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Biomedical subjects

J W Ramsdell

Publications and source records attributed to J W Ramsdell.

At least 19 recordsLinked to original sources

Comparison of once-daily to twice-daily treatment with mometasone furoate dry powder inhaler.

BACKGROUND: Once-daily dosing with an effective inhaled corticosteroid (ICS) would likely enhance compliance and, therefore, aid in the management of asthma. OBJECTIVE: Several once-daily dosing regimens of mometasone furoate (MF) administered by dry powder inhaler (DPI) were compared with a twice-daily dosing regimen in 286 patients with mild to moderate persistent asthma who were previously being treated with ICS. METHODS: During a 2-week open-label phase, patients received MF-DPI, 200 microg twice daily. They were then randomized to continue MF-DPI, 200 microg twice-daily treatment or to receive MF-DPI, 200 microg once daily in the morning (AM), 200 microg once daily in the evening (PM), 400 microg once daily AM, or placebo as part of the 12-week, double-blind phase. The primary efficacy variable was the mean change from the baseline to endpoint (last evaluable observation) for FEV1. RESULTS: Once-daily MF-DPI, 400 microg, AM maintained FEV1, and morning peak expiratory flow rate, FVC, FEF25%-75%, and asthma symptom scores, at levels similar to those for MF-DPI, 200 microg twice daily and significantly better than placebo. Once-daily MF-DPI, 200 microg, PM was effective in maintaining pulmonary function, but was less effective on other efficacy measures. In comparison to the other MF-DPI groups, once-daily MF-DPI, 200 microg, AM was not as effective overall. The incidence of local adverse events, including oral candidiasis, was low with all dosages. CONCLUSIONS: Once-daily MF-DPI, 400 microg, AM was as effective as MF-DPI, 200 microg twice daily, whereas once-daily MF-DPI, 200 microg, was more effective when administered in the evening compared with morning, for patients receiving ICS therapy. Once-daily dosing offers an effective and convenient treatment that could aid compliance in the treatment of asthma.

Administration, Intranasal↗

Inhaled mometasone furoate reduces oral prednisone requirements while improving respiratory function and health-related quality of life in patients with severe persistent asthma.

BACKGROUND: Inhaled corticosteroid therapy in severe persistent asthma has been shown to reduce or eliminate oral corticosteroid (OCS) use while retaining effective asthma control. OBJECTIVE: We sought to evaluate the ability of mometasone furoate (MF) delivered by means of dry powder inhaler to reduce daily oral prednisone requirements in OCS-dependent patients with severe persistent asthma. METHODS: We performed a 12-week, double-blind, placebocontrolled trial (21 centers, 132 patients) comparing 2 doses of MF (400 and 800 microg administered twice daily) with placebo, followed by a 9-month open-label phase in which 128 patients received treatment with MF. RESULTS: At the endpoint of the double-blind trial, MF 400 and 800 mg twice daily reduced daily OCS requirements by 46.0% and 23.9%, respectively, whereas placebo increased OCS requirements by 164.4% (P <.01). Oral steroids were eliminated in 40%, 37%, and 0% of patients in the MF 400 and 800 mg twice daily and placebo groups, respectively. Pulmonary function and quality of life significantly increased for MF-treated patients. Further reductions in OCS requirements were achieved with long-term MF treatment in the open-label phase. CONCLUSION: MF inhaled orally as a dry powder is an effective alternative to systemic corticosteroids in patients with severe persistent asthma.

Administration, Inhalation↗

Safety of long-term treatment with HFA albuterol.

