Search

OBJECTIVE: To determine the potential for additive or synergistic effects of combination therapy with the selective anti-tumor necrosis factor alpha agent etanercept and the anti-interleukin-1 agent anakinra. METHODS: Two hundred forty-four patients in whom rheumatoid arthritis (RA) was active despite methotrexate therapy were treated with subcutaneous etanercept only (25 mg twice weekly), full-dosage etanercept (25 mg twice weekly) plus anakinra (100 mg/day), or half-dosage etanercept (25 mg once weekly) plus anakinra (100 mg/day) for 6 months in a double-blind study at 41 centers in the US. Patients had never previously received anticytokine therapy. Patient response was measured with the American College of Rheumatology (ACR) core set criteria, a health-related quality-of-life questionnaire, and the Disease Activity Score. Safety was assessed by the number of adverse events and clinical laboratory values. Plasma concentrations of both agents and antibody formation against both agents were also assessed. RESULTS: Combination therapy with etanercept plus anakinra provided no treatment benefit over etanercept alone, regardless of the regimen, but was associated with an increased safety risk. Thirty-one percent of the patients treated with full-dosage etanercept plus anakinra achieved an ACR 50% response, compared with 41% of the patients treated with etanercept only. This result was not statistically significant (P = 0.914). The incidence of serious infections (0% for etanercept alone, 3.7-7.4% for combination therapy), injection-site reactions, and neutropenia was increased with combination therapy. Combination therapy had no effect on the pharmacokinetics or immunogenicity of either agent. CONCLUSION: Combination therapy with etanercept and anakinra provides no added benefit and an increased risk compared with etanercept alone and is not recommended for the treatment of patients with RA. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate a multivariate model for predicting respiratory status in patients with advanced chronic obstructive pulmonary disease (COPD).Design: Prospective, double-blind study of peak flow monitoring.Setting: Albuquerque Veterans Affairs Medical Center.Patients: Male veterans with an irreversible component of airflow obstruction on baseline pulmonary function tests.Measurements: This study was conducted between January 1995 and May 1996. At entry, subjects were instructed in the use of the modified Medical Research Council Dyspnea Scale and a mini-Wright peak flow meter equipped with electronic storage. For the next 6 months, they recorded their dyspnea scores once daily and peak expiratory flow rates twice daily, before and after the use of bronchodilators. Patients were blinded to their peak expiratory flow rates, and medical care was provided in the customary manner. Readings were aggregated into 7-day sampling intervals, and interval means were calculated for dyspnea score and peak expiratory flow rate parameters. Intervals from all subjects were then pooled and randomized to separate groups for model development (training set) and validation (test set). In the training set, logistic regression was used to identify variables that predicted future respiratory status. The dependent variable was the log odds that the subject would attain his highest level of dyspnea in the next 7 days. The final model was used to stratify the test set into "high-risk" and "low-risk" categories. The analysis was repeated for 3-day intervals.Main Results: Of the 40 patients considered eligible for study, 8 declined to participate, 4 could not master the technique of peak flow monitoring, and 6 had no fluctuations in their dyspnea level. The remaining 22 subjects form the basis of this report. Fourteen (64%) of the latter completed the 6-month protocol. Data from the 8 who were dropped or died were included up to the point of withdrawal. For 7-day forecasts, mean dyspnea score and mean daily prebronchodilator peak expiratory flow rate were identified as predictor variables. The adjusted odds ratio (OR) for mean dyspnea score was 2.71 (95% confidence interval [CI] 1.79, 4.12) per unit. For mean prebronchodilator peak expiratory flow rate, it was 1.05 (95% CI 1.01, 1.09) per percentage predicted. For 3-day forecasts, the model was composed of mean dyspnea score and mean daily bronchodilator response. The ORs for these terms were 2.66 (95% CI 2.06, 3.44) per unit and 0.980 (95% CI 0.962, 0.998) per percentage of improvement over baseline, respectively. For a given level of dyspnea, higher pre-bronchodilator peak expiratory flow rate and lower bronchodilator response were poor prognostic findings. When the models were applied to the test sets, "high-risk" intervals were 4 times more likely to be followed by maximal symptoms than "low-risk" intervals.Conclusions: Dyspnea scores and certain peak expiratory flow rate parameters are independent predictors of respiratory status in patients with COPD. However, our results suggest that monitoring is of little benefit except in patients with the most advanced form of this disease, and its contribution to their management is modest at best. [ABSTRACT FROM AUTHOR]

