Future policy and research for advance care planning in dementia: consensus recommendations from an international Delphi panel of the European Association for Palliative Care.

Advance care planning (ACP) is increasingly recognised in the global agenda for dementia care. The European Association for Palliative Care (EAPC) Taskforce on ACP in Dementia aimed to provide recommendations for policy initiatives and future research. We conducted a four-round Delphi study with a 33-country panel of 107 experts between September, 2021, and June, 2022, that was approved by the EAPC Board. Consensus was achieved on 11 recommendations concerning the regulation of advance directives, equity of access, and dementia-inclusive approaches and conversations to express patients' values. Identified research gaps included the need for an evidence-based dementia-specific practice model that optimises engagement and communication with people with fluctuating and impaired capacity and their families to support decision making, while also empowering people to adjust their decisions if their goals or preferences change over time. Policy gaps included insufficient health services frameworks for dementia-inclusive practice. The results highlight the need for more evidence and policy development that support inclusive ACP practice models.

Health utility values of breast cancer treatments and the impact of varying quality of life assumptions on cost-effectiveness.

In breast cancer research, utility assumptions are outdated and inconsistent which may affect the results of quality adjusted life year (QALY) calculations and thereby cost-effectiveness analyses (CEAs). Four hundred sixty four female patients with breast cancer treated at Erasmus MC, the Netherlands, completed EQ-5D-5L questionnaires from diagnosis throughout their treatment. Average utilities were calculated stratified by age and treatment. These utilities were applied in CEAs analysing 920 breast cancer screening policies differing in eligible ages and screening interval simulated by the MISCAN-Breast microsimulation model, using a willingness-to-pay threshold of €20,000. The CEAs included varying sets on normative, breast cancer treatment and screening and follow-up utilities. Efficiency frontiers were compared to assess the impact of the utility sets. The calculated average patient utilities were reduced at breast cancer diagnosis and 6 months after surgery and increased toward normative utilities 12 months after surgery. When using normative utility values of 1 in CEAs, QALYs were overestimated compared to using average gender and age-specific values. Only small differences in QALYs gained were seen when varying treatment utilities in CEAs. The CEAs varying screening and follow-up utilities showed only small changes in QALYs gained and the efficiency frontier. Throughout all variations in utility sets, the optimal strategy remained robust; biennial for ages 40-76 years and occasionally biennial 40-74 years. In sum, we recommend to use gender and age stratified normative utilities in CEAs, and patient-based breast cancer utilities stratified by age and treatment or disease stage. Furthermore, despite varying utilities, the optimal screening scenario seems very robust.

Health-related Quality of Life using the EQ-5D-5L: normative utility scores in a Dutch female population.

PURPOSE: Normative utility scores represent the health related quality of life of the general population, are of utmost importance in cost-effectiveness studies and should reflect relevant sexes and age groups. The aim of this study was to estimate EQ-5D-5L normative utility scores in a population of Dutch females, stratified by age, and to compare these scores to those of female populations of three other countries. METHODS: Dutch women completed the EQ-5D-5L online between January and July 2020. Mean normative utilities were computed using the Dutch EQ-5D-5L value set, stratified by age, tested for differences using the Kruskall-Wallis test, and compared to normative utility scores of female populations elsewhere. Additionally, to support the use of the Dutch EQ-5D-5L data in other settings, normative utility scores were also calculated by applying the value sets of Germany, United Kingdom and USA. RESULTS: Data of 9037 women were analyzed and the weighted mean utility score was 0.911 (SD 0.155, 95% CI 0.908-0.914). The mean normative utility scores differed between age groups, showing lower scores in older females. Compared to other normative utility scores of female populations, Dutch mean utilities were consistently higher except for age groups 18-24 and 25-34. With the three country-specific value sets, new age-specific mean normative utility scores were provided. CONCLUSION: This study provides mean normative utility scores of a large cohort of Dutch females per age group, which were found to be lower in older age groups. Utility scores calculated with three other value sets were made available.

Healthcare use and healthcare costs for patients with advanced cancer; the international ACTION cluster-randomised trial on advance care planning.

