Joel Bobula

Household Members of Persons with Alzheimer's Disease: Health Conditions, Healthcare Resource Use, and Healthcare Costs

To compare medical condition burden, healthcare resource use, and healthcare costs of household members (HHMs) of individuals diagnosed with Alzheimers disease (AD) with those of HHMs of matched individuals without AD.

The Association Between Vulvovaginal Atrophy Symptoms and Quality of Life Among Postmenopausal Women in the United States and Western Europe

BACKGROUND Vulvovaginal atrophy (VVA) is a condition associated with decreased estrogenization of the vaginal tissue, which can result in vaginal dryness, irritation, and dyspareunia. This study quantified the burden associated with VVA symptoms across the United States and Europe and compared this burden with other chronic conditions. METHODS Data were analyzed from the International Womens Health Study, a cross-sectional Internet survey of women aged 40-75 years in the United States and Europe. All postmenopausal women aged 40-75 years were included in the analyses (Germany n=970, Spain n=294, France n=1054, Italy n=387, United Kingdom n=1096, United States n=3267). VVA symptom severity (none, mild, moderate, severe) was assessed using the Menopause Rating Scale and included in general linear models to predict EuroQol-5D (EQ-5D) quality of life scores. RESULTS The prevalence of VVA symptoms varied between 40.00% (Germany) and 54.42% (Spain), with half of women reporting their symptoms as either moderate or severe. Pooling data from all countries together, each incremental level of severity (none through severe) was associated with a significant decrement in EQ-5D scores (none=0.84 vs. mild=0.81 vs. moderate=0.79 vs. severe=0.74; p<0.05). The decrements in EQ-5D scores associated with moderate to severe VVA symptoms were comparable to those observed in other serious conditions including arthritis, chronic obstructive pulmonary disease, asthma, and irritable bowel syndrome. CONCLUSIONS VVA symptoms are associated with clinically meaningful decrements in quality of life that may be comparable to serious conditions such as arthritis, chronic obstructive pulmonary disease, asthma, and irritable bowel syndrome. Improved management of VVA symptoms may be required to alleviate the impact of VVA on the quality of life of affected women.

Quality of Life and Utility Measurement in a Large Clinical Trial Sample of Patients with Mild to Moderate Alzheimer's Disease: Determinants and Level of Changes Observed.

OBJECTIVE To evaluate the performance (in terms of responsiveness to change, associations with other criterion standards, and indicators of Alzheimers disease [AD] severity) of a quality-of-life measure (Quality of Life in Alzheimers Disease [QOL-AD]) and a health utility measure (Health Utilities Index Mark 3 [HUI-3]) from two recently completed clinical trials of a new drug for AD. METHODS Change from baseline scores was calculated, and treatment effects were analyzed using mixed models for repeated measures. Three separate models were then estimated to examine the association between the quality-of-life/utility end points and the clinical and other health outcome end points measured during the trials, including cognition, function, behavior, and dependence. RESULTS The performance of the two measures differed. Subject-assessed QOL-AD was found to be weakly associated with clinical measures of cognition, and with caregiver reports of function, behavior, and dependence, and showed little movement over time and did not appear to differ by baseline AD severity. Proxy-assessed QOL-AD scores were consistently lower than subject-assessed scores, and the level of decline in QOL-AD was greater using proxy-assessed QOL-AD. Proxy-assessed HUI-3 scores were more strongly associated with clinical measures of cognition, function, behavior, and dependence than the subject- and proxy-assessed QOL-AD scores. Larger proportionate changes over 78 weeks were observed with HUI-3 scores and greater separation in HUI-3 scores by baseline severity. CONCLUSIONS Subject-assessed QOL-AD is less likely than proxy-assessed QOL-AD to respond to changes in clinical measures used to track progression in clinical trials of subjects with mild to moderate AD. Proxy-assessed HUI-3 assessments were more in line with other outcome assessments and could therefore be better outcome measures to evaluate clinical progression in mild to moderate AD.

COPD exacerbations associated with the modified Medical Research Council scale and COPD assessment test among Humana Medicare members

Background The Global initiative for chronic Obstructive Lung Disease guidelines recommend assessment of COPD severity, which includes symptomatology using the modified Medical Research Council (mMRC) or COPD assessment test (CAT) score in addition to the degree of airflow obstruction and exacerbation history. While there is great interest in incorporating symptomatology, little is known about how patient reported symptoms are associated with future exacerbations and exacerbation-related costs. Methods The mMRC and CAT were mailed to a randomly selected sample of 4,000 Medicare members aged >40 years, diagnosed with COPD (≥2 encounters with International Classification of Dis eases-9th Edition Clinical Modification: 491.xx, 492.xx, 496.xx, ≥30 days apart). The exacerbations and exacerbation-related costs were collected from claims data during 365-day post-survey after exclusion of members lost to follow-up or with cancer, organ transplant, or pregnancy. A logistic regression model estimated the predictive value of exacerbation history and symptomatology on exacerbations during follow-up, and a generalized linear model with log link and gamma distribution estimated the predictive value of exacerbation history and symptomatology on exacerbation-related costs. Results Among a total of 1,159 members who returned the survey, a 66% (765) completion rate was observed. Mean (standard deviation) age among survey completers was 72.0 (8.3), 53.7% female and 91.2% white. Odds ratios for having post-index exacerbations were 3.06, 4.55, and 16.28 times for members with 1, 2, and ≥3 pre-index exacerbations, respectively, relative to members with 0 pre-index exacerbations (P<0.001 for all). The odds ratio for high vs low symptoms using CAT was 2.51 (P<0.001). Similarly, exacerbation-related costs were 73% higher with each incremental pre-index exacerbation, and over four fold higher for high-vs low-symptom patients using CAT (each P<0.001). The symptoms using mMRC were not statistically significant in either model (P>0.10). Conclusion The patient-reported symptoms contribute important information related to future COPD exacerbations and exacerbation-related costs beyond that explained by exacerbation history.

