Validation of the Spanish translation Sheffield Profile for Assessment and Referral for Care (SPARC-Sp) at the Hospital Universitario San Jose of Popayan, Colombia.

OBJECTIVES: We determined the validity and reliability of the Spanish translation Sheffield Profile for Assessment and Referral for Care (SPARC-Sp) questionnaire to identify the palliative care (PC) needs of patients with chronic noncommunicable diseases (NCDs) in Colombia. METHODS: We developed a cross-sectional observational study of scale assessment in adults with the aim of determining the validity and reliability of the SPARC-Sp questionnaire to identify the PC needs of patients with NCDs receiving outpatient or inpatient care at the Hospital Universitario San Jose of Popayan - ESE, Colombia, from 2021 to 2022. RESULTS: We applied a questionnaire consisting of demographic, clinical data, and SPARC-Sp to 507 participants. The constructed model explained 75% of the variance with an adequate fit according to the root mean square residual (0.03), the comparative fit index (0.98), and acceptable reliability (McDonald's total omega 0.4-0.9). Opportunities for improvement are the reformulation and inclusion of particular words to improve the representativeness and clarity of the domains of communication and information, religious, and spiritual issues. SIGNIFICANCE OF RESULTS: This research represents the first validation of SPARC in Spanish. SPARC-Sp is an instrument that allows initiating a conversation of the patient's main needs through a systematic assessment of the patients' main needs. Its psychometric validation demonstrated good fit and acceptable reliability.

Translation and linguistic validation of the Sheffield Profile for Assessment and Referral for Care (SPARC) to Colombian Spanish.

OBJECTIVES: We aimed to translate and linguistically and cross-culturally validate Sheffield Profile for Assessment and Referral for Care (SPARC) in Spanish for Colombia (SPARC-Sp). METHODS: The linguistic validation of SPARC followed a standard methodology. We conducted focus groups to assess the comprehensibility and feasibility. The acceptability was assessed using a survey study with potential users. RESULTS: The comprehensibility assessment showed that additional adjustments to those made during the translation-back-translation process were required to apply SPARC-Sp in rural and low-schooled populations. It also identified the need for alternative administration mechanisms for illiterate people. The acceptability survey showed that potential users found SPARC-Sp as not only acceptable but also highly desirable. However, they desired to expand the number of items in all domains. SIGNIFICANCE OF RESULTS: Beyond the semantic and conceptual validity attained through the back-translation process, actual cultural validity could be acquired thanks to the comprehensibility tests. Although extending the instrument is something potential users would like to do, it would make it less feasible to utilize the SPARC-Sp in clinical settings. Nonetheless, the instrument might benefit from the inclusion of a domain that evaluates challenges encountered when accessing the health-care system. For communities lacking literacy, alternate administration methods must also be considered.

Validation of traditional Chinese version of Sheffield Profile for Assessment and Referral for Care Questionnaire in Taiwanese patients.

BACKGROUND: Holistic health care considers all aspects of patient care, namely the physical, psychological, spiritual, and social aspects. To assess which patient needs are unmet, a screening questionnaire covering the four aforementioned aspects is required. Therefore, the Sheffield Profile for Assessment and Referral for Care (SPARC), a multidimensional, self-reported questionnaire designed to screen patients regardless of diagnosis, was developed. This study developed a translated and validated traditional Chinese version of the SPARC for patients in Taiwan. METHODS: The original English version of the SPARC was translated into a traditional Chinese version (SPARC-T) through forward-backward translation. Semistructured debriefing interviews were conducted with participants to evaluate the SPARC-T. The reliability and validity of the SPARC-T were assessed through Cronbach's alpha coefficients and a correlation analysis conducted using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. RESULTS: Fifty-three patients were enrolled from our hospital: 22 had cancer but the majority had nonmalignant chronic conditions. About internal consistency, the Cronbach's alpha values for all domains of the SPARC-T were favorable. A correlation analysis of the SPARC-T and FACT-G revealed significant correlations for the domains of physical symptoms, independence and activity, family and social issues, sleep, and treatment issues; no significant correlation was identified for the "psychological issues" domain. CONCLUSION: This study revealed that the SPARC-T is an effective tool for screening Mandarin-speaking patients. Thus, it can be used in hospitals to holistically screen and identify the needs of patients to ensure they can receive appropriate professional support and holistic health care.

