Estimates of the Lifetime Direct Costs of Treatment for Metastatic Breast Cancer

OBJECTIVE: Breast cancer remains the highest incident cancer among females in the United States and previous research suggests that a considerable portion of patients will eventually progress to the metastatic phase of the disease. This paper provides the first estimate of the lifetime direct costs of treating metastatic disease for one annual diagnostic cohort of breast cancer patients. METHODS: Incidence rates were combined with US population counts to estimate the number of breast cancer cases diagnosed in 1994. Estimates of progression to metastatic disease (from Canadian provincial cancer registry data), costs of care (derived from patients' claims histories), survival (from SEER data), and national mortality rates (from US Census Bureau) were integrated, using Statistics Canada's Population Health Model (POHEM) to calculate lifetime costs. RESULTS: This study estimates that more than 40% of the women diagnosed with breast cancer will progress to metastatic disease. On average, women with metastatic disease are expected to live 3 years and to incur direct treatment costs of approximately dollar 60,000 per case, resulting in a total lifetime cost for the cohort of almost dollar 4.2 billion. CONCLUSIONS: The high rate of recurrence of breast cancer argues for the development of interventions that can prevent or delay the onset of metastatic disease. These estimates of lifetime costs and the methodology on which they are based can be used to evaluate the cost-effectiveness of such secondary prevention strategies. These estimates also can serve as a benchmark against which the lifetime costs of treating other diseases can be assessed.     

Costs of Early Invasive Breast Cancer in England Using National Patient-Level Data

ObjectivesThis study aimed to use patient-level data to provide up-to-date estimates of early invasive breast cancer care costs by stage in England and to explore to what extent these costs varied based on patients’ ages and geographic regions.MethodsThis study identified women aged 50 years and older who had been diagnosed with early invasive breast cancer between January 1, 2014, and December 31, 2015, using linked cancer registrations and routine hospital data sets generated from the usual care for all National Health Service trusts in England. Cost estimates were derived from hospital records in Hospital Episodes Statistics with additional chemotherapy and radiotherapy information from the national data sets. We fitted general linear regression models to analyze the cost data. The model that best fit the data was selected using the model selection criteria of Akaike information criterion.Results55 662 women with early invasive breast cancer in England were included. The generalized linear model with log-gamma distribution fit the data best. The costs of breast cancer care for 1 year after diagnosis were strongly dependent on stage at diagnosis, controlling for other covariates. The estimated average per-patient hospital-related costs were £5167 at stage I, £7613 at stage II, and £13 330 at stage IIIA. Costs decreased with increasing age (P < .001) and varied across region (P < .001), deprivation level (P < .001), referral source (P < .01), presence of comorbidities (P< .001), and tumor receptor (ER/PR/HER2) status (P < .001).ConclusionsIn England, the costs of breast cancer care increased with advancing stage of the disease at diagnosis. Breast cancer costs varied by age and geographic region.     

The Direct Medical Costs of Undiagnosed Chronic Obstructive Pulmonary Disease

Objective:  To estimate the costs of undiagnosed chronic obstructive pulmonary disease (COPD) by describing inpatient, outpatient, and pharmacy utilization in the years before and after the diagnosis.
Methods:  A total of 6864 patients who were enrolled in the Lovelace Health Plan for at least 12 months during the study period (January 1, 1999 through December 31, 2004) were identified. The first date that utilization was attributed to COPD was considered the first date of diagnosis. Each COPD case was matched to up to three age- and sex-matched controls. All utilization and direct medical costs during the study period were compiled monthly and compared based on the time before and after the initial diagnosis.
Results:  Total costs were higher by an average of $1182 per patient in the 2 years before the initial COPD diagnosis, and $2489 in the 12 months just before the initial diagnosis, compared to matched controls. Most of the higher cost for undiagnosed COPD was attributable to hospitalizations. Inpatient costs did not increase after the diagnosis was made, but approximately one-third of admissions after the diagnosis were attributed to respiratory disease. Outpatient and pharmacy costs did not differ substantially between cases and matched controls until just a few months before the initial diagnosis, but remained 50% to 100% higher than for controls in the 2 years after diagnosis.
Conclusions:  Undiagnosed COPD has a substantial impact on health-care costs and utilization in this integrated managed care system, particularly for hospitalizations.     

