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Margaret K Pasquale,1 Yihua Xu,1 Christine L Baker,2 Kelly H Zou,3 John G Teeter,4 Andrew M Renda,5 Cralen C Davis,1 Theodore C Lee,6 Joel Bobula2 1Comprehensive Health Insights, Inc., Humana Inc., Louisville, KY, 2Outcomes and Evidence, Global Health & Value, Pfizer Inc., 3Statistical Center for Outcomes, Real-World and Aggregate Data, Global Innovative Pharma Business, Pfizer Inc., New York, NY, 4Global Medical Development, Global Innovative Pharma Business, Pfizer Inc., Groton, CT, 5Retail Strategy & Execution, Humana Inc., Louisville, KY, 6Global Medical Affairs, Global Innovative Pharma Business, Pfizer Inc., New York, NY, USA 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 Dis­eases-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 (P0.10).Conclusion: The patient-reported symptoms contribute important information related to future COPD exacerbations and exacerbation-related costs beyond that explained by exacerbation history. Keywords: Global initiative for chronic Obstructive Lung Disease, COPD symptomatology, exacerbations, exacerbation-related cost, survey data

Objective To evaluate the effects of the tissue selective estrogen complex (TSEC) pairing bazedoxifene (BZA) with conjugated estrogens (CE) on sexual function and quality of life in postmenopausal women. Methods In this 12-week, double-blind, placebo-controlled study, postmenopausal, non-hysterectomized women ( n = 652) with symptoms of moderate to severe vulvar/vaginal atrophy were randomized to once-daily treatment with BZA 20 mg/CE 0.45 or 0.625 mg, BZA 20 mg, or placebo. The Arizona Sexual Experiences (ASEX) Scale, Menopause-Specific Quality of Life (MENQOL) questionnaire, and Menopause Symptoms Treatment Satisfaction Questionnaire (MS-TSQ) were secondary measures used to assess the effects of BZA/CE on sexual function, menopausal symptoms, and satisfaction with treatment, respectively. Results At week 12, both BZA/CE doses were associated with significant improvement in ease of lubrication score from baseline compared with placebo ( p < 0.05) on the ASEX scale, although there was no difference in the change in total score. The MENQOL questionnaire results at week 12 showed significant improvements in vasomotor function, sexual function and total scores with both BZA/CE doses vs. placebo or BZA 20 mg ( p < 0.001). The MS-TSQ results showed that BZA/CE-treated subjects reported significantly greater overall satisfaction with treatment, as well as satisfaction with control of hot flushes during the day and night, effect on quality of sleep, and effect on mood or emotions, compared with subjects treated with placebo or BZA 20 mg (all p < 0.05). Conclusion Treatment with BZA/CE for 12 weeks was shown to significantly improve sexual function and quality-of-life measures in symptomatic postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: Families have faced unprecedented challenges during the COVID-19 pandemic, leading to increased maternal mental health problems and barriers to accessing care. Innovative programs are needed to support both maternal mental health and parenting, and to buffer the long-term impacts of stress on young children. Using a patient-oriented approach, our research team aimed to co-develop and pilot test an App-based psychoeducation and social-connection platform: Building Emotional Awareness and Mental Health (BEAM)., Methods: The co-development process involved a parent advisory board from conceptualization and design, through to direct participation in the program delivery. The BEAM program includes weekly videos and activities based on Unified Protocol therapy modules and emotion-focused parenting strategies, a weekly telehealth group review session, and access to a private online forum for support from other mothers and clinical coaches. A parallel randomized control trial was conducted across two provinces in Canada. Mothers of preschool children (aged 18-36 months old), with moderate-to-severe depression (Patient Health Questionaire-9 ≥ 10), were recruited online and randomized to either the 10-week BEAM intervention or treatment as usual (TAU) control group. Online surveys (ensuring researcher blinding) included questions about feasibility and acceptability of the program and pre/post self-report measures of mental health, parenting, positive coping and child behavior outcomes. The primary outcome measures were symptoms of depression and parenting stress. Data were analyzed using mixed models and an intention-to-treat approach., Results: 65 participants were randomized, by an online allocation tool, to the BEAM ( n = 33) and TAU ( n = 32) groups. Engagement was relatively high at the beginning of the program, with 78.8% starting the BEAM App and 70.6% attending ≥1 telehealth session. Most respondents felt socially supported, satisfied with the App, and found it easy to use. Pre-post results indicated interaction effects with greater reductions in overall mental health problems, and specifically anxiety and sleep symptoms, among BEAM vs. control participants. There were also time effects with reductions in depression symptoms across both groups. No significant treatment effects emerged for the other mental health symptoms, parenting problems, positive coping, or child behavior outcomes. Descriptive data are included to highlight possible areas of promise for future large efficacy trials. Technological difficulties and other challenges that may have led to attrition and impacted outcomes are discussed. There were no adverse events related to study participation., Conclusions: The BEAM program has promise as a novel, feasible and acceptable intervention for improving mental health among mothers of young children., Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04772677]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 MacKinnon, Simpson, Salisbury, Bobula, Penner-Goeke, Berard, Rioux, Giesbrecht, Giuliano, Lebel, Protudjer, Reynolds, Sauer-Zavala, Soderstrom, Tomfohr-Madsen and Roos.)