Co-Designing a Strategy for Implementing the SPARC Holistic Needs Assessment Tool in the Colombian Clinical Context.

In Colombia, timely access to palliative care (PC) is hampered by difficulties in identifying and referring to necessary services. The SPARC (Sheffield Profile for Assessment and Referral for Care) instrument provides a holistic needs assessment to improve referrals for different forms of care. SPARC was recently validated in Colombian Spanish (SPARC-Sp) but has not yet been implemented in clinical practice. We undertook workshops that aimed to co-design an implementation strategy to inform a future trial testing SPARC-Sp in the Colombian healthcare system. Workshop attendees included patients, informal caregivers, healthcare professionals, volunteers, administrative staff and decision makers. Discussions within the workshops refined implementation and dissemination strategies for SPARC-Sp in practical scenarios. Results include the need for education, clarification and demystification of PC and the lack of time and skills of professionals to identify patients' needs. Attendees recognized SPARC-Sp as a valuable tool for highlighting patients' concerns, whose adaptations are needed in Colombia to address the low literacy of the population and specificities of the healthcare system. We proposed local adaptations to SPARC-Sp and produced five educational videos aimed at health professionals, patients and caregivers to strengthen understanding of holistic needs in PC while building a strategy for SPARC-Sp implementation in the Colombian context.

Correction: A Web-Based Prostate Cancer-Specific Holistic Needs Assessment (CHAT-P): Multimethod Study From Concept to Clinical Practice.

[This corrects the article DOI: 10.2196/32153.].

A Web-Based Prostate Cancer-Specific Holistic Needs Assessment (CHAT-P): Multimethod Study From Concept to Clinical Practice.

BACKGROUND: Men with prostate cancer experience immediate and long-term consequences of the disease and its treatment. They require both long-term monitoring for recurrence or progression and follow-up to identify and help manage psychosocial and physical impacts. Holistic Needs Assessment aims to ensure patient-centered continuing cancer care. However, paper-based generic tools have had limited uptake within cancer services, and there is little evidence of their impact. With the expansion of remote methods of care delivery and to enhance the value of generic tools, we developed a web-based Composite Holistic Needs Assessment Adaptive Tool-Prostate (CHAT-P) specifically for prostate cancer. OBJECTIVE: This paper described the context, conceptual underpinning, and approach to design that informed the development of CHAT-P, starting from the initial concept to readiness for deployment. Through this narrative, we sought to contribute to the expanding body of knowledge regarding the coproduction process of innovative digital systems with potential for enhanced cancer care delivery. METHODS: The development of CHAT-P was guided by the principles of coproduction. Men with prostate cancer and health care professionals contributed to each stage of the process. Testing was conducted iteratively over a 5-year period. An initial rapid review of patient-reported outcome measures identified candidate items for inclusion. These items were categorized and allocated to overarching domains. After the first round of user testing, further items were added, improvements were made to the adaptive branching system, and response categories were refined. A functioning version of CHAT-P was tested with 16 patients recruited from 3 outpatient clinics, with interviewers adopting the think-aloud technique. Interview transcripts were analyzed using a framework approach. Interviews and informal discussions with health care professionals informed the development of a linked care plan and clinician-facing platform, which were incorporated into a separate feasibility study of digitally enhanced integrated cancer care. RESULTS: The findings from the interview study demonstrated the usability, acceptability, and potential value of CHAT-P. Men recognized the benefits of a personalized approach and the importance of a holistic understanding of their needs. Preparation for the consultation by the completion of CHAT-P was also recognized as empowering. The possible limitations identified were related to the importance of care teams responding to the issues selected in the assessment. The subsequent feasibility study highlighted the need for attention to men's psychological concerns and demonstrated the ability of CHAT-P to capture red flag symptoms requiring urgent investigation. CONCLUSIONS: CHAT-P offers an innovative means by which men can communicate their concerns to their health care teams before a physical or remote consultation. There is now a need for a full evaluation of the implementation process and outcomes where CHAT-P is introduced into the clinical pathway. There is also scope for adapting the CHAT-P model to other cancers.

