Onset of therapeutic effect of fluticasone propionate aqueous nasal spray.

BACKGROUND: The effectiveness of fluticasone propionate (FP) aqueous nasal spray in the treatment of rhinitis has been demonstrated in multiple controlled clinical studies. The onset of therapeutic effect of FP in these clinical trials appears to occur within 12 hours after administration of the initial dose. OBJECTIVE: This article presents an analysis from previous clinical trials that examined the efficacy of intranasal FP in patients with rhinitis to ascertain whether the time to onset of the therapeutic effect of this medication could be determined. METHODS: Completed randomized, double-blind, placebo-controlled studies with FP were evaluated to determine whether onset of effect could be evaluated based on the study designs. A study was deemed acceptable for evaluation of onset of effect if at least one evaluation of the intensity of nasal symptoms was completed within 12 hours after the initial dose of study medication and daily evaluations were made thereafter. Adult patients were included in the onset analysis if they received an initial FP dose of 200 microg. Pediatric patients who received an initial FP dose of 100 microg were also included. Onset of effect was evaluated by 1) examining the timepoints at which statistically significant differences were observed between FP and placebo in mean change from baseline for total nasal symptom score (TNSS); and by 2) using a binary probability model of success/failure to determine statistically significant differences from placebo. RESULTS: Twenty-two studies met the criteria to evaluate onset of therapeutic effect; 3,605 patients with rhinitis received FP and 2,271 patients received placebo. This database represents the largest compilation of data ever assembled to determine the onset of therapeutic effect of a corticosteroid nasal spray. Two studies used a "park design" to examine onset of effect; statistically significant differences in TNSS favoring FP were achieved at hours 2 to 4 and at hour 12, respectively. Using a binary probability model of success/failure for analysis of TNSS in the remaining 20 studies not specifically designed to evaluate onset of effect, numerically greater improvements in TNSS for FP compared with placebo were found in 19 of the 20 studies within 12 hours of the administration of the first dose (P < .001). Pairwise comparisons showed statistically significant improvement for TNSS within 12 hours postdose in five of the studies for FP compared with placebo and in none for placebo compared with FP. CONCLUSIONS: Onset of therapeutic effect occurs within 12 hours, and as early as 2 to 4 hours in some patients, after administration of the first dose of FP aqueous nasal spray.

Absence of nasal mucosal atrophy with fluticasone aqueous nasal spray.

OBJECTIVE: To evaluate whether 1 year of continuous treatment with intranasal fluticasone propionate would lead to atrophy in the nasal mucosa compared with an active control, oral terfenadine. DESIGN: Prospective, randomized, multicenter, open-label, parallel-group study. SETTING: Two tertiary care academic institutions. PATIENTS: Seventy-five subjects older than 18 years with perennial allergic rhinitis. INTERVENTIONS: Patients received either fluticasone propionate aqueous nasal spray, 200 microg once daily, or terfenadine, 60 mg twice daily, for 1 year. Nasal biopsy specimens were obtained before and after 1 year of treatment and were evaluated for evidence of atrophy. MAIN OUTCOME MEASURES: Epithelial and collagen layer thickness of the nasal mucosa as assessed by light microscopy and the presence and degree of edema, and regularity of collagen fibrils as assessed by electron microscopy. Analyses were performed without knowledge of subject identity or treatment assignment. RESULTS: Neither fluticasone nor terfenadine treatment led to atrophy in the nasal mucosa by clinical or histologic observation. No significant changes from baseline were observed for any assessment of atrophy. In contrast to what would have been expected if atrophy were to occur, mean epithelial layer thickness in the fluticasone group significantly increased compared with terfenadine treatment (P = .03). CONCLUSIONS: Treatment with intranasal fluticasone for 1 year increases the thickness of the nasal epithelium as compared with a year's treatment with terfenadine and does not lead to atrophy in the nasal mucosa. The increased thickness in the fluticasone treatment may represent repair from epithelial damage caused by chronic allergic inflammation.

A comparison of the efficacy of fluticasone propionate aqueous nasal spray and loratadine, alone and in combination, for the treatment of seasonal allergic rhinitis.