Background: Research to date on sprains, strains, and contusions has focused mainly on the analysis of sports-related injuries, occupational injuries, injuries resulting from automobile accidents, and severe injuries that result in inpatient hospital stays. Little is known about real-world acute sprains, strains, and contusions in an aging population. Patients may be treated with over-the-counter, oral, non-steroidal anti-inflammatory drugs (NSAIDs) for acute sprains, strains, and contusions or may require the use of prescription NSAIDs. For sprains, strains, and contusions treated with prescription NSAIDs, the choice of topical administration or oral administration likely depends on a number of factors such as age and comorbid conditions., Objectives: The objective of the study was to identify factors associated with the use of a prescription topical NSAID or a prescription oral NSAID for the treatment of sprains, strains, and contusions among patients aged 65-89 years enrolled in the Medicare Advantage with Prescription Drug plan., Methods: The study sample was selected from the Humana Research Database (Louisville, KY, USA). Study subjects were identified as patients enrolled in Medicare Advantage with Prescription Drug plans, aged 65-89 years, having a medical claim with an International Classification of Diseases, Ninth Revision, Clinical Modification indicative of an acute sprain, strain, and contusion between 1 January, 2010 and 31 March, 2014 (identification period). The date of the first claim was considered the index date, and subjects were required to have 12 months of continuous enrollment before the index date and a minimum of 3 months continuous enrollment after the index date. Prescription NSAID use during the 3 months after the index sprain, strain, and contusion diagnosis was required for study inclusion and was identified based on a pharmacy claim for a topical or an oral NSAID. Patients with prescription NSAID use leading up to the sprains, strains, and contusions were excluded. Potential factors related to the use of a topical vs. oral NSAID were identified using stepwise logistic regression with backward elimination., Results: After applying the inclusion and exclusion criteria, 42,283 patients were prescribed an oral or topical NSAID (39,294 oral; 2989 topical) within 3 months of the index sprain, strain, and contusion diagnosis. After applying stepwise logistic regression, and retaining variables with statistically significant parameter estimates (p < 0.05), use of topical NSAIDs was higher among female individuals [odds ratio and 95% confidence interval = 1.34 (1.24-1.45)], and appeared to increase with age [odds ratio = 1.04 (1.04-1.05)]. Topical NSAID use was lower in the Midwest region [odds ratio = 0.85 (0.77-0.94)] in comparison to the Southern region. Clinical factors associated with topical NSAID use included Elixhauser Comorbidity Index score [odds ratio = 1.06 (1.04-1.09)], medication burden [odds ratio = 1.06 (1.04-1.08), pill burden [odds ratio = 1.02 (1.01-1.03), specific comorbid conditions, including site-specific osteoarthritis of the upper arm [odds ratio = 2.34 (1.19-4.60)], ankle/foot [odds ratio = 1.46 (1.14-1.87)], or lower leg [odds ratio = 1.21 (1.07-1.36)], myofascial pain [odds ratio = 1.31 (1.21-1.42)], gastrointestinal/hepatic disorders [odds ratio = 1.15 (1.05-1.25)], systemic/central pain [odds ratio = 1.12 (1.01-1.23)], and cataracts [odds ratio = 1.10 (1.02-1.20)]. Conversely, a diagnosis of diabetes mellitus was related to use of an oral NSAID rather than a topical NSAID [odds ratio = 0.86 (0.78-0.94)]. Diagnosis of the index sprain, strain, and contusion in an emergency department instead of a physician's office was also associated with oral NSAID use [odds ratio = 0.42 (0.37-0.47)]., Conclusions: Topical NSAIDs were used less often than oral NSAIDs following a sprain, strain, or contusion. Age, medication burden, pill burden, evidence of gastrointestinal disorder, and evidence of certain pain-related conditions were significant factors associated with topical NSAID as opposed to oral NSAID use. In comparison to oral NSAIDs, topical NSAIDs were more likely to be prescribed in a physician's office than an emergency department, possibly because a patient's physician has a better understanding of the patient's concomitant medications and comorbidities. Although topical NSAIDs were more likely to be used than oral NSAIDs in patients with gastrointestinal disorders, the use of oral NSAIDs among patients with gastrointestinal bleeding was substantial.