Informal Care Time and Cost in a Large Clinical Trial Sample of Patients with Mild to Moderate Alzheimer’s Disease: Determinants and Level of Change Observed

IntroductionWe evaluate the association between caregiver (informal) time/cost and illness severity from two recently completed clinical trials of an investigational drug for Alzheimer’s disease (AD).MethodsChanges from baseline caregiver time were calculated and treatment effects analyzed using a restricted maximum likelihood-based mixed model for repeated measures. Four separate models were then estimated to examine the association between caregiver time costs and the clinical endpoints measured during the trials, including cognition (MMSE), function (DAD), behavior (NPI), global disability (CDR) and dependence (DS).ResultsCaregiver time cost was significantly associated with all clinical measures of illness severity with a 1-unit change in MMSE, DAD, NPI, CDR and DS associated with a 11.57%, 4.81–4.97%, 3.58–3.67%, 42.52% and 71.05% change, respectively, in primary caregiver time cost. The association between caregiver time cost and DS was the strongest of all the associations examined.ConclusionCaregiver time costs increase with increasing AD severity in all key domains of AD (cognition, function, behavior, global disability and dependence on others). Our analysis demonstrated that patient dependence is a particularly important predictor of caregiver time costs and should be considered as a potential outcome measure in intervention clinical trials in AD.FundingPfizer Inc. and Janssen Alzheimer Immunotherapy Research and Development.

Hot flush frequency and severity at baseline as predictors of time to transient and stable treatment success: pooled analysis of two Ce/bza studies

Objective: To evaluate the impact of baseline hot flush frequency and severity on time to symptom improvement during treatment with conjugated estrogens/bazedoxifene (CE/BZA). Methods: Data were pooled through week 12 from two randomized placebo-controlled trials (SMART-1 and SMART-2) of nonhysterectomized postmenopausal women with hot flushes treated with CE 0.45 mg/BZA 20 mg or CE 0.625 mg/BZA 20 mg. Time to transient and stable improvement (≥ 50% reduction in hot flush frequency/severity) was estimated using nonparametric models. Results: Transient improvement in hot flush frequency occurred earlier in women treated with CE 0.45 mg/BZA 20 mg with less frequent versus more frequent baseline hot flushes per day: median time to transient improvement was 2, 7, and 11 days for women with < 3, 3 to < 8, and ≥ 8 hot flushes per day at baseline, respectively (P = 0.0009). Transient improvement in severity occurred earlier for women with less severe versus more severe baseline hot flushes: median time to transient improvement was 2, 6, and 16 days for women with mild, moderate, and severe hot flushes at baseline, respectively (P < 0.0001). Stable improvement typically occurred 2 to 3 days after the transient event and was less influenced by baseline status. A similar pattern was observed with CE 0.625 mg/BZA 20 mg treatment, though improvement occurred a few days earlier than with CE 0.45 mg/BZA 20 mg. Conclusion: Women with more frequent/severe hot flushes take longer to achieve transient improvements with CE/BZA and should be encouraged to continue treatment, as it may take longer than a few weeks to achieve significant improvement.

Time to transient and stable reductions in hot flush frequency in postmenopausal women using conjugated estrogens/bazedoxifene

Objective: This post hoc analysis estimates time to transient and stable reductions in hot flush frequency in postmenopausal women using conjugated estrogens/bazedoxifene. Methods: In the 12-week Selective estrogens, Menopause, And Response to Therapy (SMART)-2 trial of conjugated estrogens/bazedoxifene 0.45 mg/20 mg and 0.625 mg/20 mg, women with at least seven moderate/severe hot flushes per day or 50 per week at screening recorded frequency of moderate/severe hot flushes in diaries. Nonparametric models and SAS Proc Lifetest were used to estimate median times to various degrees of transient reductions (first day with improvement) and stable reductions (first day with improvement maintained through studys end) in hot flush frequency. Results: Treatment produced transient hot flush reductions of 40% to 100% and stable reductions of 30% to 100% significantly faster than placebo. Median time to a transient 50% reduction was 8 days for conjugated estrogens/bazedoxifene 0.45 mg/20 mg, 9.5 for 0.625 mg/20 mg, and 10 for placebo; median time to a stable 50% reduction was 9, 10, and 38 days. Median time to a transient 90% reduction was 32 and 22.5 days for 0.45 mg/20 mg and 0.625 mg/20 mg, and median time to a stable 90% reduction was 83 and 29 days, respectively; median times to transient/stable 90% reductions were not reached during the 12-week study in the placebo group. Conclusions: Although not all women using conjugated estrogens/bazedoxifene achieve permanent elimination of hot flushes, the frequency is likely to be substantially reduced during the first week to month. Women can expect approximately 50% reduction in hot flush frequency after about 8 to 10 days, and sustained improvement with continued treatment.