BACKGROUND: Intranasal corticosteroids and oral antihistamines are both effective in the treatment of seasonal allergic rhinitis, although the therapeutic value of administering the two types of agents concurrently has rarely been evaluated. This study was designed to compared the efficacy, safety, and impact on quality of life of fluticasone propionate aqueous nasal spray (FP ANS), loratadine, FP ANS plus loratadine, and placebo (an aqueous nasal spray plus tablet) in the treatment of seasonal allergic rhinitis during the mountain cedar allergy season in south central Texas. METHODS: Six hundred patients with seasonal allergic rhinitis were treated for 2 weeks with either FP ANS 200 microgram once daily, loratadine 10 mg once daily, the FP ANS and loratadine regimens combined, or placebo in a multicenter, randomized, double-blind, double-dummy, parallel-group study. RESULTS: Clinician- and patient-rated total and individual nasal symptom scores after 7 and 14 days of therapy and overall evaluations were significantly lower (P < .001) in the FP ANS and FP ANS plus loratadine groups compared with the loratadine only and placebo groups. Loratadine was not statistically different from placebo in clinician and patient symptom score ratings nor in overall clinician and patient evaluations. FP ANS plus loratadine and FP ANS monotherapy were comparable in efficacy in almost all evaluations; for some patient-rated symptoms the combination was found superior. Mean score changes in the Rhinoconjunctivitis Quality of Life Questionnaire from baseline to day 14 showed significantly greater improvement (P < .001) in quality of life in the FP ANS group than in the group of patients receiving loratadine only or placebo and no significant benefit was demonstrated in the FP ANS plus loratadine group over the FP ANS monotherapy group. No serious or unusual drug-related adverse events were reported. Combining loratadine with FP ANS did not alter the adverse events profile or frequency.

Functional status in depressed patients: the relationship to disease severity and disease resolution.

BACKGROUND: We set out to measure the impact of depression and its clinical resolution on patients' functional status. METHOD: The Work and Social Disability Scale (WSDS), a five-category investigator-rated scale measuring patient functional status, was completed at baseline and study discontinuation in a 56-day, open, uncontrolled study evaluating the safety of a sustained release (SR) formulation of bupropion in 3167 patients at 105 sites. To be included in the study, patients had to be 18 years or older, have a diagnosis of depression, and be considered appropriate for treatment with bupropion SR. The proportion of patients in each WSDS category, for those patients taking more than 7 days of bupropion SR (N = 2915), was assessed at screen and study discontinuation. The percentage of patients with improved WSDS scores at 56 days was also measured for all patients and correlated with patient and treatment characteristics. RESULTS: Of the patients entering the trial, 61.8% were markedly or severely impaired in their work or social activities, and only 5.4% were mildly or not impaired. At study discontinuation, more than 54% of patients were judged by the investigator to have very much or much improvement in their clinical symptoms. Results on the WSDS correlated with the clinical improvements; only 22.3% were markedly or severely impaired; and 50.0% were mildly or not impaired at study discontinuation. In addition, 63.9% of patients had less work or social disability at the end of the trial than at study entry. Functional status improved more in patients who had not previously been treated for the episode, had more severe depression at study entry, and had a higher dose and duration of treatment with bupropion SR. CONCLUSION: The results show that depression results in significant impairment in patients' functional status. Functional status improved in patients treated with bupropion SR for up to 56 days. This improvement was highly correlated with improvement in clinical symptoms and was related to patient characteristics at study entry as well as to treatment patterns during the study.

Do racial differences in hypertension persist in successful agers? Findings from the MacArthur Study of Successful Aging.

The objective of this study was to determine whether racial differences in hypertension in a random sample of community-dwelling older adults also remained significant in a sample of successful agers. Data for the random sample of community-dwelling older adults came from the Duke University Established Populations for Epidemiologic Studies of the Elderly (4,162 community-dwelling adults age 65 and older) and showed strong racial differences in hypertension. Data for successful agers came from the Duke MacArthur (428 of EPESE respondents in the top 30% in terms of physical, cognitive, and psychosocial performance). The mean of two sitting blood pressure measurements was the dependent variable for both sets of analyses. Independent variables included demographics and health factors. Using logistic regression, odds ratios in the Duke EPESE and Duke MacArthur samples for race were similar (Duke EPESE odds ratio = 1.30; Duke MacArthur odds ratio = 1.29). Sample size differences affected statistical significance. However, race differences in hypertension in older adults appear to be unexplained by socioeconomic status or other usual explanatory variables. Even among successful agers, racial differences in hypertension persist.