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.

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.

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 study's 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.

Introduction: We 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)., Methods: Changes 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)., Results: Caregiver 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., Conclusion: Caregiver 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., Funding: Pfizer Inc. and Janssen Alzheimer Immunotherapy Research and Development.

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 Women's 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.

Objective: To evaluate the performance (in terms of responsiveness to change, associations with other criterion standards, and indicators of Alzheimer's disease [AD] severity) of a quality-of-life measure (Quality of Life in Alzheimer's 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., (Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: There has been an increasing interest in the relationship between severity of disease and costs in the care of people with dementia. Much of the current evidence is based on cross-sectional data, suggesting the need to examine trends over time for this important and growing cohort of the population., Methods: This paper estimates resource use and costs of care based on longitudinal data for 72 people with dementia in Ireland. Data were collected from the Enhancing Care in Alzheimer's Disease (ECAD) study at two time points: baseline and follow-up, two years later. Patients' dependence on others was measured using the Dependence Scale (DS), while patient function was measured using the Disability Assessment for Dementia (DAD) scale. Univariate and multivariate analysis were used to explore the effects of a range of variables on formal and informal care costs., Results: Total costs of formal and informal care over six months rose from €9,266 (Standard Deviation (SD): 12,947) per patient at baseline to €21,266 (SD: 26,883) at follow-up, two years later. This constituted a statistically significant (p = 0.0014) increase in costs over time, driven primarily by an increase in estimated informal care costs. In the multivariate analysis, a one-point increase in the DS score, that is a one-unit increase in patient's dependence on others, was associated with a 19% increase in total costs (p = 0.0610)., Conclusions: Higher levels of dependence in people with Alzheimer's disease are significantly associated with increased costs of informal care as the disease progresses. Formal care services did not respond to increased dependence in people with dementia, leaving it to families to fill the caring gap, mainly through increased supervision with the progress of disease.

Background: Considerable advances have been made in modeling Alzheimer's disease (AD), with a move towards individual-level rather than cohort models and simulations that consider multiple dimensions when evaluating disease severity. However, the possibility that disease-modifying agents (DMAs) may emerge requires an update of existing modeling frameworks., Objectives: The aim of this study was to develop a simulation allowing for economic evaluation of DMAs in AD., Methods: The model was developed based on a previously published, well-validated, discrete event simulation which measures disease severity on the basis of cognition, behaviour, and function, and captures the interrelated changes in these measures for individuals. The updated model adds one more domain, patient dependence, in addition to cognition, behaviour, and function to better characterize disease severity. Furthermore, the model was modified to have greater flexibility in assessing the impact of various important assumptions, such as the long-term effectiveness of DMAs and their impact on survival, on model outcomes. A validation analysis was performed to examine how well the model predicted change in disease severity among patients not receiving DMA treatment by comparing model results to those observed in two recent phase III clinical trials of bapineuzumab. In addition, various hypothetical scenarios were tested to demonstrate the improved features of the model., Results: Validation results show that the model closely predicts the mean changes in disease severity over 18 months. Results from different hypothetical scenarios show that the model allows for credible assessment of those major uncertainties surrounding the long-term effectiveness of DMAs, including the potential impact of improved survival with DMA treatment. They also indicate that varying these assumptions could have a major impact on the value of DMAs., Conclusions: The updated economic model has good predictive power, but validation against longer-term outcomes is still needed. Our analyses also demonstrate the importance of designing a model with sufficient flexibility such that the model allows for assessment of the impact of key sources of uncertainty on the value of DMAs.

