (baseline) and at 1 hr and 2 hrs after the initiation of treatment. The primary measure of efficacy was the change in percent of predicted forced expiratory volume in 1 sec (FEV1) over the treatment period. A secondary measure of efficacy was the change in percentage of predicted forced expiratory flow after 25% to 75% of vital capacity had been expelled (FEF25-75).
                Twenty-five patients were randomized to each treatment group. Three patients (1 HELIOX, 2 AIR) were unable to complete the study. The baseline FEV1was 44% (95% confidence interval, 35% to 52%) of predicted in the HELIOX group and 39 (31% to 46%) of predicted in the AIR group. There were no adverse outcomes observed in either the HELIOX group or the AIR group. There were no significant differences in the change of FEV1 between the two groups by either the 1 hr or 2 hr time point (1 hr, HELIOX + 10% [7% to 13%], AIR + 9% [5% to 13%]; 2 hr HELIOX + 10% [6% to 15%], AIR + 10% [6% to 14%]). The improvement in FEF25-75 was significantly greater in the HELIOX group than in the AIR group at both the 1 hr time point (HELIOX + 14% [7% to 22%] vs. AIR + 7% [3% to 10%], p = .05) and at the 2 hr time point (HELIOX + 15% [8% to 21%] vs. AIR + 7% [4% to 11%], p = .05).
                Use of HELIOX as a driving gas for the updraft nebulization of bronchodilators during the first 2 hrs of treatment of an acute COPD exacerbation failed to improve FEV1 faster than the use of AIR. The faster improvement in FEF25-75 during the first 2 hrs of treatment was small and of uncertain clinical significance. To evaluate the effectiveness of a helium-oxygen mixture (79%He- 21%O(2)) as an aerosolizing compressed gas for beta(2)-agonist therapy in patients with an asthma exacerbation.
                Twenty-four patients in the outpatient department with a mild to moderate exacerbation of asthma were enrolled. The patients were randomly divided into an experimental group (13 cases) and a control group (11 cases). The experimental group inhaled Berotec with heliox-driven, and the control group inhaled Berotec with compressed air-driven. Eight hospitalized patients in the respiratory department with severe exacerbation of asthma were enrolled. The patients inhaled Berotec with heliox-driven or compressed air-driven in a random order.
                The results of spirometric parameters and arterial blood-gas analysis were measured. In the mild to moderate asthma patients, no statistical differences between the two groups for forced vital capacity (FVC), forced expired volume in one second (FEV(1)), and expiratory flow in 50% forced vital capacity (FEF(50)) were presented. But the severe patients showed significant differences between heliox-driven and compressed air-driven for FVC, FEV(1), FEF(50) and partial pressure of oxygen (PaO(2)).
                Compared with the traditional inhalation of beta(2)-agonist therapy using compressed air-driven, the method of inhaling beta(2)-agonist with heliox-driven has more obvious benefits for those suffering from severe asthma. This is likely due to the cooperative effects between inhaling heliox on its physical gas properties and improving delivery of beta(2)-agonist in the treatment of exacerbation of severe asthma. To compare the effectiveness of a helium-oxygen mixture with that of oxygen alone as an aerosolizing gas for beta-agonist therapy in patients with mild to moderate exacerbation of asthma.
                A prospective, single-blinded study was performed in an urban teaching hospital over a period of 5 months. A convenience sample of 205 patients with mild to moderate exacerbation of asthma were enrolled. The participants were randomly assigned to 1 of 2 groups. The first group received 3 doses of albuterol, 5.0 mg aerosolized in 10 L/min of oxygen, 15 minutes apart. The second group received 3 doses of albuterol, 5.0 mg aerosolized in 10 L/min of a 70:30 helium-oxygen mixture (heliox), 15 minutes apart. Peak expiratory flow rate (PEFR), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1 ) were measured before and after each treatment. Only PEFR and FEV1 were used in data analysis.
                Although both the heliox and the oxygen group showed significant improvement in PEFR from baseline after 45 minutes (72% and 70%, respectively), the difference between the 2 groups was clinically and statistically insignificant (P =.56). Similar findings were observed for FEV1. There was no difference in rate of admission or rate of complications between the 2 groups.
                Despite its ability to decrease the turbulent flow in airways and to reach distal pulmonary tissues, heliox had no clinically significant advantage over standard therapy in the treatment of mild to moderate asthma. Further large-scale studies are necessary to determine the clinical efficacy of heliox in this setting. A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy.
                The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs.
                A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV(1) and PC(20); risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 microg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 microg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 microg/day.
                Maximum FEV(1) response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC(20) improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV(1) response, in contrast to poor (<5%) response, was found to be associated with high exhaled nitric oxide (median, 17.6 vs 11.1 ppb), high bronchodilator reversibility (25.2% vs 8.8%), and a low FEV(1)/forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC(20), in contrast to poor (<1 doubling dilution) improvement, was found to be associated with high sputum eosinophil levels (3.4% vs 0.1%) and older age at onset of asthma (age, 20-29 years vs <10 years).
                Near-maximal FEV(1) and PC(20) effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations. In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD. To assess the clinical usefulness of 2 novel therapies for treatment-resistant myositis.
                Thirty patients with refractory myositis, of whom 25 had an inadequate or no response to previous cytotoxic therapy, were randomized to begin either a combination of weekly oral methotrexate and daily azathioprine (MTX/AZA) or intravenous methotrexate with leucovorin rescue (I.V. MTX) every 2 weeks for 6 months. Crossover to the alternate therapy occurred according to defined rules; evaluations of muscle strength and functional abilities were performed at the beginning, and after 3 and 6 months, of each treatment.
                Of the 15 patients initially randomized to oral MTX/AZA, 8 improved with oral therapy and 1 improved with I.V. MTX during the crossover period. Of the 15 patients initially randomized to I.V. MTX therapy, 3 improved with the I.V. therapy and 4 with the oral combination during the crossover period. Although the study lacked the power to directly compare both treatments, intention-to-treat analysis showed a trend in favor of those patients who first received oral combination therapy (P = 0.025). There were 0.09 adverse events per patient-month with oral combination therapy and 0.16 per patient-month with I.V. therapy (P = 0.09).
                Combination oral MTX/AZA may benefit patients with treatment-resistant myositis, including those who previously had inadequate responses to either MTX or AZA alone. I.V. MTX with leucovorin rescue may also benefit some patients with refractory myositis.
Recompression therapy is standard for the treatment of DCI, but there is no randomized controlled trial evidence for its use. Both the addition of a non-steroidal anti-inflammatory drug (NSAID) and the use of heliox may reduce the number of recompressions required, but neither improve the odds of recovery. The application of either of these strategies may be justified. The modest number of patients studied demands a cautious interpretation. Benefits may be largely economic and an economic analysis should be undertaken. There is a case for large randomized trials of high methodological rigour in order to define any benefit from the use of different breathing gases and pressure profiles during recompression therapy.