Cost-Effectiveness of Posthospital Management of Acute Coronary Syndrome: A Real-World Investigation From Italy

ObjectivesThis study aimed to assess the cost-effectiveness profile of adherence to recommendations for the community management of patients discharged with a diagnosis of acute coronary syndrome (ACS).MethodsThe cohort of 50 282 residents in the Lombardy Region (Italy) who were discharged with a diagnosis of ACS during 2011 to 2015 was followed up until 2018. Adherence to selected recommendations including drug therapies (DTs), outpatient controls, and rehabilitation, experienced during the first year after index discharge, was considered. Adherent and nonadherent cohort members were matched on high-dimensional propensity scores. Composite clinical outcomes (cardiovascular hospital admissions and all-cause mortality) and healthcare costs were assessed for a time horizon of 5 years. Cost-effectiveness profile of adherence to recommendations was measured through the incremental cost-effectiveness ratio, that is, the incremental cost for 1 day free from the composite clinical outcome.ResultsAdherence to DTs, outpatient controls, and rehabilitation, respectively, regarded 39%, 81%, and 3% of cohort members. Compared with nonadherent patients, those adherent to DTs, outpatient controls, and rehabilitation had (1) a delay in the occurrence of the composite clinical outcome of 50, 43, and 73 days, respectively, and (2) lower (on average, €199 per year for DTs) and higher costs (€292 and €1024 for outpatient controls and rehabilitation). Cost-effectiveness profiles were better for patients with myocardial infarction than those with angina and for patients with more severe clinical complexity than those with milder conditions.ConclusionsHealth-related and economic benefits are expected from improving adherence to international guidelines recommendations concerning outpatient treatments and monitoring of patients with ACS.     

Policies for Use of Real-World Data in Health Technology Assessment (HTA): A Comparative Study of Six HTA Agencies

Background

Randomized controlled trials provide robust data on the efficacy of interventions rather than on effectiveness. Health technology assessment (HTA) agencies worldwide are thus exploring whether real-world data (RWD) may provide alternative sources of data on effectiveness of interventions. Presently, an overview of HTA agencies’ policies for RWD use in relative effectiveness assessments (REA) is lacking.

Use of Real-World Evidence for Regulatory Approval and Coverage of Medical Devices: A Landscape Assessment

ObjectivesTo enhance the generalizability of the evidence it reviews, the US Food and Drug Administration (FDA) has encouraged manufacturers to expand the submission of real-world evidence (RWE). The extent to which this evidence, which is generated outside of research settings, can support decision making remains unclear. We described the current use of RWE for medical devices, assessed manufacturers’ challenges in generating and using it for regulatory and coverage decisions, and identified opportunities to expand its use.MethodsWe conducted 27 solo and group interviews with FDA officials and representatives of device manufacturers, payers, and health technology assessment organizations. All interviews used a semistructured protocol and were transcribed to allow thematic analysis.ResultsAccessing and linking real-world data sources, identifying unique devices, capturing longitudinal data, limited staff expertise, and uncertain return on investment have hampered efforts to use real-world data. Many companies in our sample were conducting research using real-world data, but none had submitted RWE as the primary evidence supporting a premarket approval. FDA guidance was helpful, but regulatory requirements remained ambiguous and examples of successful regulatory decisions based on RWE were limited. Payers mainly used RWE to supplement experimental evidence in coverage decisions, evaluated both types of evidence in similar ways, and had concerns about the rigor of RWE.ConclusionsTechnical challenges may slow efforts to generate and use RWE in the near term. Additional regulatory guidance and examples, greater use of rigorous study designs and analytic methods, and continued stakeholder engagement could accelerate the use of RWE.     