Objectives: To compare medical condition burden, healthcare resource use, and healthcare costs of household members (HHMs) of individuals diagnosed with Alzheimer's disease (AD) with those of HHMs of matched individuals without AD., Design: Retrospective cohort study based on administrative claims data collected between January 1, 2007, and December 31, 2011., Setting: Medicare Advantage Prescription Drug (MAPD) plan., Participants: MAPD plan members with a diagnosis of AD (International Classification of Disease Ninth Revision, Clinical Modification, code 331.0) were selected and linked to a HHM to form patient-HHM dyads. AD dyads were matched to non-AD dyads., Measurements: Health-related endpoints, including medical condition burden, healthcare resource use, and direct healthcare costs, were measured during 36 months of continuous health plan enrollment., Results: Individuals with AD (n = 1,861) were linked to HHMs (n = 1,861), and these AD dyads were matched to 1,861 non-AD patient-HHM dyads. AD HHMs had greater medical condition burden scores than non-AD HHMs, with mood disorders, anxiety disorders, insomnia, substance abuse or dependence, cardiovascular disease, and rheumatoid arthritis being more prevalent in AD HHMs. Emergency department and outpatient service use were more common in AD HHMs than in non-AD HHMs, and AD HHMs had greater healthcare costs., Conclusion: HHMs of individuals diagnosed with AD demonstrated greater medical condition burden, healthcare resource use, and direct healthcare costs than non-AD HHMs. These findings demonstrate the significant clinical and financial impact of AD on HHMs of individuals with AD., (© 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.)

Objective: To assess the effects of bazedoxifene/conjugated estrogens (BZA/CE) on sleep parameters and health-related quality of life (HR-QOL)., Methods: This was a 12-week, multicenter, double-blind, placebo-controlled phase 3 study. Postmenopausal women with an intact uterus and experiencing >or=7 moderate-to-severe hot flushes daily were randomized to BZA 20 mg/CE 0.45 mg, BZA 20 mg/CE 0.625 mg, or placebo. In these secondary efficacy analyses, the Medical Outcomes Study (MOS) sleep scale and Menopause-Specific Quality of Life (MENQOL) questionnaires and the Menopause Symptoms Treatment Satisfaction Questionnaire (MS-TSQ) evaluated measures of sleep, menopausal symptoms, and satisfaction with treatment, respectively., Results: A total of 318 subjects (mean age, 53.4 years) received >or=1 dose of study drug. At Week 12, BZA 20 mg/CE 0.45 and 0.625 mg showed significant improvements over placebo in the MOS sleep scale for time to fall asleep, sleep adequacy, sleep disturbance, and sleep problems indexes I and II (P<0.001). A reduction in hot flush frequency was significantly associated with improvement in sleep parameters (P<0.05) based on linear regression and responder analyses. Both BZA/CE doses showed significantly greater improvements over placebo in vasomotor function and total MENQOL score (P<0.001). Results of the MS-TSQ showed that subjects treated with BZA/CE versus placebo reported significantly greater overall satisfaction with treatment (P<0.05), as well as greater satisfaction with sleep quality, ability to control hot flushes during the day and night, effect on mood/emotions, and tolerability., Conclusion: Symptomatic postmenopausal women treated with BZA/CE experienced significant improvements in sleep parameters and overall HR-QOL.

Background: Several studies suggest that the gender of patients and their healthcare providers affects overall patient satisfaction., Aims: We sought to determine whether the gender of patients or providers was associated with the number of complaints filed by patients against providers., Methods: In this case-controlled study, complaints from a health maintenance organisation were analysed for gender disparity during a 12-month period., Results: The odds ratio for patients' female gender to be associated with complaints was 3.10 (95% confidence interval 1.73-5.55, P<0.001). Women were also more likely than men to cite providers' behaviour as the cause of complaints. No significant associations were noted between the number of complaints and a complainant's age, diagnosis of chronic pain or psychiatric illness, or with the provider's gender, age or length of employment in the organisation. The heterogeneity of gender effect demonstrated in the literature suggests that this effect is likely to be unique to the different practice settings., Conclusion: Evaluating the presence of this phenomenon in the different practice settings is recommended, to improve patient satisfaction and subsequently the quality of care.