Medication taking behaviors in the high- and low-functioning elderly: MacArthur field studies of successful aging.

OBJECTIVE: To describe and compare medication-taking behaviors in the high- and low-functioning elderly living in the community. DESIGN: A cross-sectional design with data collected by interview. SETTING: The study included 5 counties in the southern Piedmont area of North Carolina. PARTICIPANTS: Respondents included 242 elderly aged 70-79 years selected from the Piedmont Health Survey of the Elderly and the MacArthur Research Program on Successful Aging. MAIN OUTCOME MEASURES: Outcome measures included strategies used to remember to take drugs, reasons given for skipping medications, factors associated with understanding of drugs, the number of over-the-counter and prescribed drugs used, and the number of drugs used in therapeutic categories. RESULTS: Low-functioning elderly white respondents took greater numbers of prescribed drugs than did blacks or high-functioning whites. Respondents had a better understanding of prescribed than of over-the-counter drugs, with the poorest understanding of nutritional supplements. Men and blacks had poorer understanding of drugs than women and whites. The strategies subjects used to remember to take drugs included (from most to least frequently used): making it a routine activity, reading labels, a self-devised memory aid, a habit, being reminded by someone else, sorting, and noticing symptoms. CONCLUSIONS: Clinicians should provide their patients with information about over-the-counter agents as well as prescribed drugs, be alert to cues that blacks and men give indicating their need for additional explanation about a drug's purposes, and be sensitive to differential prescribing patterns with respect to race. When planning a regimen for multiple doses of a drug, clinicians should account for their patients' tendencies to use routine activities as memory prompts.

Community dwelling elderly are appropriate subjects for intensive dietary choice restriction studies.

There is a traditional belief that the elderly have difficulty coping with dietary change, and therefore have a diminished likelihood of successfully responding to nutritional interventions or restrictions. Using a controlled mild zinc-deficiency feeding study as a model for strict dietary intervention, we assessed psychological responses to severe dietary choice restriction in 15 Caucasian, elderly (66.12 +/- 4.43 years) males (n= 7) and females (n = 8). Participants completed the Medical Outcomes Study Short Form 36-Item Questionnaire (SF-36) as an index of QOL and the Multi-dimensional Health Locus of Control (MHLC) as a measure of health beliefs at pre-intervention baseline, post-intervention, and follow-up. No subjects dropped out nor were any meals missed during the entire 21-day feeding study period. No significant differences were detected across time on the MHLC (Internal F = 0.53, P = 0.6; Powerful Others F = 0.28, P = 0.8; Chance F = 1.1, P = 0.4.) by one-way ANOVA. Similarly, for the SF-36 no significant differences were found across time (F = 0.76, P = 0.5). Our results suggest that restricting dietary choices does not negatively impact older adult subjects and that they can cope well with dietary choice restriction and change. Older adults should not be overlooked for nutritional intervention solely due to age considerations.

Rehabilitation in the nursing home: how much, why, and with what results.

Although rehabilitation is considered an important component of long-term care, few studies have looked at the factors associated with the provision of rehabilitation in this setting. The authors examined one State's skilled nursing homes to gain information on their rehabilitation practices. Data for this study came from a mail survey and from the licensing applications filed with the State Division of Facility Services. Sixty-nine percent of the State's nursing homes responded to the survey. All reported that they provided specialized physical therapy, occupational therapy, or speech therapy, or all three, but the numbers of patients reported to be enrolled in such therapies on a daily basis varied from 0 to 64 percent of the facility's census. Factors positively associated with the provision of rehabilitation included the number of full-time registered nurses on the staff and the belief of the facility administrator that the purpose of rehabilitation is to restore function so that patients can be discharged. Facilities that employed their own therapists rather than contract for these services reported significantly more patients enrolled in daily therapies. And a significant positive correlation was observed between the provision of daily rehabilitation services and discharge of patients in those facilities that hired their own rehabilitation staff. These findings suggest that the provision of rehabilitation in nursing homes has different goals and outcomes and that there are facilities with identifiable characteristics that appear more successful in returning patients to their homes.