BACKGROUND: Advance care planning supports patients to reflect on and discuss preferences for future treatment and care. Studies of the impact of advance care planning on healthcare use and healthcare costs are scarce. AIM: To determine the impact on healthcare use and costs of an advance care planning intervention across six European countries. DESIGN: Cluster-randomised trial, registered as ISRCTN63110516, of advance care planning conversations supported by certified facilitators. SETTING/PARTICIPANTS: Patients with advanced lung or colorectal cancer from 23 hospitals in Belgium, Denmark, Italy, the Netherlands, Slovenia and the UK. Data on healthcare use were collected from hospital medical files during 12 months after inclusion. RESULTS: Patients with a good performance status were underrepresented in the intervention group (p< 0.001). Intervention and control patients spent on average 9 versus 8 days in hospital (p = 0.07) and the average number of X-rays was 1.9 in both groups. Fewer intervention than control patients received systemic cancer treatment; 79% versus 89%, respectively (p< 0.001). Total average costs of hospital care during 12 months follow-up were €32,700 for intervention versus €40,700 for control patients (p = 0.04 with bootstrap analyses). Multivariable multilevel models showed that lower average costs of care in the intervention group related to differences between study groups in country, religion and WHO-status. No effect of the intervention on differences in costs between study groups was observed (p = 0.3). CONCLUSIONS: Lower care costs as observed in the intervention group were mainly related to patients' characteristics. A definite impact of the intervention itself could not be established.

Assessing Emotional Functioning with Increased Power: Relative Validity of a Customized EORTC Short Form in the International ACTION Trial.

OBJECTIVES: There is a need to improve the assessment of emotional functioning (EF). In the international Advance Care Planning: an Innovative Palliative Care Intervention to Improve Quality of Life in Cancer Patients - a Multi-Centre Cluster Randomized Clinical Trial (ACTION) trial involving patients with advanced cancer, EF was assessed by a customized 10-item short form (EF10). The EF10 is based on the European Organisation for Research and Treatment of Cancer (EORTC) EF item bank and has the potential for greater precision than the common EORTC Quality of Life Questionnaire Core 30 four-item scale (EF4). We assessed the relative validity (RV) of EF10 compared with EF4. METHODS: Patients from Belgium, Denmark, Italy, the Netherlands, Slovenia, and the United Kingdom completed EF10 and EF4, and provided data on generic quality of life, coping, self-efficacy, and personal characteristics. Based on clinical and sociodemographic variables and questionnaire responses, 53 "known groups" that were expected to differ were formed, for example, females versus males. The EF10 and EF4 were first independently compared within this known group, for example, the EF10 score of females vs the EF10 score of males. When these differences were significant, the RV was calculated for the comparison of the EF10 with the EF4. RESULTS: A total of 1028 patients (57% lung, 43% colorectal cancer) participated. Forty-five of the 53 known-groups comparisons were significantly different and were used for calculating the RV. In 41 of 45 (91%) comparisons, the RV was more than 1, meaning that EF10 had a higher RV than EF4. The mean RV of EF10 compared with that of EF4 was 1.41, indicating superior statistical power of EF10 to detect differences in EF. CONCLUSIONS: Compared with EF4, EF10 shows superior power, allowing a 20% to 34% smaller sample size without reducing power, when used as a primary outcome measure.

Trajectories and predictors of women's health-related quality of life during pregnancy: A large longitudinal cohort study.