Objective: The health care workforce is evolving and part-time practice is increasing. The objective of this work is to determine the relationship between part-time status, workplace conditions, and physician outcomes., Design: Minimizing error, maximizing outcome (MEMO) study surveyed generalist physicians and their patients in the upper Midwest and New York City., Measurements and Main Results: Physician survey of stress, burnout, job satisfaction, work control, intent to leave, and organizational climate. Patient survey of satisfaction and trust. Responses compared by part-time and full-time physician status; 2-part regression analyses assessed outcomes associated with part-time status. Of 751 physicians contacted, 422 (56%) participated. Eighteen percent reported part-time status (n = 77, 31% of women, 8% of men, p < .001). Part-time physicians reported less burnout (p < .01), higher satisfaction (p < .001), and greater work control (p < .001) than full-time physicians. Intent to leave and assessments of organizational climate were similar between physician groups. A survey of 1,795 patients revealed no significant differences in satisfaction and trust between part-time and full-time physicians., Conclusions: Part-time is a successful practice style for physicians and their patients. If favorable outcomes influence career choice, an increased demand for part-time practice is likely to occur.

Background: Clinical medicine and healthcare policy are increasingly guided by randomized controlled trials, which in turn are dependent on the validity of placebo control. It is important to understand the effects of placebo control on outcome measurement, especially for assessment of symptoms and functional impairments where subjectivity, expectancy, and motivation may significantly impact outcome evaluation. This paper describes the rationale and methodology of a trial designed to evaluate placebo effects related to taking pills and to compare these with effects attributable to standard or enhanced (patient-oriented) doctor-patient interaction., Design: This trial uses two-way factorial allocation to randomize people with new onset common cold in two directions: pill related and doctor related. In one direction, participants are randomized to (1) no pills, (2) blinded placebo, (3) blinded echinacea, or (4) unblinded open-label echinacea. In the other direction, participants are randomized to: (1) no doctor-patient interaction, (2) standard doctor-patient interaction, and (3) enhanced doctor-patient interaction. Enhanced interaction includes education, empathy, empowerment, positive prognosis, and connectedness. Area under the time severity curve is the primary outcome, with the Wisconsin Upper Respiratory Symptom Survey (WURSS-21) the measure of severity. A priori power studies called for a sample size of N = 720 trial finishers to detect 15% to 20% between-group differences in this outcome. Secondary outcomes include general health-related quality of life, perceived stress, interpersonal support, optimism, patient satisfaction, and positive and negative affectivity. Two biomarkers are also assessed: interleukin-8 (inflammatory cytokine) and neutrophil count from nasal wash., Importance: This paper describes the rationale and methodology of a trial assessing placebo effects related to pills and to doctor-patient interaction. This is one of very few similar studies and is the first in the common cold. Data collected will also provide an excellent opportunity to investigate relationships among demographic (age, sex, education, income) and psychosocial (perceived stress, interpersonal support, optimism, affectivity) indicators in relation to common cold outcomes.

The malfunctioning of molecular chaperones may result in uncovering genetic variation. The molecular basis of this phenomenon remains largely unknown. Chaperones rescue proteins unfolded by environmental stresses and therefore they might also help to stabilize mutated proteins and thus mask damages. To test this hypothesis, we carried out a genomewide mutagenesis followed by a screen for mutations that were synthetically harmful when the RAC-Ssb1/2 cytosolic chaperones were inactive. Mutants with such a phenotype were found and mapped to single nucleotide substitutions. However, neither the genes identified nor the nature of genetic lesions implied that folding of the mutated proteins was being supported by the chaperones. In a second screen, we identified temperature-sensitive (ts) mutants, a phenotype indicative of structural instability of proteins. We tested these for an association with sensitivity to loss of chaperone activity but found no such correlation as might have been expected if the chaperones assisted the folding of mutant proteins. Thus, molecular chaperones can mask the negative effects of mutations but the mechanism of such buffering need not be direct. A plausible role of chaperones is to stabilize genetic networks, thus making them more tolerant to malfunctioning of their constituents.