Time to first occurrence of breast pain and vaginal bleeding in phase 3 trials of Ce/bza

Objective: In studies of the menopausal therapy, conjugated estrogens/bazedoxifene, breast pain and vaginal bleeding rates were comparable to placebo and lower than conjugated estrogens/medroxyprogesterone acetate (MPA). This post hoc analysis determined median time to occurrence of these events. Methods: Participants in phase 3 conjugated estrogens/bazedoxifene trials recorded breast pain and vaginal bleeding in daily diaries. Median time to first incident was determined in women taking conjugated estrogens 0.45 mg/bazedoxifene 20 mg, conjugated estrogens 0.625 mg/bazedoxifene 20 mg, placebo, and conjugated estrogens 0.45 mg/MPA 1.5 mg (active control in Selective estrogens, Menopause, And Response to Therapy [SMART]-5 trial). We included on-treatment data (12 weeks-2 years) in healthy postmenopausal women (SMART-1), those seeking treatment for menopausal symptoms (SMART-5), and those with moderate/severe vasomotor symptoms (SMART-2). Analyses were performed using SAS Proc Lifetest. Results: With conjugated estrogens/MPA as comparator, median time to breast pain was 299 days for conjugated estrogens/MPA, 353 for placebo, and more than 365 (median not reached) for conjugated estrogens 0.45 mg/bazedoxifene 20 mg and conjugated estrogens 0.625 mg/bazedoxifene 20 mg. Median time to vaginal bleeding was 314, 341, 357, and 362 days, respectively. Breast pain and vaginal bleeding survival curves were not significantly different for conjugated estrogens/bazedoxifene and placebo in any study, but were (P < 0.0001) when conjugated estrogens/MPA was added to the sample in SMART-5. Conclusions: The time course of breast pain and vaginal bleeding with conjugated estrogens/bazedoxifene was similar to that of placebo during treatment for up to 2 years. Events occurred significantly earlier with conjugated estrogens/MPA versus conjugated estrogens/bazedoxifene or placebo.

PREDICTING THE HEALTH ECONOMIC IMPACT OF EARLY TREATMENT IN PRE-DEMENTIA ALZHEIMER’S DISEASE

Framework analysis was conducted to identify themes or consistencies in the data.Results:Preliminary findings suggest that blurred boundaries, the need for communication, the constant flux of a home care worker’s role and their perceptions of a client’s death were important factors in their work. This paper elaborates on the theme of “perceptions of a client’s death”. This encompasses participants’ experiences of a client’s death; the relevance of ‘emotional labour’ to explain the impact of their actions and reactions; and support in place to contextualise their experiences. Participants described close relationships with clients, at times resulting in strong attachments that made the process of grieving harder. A blurring of boundaries was reported regarding their role when the client’s death occurred, with some families wanting to be left alone, whilst current employment practices require the worker to stay in the home until professionals arrived. Moreover, home care workers were generally instructed not to touch the body, while some family requested assistance with cleaning, laying out, preparing or moving the body. Participants reported a range of sources of support, mainly from personal family and friends, and other colleagues. However, only a small proportion of staff reported being offered individual telephone support or group supervision to discuss work experiences. Many worked in isolation and felt there were few avenues for support from their employers. Conclusions: Home care workers provide care to people with dementia at the end of life in isolation, with many experiencing lack of clarity in their caring role and limited support as their client nears the end of their life. Preliminary findings from this study may be helpful in developing support resources for home care practice and human resources management.

Assessing the economic value of potential disease-modifying agents in Alzheimer's disease using simulation

not available. P2-299 TENDENCIES OF TREATMENTAMONG PEOPLE WITH ALZHEIMER’S DISEASE IN MEXICO: FINDINGS FROM THE NATIONAL DEMENTIA SURVEY—STUDY FROM THE MEXICAN GROUP OF SPECIALISTS IN DEMENTIAS Santiago Ramirez Diaz, Carolina Gomez, Leonardo Barba, Guillermo Albert, Sarug Reyes, Jose Antonio Caldera, Juan Pablo Acero, Claudia Medina, Biomedical Research Institute, Aguascalientes, Mexico; Spanish Hospital, Mexico City, Mexico. Contact e-mail: ramirezdiazsp@gmail.com Table 3 Spearman correlation between costs and caregiver burden (Zarit in Total Score) for the total sample and stratified by severity of dementia among patients. Variables ZARIT (total score) Total sample Mild Moderate Severe Rho p-value Rho p-value Rho p-value Rho pvalue Indirect Costs Time/ Cost expensive with ADL h/day 0.14 0.309 0.40 0.046 -0.12 0.610 0.18 0.618 R