BACKGROUND: Chlorofluorocarbons (CFCs) used as propellants in metered-dose inhalers deplete stratospheric ozone, which results in serious public health concerns. Albuterol has been reformulated in the non-ozone-depleting propellant, hydrofluoroalkane-134a (HFA albuterol). OBJECTIVES: The primary objective was to compare the safety of HFA albuterol to an albuterol product formulated in chlorofluorocarbon propellants (CFC albuterol) during 1 year of treatment in asthmatics. Bronchodilator efficacy of the two products was assessed as a secondary objective. METHODS: The results from two open-label, parallel-group trials of similar design in asthmatics requiring short-acting beta-agonists for symptom control were combined. Patients took two puffs bid of either HFA albuterol or CFC albuterol for 1 year. Additional puffs of study drug were allowed as needed to control asthma symptoms. Adverse events were recorded at clinic visits. Patients self-administered study drug at quarterly visits and underwent serial spirometry during a 6-h period postdose. Bronchodilator efficacy variables, based on FEV1 response to study drug, were proportion of responders, time to onset of effect, peak percent change, time to peak effect, duration of effect, and area under the curve. Differences between products and changes over time in efficacy variables were assessed using an analysis of variance model. Regression analyses with FEV1 as a covariate were performed post-hoc to analyze changes in bronchodilator efficacy over time. RESULTS: Demographic and baseline characteristics were similar for patients receiving HFA albuterol (n = 337) and CFC albuterol (n = 132). Total reported adverse events were similar for the two treatments. Differences in only four individual adverse events were noted: the HFA albuterol group reported more gastroenteritis and dizziness; the CFC albuterol group reported more epistaxis and expectoration. Adverse events attributed to study drug use were infrequent. No serious adverse events were related to study drug use. Predose FEV1 at quarterly visits increased to a small extent in both groups from month 0 to month 12. The bronchodilator efficacy of HFA albuterol was comparable to that of CFC albuterol at the quarterly visits, but decreased from baseline for both products over the 12 months of treatment. Use of inhaled corticosteroids, nasal corticosteroids, or theophylline did not explain the increase in predose FEV1 over time and did not protect patients from developing reduced bronchodilator efficacy by month 12. The change in predose FEV1 did not entirely account for the reduced bronchodilator efficacy over time. CONCLUSIONS: HFA albuterol has a safety profile similar to that of CFC albuterol during chronic, scheduled use, and both drugs are well tolerated. HFA albuterol and CFC albuterol provided comparable bronchodilator efficacy, but bronchodilator efficacy decreased for both products with 1 year of use.

Administration, Inhalation↗

A short-term cost-of-treatment model for type 2 diabetes: comparison of glipizide gastrointestinal therapeutic system, metformin, and acarbose.

OBJECTIVE: To compare, from a managed care perspective, the 3-year costs of 3 first-line monotherapy strategies in type 2 diabetes patients: glipizide gastrointestinal therapeutic system (GITS), metformin, and acarbose. STUDY DESIGN: A Markov model, with a Monte Carlo simulation, was developed to compare the costs to achieve full glycemic control (hemoglobin A1c of < or = 7%) with each first-line strategy. PATIENTS AND METHODS: The patient population for the model was assumed to be all newly diagnosed type 2 diabetes patients eligible for monotherapy with an oral agent. Each monotherapy could be succeeded by add-on treatments. The model included the costs of routine medical care and supplies, medication, adverse events, and treatment failures. RESULTS: Using a Monte Carlo simulation, the mean 3-year cumulative costs per patient were $4971, $5273, and $5311 for glipizide GITS, metformin, and acarbose first-line strategies, respectively. The main cost drivers were drug prices. Mean 3-year cost savings for first-line glipizide GITS were $301 over metformin and $340 over acarbose. Between 83% and 85% of all simulations showed cost savings with glipizide GITS compared with the other agents. CONCLUSIONS: The model suggests first-line monotherapy with glipizide GITS should result in desirable short-term economic benefits for managed care. Because the model incorporates recommended glycemic goals and performed well in sensitivity analyses, it should be applicable to a variety of clinical practices and useful for economic assessments of new therapies. Results of this model should be verified prospectively in typical care settings.

Acarbose↗

Cumulative dose response study comparing HFA-134a albuterol sulfate and conventional CFC albuterol in patients with asthma.