Purpose: The number of problems managed concurrently by family physicians during patient encounters has not been fully explored despite the implications for quality assessment, guideline implementation, education, research, administration, and funding. Our study objective was to determine the number of problems physicians report managing at each visit and compare that with the number reflected in the chart and the bill., Methods: Twenty-nine members of the Wisconsin Research Network reported on encounters with 572 patients using a physician problem log. The patient chart notes and the diagnoses submitted for billing from the encounters were compared with the information in these logs., Results: The physicians reported managing an average of 3.05 problems per encounter and recorded 2.82 in the chart and 1.97 on the bill. For all patients, 37% of encounters addressed more than 3 problems, and 18% addressed more than 4. For patients older than 65 years, there was an average of 3.88 problems at each visit, and for diabetic patients there was an average of 4.60. There was evidence for the selective omission of mental health and substance problems from the diagnoses used for billing., Conclusions: Family medicine involves the concurrent care of multiple problems, which billing data do not adequately reflect. Our findings suggest a mismatch between family medicine and current approaches to quality assessment, guideline implementation, education, research, administration, and funding. Activities in all these areas need to address the physician's task of prioritizing and integrating care for multiple problems concurrently.

Objectives: To test whether daily hypertonic saline nasal irrigation improves sinus symptoms and quality of life and decreases medication use in adult subjects with a history of sinusitis., Study Design: Randomized controlled trial. Experimental subjects used nasal irrigation daily for 6 months., Population: Seventy-six subjects from primary care (n=70) and otolaryngology (n=6) clinics with histories of frequent sinusitis were randomized to experimental (n=52) and control (n=24) groups., Outcomes Measured: Primary outcome measures included the Medical Outcomes Survey Short Form (SF-12), the Rhinosinusitis Disability Index (RSDI), and a Single-Item Sinus-Symptom Severity Assessment (SIA); all 3 were completed at baseline, 1.5, 3, and 6 months. Secondary outcomes included daily assessment of compliance and biweekly assessment of symptoms and medication use. At 6 months, subjects reported on side effects, satisfaction with nasal irrigation, and the percentage of change in their sinus-related quality of life., Results: No significant baseline differences existed between the 2 groups. Sixty-nine subjects (90.8%) completed the study. Compliance averaged 87%. Experimental group RSDI scores improved from 58.4 -/+ 2.0 to 72.8 -/+ 2.2 (P < or =.05) compared with those of the control group (from 59.6 -/+ 3.0 to 60.4 -/+ 1.1); experimental group SIA scores improved from 3.9 -/+ 0.1 to 2.4 -/+ 0.1 (P < or =.05) compared with those of the control group (from 4.08 -/+ 0.15 to 4.07 -/+ 0.27). The number needed to treat to achieve 10% improvement on RSDI at 6 months was 2.0. Experimental subjects reported fewer 2-week periods with sinus-related symptoms (P <.05), used less antibiotics (P <.05), and used less nasal spray (P =.06). On the exit questionnaire 93% of experimental subjects reported overall improvement of sinus-related quality of life, and none reported worsening (P <.001); on average, experimental subjects reported 57 -/+ 4.5% improvement. Side effects were minor and infrequent. Satisfaction was high. We found no statistically significant improvement on the SF-12., Conclusions: Daily hypertonic saline nasal irrigation improves sinus-related quality of life, decreases symptoms, and decreases medication use in patients with frequent sinusitis. Primary care physicians can feel comfortable recommending this therapy.

Objective: To develop a sensitive, reliable, responsive, easy-to-use instrument for assessing the severity and functional impact of the common cold., Study Design: We created an illness-specific health-related quality-of-life outcomes instrument. This original questionnaire was used in a 1999 randomized trial of echinacea for the common cold. In 2000 we used cognitive interview and focus group qualitative methods to further develop the instrument. Semistructured interviews used open-ended questions to elicit symptoms, terminology, and perceived functional impact. Responses were used to improve the instrument., Population: The randomized trial watched 142 University of Wisconsin students for a total of 953 days of illness. The subsequent qualitative instrument development project recruited 74 adults with self-diagnosed colds for 56 in-person interviews and 3 focus groups., Outcomes Measured: We measured specific symptoms, symptom clusters (dimensions), functional impact, and global severity., Results: The original questionnaire included 20 questions: a global severity indicator, 15 symptom-severity items using 9-point severity scales, and 4 yes/no functional assessments. Data from the trial provided evidence of 4 underlying dimensions: nasal, throat, cough, and fever and aches, with reliability coefficients of 0.663, 0.668, 0.794, and 0.753, respectively. Qualitative assessments from the interviews and focus groups led us to expand from 15 to 32 symptom-specific items and from 4 to 10 functional impairment items. The original 9-point severity scale was revised to 7 points. Two global severity questions bring the item count to 44. The instrument fits comfortably on the front and back of a single sheet of paper., Conclusions: The Wisconsin Upper Respiratory Symptom Survey (WURSS) is ready for formal validity testing or practical use in common cold research.

