Investigating the Accuracy of the Digihaler, a New Electronic Multidose Dry-Powder Inhaler, in Measuring Inhalation Parameters.

Background: The Digihaler® is a Food and Drug Administration-approved, digital multidose dry powder inhaler with an integrated electronic module that provides patients and health care professionals with feedback on inhalation parameters, including usage, adherence, and technique. This study compared inhalation parameters measured using the Digihaler with readings made simultaneously using an inhalation profile recorder (IPR). Methods: This single-visit, open-label study enrolled children (4-17 years) and adults (18-55 years) with asthma, and adults (≥55 years) with chronic obstructive pulmonary disease (COPD). Participants made three separate inhalations using an empty Digihaler device, each measured simultaneously by the Digihaler and IPR. Inhalation profiles were downloaded from the devices at the end of the study. Inhalation parameters measured included peak inspiratory flow (PIF) and inhaled volume (inhV). The profile with the highest PIF and corresponding IPR profile were analyzed. Results: Overall, 150 participants were enrolled; inhalation data were available for 148 (50 children and 49 adults with asthma, and 49 with COPD). Mean (standard deviation [SD]) age was 39.1 (24.5) years; 51% of participants were male. Overall mean (SD) PIFs as measured by the Digihaler and IPR were 70.62 (17.73) L/min and 72.55 (19.42) L/min, respectively, with a mean percentage difference of -1.75% (95% confidence interval [CI]: -3.64 to 0.15). Mean percentage differences between the Digihaler and IPR measurements of PIF ranged from -2.97% among adults with COPD to 0.16% among children with asthma. Overall mean (SD) inhV for the Digihaler and IPR were 1.57 (0.69) L and 1.67 (0.73) L, respectively, with a mean percentage difference of -6.11 (95% CI: -8.08 to -4.13). There was a strong correlation between PIF and inhV measurements taken by the Digihaler and those taken by the IPR (Spearman's correlation coefficient = 0.96). Conclusions: Our findings confirm the ability of the Digihaler to provide accurate measurement of inhalation parameters when used by patients.

Use of a Digital Chronic Obstructive Pulmonary Disease Respiratory Tracker in a Primary Care Setting: A Feasibility Study.

INTRODUCTION: Telemonitoring is a promising self-management strategy to improve health care outcomes. This study evaluated real-world adoption of the chronic obstructive pulmonary disease (COPD) Co-Pilot daily symptom monitoring tool by patients and primary care providers (PCPs). METHODS: An open-label, 6-month, single-arm, multicenter, noninterventional feasibility study enrolled 97 patients aged ≥ 40 years with symptomatic or poorly controlled COPD and ≥ 10 pack-year smoking history. Patients received smartphones and training to use the COPD Co-Pilot application. During the study, patients tracked symptoms daily; an increase in symptom score of ≥ 1.0 point from baseline (symptom alert) prompted patients to contact their PCP via toll-free number. The primary endpoint was time to clinical recommendation (TTCR) from a symptom alert; adherence to completing daily symptom reports through the COPD Co-Pilot application and patient satisfaction were also measured. RESULTS: Overall, 87 of 96 patients (90.6%) received 2142 symptom alerts; 42 alerts (equivalent to 2% of all symptom alerts) resulted in 23 patients contacting their PCP. Median TTCR was 7.1 h (interquartile range [IQR]: 4.0-29.9). Among 15 patients using the toll-free number, median TTCR was 2.1 h (IQR 0.0-7.2) versus 19.6 h (IQR 4.5-45.2) for eight patients using other contact methods. Average COPD Co-Pilot adherence overall was 75.2% (95% CI 74.6-75.9). Patients responded favorably regarding the application's ease of use, functionality, and information provided. CONCLUSIONS: The COPD Co-Pilot tool was associated with relatively high levels of adherence, suggesting patients' willingness to monitor symptoms daily. Although a limited number of patients initiated PCP contact, patients who used the study-provided toll-free number had substantially shorter median TTCR, suggesting that this tool could help empower patients to better manage their COPD.