BACKGROUND: As a result of the pending ban on chlorofluorocarbon production, the non-chlorofluorocarbon propellant 1,1,1,2-tetrafluoroethane (HFA-134a) is being evaluated as a replacement for CFCs in metered-dose inhalers. OBJECTIVES: This cumulative dose response study compared the safety and bronchodilator efficacy of 16 cumulative inhalations of albuterol sulfate in an HFA-134a, CFC-free propellant system (108 microg of albuterol sulfate, equivalent to 90 microg of albuterol base) with that of equivalent doses of albuterol in a conventional CFC propellant system. METHODS: Twenty-two patients with at least a 12-month history of stable asthma, who were currently taken an inhaled beta-adrenergic bronchodilator, and who had a FEV1 between 40% and 80% of predicted, were enrolled in this randomized, modified-blind, two-period crossover study. One, 1, 2, 4, and 8 inhalations of study drug were self-administered at 30-minute intervals, resulting in 16 cumulative inhalations. Pulmonary function and safety measures were assessed after each dosing interval. RESULTS: A significant dose response was found for HFA-134a albuterol sulfate and CFC albuterol with regard to changes in FEV1, serum potassium, heart rate, and blood pressure after 16 cumulative inhalations. No significant differences were demonstrated between HFA-134a albuterol sulfate and CFC albuterol for any FEV1 or safety parameter at any cumulative dose level. No clinically meaningful laboratory or physical examination abnormalities were found with administration of either HFA-134a albuterol sulfate or CFC albuterol. CONCLUSIONS: HFA-134a albuterol sulfate provides bronchodilation comparable to CFC albuterol and has a similar safety profile.

Adult↗

A controlled trial of twice daily triamcinolone oral inhaler in patients with mild-to-moderate asthma.

BACKGROUND: National and international guidelines recommend inhaled anti-inflammatory medications for patients with all but the mildest forms of asthma. Patients may also be more compliant with twice daily dosing. OBJECTIVE: To evaluate the efficacy and safety of triamcinolone acetonide (triamcinolone acetonide), 400 microg bid, in mild-to-moderate asthma patients. METHODS: A multicenter, randomized, double-blind, placebo-controlled study with a 7- to 21-day baseline and 6-week treatment period. Adult mild-to-moderate asthma patients poorly controlled by beta2-agonists alone were randomized to receive placebo (48) or triamcinolone acetonide (53). Patients recorded daytime and nighttime asthma symptoms, albuterol use, and morning and evening peak expiratory flow (PEF) rates on diary cards. Clinic spirometry measures included FEV1, FEF25-75%, FVC, FEV1/FVC, and PEF. RESULTS: Triamcinolone acetonide treatment resulted in improvement from baseline of 17% for FEV1 (P < .0001); 44% for albuterol use (P = .0009); 9% for FVC (P = .0185); 19% for PEF (P = .0011); 42% for FEF25-75% (P < .0001); 8% for FEV1/FVC (P = .0016); 36% for daytime, 39% for nighttime, and 38% for total asthma symptoms (P < or = .0001); and 12% for morning, and 10% for evening PEF (P < or = .001). These changes were highly significant when compared with placebo (P < or = .0185). Significant improvement for all variables was demonstrated within 1 to 2 weeks of active treatment, and maintained for most variables over the 6-week treatment phase. Both treatments were well tolerated. Respiratory adverse events occurred more frequently with placebo; pharyngitis was reported more frequently with triamcinolone acetonide. CONCLUSIONS: Triamcinolone acetonide, administered twice daily, can effectively and safely treat patients with milder forms of asthma. In these patients, triamcinolone acetonide improves asthma symptoms and decreases the need for as-needed beta2-agonists.

Administration, Inhalation↗

Nutritional status of patients with Alzheimer's disease: a 1-year study.

OBJECTIVE: To describe the effects of activity level and energy intake over time on the body weight of patients with Alzheimer's disease compared with cognitively normal subjects. DESIGN: Repeated measures, case-control design with measurements taken at quarterly intervals for 12 months. Subjects were grouped by gender and activity level (sedentary or active) within cognitive status. SETTING: The Alzheimer's disease Special Care Unit, The Clinical Research Center at University of California, San Diego, and the Fred Kasch Exercise Physiology Laboratories at San Diego State University. PATIENTS: Seventeen institutionalized subjects with Alzheimer's disease and 23 community-dwelling control subjects successfully completed the 1-year study. MEASUREMENTS: Before admission to the nursing home, the patients with Alzheimer's disease had a formal assessment for dementia, which showed that they met the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association work group for probable or possible Alzheimer's disease. Control subjects were screened using the Information-Memory-Concentration Mental Status Test and were found to have no cognitive disabilities. Baseline and quarterly measurements included height, weight, bioimpedance for body composition, and activity by accelerometer counts. Dietary intake of energy and protein was determined at baseline and at 6 and 12 months. RESULTS: Patients with Alzheimer's disease had a significantly higher energy intake than patients in the control group. Both women and men with Alzheimer's disease maintained their weight. Women with Alzheimer's disease had higher percentage of fat-free mass than the control group, but there were no differences in body composition between the groups of men. CONCLUSION: Subjects with Alzheimer's disease can maintain their weight if they are given a diet with adequate energy (35 kcal/kg of body weight).