The objective of this study was to identify distinct trajectories and their predictors of health-related quality of life (HRQOL) of women during pregnancy in a prospective mother and child cohort. Analyses were based on 3936 Dutch pregnant women in Rotterdam area, the Netherlands. Information on potential predictors was collected in early pregnancy by questionnaire. Latent Class Mixture Modelling and Multinomial Logistic Regression were applied to assess the trajectory and predictors of HRQOL during pregnancy. HRQOL was measured by SF-12 in early, mid- and late pregnancy; physical and mental component summary (PCS-12/MCS-12) scores were calculated. Four physical HRQOL trajectories were identified: a healthy trajectory ('healthy') in 63.3%, consistently low ('vulnerable') in 10.8%; a small increase ('recovering') in 12.8% and a large decrease ('at risk') in 13.1%. Three mental HRQOL trajectories were identified: a healthy trajectory ('healthy') in 86.1%; a large increase ('recovering') in 7.5%; and a large decrease ('at risk') in 6.4%. Compared with healthy trajectories, the likelihood of following the 'vulnerable' physical HRQOL trajectory rather than a healthy trajectory was increased by daily fatigue(OR: 4.82[2.76, 8.40]), pelvic pain (OR:4.76[2.91, 7.78]) and back pain (OR:5.29[3.21, 8.70]); pregnancy-specific anxiety increased the likelihood of following the 'at risk' mental HRQOL trajectory (OR:7.95[4.84, 13.05]). Healthy physical and mental HRQOL trajectories during pregnancy were most common. Predictors indicative of poor HRQOL trajectories included pregnancy-related symptoms and anxiety.

Quality of life assumptions determine which cervical cancer screening strategies are cost-effective.

Quality-adjusted life years are used in cost-effectiveness analyses (CEAs). To calculate QALYs, a "utility" (0-1) is used for each health state induced or prevented by the intervention. We aimed to estimate the impact of quality of life (QoL) assumptions (utilities and durations of health states) on CEAs of cervical cancer screening. To do so, 12 alternative sets of utility assumptions were retrieved from published cervical cancer screening CEAs. Two additional sets were based on empirical QoL data that were integrally obtained through two different measures (SF-6D and EQ-5D) from eight groups of women (total n = 3,087), from invitation for screening to diagnosis with cervical cancer. Per utility set we calculated the number of quality-adjusted days lost (QADL) for each relevant health state in cervical cancer screening, by multiplying the study-specific assumed disutilities (i.e., 1-utility) with study-specific durations of the loss in QoL, resulting in 14 "QADL-sets." With microsimulation model MISCAN we calculated cost-effectiveness of 342 alternative screening programs (varying in primary screening test [Human Papillomavirus (HPV) vs. cytology], starting ages, and screening interval) for each of the 14 QADL-sets. Utilities used in CEAs appeared to differ largely. We found that ten QADL-sets from the literature resulted in HPV and two in cytology as preferred primary test. The SF-6D empirical QADL-set resulted in cytology and the EQ-5D one in HPV as preferred primary test. In conclusion, assumed utilities and health state durations determine cost-effectiveness of cervical cancer screening. Also, the measure used to empirically assess utilities can be crucial for CEA conclusions.

A prospective study on the variation in falling and fall risk among community-dwelling older citizens in 12 European countries.

OBJECTIVES: The rate of falling among older citizens appears to vary across different countries, but the underlying aspects causing this variation are unexplained. We aim to describe between-country variation in falling and explore whether intrinsic fall risk factors can explain possible variation. DESIGN: Prospective study on data from the cross-national Survey of Health, Ageing and Retirement in Europe (SHARE). SETTING: Twelve European countries (Austria, Belgium, Czech Republic, Denmark, Estonia, France, Germany, Italy, The Netherlands, Spain, Sweden, Switzerland). PARTICIPANTS: Community-dwelling persons aged ≥65 years (n=18 596). MEASUREMENTS: Socio-demographic factors (age, gender, education level and living situation) and intrinsic fall risk factors (less than good self-rated health (SRH), mobility limitations, limitations with activities of daily living (ADL), dizziness, impaired vision, depression and impaired cognition) were assessed in a baseline interview. Falling was assessed 2 years later by asking whether the participant had fallen within the 6 months prior to the follow-up interview. RESULTS: There was significant between-country variation in the rate of falling (varying from 7.9% in Switzerland to 16.2% in the Czech Republic). The prevalence of intrinsic fall risk factors varied twofold to fourfold between countries. Associations between factors age ≥80 years, less than good SRH, mobility limitations, ADL limitations, dizziness and depression, and falling were different between countries (p<0.05). Between-country differences in falling largely persisted after adjusting for socio-demographic differences but strongly attenuated after adjusting for differences in intrinsic fall risk factors. CONCLUSION: There is considerable variation in the rate of falling between European countries, which can largely be explained by between-country variation in the prevalence of intrinsic fall risk factors. There are also country-specific variations in the association between these intrinsic risk factors and falling. These findings emphasise the importance of addressing intrinsic fall risk in (inter)national fall-prevention strategies, while highlighting country-specific priorities.