Association of genetic variants with patient reported quality of life and pain experience in patients in the UK NCRI Myeloma X Relapse [Intensive]) trial; an exploratory study.

The Myeloma X trial provided a platform to explore genetics in relation to systematic assessment of patient-reported outcomes at key points during salvage treatment in multiple myeloma (MM) patients. Blood DNA was obtained in 191 subjects for single nucleotide polymorphism (SNP) genotyping. By univariable analysis, the non-coding rs2562456 SNP, upstream of LINC00664, was associated with several relevant pain and health-related quality-of-life (HRQoL) scores at 100 days after allocation to consolidation with autologous stem cell transplantation or weekly cyclophosphamide. Presence of the minor (C) allele was associated with lower pain interference (p = 0.014) and HRQoL pain (p = 0.003), and higher HRQoL global health status (p = 0.011) and physical functioning (p = 0.007). These effects were not modified by treatment arm and were no longer significant at 6 months. Following induction therapy, the rs13361160 SNP near the CCT5 and FAM173B genes was associated with higher global health (p = 0.027) and physical functioning (p = 0.013). This exploratory study supports associations between subjective parameters in MM with SNPs previously identified in genome-wide association studies of pain. Conversely, SNPs in candidate genes involved in opioid and transporter pathways showed no effect. Further studies are warranted in well-defined cancer populations, and potentially assisted by whole genome sequencing with germline analysis in routine diagnostics in haematological cancers.

Oxycodone/naloxone prolonged-release tablets in patients with moderate-to-severe, chronic cancer pain: Challenges in the context of hepatic impairment.

Opioids such as oxycodone are recommended in the management of moderate-to-severe, chronic cancer pain. All opioids can potentially cause constipation, which may be a significant barrier to their use. Multiple randomised clinical trials have shown that the use of naloxone as a peripherally acting mu-opioid receptor antagonist, in combination with oxycodone can prevent or reduce opioid-induced constipation while having equivalent analgesic efficacy to oxycodone alone. However, clinical experience has shown that unexpected events may occur in some patients when unrecognized liver impairment is present. We describe the underlying biological reasons and propose simple, but effective steps to avoid this unusual but potentially serious occurrence. In healthy individuals, naloxone undergoes extensive hepatic first pass metabolism resulting in low systemic bioavailability. However, in patients with hepatic impairment, porto-systemic shunting can increase systemic bioavailability of naloxone, potentially compromising the analgesic efficacy of oral naloxone-oxycodone combinations. This reduced first pass effect can occur in a range of settings that may not always be apparent to the treating clinician, including silent cirrhosis, non-cirrhotic portal hypertension and disruption of liver internal vasculature by metastases. Hepatic function test results correlate poorly with presence and extent of liver disease, and are not indicative of porto-systemic shunting. Presence of hepatic impairment should thus be considered when medication-related outcomes with oxycodone-naloxone combination are not as expected, even if liver function test results are normal.

Knowledge of end-of-life wishes by physicians and family caregivers in cancer patients.

OBJECTIVES: To describe communication regarding cancer patient's end-of-life (EoL) wishes by physicians and family caregivers. METHODS: An online questionnaire and telephone-based surveys were performed with physicians and family caregivers respectively in three teaching hospitals in Colombia which had been involved in the EoL care of cancer patients. RESULTS: For 138 deceased patients we obtained responses from physicians and family caregivers. In 32 % physicians reported they spoke to the caregiver and in 17 % with the patient regarding EoL decisions. In most cases lacking a conversation, physicians indicated the treatment option was "clearly the best for the patient" or that it was "not necessary to discuss treatment with the patient". Twenty-six percent of the caregivers indicated that someone from the medical team spoke with the patient about treatment, and in 67% who had a conversation, caregivers felt that the provided information was unclear or incomplete. Physicians and family caregivers were aware if the patient had any advance care directive in 6% and 26% of cases, respectively, with low absolute agreement (34%). CONCLUSIONS: There is a lack of open conversation regarding EoL in patients with advanced cancer with their physicians and family caregivers in Colombia. Communication strategies are urgently needed.