Use of spectacle mounted telescope systems by the visually impaired.

BACKGROUND: Spectacle mounted telescope low vision aids are designed to magnify objects Spectacle telescopes are often rejected by the visually impaired because of their unusual cosmetic appearance which may call attention to their disability. METHODS: Fifty-six subjects were recruited at four independent low vision clinics and divided into two categories: 24 were current wearers of expanded field spectacle mounted telescope systems, and 32 were new wearers. New wearers underwent a randomized cross-over trial, comparing the experimental device (Ocutech VES) to one of two controls (DFV Expanded Field or Walter's Keplarian Close-focus Telescope). RESULTS: Our data show that previous telescope wearers increased their use of telescopes after introduction of the experimental device (Ocutech VES) and there was an equivalent utilization rate for new wearers. CONCLUSIONS: Visual activity patterns are not a sensitive measure of telescope benefit, but frequency of use patterns do change and appear to demonstrate a valid benefit of spectacle mounted telescopes for the visually impaired.

Abbreviating the Duke Social Support Index for use in chronically ill elderly individuals.

The 35-item Duke Social Support Index (DSSI) measures multiple dimensions of social support and has been used extensively in cross-sectional and longitudinal studies of aging. Epidemiological studies of chronically ill, frail elderly individuals often wish to include a measure of social support. However, most multidimensional measures (including the DSSI) are long and may exhaust the patient, especially when included in an often already congested interview schedule. The authors have developed two abbreviated versions of the DSSI (23-item and 11-item) that capture the essential components of social support related to mental health outcomes and use of health services in treating elderly individuals with nonpsychiatric medical illness.

A brief depression scale for use in the medically ill.

OBJECTIVE: Using items from two existing depression scales, we have sought to develop a brief self-rated instrument for detecting major depressive disorder (M.D.D.) in medically ill, hospitalized patients. METHOD: Forty-two items from the Geriatric Depression Scale (G.D.S.) and Carroll Depression Scale were administered to 559 men under age 40 or over age 70 consecutively admitted to the hospital. Eighty-two M.D.D.'s were diagnosed in this group by structured psychiatric interview. After eliminating 12 items confounded by medical illness, 11 items were selected using regression analysis, correlation with the total score, and factor analysis. The 11-item scale includes an assessment of the five DSM-III-R criteria for M.D.D. which are least confounded by medical illness (mood, suicidal intent, guilt or worthlessness, concentration, and psychomotor agitation). The scale was then tested in 78 medical inpatients who were later assessed for M.D.D. using a structured psychiatric interview. RESULTS: Ten out of twelve M.D.D.'s were identified (83% sensitivity) and depression excluded in 51 of 66 non-depressed subjects (77% specificity) (compared with 82% sensitivity and 76% specificity for the 30-item G.D.S.). Scores on the 11-item scale were also correlated with the G.D.S. (.92), the Zung Depression Scale (.58), and the C.E.S.-D (.67). CONCLUSION: The 11-item scale is a practical tool for clinicians who screen patients for depression and for investigators who need a brief measure of depression in studies involving medical inpatients.

Osteoporosis in late life: does health locus of control affect psychosocial adaptation?

Osteoporosis, a metabolic bone disease most prevalent in older adults, is a major public health problem. Although management of osteoporosis through diet, exercise, and medication has improved, little is known about the psychosocial consequences of this disabling disease. In an attempt to identify patient characteristics that would provide physicians with insight into appropriate management styles for older osteoporotics, we assessed 103 patients with osteoporosis for their health locus of control (HLOC) orientation. We examined the relationship between HLOC and patient outcomes after participation in the Duke University Preventive and Therapeutic Program for Osteoporosis (DUPATPO) to determine whether HLOC was associated with functioning after program participation. More specifically, we asked whether internal or external HLOC was associated with decreases in depression, psychiatric symptoms, and stress symptoms, or with increases in self-esteem, exercise, and disease knowledge. We have shown in our earlier work (Gold et al, J Am Geriatr Soc 1989; 37:417) that program participation is associated with improved functioning in older adults. We now asked whether knowledge of a patient's HLOC would help predict these improvements. A comparison group (ie, older osteoporotics who did not participate in DUPATPO) was also assessed for HLOC to examine the possible association between HLOC and health behaviors regardless of the DUPATPO intervention. Our findings indicate that HLOC provided little useful information regarding patient outcomes. Although improvements were seen in the mental health of program participants, no association between these improvements and HLOC could be found.

