Residual Disease Burden After Neoadjuvant Therapy Among US Patients With High-Risk HER2-positive Early-Stage Breast Cancer: A Population Effectiveness Model.

BACKGROUND: Approximately half of patients with high-risk HER2-positive early-stage breast cancer (ESBC) do not have pathologic complete response (pCR) after neoadjuvant therapy. The residual burden of disease among this population has not been previously quantified. MATERIALS AND METHODS: We used decision-modeling techniques to simulate recurrence, progression from locoregional to distant cancer, breast cancer-related mortality, and mortality from other causes over a 10-year period in a hypothetical cohort. We derived progression probabilities primarily from the KATHERINE trial of T-DM1 (ado-trastuzumab emtansine) and mortality outcomes from the published literature. Modeled outcomes included recurrences, breast cancer deaths, deaths from other causes, direct medical costs, and costs due to lost productivity. To estimate the residual disease burden, we compared outcomes from a cohort of patients treated with T-DM1 versus a hypothetical cohort with no disease recurrence. RESULTS: We estimated that 9,300 people would experience incident high-risk HER2-positive ESBC in the United States in 2021 based on cancer surveillance databases, clinical trial data, and expert opinion. We estimated that, in this group, 2,118 would experience disease recurrence, including 1,576 distant recurrences, and 1,358 would experience breast cancer deaths. This residual disease burden resulted in 6,435 life-years lost versus the recurrence-free cohort, and healthcare-related costs totaling $644 million, primarily associated with treating distant cancers. CONCLUSION: Patients with HER2-positive ESBC who do not achieve pCR after neoadjuvant therapy are at ongoing risk of recurrence despite the effectiveness of neoadjuvant treatment. There is substantial clinical and economic value in further reducing the residual disease burden in this population.

Correction to: Cost-Effectiveness Analysis of Patiromer and Spironolactone Therapy in Heart Failure Patients with Hyperkalemia.

Correction to Bounthavong M, Butler J, Dolan CM, Dunn JD, Fisher KA, Oestreicher N, Pitt B, Hauptman PJ, Veenstra DL.

Key factors to consider when measuring multimorbidity: Results from an expert panel and online survey.

BACKGROUND: There are multiple multimorbidity measures but little consensus on which measures are most appropriate for different circumstances. OBJECTIVE: To share insights gained from discussions with experts in the fields of ageing research and multimorbidity on key factors to consider when measuring multimorbidity. DESIGN: Descriptive study of expert opinions on multimorbidity measures, informed by literature to identify available measures followed by a face-to-face meeting and an online survey. RESULTS: The expert group included clinicians, researchers and policymakers in Canada with expertise in the fields of multimorbidity and ageing. Of the 30 experts invited, 15 (50%) attended the in-person meeting and 14 (47%) responded to the subsequent online survey. Experts agreed that there is no single multimorbidity measure that is suitable for all research studies. They cited a number of factors that need to be considered in selecting a measure for use in a research study including: (1) fit with the study purpose; (2) the conditions included in multimorbidity measures; (3) the role of episodic conditions or diseases; and (4) the role of social factors and other concepts missing in existing approaches. CONCLUSIONS: The suitability of existing multimorbidity measures for use in a specific research study depends on factors such as the purpose of the study, outcomes examined and preferences of the involved stakeholders. The results of this study suggest that there are areas that require further building out in both the conceptualization and measurement of multimorbidity for the benefit of future clinical, research and policy decisions.

Cost-Effectiveness Analysis of Patiromer and Spironolactone Therapy in Heart Failure Patients with Hyperkalemia.

BACKGROUND AND OBJECTIVE: Certain patients with heart failure (HF) are unable to tolerate spironolactone therapy due to hyperkalemia. Patiromer is a novel agent used to treat hyperkalemia and has been shown to be efficacious, safe, and well-tolerated. The potential clinical outcomes and economic value of using patiromer and spironolactone in patients with HF unable to otherwise tolerate spironolactone due to hyperkalemia are unclear. The objective of this analysis was to model the potential pharmacoeconomic value of using patiromer and spironolactone in patients with a history of hyperkalemia that prevents them from utilizing spironolactone. METHODS: We performed a cost-effectiveness analysis of treatment with patiromer, spironolactone, and an angiotensin-converting enzyme inhibitor (ACEI) in patients with New York Heart Association (NYHA) class III-IV HF compared with ACEI alone. A Markov model was constructed to simulate a cohort of 65-year-old patients diagnosed with HF from the payer perspective across the lifetime horizon. Clinical inputs were derived from the RALES and OPAL-HK randomized trials of spironolactone and patiromer, respectively. Utility estimates and costs were derived from the literature and list prices. Outcomes assessed included hospitalization, life expectancy, and quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analyses were performed to test the robustness of the model findings. RESULTS: Treatment with patiromer-spironolactone-ACEI was projected to increase longevity compared with ACEI alone (5.29 vs. 4.62 life-years gained, respectively), greater QALYs (2.79 vs. 2.60), and costs (US$28,200 vs. US$18,200), giving an ICER of US$52,700 per QALY gained. The ICERs ranged from US$40,000 to US$85,800 per QALY gained in 1-way sensitivity analyses. CONCLUSION: Our results suggest that the use of spironolactone-patiromer-ACEI may provide clinical benefit and good economic value in patients with NYHA class III-IV HF unable to tolerate spironolactone due to hyperkalemia.