The Impact of Budesonide/Formoterol pMDI Medication Reminders on Adherence in Chronic Obstructive Pulmonary Disease (COPD) Patients: Results of a Randomized, Phase 4, Clinical Study.

PURPOSE: Among patients with chronic obstructive pulmonary disease (COPD), adherence to inhaled medication leads to fewer exacerbations and improved health status. The goal of the present study was to evaluate the effects of medication reminders via the BreatheMate device on adherence in patients with COPD. PATIENTS AND METHODS: A 6-month, phase 4, randomized, multicenter, open-label US study (NCT02864342) enrolled 138 patients aged ≥40 years with moderate to very severe COPD and ≥10 pack-year smoking history. Patients in the intervention (n = 68) and control (n = 70) groups received the BreatheMate device, smartphone application, and vouchers to redeem pressurized metered-dose inhalers (pMDIs) for the prescribed 2 puffs of budesonide/formoterol 160/4.5 µg twice daily. The intervention group also received twice-daily electronic reminders to take budesonide/formoterol. The primary endpoint was the mean number of sets of adherent puffs/day (4 puffs: 2 puffs within 60 minutes, twice daily) over 6 months. Secondary endpoints included adherence by three 60-day intervals, usage days, prescription refills, and Clinical COPD Questionnaire (CCQ) score. Study enrollment terminated early due to issues with inconsistent syncing. RESULTS: A higher mean proportion of adherent days (77.6% vs 60.2%; P <0.001) and sets of adherent puffs/day (1.61 vs 1.33; P <0.001) were recorded for the intervention group versus the control group. Intervention group adherence was higher than that of the control group for each 60-day interval (P <0.001); the intervention group was 3.07 (95% confidence interval: 1.49-6.52) times more likely than the control group to be adherent for ≥80% of study days. Overuse (>2 sets of 2 puffs/day), underuse (<2 sets of 2 puffs/day), and no use days were lower in the intervention group versus control (P <0.05). Patients aged ≥65 years had higher adherence (P <0.001). CONCLUSION: Medication reminders through the BreatheMate device and application produced greater adherence to inhaled therapy in patients with COPD.

Results from a drug utilization study of extended release quetiapine fumarate prescribed by psychiatrists as treatment for major depressive disorder in selected countries in the European Union.

This multicenter, observational drug utilization (DU) study (NCT01594996) investigated the profile of patients and specialist providers who prescribed extended release quetiapine fumarate (quetiapine XR) for treatment of major depressive disorder (MDD) across five European countries (Germany, Italy, Romania, Spain, and Sweden). A DU data abstraction form captured information on the characteristics of physicians, patients, and drugs utilized in the medical management of depressive episodes in MDD, where the therapeutic regimen included quetiapine XR. Data were reported descriptively. This analysis included 811 patients. Psychiatric histories indicated a burden of severe MDD in these patients. Patient demographics were similar across countries; however, those in Sweden had a younger mean age. Physicians' ratings of the therapeutic effect of prior treatment with antidepressants suggested the need for an add-on treatment for most patients. Overall, 15.7% of patients initiated quetiapine XR treatment as monotherapy. Presence of psychotic symptoms during depressive episodes predicted treatment with higher than recommended doses of quetiapine XR (odds ratio=3.11; 95% confidence interval: 1.6-6.0). This analysis demonstrated similarities in DU across the countries analyzed, largely in accordance with the recommended dose of quetiapine XR as an adjunctive therapy to antidepressants in MDD (50-300 mg/day).

Perception gap in quality-of-life ratings: an empirical investigation of nursing home residents and caregivers.