Setting an Agenda for Assessment of Health-related Quality of Life Among Men with Prostate Cancer on Active Surveillance: A Consensus Paper from a European School of Oncology Task Force.

BACKGROUND: Literature on the health-related quality of life (HRQoL) for men with localized prostate cancer (PCa) on active surveillance (AS) shows a need for methodological guidance regarding HRQoL issues and how to address them. OBJECTIVE: The European School of Oncology Task Force (ESO TF) aimed to identify a core set of research questions and related measures to include in AS HRQoL studies. DESIGN, SETTING, AND PARTICIPANTS: A modified Delphi study was used to reach consensus on AS HRQoL research topics and tools between 2014 and 2015. Data were collected by engaging a multidisciplinary team of 15 experts. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: An open-ended questionnaire was used to collect information from ESO TF members regarding issues in AS HRQoL research. Then a structured questionnaire was used to collect ratings on the usefulness/importance of different AS HRQoL aspects. Items that ≥80% of ESO TF members rated as useful/important were retained. Items with a 50-80% rating were discussed to reach final agreement. RESULTS AND LIMITATIONS: Six main research questions concerning the selection of outcome measures, measurement tools, and comparison groups were identified as relevant. The core set of measures identified were related to individual characteristics, psychological dimensions; decision-making-related issues, and physical functioning. The multidisciplinary expertise of ESO TF members was a significant asset, even if bringing different backgrounds to the discussion table represented a challenge. CONCLUSIONS: HRQoL measures have to be sensitive to the specific needs of men on AS. The definition of HRQoL outcomes will enhance a broader understanding of the HRQoL of men on AS and sustain patient-centered medicine. PATIENT SUMMARY: An international panel agreed on a set of health-related quality-of-life aspects to be assessed among men on active surveillance for prostate cancer. Valid relevant questionnaires were identified. The experts' indications lay a foundation for future research and clinical practice.

A cluster randomized controlled trial on the effects and costs of advance care planning in elderly care: study protocol.

BACKGROUND: Currently, health care and medical decision-making at the end of life for older people are often insufficiently patient-centred. In this trial we study the effects of Advance Care Planning (ACP), a formalised process of timely communication about care preferences at the end of life, for frail older people. METHODS/DESIGN: We will conduct a cluster randomised controlled trial among older people residing in care homes or receiving home care in the Netherlands. The intervention group will receive the ACP program Respecting Choices® in addition to usual care. The control group will receive usual care only. Participants in both groups will fill out questionnaires at baseline and after 12 months. We hypothesize that ACP will lead to better patient activation in medical decision making and quality of life, while reducing the number of medical interventions and thus health care costs. Multivariate analysis will be used to compare differences between the intervention group and the control group at baseline and to compare differences in changes after 12 months following the inclusion. DISCUSSION: Our study can contribute to more understanding of the effects of ACP on patient activation and quality of life in frail older people. Further, we will gain insight in the costs and cost-effectiveness of ACP. This study will facilitate ACP policy for older people in the Netherlands. TRIAL REGISTRATION: Nederlands Trial Register: NTR4454.

Acceptance of vaccinations in pandemic outbreaks: a discrete choice experiment.