Aged↗

Effects of theophylline and ipratropium on cognition in elderly patients with chronic obstructive pulmonary disease.

OBJECTIVES: To determine whether chronic therapy with theophylline or ipratropium has an adverse effect on cognition and psychomotor skills in geriatric patients with chronic obstructive pulmonary disease. DESIGN: The study design was a randomized, repeated measures, double-blind, double-dummy, placebo-controlled comparison of theophylline and ipratropium treatments. SETTING: Ambulatory patients were tested at the Clinical Trials Center of the University of California, San Diego, Medical Center. PATIENTS: Ambulatory patients with chronic obstructive pulmonary disease aged 65 years or more with FEV1 less than 60% predicted, FEV1/FVC less than 70%, and post bronchodilator FEV1 less than 70%. INTERVENTIONS: Patients received either theophylline or ipratropium for 2 weeks, followed by a 1-week placebo control period, then a 2-week treatment period of the alternative drug therapy. A standard therapy of albuterol MDI, 2 puffs (180 microg) qid was given throughout the study. MEASUREMENTS: The main response level was an 11-part battery of psychometric tests. Tests were administered at the end of each treatment period and at the end of the washout period. Covariates were sequence of treatment, pulmonary function tests, age, and baseline psychometric test scores. RESULTS: There was no difference in performance scores on the cognitive tests among the three treatment periods. CONCLUSIONS: We were unable to detect a harmful effect of treatment with either theophylline or ipratropium on the performance of elderly patients with chronic obstructive pulmonary disease on a battery of psychometric tests, suggesting that significant cognitive impairment in the elderly is not commonly associated with treatment with either theophylline or ipratropium.

Aged↗

The effects of theophylline on metabolic rate in chronic obstructive lung disease patients.

OBJECTIVE: To study the effect of theophylline and an alternative bronchodilator, ipratropium, on resting energy expenditure (REE) and thermic effect of food (TEF). DESIGN: 5-week randomized, repeated measures, double-blind, cross-over design, comparing the effects of theophylline and ipratropium drug treatments on metabolic measurements made during a baseline period. SETTING: Ambulatory Clinical Trials Center at University of California, San Diego. SUBJECTS: 14 patients at least 65 years old with a clinical diagnosis of chronic obstructive pulmonary disease. MEASUREMENTS: Resting energy expenditure and thermic effect of food were measured by indirect calorimetry. Body composition was determined using bioimpedance. RESULTS: Resting energy expenditure did not differ between baseline and either of the two drug treatments. In men, the thermic effect of food increased significantly during theophylline and ipratropium drug treatment periods (p < 0.03). CONCLUSIONS: Theophylline or ipratropium does not appear to increase resting energy expenditure in patients with chronic obstructive lung disease. The elevated values for thermic effect of food in men need further study.

Aged↗

Body composition of patients with Alzheimer's disease.

Low body weight is frequently reported in patients with Alzheimer's disease. We sought to discover why by comparing the body composition of 28 cognitively normal elders and 23 institutionalized individuals with Alzheimer's disease. Body mass index was calculated from standing height and weight. Percentages of lean body mass, body fat, and body water were derived from bioimpedance measurements of resistance and reactance. Skinfold thickness was measured at seven body sites to estimate regional fat distribution. Variables were analyzed by analysis of variance with subjects grouped by cognitive status within gender. Activity level and age were not significant covariates. Both women and men with Alzheimer's disease weighed less than control subjects. Differences in body composition were more pronounced in women with Alzheimer's disease, who had lower body mass index (22.0 +/- 3.0 vs 26.1 +/- 5.1), higher percentage of lean body mass (73.8 +/- 5.1 vs 66.9 +/- 6.5), lower percentage of body fat (26.1 +/- 5.1 vs 33.1 +/- 6.5), and higher percentage of body water (55.8 +/- 5.0 vs 49.3 +/- 6.5) compared with control women. Except for lower body weight, the body composition of men with Alzheimer's disease was not significantly different from that of control men. Patients of both sexes with Alzheimer's disease had less truncal body fat compared with controls, which gave them a youthful body habitus. These differences were not accounted for by age, diet, or activity. Our findings indicate that patients with Alzheimer's disease have lower body weight and may require higher energy intake than cognitively normal elders.