PURPOSE: Several studies have previously documented the existence of a perception gap-the extent to which quality-of-life ratings provided by nursing home residents and caregivers diverge. In this study we use Helson's adaptation-level theory to investigate three types of antecedents: (a) focal factors, (b) background factors, and (c) residual factors. DESIGN AND METHODS: We calculated the perception gap for 11 quality-of-life domains. Caregivers rated both job satisfaction and their perception of quality of life of residents in the unit where they provided service. Concurrently, residents from these units completed quality-of-life interviews. We computed the perception gap by subtracting the residents' ratings from the caregivers' ratings for each quality-of-life domain. We conducted a hierarchical linear model using 3,850 observations to predict the perception gap. RESULTS: Caregivers perceive quality of life to be lower than residents do across all domains fairly consistently. Caregiver demographics do not directly predict the perception gap. However, satisfaction with work, pay, and promotion were significant predictors (p <.05), and satisfaction with supervisor was a marginally significant predictor (p <.10), of the perception gap. As satisfaction with these job dimensions increased, the perception gap decreased. Additional models show that several caregiver demographics directly influence job-satisfaction dimensions, though they did not influence the perception gap. IMPLICATIONS: Job-satisfaction dimensions, rather than caregiver characteristics, are the appropriate predictors of the perception gap. However, caregiver demographics exert their influence indirectly by means of job satisfaction. A key finding is that higher job satisfaction leads to a smaller perception gap. Helson's adaptation-level theory appears to be a useful approach for understanding the antecedents of the perception gap.

Interrater reliability in clinical trials of depressive disorders.

OBJECTIVE: The goal of this study was to review the reported methods of rater training, assessment of interrater reliability, and rater drift in clinical trials of treatments for depressive disorders. METHOD: Two psychiatrists independently identified all original reports of clinical trials relevant to depressive disorders published between 1996 and 2000 in the American Journal of Psychiatry and the Archives of General Psychiatry. Reported methods of rater training, assessment of interrater reliability, and rater drift were systematically summarized. RESULTS: Sixty-three original papers met criteria for inclusion. Only 11 (17%) of the studies reported the number of raters. Only two (9%) of the 22 multicenter and four (10%) of the 41 single-center trials documented rater training. Only nine (22%) of the single-center trials and three (14%) of the multicenter trials reported interrater reliability, despite a median number of five raters (range=2-20). Only three (5%) of the 63 articles reported rater drift. CONCLUSIONS: Few published reports of clinical trials of treatments for depressive disorders document adequately the number of raters, rater training, assessment of interrater reliability, and rater drift.

Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients.

OBJECTIVE: Until recently, conventional antipsychotics were the standard pharmacotherapy for psychosis and behavioral disturbances associated with dementia. This double-blind, placebo-controlled study compared the acute efficacy of the selective serotonin reuptake inhibitor citalopram and the neuroleptic perphenazine with placebo for the treatment of psychosis and behavioral disturbances in nondepressed patients with dementia. METHOD: Eighty-five hospitalized patients with at least one moderate to severe target symptom (aggression, agitation, hostility, suspiciousness, hallucinations, or delusions) were randomly assigned to receive either citalopram, perphenazine, or placebo under double-blind conditions for up to 17 days. RESULTS: Patients treated with citalopram or perphenazine showed statistically significant improvement on several Neurobehavioral Rating Scale factor scores. Compared to those receiving placebo, only patients treated with citalopram showed significantly greater improvement in their total Neurobehavioral Rating Scale score as well as in the scores for the agitation/aggression and lability/tension factors. Side effect scores were similar among the three treatment groups. CONCLUSIONS: Citalopram was found to be more efficacious than placebo in the short-term hospital treatment of psychotic symptoms and behavioral disturbances in nondepressed, demented patients.

Risperidone and 9-hydroxyrisperidone concentrations are not dependent on age or creatinine clearance among elderly subjects.