Screening Mammography and Late-Stage Breast Cancer: A Population-Based Study

BACKGROUND: Among 50- to 69-year-old women, randomized clinical trials show breast cancer mortality reductions from screening mammography. However, few studies examine the long-term health effects and outcomes from screening mammography in community practice. The purpose of this study was to evaluate one approach for determining the effectiveness of screening mammography, as it is practiced in community settings, and to measure the prevalence of prior screening mammography among women with incident breast cancer. METHODS: This study was a population-based survey of the general community. Participants were 406 women with breast cancer diagnosed in 1993. The main outcome measure was breast cancer, late stage at diagnosis or fatal within 2 to 3 years of diagnosis. RESULTS: Sixty-four (57.7%) of 111 women with late-stage and 123 (42.1%) of 292 women with early-stage breast cancer did not have a screening mammogram in the 4 calendar years (1989-1992) before diagnosis. Relative to women with early-stage breast cancer, mammography nonuse in 1989-1992 was significantly more frequent among women with late-stage breast cancer (age-adjusted odds ratio 2.3, 95% confidence interval 1.3-4.3). Prior mammography was particularly infrequent among 42 women with breast cancer incident in 1993 and fatal before January 1996. CONCLUSIONS: Prior mammography among women with late-stage or fatal breast cancer was relatively infrequent. Late-stage or fatal breast cancer lacking prior mammography constitutes a missed public health opportunity. Also, this population-based study showed the expected association between prior mammography and late-stage or fatal breast cancer. These results are consistent with the effective practice of mammography in a community setting. The results illustrate and validate a public health approach that uses prior mammography histories among women with incident breast cancer to evaluate mammography penetration and quality in defined communities.     

手术部位感染直接经济损失的病例对照研究

目的　了解手术部位感染所造成的直接经济损失。方法　采用 1∶1配比病例对照方法对患者进行研究。结果　病例组住院费用的中位数是 12 0 85元 ,对照组为 74 4 7元 (P <0 0 0 1) ,手术部位感染的直接额外费用是3419元 ,病例组术后住院日的中位数是 18 5d ,对照组为 10d(P <0 0 0 1) ,手术部位感染引起的额外术后住院日是 8d ,手术部位感染经济损失因科室、疾病不同而异。结论　手术部位感染的直接经济损失十分可观 ,有效地监控计划可以减轻患者和医院的经济负担     

Diabetes in Canada: Direct Medical Costs of Major Macrovascular Complications

Objectives: To estimate direct medical costs of managing major macrovascular complications in diabetic patients.
Methods: Costs were estimated for acute myocardial infarction (AMI) and ischemic stroke by applying unit costs to typical resource use profiles. Data were obtained from many Canadian sources, including the Ontario Case Cost Project, provincial physician and laboratory fee schedules, provincial formularies, government reports, and peer-reviewed literature. For each complication, the event costs per patient are those associated with resource use specific to the acute episode and any subsequent care occurring in the first year. State costs are the annual costs per patient of continued management. All costs are expressed in 1996 Canadian dollars.
Results: Acute hospital care accounts for approximately half of the first year management costs ($15,125) of AMI. Given the greater need for postacute care, acute hospital care has less impact (28%) on event costs for stroke ($31,076). The state costs for AMI and stroke are $1544 and $8141 per patient, respectively.
Conclusions: Macrovascular complications of diabetes potentially represent a substantial burden to Canada's health care system. As new therapies emerge that may reduce the incidence of some diabetic complications, decision makers will need information to make critical decisions regarding how to spend limited health care dollars. Published literature lacks Canadian-specific cost estimates that may be readily translated into patient-level cost inputs for an economic model. This paper provides two key pieces of the many needed to understand the scope of the economic burden of diabetes and its complications for Canada.     

Healthcare Costs for Pneumococcal Disease in the Era of Infant Immunization With 13-Valent Pneumococcal Conjugate Vaccine: A Population-Based Study