Community Program Improves Quality of Life and Self-Management in Older Adults with Diabetes Mellitus and Comorbidity.

OBJECTIVES: To compare the effect of a 6-month community-based intervention with that of usual care on quality of life, depressive symptoms, anxiety, self-efficacy, self-management, and healthcare costs in older adults with type 2 diabetes mellitus (T2DM) and 2 or more comorbidities. DESIGN: Multisite, single-blind, parallel, pragmatic, randomized controlled trial. SETTING: Four communities in Ontario, Canada. PARTICIPANTS: Community-dwelling older adults (≥65) with T2DM and 2 or more comorbidities randomized into intervention (n = 80) and control (n = 79) groups (N = 159). INTERVENTION: Client-driven, customized self-management program with up to 3 in-home visits from a registered nurse or registered dietitian, a monthly group wellness program, monthly provider team case conferences, and care coordination and system navigation. MEASUREMENTS: Quality-of-life measures included the Physical Component Summary (PCS, primary outcome) and Mental Component Summary (MCS, secondary outcome) scores of the Medical Outcomes Study 12-item Short-Form Health Survey (SF-12). Other secondary outcome measures were the Generalized Anxiety Disorder Scale, Center for Epidemiologic Studies Depression Scale (CES-D-10), Summary of Diabetes Self-Care Activities (SDSCA), Self-Efficacy for Managing Chronic Disease, and healthcare costs. RESULTS: Morbidity burden was high (average of eight comorbidities). Intention-to-treat analyses using analysis of covariance showed a group difference favoring the intervention for the MCS (mean difference = 2.68, 95% confidence interval (CI) = 0.28-5.09, P = .03), SDSCA (mean difference = 3.79, 95% CI = 1.02-6.56, P = .01), and CES-D-10 (mean difference = -1.45, 95% CI = -0.13 to -2.76, P = .03). No group differences were seen in PCS score, anxiety, self-efficacy, or total healthcare costs. CONCLUSION: Participation in a 6-month community-based intervention improved quality of life and self-management and reduced depressive symptoms in older adults with T2DM and comorbidity without increasing total healthcare costs.

Physical health in a Canadian Old Order Mennonite community.

INTRODUCTION: This article explores physical health and its determinants in two rural populations in Waterloo, Canada: Old Order Mennonites (OOMs) and non-OOM farmers. OOMs were selected because their distinct lifestyle might offer health benefits, and cultural homogeneity and isolation might more clearly expose the determinants shaping their health. Comparing the two Waterloo groups reduces the effect of contextual features impacting both, such as local economic conditions. The study considers a comprehensive list of determinants in order to evaluate their relative importance in shaping physical health. This information enables policy action to focus on the determinants having the greatest impact. METHODS: A survey was used to obtain information from both groups on health status and health determinants. The survey was distributed in spring-summer 2010. All members of both groups were invited to complete the survey anonymously. The physical component summary (PCS) score of the SF-12 survey was used to measure physical health status. Age-gender breakdowns of PCS scores for both groups were compared, and differences evaluated using statistical significance and the interpretation cut-off recommended by SF-12 developers. Multiple (ordinary least squares) regression was used to identify key determinants shaping health. In the regressions, PCS scores represented the (continuous) dependent variable and the determinants of health were the independent variables. RESULTS: Non-OOMs were found to experience better physical health than OOMs, with mean PCS scores of 49.24 for non-OOMs versus 47.39 for OOMs. The difference in PCS scores (1.85) was statistically significant (p=.002) and above the interpretation cut-off. While PCS score differences were significant for both genders, differences among the women were larger. OOM men and women may face health risks due to low incomes, offspring out-migrations and health service usage. OOM women may face additional risks related to reproductive health and gender role. Physical health in both groups is significantly shaped by coping, body mass index, childhood disease history and age. These determinants were more influential than factors such as social capital, sense-of-place and spirituality, which is particularly unexpected in OOMs given the strength of the social factors. CONCLUSIONS: The determinants shaping physical health in both groups (coping, body mass index, childhood disease history, age) are consistent with other studies on urban populations and people whose life circumstances vary widely. Therefore, these determinants represent targets for policy action because of their potential for widespread population health impacts. Ultimately, the fundamental health risk factors faced by small, isolated populations like OOMs appear to be common to other rural and general populations. The absence of social factors in shaping physical health in both groups differs from a number of social capital studies, and suggests there may be unique characteristics of rural or farming populations (eg high levels of self-reliance and independence). However, this could also reflect fundamental differences between physical and mental health, since other analyses show that social factors influence mental health. Understanding the absence of social factors in shaping physical health would benefit from better reconciliation of this study with others, but this is hampered by differences in health outcomes, models and measures employed across studies.