Physicians' attitudes towards living wills and cardiopulmonary resuscitation.

OBJECTIVE: To determine whether a physician's familiarity with the living will directly relates to an expressed willingness to discuss resuscitation issues with patients. DESIGN: Survey of selected primary care and medical sub-specialist physicians most likely to care for seriously or terminally ill patients. SETTING: Private-practice clinicians practicing in an urban county. PARTICIPANTS: Internists, family practitioners, cardiologists, oncologists, and neurologists in private practice. INTERVENTIONS: None. RESULTS: Almost all responding physicians (97.2%) knew of the living will, although few (13.5%) had executed one for themselves. Most were willing to keep a copy of their patients' living wills with their office records. However, only a few physicians (20%) indicated they routinely discussed extraordinary care issues with their patients. In fact, most (70%) reported they rarely or never discussed cardiopulmonary resuscitation (CPR) with their patients. With terminally ill patients, physician initiative was greater: 69% reported discussing resuscitation preferences. Comparable discussions with elderly patients were undertaken only if the physician believed they would be warranted by the clinical circumstances. When questioned about their own sentiments towards resuscitation, most physicians indicated they would not want CPR if they were terminally ill (86%) or mentally incompetent (93%). A similar number (92%) would refuse artificial feeding if permanently comatose. CONCLUSIONS: Many physicians recognize the importance of living wills as an expression of patient treatment preferences. Nevertheless, discussion of patient preferences is unlikely because of physicians' reluctance, except in limited circumstances, to initiate a dialogue about life-sustaining measures. Because patients also are often unwilling to begin such discussions, better methods of facilitating discussion of CPR and other extraordinary health care measures must be sought.

The metabolic effects of calcium supplementation in the elderly.

Because the value of calcium supplementation in age-related bone loss is controversial, we conducted a study to examine the effects of six months of calcium supplementation on parathyroid hormone (PTH) and other indices of bone metabolism. Calcium carbonate (1.2 grams elemental calcium/day) or placebo was administered for 6 months to a group of 42 healthy, ambulatory men and women with a mean age of 71. Fasting blood samples and 2-hour urine collections were performed at baseline and at 1 and 6 months. The decline in serum PTH levels from baseline in the calcium-supplemented group was significant in comparison with the placebo group changes (for the calcium group: 40.9 pg/mL at baseline to 34.0 pg/mL at 1 month and 33.2 at 6 months). This drop in PTH was associated with a decline in 1,25 OH-Vitamin D levels from a mean of 38.3 pg/mL to 30.4 pg/mL at 1 month and 31.9 at 6 months. During calcium supplementation, no changes were observed in serum bone Gla protein values. A decline in urinary hydroxyproline excretion was observed at 6 months, but this did not reach significant levels. The present study demonstrates suppression of PTH levels with calcium supplementation, an effect which lasts at least 6 months. This change was accompanied by a decrease in serum 1,25 OH-Vitamin D. The lack of significant changes in either serum bone gla protein or urine hydroxyproline excretion fails to support any significant change in bone turnover occurring with this decrease in PTH.

The Ocutech Vision Enhancing System (VES): utilization and preference study.

An NIH-sponsored user and prescriber preference trial was conducted comparing a new low vision telescope system, the Ocutech Vision Enhancing System (VES) to two conventional Keplarian spectacle telescope systems in a controlled cross-over clinical study performed at four independent low vision clinics. Fifty-five visually impaired individuals, 18-81 years of age, with both previous and no telescope experience, were followed for 8-16 weeks. The experimental and control devices were compared on a series of subject-selected visual tasks using a standardized clinical protocol. Subjects were trained in the use of the systems with standardized clinical methods. The data shows a statistically significant preference of the new design by both patient and clinician with the overriding factors relating to appearance, weight, adjustability and the fit of the frame.