ObjectivesInvasive pneumococcal disease (IPD) and a variety of clinical syndromes caused by pneumococci, such as acute otitis media (AOM), acute sinusitis (AS), and community-acquired pneumonia (CAP), cause a substantial burden on healthcare systems. Few studies have explored the short-term financial burden of pneumococcal disease after the 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the infant immunization programs. This population-based study evaluated changes in costs associated with healthcare utilization for pneumococcal disease after the PCV13 introduction in the infant immunization program in British Columbia, Canada.MethodsIndividuals with pneumococcal disease were identified using provincial administrative data for the 2000 to 2018 period. Total direct healthcare costs were determined using case-mix methodology for hospitalization and fee-for-service codes for outpatient visits and medications dispensed. Costs were adjusted to 2018 Canadian dollars. Changes in the annual healthcare costs were evaluated across vaccine eras (pre-PCV13, 2000-2010; PCV13, 2011-2018) using generalized linear models, adjusting for the 7-valent pneumococcal conjugate vaccine program (2004-2010).ResultsDuring the 19-year study period, pneumococcal disease resulted in 6.3 million cases among 85 million total patient-years, resulting in total healthcare costs of $7.9 billion. More than 6.2 million cases were treated in outpatient setting, costing $0.65 billion (8% of total costs associated with pneumococcal disease treatment), whereas 370 000 hospitalized cases were 3% of all cases, which accrued $7.25 billion (92% of total costs) in costs. Healthcare costs for all studied infections nearly doubled over the study period from $248 million in 2000 to $476 million in 2018 (P = .003). In contrast, there were large declines in total annual costs in the PCV13 era for IPD (adjusted relative rate (aRR) 0.73; 95% confidence interval [CI] 0.56-0.95; P = .032), AOM (aRR 0.70; 95% CI 0.59-0.83; P = .001), and AS (aRR 0.68; 95% CI 0.54-0.85; P = .004) compared with the pre-PCV13 era. Total costs increased marginally in the PCV13 era for all-cause CAP (aRR 1.04; 95% CI 0.94-1.15; P = .484).ConclusionsThis study confirms a temporal association in declining economic burden for IPD, AOM, and AS after the PCV13 introduction. Nevertheless, the total economic burden continues to be high in the PCV13 era, mainly driven by increasing CAP costs.     

多西他赛联合表阿霉素治疗晚期乳腺癌的临床观察

目的观察多西他赛联合表阿霉素治疗晚期乳腺癌的临床疗效及毒副作用,并对其安全性进行评估。方法用多西他赛联合表阿霉素治疗晚期乳腺癌患者41例,其中初治患者18例,复治患者23例。结果41例患者中,3例达到完全缓解,21例部分缓解,9例病情稳定,8例出现进展,其中有效率达58．5％,临床获益率达80．5％。结论多西他赛联合表阿霉素对晚期乳腺癌具有较好的疗效和耐受性,可作为晚期乳腺癌的解救方案。     

The Costs of Change: Direct Medical Costs of Solid Organ Transplantation in British Columbia, Canada, 1995–2003

Objectives:  Solid organ transplantations are among the most expensive treatments yet relatively few investigators have reported well-characterized and reliable information on costs. The objective here was to compare the direct medical costs of kidney, liver, heart, and lung transplantations in British Columbia (BC), Canada.
Methods:  Using data from a province-wide population-based registry, resource utilization data were collated for 1333 patients who underwent solid organ transplantation between 1995 and 2003. Resource categories included hospital stays, physician fees, laboratory and diagnostic testing, and immunosuppressants. Mean costs (2003 $CDN) were derived for the index hospitalization and each of the 2 years after hospital discharge. To enable valid comparisons, the same costing methodology was applied to all four programs.
Results:  The mean costs of transplantation varied from $27,695 for kidney recipients to $89,942 for lung recipients, with inpatient hospital stays comprising the largest component. Mean costs for the first and second follow-up years ranged from $27,592 and $11,424 for lung recipients to $21,144 and $8086 for liver recipients. Immunosuppressants accounted for between two-thirds and three-fourths of costs by the second year. Within each program, variations in costs could not be accounted for by demographic factors.
Conclusions:  We observed in BC a threefold variation in mean costs of organ transplantation procedures, with the variations between programs diminishing during follow-up. Policymakers and decision-makers seeking to better understand the deployment of resources for transplantation may focus on clinical factors at the time of hospitalization and factors that influence use and costs of immunosuppressants during the induction and maintenance phases.     

紫杉醇加阿霉素新辅助化疗治疗局部晚期乳腺癌的疗效观察

目的:了解紫杉醇加阿霉素的新辅助化疗在局部晚期乳腺癌治疗中的作用。方法:回顾分析28例局部晚期患者进行辅助化疗,化疗方案为TAX135 mg/m2d1+ADM45 mg/m2d1,每3周为1个疗程,术前用药2~3疗程,评估新辅助化疗后肿瘤的缓解情况和随访生存率。结果:总体化疗有效率为78.6%,肿瘤原发灶完全缓解(CR)2例,部分缓解(PR)20例,无变化(SD)6例。术后中位随访期32个月,术后死亡3例,复发7例,健在18例。结论:紫杉醇加阿霉素的联合术前化疗能使局部晚期乳腺癌原发灶缩小,降低肿瘤分期,减少肿瘤复发和远处转移。     