Adipose Tissue↗

Recommendations for a change in living situation resulting from an outpatient geriatric assessment: type, frequency and risk factors.

We analyzed the outcomes of 480 comprehensive outpatient geriatric assessments to determine the frequency of recommendations for home help or a change in residence and to determine whether simple clinical observations could predict such recommendations. Fifty-eight percent (280) of the patients received no recommendation for a change in the living situation. Of the 200 patients receiving a recommendation for a change in living situation, 97 (49%) were felt to be able to stay at home with increased in-home support and/or day care, and 51.5% (103) were advised to seek placement. After adjusting for age and gender, risk factors predicting a recommendation for change were dementia (odds-ratio = 9.98), vision deficits (odds ratio = 2.02), lower education level compared to college (odds-ratio = 1.88 high school, 1.42 for less than high school), an increasing number of medical diagnoses (odds-ratio = 1.49 per diagnosis), and a functional impairment on the Katz index (odds-ratio = 1.09). The presence of these risk factors should lead to consideration of further evaluation of the home environment in this study. We conclude that geriatric patients presenting for a comprehensive outpatient evaluation commonly need a change in home situation, though most can remain in their home, and that simple clinical observations can be helpful in screening patients for further evaluation of their home environment.

Aged↗

Geriatric assessment in the home.

Home assessment of health, environmental, and social factors, and their interactions that may impair the patient's functional capabilities and quality of life can play a critical role in the care of frail elderly patients. Home assessments can reveal important new health and social problems not identified in a clinical visit. Recent information suggests that home assessment is identified with good patient outcomes. Although this type of assessment is traditionally carried out by a nurse in the context of an interdisciplinary team, an individual primary care physician can also establish an ad hoc, multidisciplinary team to help care for frail elderly patients using principles derived from a comprehensive home assessment.

Aged↗

Cognitive function testing in comprehensive geriatric assessment. A comparison of cognitive test performance in residential and clinic settings.

Tests of cognitive function are frequently used in geriatric assessment, but the effect of test setting has rarely been explored. To determine the effect of testing site on the performance of elderly patients undergoing a comprehensive geriatric assessment, we administered the Mini-Mental State Exam to 116 geriatric patients in the clinic and at their residence. Their cognitive abilities varied from normal to severely impaired. The patients' scores were 1.5 +/- 3.6 (mean +/- SD) higher at their residence. The clinical importance of a difference in score of 1.5 is not clear. For this reason a second analysis was performed in which a difference in scores of five points or greater between settings was considered clinically meaningful. Twenty-five percent (29 of 116) differed by five points or more. Of these 29 patients, 22 (76%) tested better in the residential setting. These differences were statistically significant (P = .001). We conclude that the testing site may affect test performance and that in-home assessment may reveal the optimal cognitive function of geriatric patients.

Aged↗

Airway levels of mast cell-derived mediators in exercise-induced asthma.

In order to assess the role of mast cell-derived mediators in the pathogenesis of exercise-induced asthma (EIA), we completed pre- and postexercise bronchoalveolar lavage (BAL) in seven atopic subjects with EIA. The study subjects were defined as having EIA if they exhibited a greater than 15% decrease in FEV1 after completing 6 min of treadmill exercise. There were no significant differences between mean preexercise and mean postexercise mast cell-derived BAL histamine (186 +/- 67 versus 148 +/- 36 pg/ml), tryptase (4.5 +/- 2.0 versus 2.8 +/- 2.0 ng/ml), prostaglandin D2 (26 +/- 11 versus 32 +/- 25 pg/ml), or leukotriene C4 (less than 100 versus less than 100 pg/ml). In addition, mast cells present in BAL fluid after exercise contained similar amounts of cellular histamine compared with BAL mast cells obtained before exercise (preexercise BAL cellular histamine, 26.6 +/- 12.3 ng/10(6) BAL cells; postexercise BAL cellular histamine, 22.7 +/- 9.1 ng/10(6) BAL cells), indicating that depletion of preformed mast cell mediators are unlikely to account for the refractory period in EIA. This study suggests that the cellular pathogenesis of EIA (mast cell-independent) differs from current theories of the pathogenesis of extrinsic allergen-induced asthma (mast cell-dependent).