Background and Objectives: To determine the impact of international health experiences on physicians in training, we studied 60 US medical students who participated in an International Health Fellowship Program (IHFP)., Methods: In 1995 and 1996, US medical students were selected to participate in the IHFP, which included training at three US medical schools and at seven medical schools in developing countries. The program included a 2-week preparatory course at a US school and a 6- to 8-week field experience. Evaluative data were collected prior to the course, after the course, after the field experience, and 1-2 years later., Results: A total of 60 students were selected from 145 applicants. At the end of the fellowship, a majority of participants noted that the exposure affected them in the following ways: changed world views; increased cultural sensitivity; enhanced community, social, and public health awareness; enhanced clinical and communication skills; more appropriate resource utilization; changes in career plans; and a greater understanding of the challenges of working in areas with scarce resources. After the international field experience, students more strongly agreed with the importance of oral rehydration, communication skills, and patient education. According to student self-assessments, the IHFP significantly improved core medical skills. Ninety-six percent of participants recommended international health experiences for other students., Conclusions: This study of IHFP fellows demonstrates multiple significant impacts of international health experiences on US medical students in training. The knowledge, attitudes, and skills gained through international health experiences are important for medical practice in the United States and abroad. Given the high interest of medical students in international health and the potential for positive educational impacts, medical schools should increase the availability of high-quality international experiences.

Background: Alcohol use disorders (AUDs) are prevalent in primary care patient populations. Many primary care patients with AUDs can remit without formal treatment. An understanding of the factors that predispose patients to remission may help primary care physicians provide effective brief counseling for those with mild to moderate disorders and more effectively recommend formal treatment for others., Methods: A total of 119 eligible and randomly selected primary care patients with alcohol abuse or dependence in remission (as defined in Diagnostic and Statistical Manual of Mental Disorders, third edition, revised) participated in a semistructured telephone interview., Results: Of the subjects, 59.7% were women; 50.4% had been alcohol dependent; 66.3% made a conscious decision to modify their drinking; and 62.1%, including 54.2% of the alcohol-dependent subjects, moderated their drinking without abstaining. Family, emotional, and medical issues most often prompted reduced drinking. Nearly one third of the subjects found specific strategies and rules helpful in reducing their drinking, and many cited circumstances that helped or hindered their efforts. Only 10.9% had formal alcohol treatment., Conclusions: A significant proportion of patients with AUDs remitted without formal treatment. Abstinence may not be necessary for a subset of dependent patients. When counseling patients with active AUDs, primary care clinicians are advised to counsel patients about the psychosocial and medical reasons to control drinking, promote rule-setting about drinking, help patients avoid circumstances that trigger drinking, and support patients' attempts at moderating drinking rather than abstaining. Motivational interviewing (motivational enhancement therapy) may provide a useful framework for such counseling.

Objective: To assess the frequency of osteoporosis risk assessment of postmenopausal women by family practice faculty and residents., Methods: Review of 263 charts of women over 50 from 3 residency clinics. Charts were evaluated for evidence of osteoporosis risk assessments or discussion of prevention strategies during the past 2 years., Results: Overall, 35% of the charts contained documentation of some discussion of osteoporosis. Female physicians discussed osteoporosis more than their male colleagues (p < 0.05). Documentation of osteoporosis discussions decreased as women aged (p < 0.05). There was no difference in rates among clinics or between residents and faculty., Conclusions: The documentation of osteoporosis discussions with high risk women was low in this sample. Strategies to improve osteoporosis screening are necessary.