Trends in Lung Cancer Death Rates in Belgium and The Netherlands: a Systematic Analysis of Temporal Patterns

Belgium and The Netherlands have fairly similar smoking prevalence patterns, but distinct tobacco control policies. It is our aim to use lung cancer death rates, especially among the youngest age groups (30–39 years), as indicators of past smoking behavioral patterns to evaluate recent tobacco control efforts in both countries. Lung cancer mortality rates from 1954 to 1997 and from 1950 to 2000 were investigated in Belgium and The Netherlands, respectively, using the joinpoint regression modeling technique (log-linear Poisson models) to calculate annual percent change in death rate. In the most recent period (1984–2000) overall male lung cancer death rates have been declining at a faster rate in The Netherlands than in Belgium. In contrast, overall female lung cancer death rates (between 1950 and 2000) have been increasing at a faster rate in The Netherlands than in Belgium. Since 1988, however, APCs in death rates among Dutch females have begun to level off. Interestingly, during this same period, a significant annual decline of 7.7% among the youngest Dutch women (30–39 years) has been observed. Tobacco use prevention and interventions seem to have an impact on smoking prevalence, especially among younger age groups. In The Netherlands, where aggressive anti-tobacco campaigns were introduced a few years earlier than in Belgium, male lung cancer mortality rates have been declining more rapidly, and female lung cancer mortality rates have begun to level off.     

Research Priorities for Health Care Chaplaincy in The Netherlands: A Delphi Study Among Dutch Chaplains

The aim of this study was to identify research priorities for health care chaplaincy in The Netherlands according to practicing chaplains and chaplaincy leaders. To this end, a two-round Delphi study was conducted. The first round in which participants were asked to list at least three research priorities was completed by 249 respondents. Through content analysis, the resulting 811 priorities were merged into 54 research topics in 10 domains. In the second round, 179 respondents ranked these topics on a Likert scale from 1 to 5 (low priority–high priority) from the perspective of the patient/client, the organization, and the profession. Based on the mean score of each topic, five research priorities were identified: (a) to investigate the effect of chaplain care according to the patient/client; (b) to determine the patients’/clients’ need(s) for chaplaincy; (c) to investigate the effect of chaplain care on the patient/client; (d) to identify possibilities for chaplaincy practice in outpatient care; and (e) to investigate how to develop a stronger profile for chaplaincy in The Netherlands. These priorities resonate with research on this topic from other countries and indicate directions for future research efforts to improve chaplaincy care.     

南京市雨花台区肿瘤死亡疾病负担研究——疾病诊治需求与经济损失分析

目的:研究肿瘤死亡的经济负担及其影响因素。方法:抽取南京市雨花台区2007年肿瘤死亡病例180例进行入户问卷调查,并对医药费用、相关费用、误工费用和潜在损失等肿瘤死亡的经济损失情况,住院、手术、放疗和化疗等医疗服务利用和需求情况,患者的文化程度、医疗保障和职业状况等个人情况进行统计学分析。结果:收回有效问卷151份(83.9%),平均每例医药费为62691元,相关费用为5465元,误工损失为6708元,实际损失为74857元,潜在损失为262553元,潜在寿命损失年(PYLL)均数为11.57年/例。有关经济损失主要与患者本身的文化程度、医疗保障、确诊后生存时间、住院次数和化疗次数等因素有关,其相关性具有统计学意义。结论:肿瘤死亡经济负担主要是潜在经济损失,实际损失主要是医药费用。有关肿瘤死亡经济负担分析和研究指标可归纳为个人一般情况、疾病状况、就医情况、医疗服务利用、直接经济损失和生命损失6大方面。     

Policy on AIDS and drug users: the state of affairs in The Netherlands

In The Netherlands injecting drug users (IDUs) account for 8.8%of the AIDS diagnose (135/1531 asperJanuary 1991). Data on HIVprevalence among IDUs is limited to Amsterdam. The AIDS anddrug policy is based on risk and harm reduction through informationcampaigns, needle and syringe exchange programmes and extracare. All efforts do not seem to be sufficient to stop the spreadof HIV infection among this group. Evaluation of existing projectsis carried out and additional programmes are now initiated.In the prevention policy more emphasis is laid on outreachingactivities and involving other sectors outside the drug treatmentsector in AIDS prevention. Also the needle distribution at locallevel should be improved and more ways should be encouragedto involve drug users in the AIDS policy. With respect to thecare field more pressure to start specific care facilities forHIV-infected drug users can be expected in the near future.     