Adolescent↗

Nutritional status of free-living Alzheimer's patients.

Self-reported, dietary intake and biochemical estimates of thiamine, riboflavin, folate, vitamin B-12, protein, and iron were compared in 22, free-living elders by individuals who had senile dementia of the Alzheimer's type (SDAT) and in 41 who were cognitively normal (CN). The two groups did not differ significantly in their intake of these nutrients or the number of deficiency states for intake (less than 67% RDA). Low serum transketolase (thiamin; p less than 0.055), red blood cell (RBC) folate (p less than 0.06), and serum vitamin B-12 (p less than 0.05) levels occurred more often in SDAT patients than in CN subjects. Individuals in both groups who used multivitamin supplements had significantly higher biochemical values for thiamine (p less than 0.03), riboflavin (p less than 0.01), and vitamin B-12 (p less than 0.003) than nonsupplement users. Because of the differences in vitamin B-12 and RBC folate levels between groups, a retrospective analysis was performed on a larger group of subjects drawn from a geriatric assessment clinic. Patients with SDAT had significantly lower serum vitamin B-12 (p less than 0.01) and lower RBC folate (p less than 0.03) values than CN subjects. Which mean values for vitamin B-12 and RBC folate were grouped by degree of impairment in SDAT subjects, vitamin B-12 was significantly lower in mildly and moderately impaired subjects than in those with normal cognition. Mean values for both nutrients did not differ significantly between severely impaired and CN subjects. There was a significant quadratic relationship between cognitive impairment and biochemical values for vitamin B-12.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The yield of a home visit in the assessment of geriatric patients.

Elderly patients often have problems not easily detected during an office visit. We investigated the yield of a home visit by a geriatric nurse specialist as part of an interdisciplinary assessment process. Compared with the findings of an office-based assessment by a general internist, the home visit resulted in up to four new problems (median = 2, mean = 1.7, 95% confidence interval = 1.5-1.8) and one to eight new recommendations (median = 4, mean = 3.6, 95% confidence interval = 3.4-3.9). Twenty-three percent of the problems could have resulted in death or significant morbidity. The most frequent problems related to psychobehavioral difficulties (23.1% of problems involving 38.3% of patients), safety (21.6% of problems involving 35.7% of patients), and caregiver related problems (20.4% of problems involving 33.8% of patients). The most common recommendations related to safety (30.7% of recommendations involving 81.8% of patients), caregiver well-being (19.8% of recommendations involving 52.6% of patients), and social issues (12.7% involving 33.8% of patients). Baseline clinical information did not predict the yield of the home visit in this sample. We conclude that an in-home assessment contributes unique and meaningful information to the geriatric assessment process.

Activities of Daily Living↗

Effect of medical records' checklists on implementation of periodic health measures.

Recent re-evaluation of preventive health care has resulted in more limited and directed guidelines; nonetheless, physician compliance has remained poor. This study assessed whether an inexpensive reminder system of preventive care checklists would improve physician implementation of periodic health measures. Residents in internal medicine were randomly placed into two groups: one received a copy of the appropriate checklist with each patient's medical record; the other did not. After one year, 200 randomly selected records were audited to determine the proportion of recommendations implemented for each patient. Residents who received checklists performed appropriate preventive health measures at a significantly higher rate than those who did not (0.56 +/- 0.26 versus 0.39 +/- 0.22, p less than 0.002). The actual use of the checklist to record the results was associated with an even higher rate of compliance compared with instances in which the checklists were provided but not used and instances in which checklists were not received (0.70 +/- 0.21 versus 0.44 +/- 0.24 and 0.39 +/- 0.22, respectively, p less than 0.002). These data suggest that a physician's use of simple checklists can provide an inexpensive and effective means of improving implementation of periodic health maintenance.

California↗