Objective: Native Americans (NA) have higher diabetes morbidity and mortality compared to other ethnic groups. Although exercise plays an important role in diabetes management, little is known about exercise among Native Americans with diabetes. Our goal was to describe knowledge, attitudes and behaviors related to exercise in Native American participants in New Mexico., Design: Bilingual community members administered a questionnaire to assess knowledge, stage of change (a measure of exercise readiness), and physical activity behavior. Hemoglobin A1c (HbA1c) was measured by DCA 2000 analyzer. Height and weight were measured to calculate body mass index (BMI). Average random blood glucose (RBS) levels and diabetes duration were assessed through chart audit., Setting: Questionnaires were completed in offices in or near the communities., Participants: 514 Native Americans with diabetes were identified as potential participants, 40% (142 women, 64 men) participated., Results: 37% of participants knew exercise lowers blood sugar. 82% reported they were in the preparation, action, or maintenance stage of change for exercise behavior. Seventy seven percent of this population did not meet the Surgeon General's recommendation for accumulating 30 minutes of leisure time endurance exercise on most days of the week. However, 67% of participants fell within the "high activity" category for all moderate and vigorous activities. Average age, BMI and HbA1c were 58.5 yrs., 30.5 kg/m2, 8.6%, respectively., Conclusions: Interventions to increase physical activity awareness and participation could improve diabetes management and overall health for Native Americans. When evaluating physical activity, researchers need to consider usual activities of daily living and leisure time activities specific to that population. Failure to do so would be ethnocentric and could lead to inappropriate conclusions.

The aim of this study was to look at changes in peak expiratory flow rates (PEFR) prior to emergency department visits for decompensated chronic obstructive pulmonary disease (COPD). It was designed as a prospective, double-blind study at the Albuquerque Veterans Affairs Medical Center. Twelve patients with an irreversible component of airflow obstruction on pulmonary function tests were assessed. At entry, all subjects were instructed in the use of a mini-Wright peak flow meter with electronic data storage. They then entered a 6-month monitoring phase in which they recorded PEFR twice daily, before and after bronchodilators. The meter displays were disabled so that the patients and their physicians were blinded to all values. Medical care was provided in the customary manner. Patients were considered to have respiratory decompensation if they required treatment for airflow obstruction in the Emergency Department (ED) and no other causes of dyspnea could be identified. Simple linear regression was used to model changes in PEFR over time. The 12 subjects had 22 episodes of respiratory decompensation during 1741 patient-days of observation. Two episodes could not be analysed because of missing values. Ten episodes in seven subjects were characterized by a significant linear decline in at least one peak flow parameter prior to presentation. The mean rates of change for the four daily parameters varied from 0.22% to 0.27% predicted per day (or 1.19 to 1.44 1 min-1 day-1). The average decrement in these parameters ranged from 30.0 to 33.8 1 min-1 (or 18.6%-25.9% of their baseline values). No temporal trends were found for the 10 episodes occurring in the other five subjects. We concluded that respiratory decompensation is characterized by a gradual decline in PEFR in about half of cases. Future studies should be done to elucidate the mechanisms of respiratory distress in the other cases.