Economic Evaluation of Letrozole in the Treatment of Advanced Breast Cancer in Postmenopausal Women in Canada

OBJECTIVE: To determine the cost-effectiveness of initiation of second-line hormone therapy with letrozole in the treatment of advanced breast cancer in postmenopausal women in Canada, compared to megestrol acetate. METHODS: A modified Markov model, incorporating seven health states, was designed to simulate the treatment of patients with advanced breast cancer from second-line hormone therapy to death. The model was constructed with data from a clinical trial, literature sources, and interviews with breast cancer treatment experts. Canadian experts provided information on resource utilization patterns and local costs were attached to these resources. The model was used to calculate mean survival time, time without progression, and total direct medical costs for patients initiating treatment with letrozole 2.5 mg or megestrol acetate 160 mg. RESULTS: The mean survival time and time without progression for letrozole 2.5 mg patients were 28.3 months and 19.0 months, respectively, compared to 25.7 months and 16.5 months for megestrol acetate 160 mg patients. Total treatment costs for both groups were similar with the letrozole 2.5 mg group costing dollar 20,068 per patient, dollar 1061 more than the megestrol acetate 160 mg group (dollar CAN, 1996). The cost-effectiveness ratio for letrozole 2.5 mg with respect to megestrol was dollar 5051 per year of life gained. Sensitivity analysis showed that this ratio was sensitive to variations in the probabilities governing disease progression. CONCLUSIONS: Advanced breast cancer patients initiating second-line hormone therapy with letrozole 2.5 mg have better clinical outcomes than patients receiving megestrol acetate 160 mg. Furthermore, this benefit comes at an acceptable cost to the Canadian health care system.     

Utilization of epidemiological research for the development of local public health policy in The Netherlands: a case study approach

The use of epidemiological research in local health policy development is claimed to be problematic. In three in-depth case studies in Dutch municipalities, we examined the interface between local epidemiological research and local health policy development, and the use of epidemiological reports, published as Local Health Messages (LHMs). The qualitative study design is based on an earlier developed theoretical framework of extended interaction. We collected data about 129 actors, via face-to-face semi-structured interviews, telephone interviews, internet questionnaires, observations, and organizational documents. Local health report development was characterized by multiple interactions between Regional Public Health Service epidemiologists, policy advisors, and local health officials. The LHMs as well as the policy memoranda can be considered as socially constructed. Preliminary interaction helped to manage the expectations of the local health officials and improved a specific type of use of LHMs in the policy process. However, we discovered a lack of use of the LHMs by specific groups of actors within the policy network, which could be explained by factors influencing the actors, such as personal belief systems and values, institutional interests, and contextual factors such as the design of the policy processes. We concluded that the necessity of interactions depends on the frames of references of the potential users and as a consequence it is difficult to give a single solution for improvement of epidemiological research utilization for local health policy. Different interaction mechanisms between researchers and policy actors can be active at the same time and may differ between municipalities. Therefore it becomes important to obtain insight in the policy process and tailor strategically promising ways of interaction.     

The Impact of an Increase in User Costs on the Demand for Emergency Services: The Case of Portuguese Hospitals

Evidence on the impact of user costs on healthcare demand in ‘universal’ public National Health Services (NHS) is scarce. The changes in copayments and in the regulation of the provision of free patient transportation, introduced in early 2012 in Portugal, provide a natural experiment to evaluate that impact. However, those changes in user costs were accompanied with changes in the criteria that determine which patients are exempt from copayments, implying that simple comparisons of user rates would be biased. In this paper, we develop a new methodology to evaluate the impact of increases in direct and indirect user costs on the demand for emergency services (ES) in the presence of compositional changes in co‐payment exempt and non‐exempt populations. Our results show that the increase in copayments did not have an effect in moderating ES demand by paying users, but we find significant effects of the change in transport regulation. Thus, our results support the conclusion that indirect costs may be more important than direct costs in determining healthcare demand in NHS‐countries where copayments are small and wide exemption schemes are in place, especially for older patients. Copyright © 2015 John Wiley & Sons, Ltd.