BACKGROUND: Preventive measures are essential to limit the spread of new viruses; their uptake is key to their success. However, the vaccination uptake in pandemic outbreaks is often low. We aim to elicit how disease and vaccination characteristics determine preferences of the general public for new pandemic vaccinations. METHODS: In an internet-based discrete choice experiment (DCE) a representative sample of 536 participants (49% participation rate) from the Dutch population was asked for their preference for vaccination programs in hypothetical communicable disease outbreaks. We used scenarios based on two disease characteristics (susceptibility to and severity of the disease) and five vaccination program characteristics (effectiveness, safety, advice regarding vaccination, media attention, and out-of-pocket costs). The DCE design was based on a literature review, expert interviews and focus group discussions. A panel latent class logit model was used to estimate which trade-offs individuals were willing to make. RESULTS: All above mentioned characteristics proved to influence respondents' preferences for vaccination. Preference heterogeneity was substantial. Females who stated that they were never in favor of vaccination made different trade-offs than males who stated that they were (possibly) willing to get vaccinated. As expected, respondents preferred and were willing to pay more for more effective vaccines, especially if the outbreak was more serious (€6-€39 for a 10% more effective vaccine). Changes in effectiveness, out-of-pocket costs and in the body that advises the vaccine all substantially influenced the predicted uptake. CONCLUSIONS: We conclude that various disease and vaccination program characteristics influence respondents' preferences for pandemic vaccination programs. Agencies responsible for preventive measures during pandemics can use the knowledge that out-of-pocket costs and the way advice is given affect vaccination uptake to improve their plans for future pandemic outbreaks. The preference heterogeneity shows that information regarding vaccination needs to be targeted differently depending on gender and willingness to get vaccinated.

Developing core outcomes sets: methods for identifying and including patient-reported outcomes (PROs).

BACKGROUND: Synthesis of patient-reported outcome (PRO) data is hindered by the range of available PRO measures (PROMs) composed of multiple scales and single items with differing terminology and content. The use of core outcome sets, an agreed minimum set of outcomes to be measured and reported in all trials of a specific condition, may improve this issue but methods to select core PRO domains from the many available PROMs are lacking. This study examines existing PROMs and describes methods to identify health domains to inform the development of a core outcome set, illustrated with an example. METHODS: Systematic literature searches identified validated PROMs from studies evaluating radical treatment for oesophageal cancer. PROM scale/single item names were recorded verbatim and the frequency of similar names/scales documented. PROM contents (scale components/single items) were examined for conceptual meaning by an expert clinician and methodologist and categorised into health domains. A patient advocate independently checked this categorisation. RESULTS: Searches identified 21 generic and disease-specific PROMs containing 116 scales and 32 single items with 94 different verbatim names. Identical names for scales were repeatedly used (for example, 'physical function' in six different measures) and others were similar (overlapping face validity) although component items were not always comparable. Based on methodological, clinical and patient expertise, 606 individual items were categorised into 32 health domains. CONCLUSION: This study outlines a methodology for identifying candidate PRO domains from existing PROMs to inform a core outcome set to use in clinical trials.

Erectile dysfunction and mental health in a general population of older men.

INTRODUCTION: Erectile dysfunction (ED) is more prevalent with increasing age. Previous studies showed that ED was negatively associated with mental health (MH) in specific patient groups. AIM: To examine the association, and potential mediating factors, between ED and MH in healthy elderly men. MAIN OUTCOME MEASURES: ED was defined as (almost) always having problems in achieving or maintaining an erection if desired, or not being sexually active because of erectile problems. MH was assessed with 36-item Short-Form Health Survey scale MH5 with five items on, e.g., being happy or depressed (range 0-100). Potential mediators between ED and MH were satisfaction with and importance attached to sex life. METHODS: The study population consisted of a consecutive sample of 3,810 participants from the European Randomized Study of Screening for Prostate Cancer, aged 57-78 years, who had screened negatively for prostate cancer. Associations between ED, potential mediating factors, and MH were tested by analysis of variance and analysis of covariance. RESULTS: Covariance analysis, adjusted for age, comorbidity, and use of erectile aids, showed that men with ED had significantly lower MH scores (80.8 +/- 1.2) than men without ED (83.7 +/- 1.2; P < 0.001). ED was also associated with the potential mediator "satisfaction with sex life" but not with "importance attached to sex life." Men with ED were significantly more often dissatisfied with their sex lives (P < 0.001). Adjustment for satisfaction with sex life, but not for importance attached to sex life, reduced the strength of the association (beta value) between ED and poor MH from 2.88 to -0.84. CONCLUSIONS: ED was associated with poorer MH. Satisfaction with sex life, but not importance attached to sex life, may play a mediating role in this association. These results suggest that if men with ED can be helped to be satisfied with their sex lives despite ED, MH can be preserved.