Risperidone is extensively metabolized to an active metabolite, 9-hydroxyrisperidone (9-OH), which is dependent on renal clearance. Risperidone and 9-OH clearances are reduced in the elderly when compared to young subjects. The objective of this study was to determine whether among elderly subjects, risperidone and 9-OH clearance would further decline with increasing age and decreasing creatinine clearance (CrCl). Twenty geriatric inpatients were evaluated in a naturalistic setting with regard to total daily risperidone dose and dosing interval. Creatinine clearance was determined using an 8-hour urine collection. Risperidone and 9-OH concentrations were determined by radioimmunoassay. Spearman's correlation coefficients were used to examine the impact of age and CrCl on concentrations of risperidone, 9-OH, their sum, and the quotient of 9-OH/risperidone. Mean age was 76.4 +/- 9 years (range 56-91). Mean CrCl was 55.4 +/- 32.8 mL/min/1.73 m2 (range 17-142 mL/min/1.73 m2). Mean risperidone daily dose was 1.3 +/- 0.7 mg. Steady-state risperidone and 9-OH concentrations were 4.1 +/- 5.3 ng/mL and 9.1 +/- 6.2 ng/mL, respectively. Mean 9-OH/risperidone was 6.2 +/- 6.1. Concentrations of risperidone, 9-OH, their sum, and 9-OH/risperidone were not significantly correlated with age or CrCl. These results were unchanged when concentrations were corrected for total daily risperidone dose. Among elderly subjects, risperidone and 9-OH clearance do not decline with increasing age or declining CrCl.

Mental health training for nursing home staff using computer-based interactive video: a 6-month randomized trial.

OBJECTIVE: Mental health education for the staffs of nursing homes is difficult to provide and often inadequate. The objectives of this study were to design and assess a curriculum of staff training on depression and dementia that is accessible, educational, and relevant. DESIGN: A core curriculum of 12 computer-based interactive video training modules was created in a television news-documentary format to educate nursing home staffs. A randomized trial of the first six modules, which are dedicated to mental health and aging, was conducted at a computer site (CS), a "lecture site" (LS), and control site (CON). SETTING: Three not-for-profit nursing facilities in Western Pennsylvania. PARTICIPANTS: The certified nursing assistants, and other nursing staff participated in the study as part of their required training. INTERVENTION: Nursing staffs at the two intervention sites (CS and LS) were mandated to participate in monthly educational sessions. At the CS, the computer program scheduled staff members each month for 45 minutes of individual, self-paced training using the interactive video modules. At the LS, staff members were scheduled to attend a 45-minute monthly lecture with identical learning objectives delivered by an advanced degree nurse educator. A videotape of the lectures was shown at two additionally scheduled times during the month to accommodate all shifts. MEASUREMENTS: Compliance and satisfaction with training were monitored at both intervention sites. Knowledge was assessed at the CS, LS, and CON, before each monthly training session, and with a cumulative post-training exam, administered at the end of the 6-month study. RESULTS: Over the 6-month period, training compliance was 66% and 22% at CS and LS, respectively (P < 0.001). Satisfaction with training and the relevance of training were rated significantly higher at the CS (P < 0.0001). Before the study, assessed knowledge was similar at the CS, LS, and CON. After 6 months, the CS scored significantly higher than the LS and CON in terms of knowledge (P < 0.005). CONCLUSION: Individual, self-paced, interactive video education for nursing home staff resulted in greater compliance and satisfaction with training compared to staff receiving lectures. Knowledge of core concepts was greater for staff of the computer site compared to the staffs of either the lecture or control sites at the end of this 6-month study.

Generation of particulate matter during handling of needle and syringe packaging.

PURPOSE: Generation of airborne particulate matter during the handling and opening of various syringe and needle packages in a laminar-airflow workbench (LAFW) and in a biological safety cabinet (BSC) was measured to compare the effects on air cleanliness conditions (International Organization for Standardization [ISO] class 5 within the LAFW or BSC and ISO class 7 in buffer areas). METHODS: Twenty-five to 50 packages of each of 12 needle or syringe products were opened. Probes were configured to count airborne particles during the separation of strip packages and the opening of packages by peeling back the top web or pushing the device through the packaging (for soft packages) or by twisting apart hard packages. RESULTS: The numbers of particles were not significantly different between the LAFW and BSC. The separation of strip packages generated visible particles and raised airborne particle counts. Peeling open plastic film packages and opening hard plastic packages generated fewer airborne particulates than did pushing devices through the packaging. For all methods of package opening, average counts downstream from the direct compounding area exceeded ISO class 5 conditions. Counts in the LAFW buffer area did not exceed ISO class 7. CONCLUSION: All methods of separating and opening the packaging of needles and syringes generated particles. The peel-and-present technique generated the lowest particulate volume. The LAFW and BSC were equally effective in maintaining low particle counts.