Objective: To develop and validate a multivariate model for predicting respiratory status in patients with advanced chronic obstructive pulmonary disease (COPD)., Design: Prospective, double-blind study of peak flow monitoring., Setting: Albuquerque Veterans Affairs Medical Center., Patients: Male veterans with an irreversible component of airflow obstruction on baseline pulmonary function tests., Measurements: This study was conducted between January 1995 and May 1996. At entry, subjects were instructed in the use of the modified Medical Research Council Dyspnea Scale and a mini-Wright peak flow meter equipped with electronic storage. For the next 6 months, they recorded their dyspnea scores once daily and peak expiratory flow rates twice daily, before and after the use of bronchodilators. Patients were blinded to their peak expiratory flow rates, and medical care was provided in the customary manner. Readings were aggregated into 7-day sampling intervals, and interval means were calculated for dyspnea score and peak expiratory flow rate parameters. Intervals from all subjects were then pooled and randomized to separate groups for model development (training set) and validation (test set). In the training set, logistic regression was used to identify variables that predicted future respiratory status. The dependent variable was the log odds that the subject would attain his highest level of dyspnea in the next 7 days. The final model was used to stratify the test set into "high-risk" and "low-risk" categories. The analysis was repeated for 3-day intervals., Main Results: Of the 40 patients considered eligible for study, 8 declined to participate, 4 could not master the technique of peak flow monitoring, and 6 had no fluctuations in their dyspnea level. The remaining 22 subjects form the basis of this report. Fourteen (64%) of the latter completed the 6-month protocol. Data from the 8 who were dropped or died were included up to the point of withdrawal. For 7-day forecasts, mean dyspnea score and mean daily prebronchodilator peak expiratory flow rate were identified as predictor variables. The adjusted odds ratio (OR) for mean dyspnea score was 2.71 (95% confidence interval [CI] 1.79, 4.12) per unit. For mean prebronchodilator peak expiratory flow rate, it was 1.05 (95% CI 1.01, 1.09) per percentage predicted. For 3-day forecasts, the model was composed of mean dyspnea score and mean daily bronchodilator response. The ORs for these terms were 2.66 (95% CI 2.06, 3.44) per unit and 0.980 (95% CI 0.962, 0.998) per percentage of improvement over baseline, respectively. For a given level of dyspnea, higher pre-bronchodilator peak expiratory flow rate and lower bronchodilator response were poor prognostic findings. When the models were applied to the test sets, "high-risk" intervals were 4 times more likely to be followed by maximal symptoms than "low-risk" intervals., Conclusions: Dyspnea scores and certain peak expiratory flow rate parameters are independent predictors of respiratory status in patients with COPD. However, our results suggest that monitoring is of little benefit except in patients with the most advanced form of this disease, and its contribution to their management is modest at best.

Background: The factors affecting patient compliance with peak flow monitoring in advanced chronic obstructive pulmonary disease (COPD) were examined using a prospective, blinded study., Methods: Twenty-eight male veterans were instructed in the use of an electronic, hand-held peak flow meter and the modified Medical Research Council dyspnea scale. They then entered a 6-month monitoring phase in which they recorded a dyspnea score once daily and peak expiratory flow rates twice daily, before and after bronchodilator use. The meter displays were disabled so that the patients were blinded to their values. Medical care was provided in the customary manner. Compliance was defined as the ratio of recorded values to all values specified by the protocol, exclusive of those missing due to circumstances beyond the patient's control., Results: Of 40 patients who met the entry criteria for this study, 8 refused to participate and 4 could not master the technique. The remaining 28 patients were enrolled. Overall, 25 (63% of those eligible) adhered to the protocol until its conclusion or until they became unable to comply because of medical or social problems. Compliance was 89.8+/-15.0%. Of those followed for longer than 150 days, linear regression showed that only one patient had a decline in compliance over time (r=0.84, P=0.04). Compliance was lower in the afternoons (P < 0.001) and on days with higher dyspnea scores (P < 0.001). No other clinical factors had an effect on patient measurements., Conclusions: A substantial proportion of patients with advanced COPD can be trained in the technique of peak flow monitoring. Compliance is high if patients are enrolled in a long-term, structured program of supervision and periodic retraining.