Development of a short form of the Severe Impairment Battery.

OBJECTIVE: The authors sought to develop a short form of the Severe Impairment Battery (SIB). METHODS: Authors describe the development of an empirically-derived short form of the SIB (SIB-S) by use of data from 191 subjects with severe dementia in the United States and France. RESULTS: Mean (standard deviation) Mini-Mental State Exam scores for the American and French samples were 7.7 (4.8) and 5.7 (3.4), respectively, and original SIB scores were 71.87 (18.34) and 58.38 (26.86), respectively. Exploratory factor analyses were conducted separately and in combination for the two samples, to determine the number of clinically meaningful factors. An eight-factor model, explaining 60.2% of the common variance, was selected. The eight constructs were described as: expressive language, memory (verbal and nonverbal), social interaction, color-naming, praxis, reading and writing, fluency, and attention. Derived SIB-S scores were 38.41 (9.12) and 29.79 (13.17) for the American and French samples, respectively. CONCLUSIONS: The original SIB is a valid and reliable research tool developed to enable reliable assessment of patients with severe dementia; it takes approximately 30 minutes to administer. The SIB-S takes only 10-15 minutes to administer, making it more appropriate for use in patients with very severe dementia, while it maintains the attributes of the original SIB.

A preliminary study of the effect of fluoxetine treatment on the 2:16-alpha-hydroxyestrone ratio in young women.

Cytochrome P450 isoenzymes are known to contribute to estrone metabolism. The authors hypothesized that fluoxetine, a known inhibitor of multiple P450 isoenzymes including 3A4, 2C9, and 2D6, would affect estrone metabolism, altering the 2-hydroxyestrone:16-alpha-hydroxyestrone (2OHE1:16OHE1) ratio. In this preliminary study, four of eight recruited women with regular menstrual cycles, aged 21-37 years, completed a 24-hour urine collection prior to initiation of fluoxetine therapy and after at least 5 weeks of antidepressant treatment. In three of the four women who were nonsmokers, the 2OHE1:16OHE1 ratio was significantly higher after 5 weeks of fluoxetine therapy (pretreatment, 2.08 +/- 0.11; posttreatment, 3.50 +/- 0.46; paired Student's t-test P = 4.72, P = 0.021).

Verification of scale sub-domains in elderly patients with dementia: a confirmatory factor-analytic approach.

OBJECTIVE: Use of cognitive, psychiatric and behavioral domains to assess the effectiveness of a pharmacological or behavioral intervention in the treatment of neurodegenerative disorders (e.g., Alzheimer disease) aids the identification of specific types of impairment or distress in behavioral status and quality-of-life issues in this population. With confirmatory approaches to subscale development readily available, we can obtain a more precise understanding of the sub-components of a scale, potentially providing the basis for selecting behavioral and/or quality-of-life outcome measures that may be more sensitive to the effects of pharmacological or behavioral interventions. METHODS: The authors illustrate the use of a confirmatory factor-analytic approach to verify scale sub-domains of the Neurobehavioral Rating Scale (NBRS) in elderly patients with dementia. With data collected from two groups of patients being treated for significant psychiatric and behavioral symptoms, authors investigated the relationships among scale items in order to test several competing models, including a general one-factor model, a first-order multifactor model, and a second-order factor model. RESULTS: The first-order model, with seven factors, provided the best fit to the correlations among items in the NBRS, indicating the multidimensionality of problematic behaviors and symptoms exhibited by dementia patients. CONCLUSION: Authors advocate the use of a confirmatory factor-analytic approach to verify scale sub-domains in other, more widely used rating scales for patients with dementia.