Palliative Care and Oncology in Colombia: The Potential of Integrated Care Delivery.

Palliative care is on the global health agenda, as only approximately 14% of people who require palliative care receive it [...].

Pilot study for the Psychometric Validation of the Sheffield Profile for Assessment and Referral to Care (SPARC) in Korean Cancer Patients.

PURPOSE: This study aimed to validate the Sheffield Profile for Assessment and Referral to Care (SPARC) as an effective tool for screening palliative care needs among Korean cancer patients. MATERIALS AND METHODS: The English version of the SPARC was translated by four Korean oncologists and reconciled by a Korean language specialist and a medical oncologist fluent in English. After the first version of the Korean SPARC (K-SPARC) was developed, back-translation into English was performed by a professional translator and bilingual oncologist. The back-translated version was reviewed by the original author (S.H.A.), and modifications were made (ver. 2). The second version of the K-SPARC was tested against other questionnaires, including the Functional Assessment of Cancer Therapy-General (FACT-G) and the Edmonton Symptom Assessment System (ESAS). RESULTS: Thirty patients were enrolled in the pilot trial. Fifteen were male, and the median age was 64.5 years. Six patients had an Eastern Cooperative Oncology Group performance status of 2 or more. All patients except one were receiving chemotherapy. Regarding internal consistency, the Cronbach's α scores for physical symptoms, psychological issues, religious and spiritual issues, independency and activity, family and social issues, and treatment issues were 0.812, 0.804, 0.589, 0.843, 0.754, and 0.822, respectively. The correlation coefficients between the SPARC and FACT-G were 0.479 (p=0.007) for the physical domain and -0.130 (p=0.493) for the social domain. CONCLUSION: This pilot study indicates that the K-SPARC could be a reliable tool to screen for palliative care needs among Korean cancer patients. A further study to validate our findings is ongoing.

The geriatrician's role in end-of-life care.

Healthcare aims to help older people to live well, but ultimately must also support them to die well. Most people die in old age, but predicting death in both short- and long-term is impossible for many, although not all, older people. Frail older people live with hope and pride in coping, and often anticipate recovery when ill. Key objectives of healthcare for older people are to maintain independence, minimise suffering and preserve dignity, which requires active medical, mental health and rehabilitation management, even when extending life is not the main goal. Thorough medical diagnosis and appropriate treatment and rehabilitation minimise disability, physical and mental distress and problems resulting from acute illness and crises. In these terms, 'health gain' can be achieved from medical intervention, even when life expectancy is short. Assumptions derived from cancer care about lack of reversibility with medical interventions are sometimes unwarranted. This has to be balanced against investigation- and treatment-burden, including that associated with hospital admission and the adverse effects of drugs and therapy interventions, and the need to respect the identity and autonomy of individuals. The resolution of these tensions requires anticipation of care options, multi-professional assessment, judicious and targeted treatment, good communication with patients and stakeholders and rigorous shared decision-making. In this commentary, we compare geriatric and palliative medicine, and describe how the geriatric medical approach can deliver appropriate healthcare towards the end of life. This is well supported by the broad knowledge, skill-set, flexibility and professional values displayed by geriatricians working in multi-professional teams.

Development of the Recommended Summary Plan for eEmergency Care and Treatment (ReSPECT).

INTRODUCTION: Do-not-attempt-cardiopulmonary-resuscitation (DNACPR) practice has been shown to be variable and sub-optimal. This paper describes the development of the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT). ReSPECT is a process which encourages shared understanding of a patient's condition and what outcomes they value and fear, before recording clinical recommendations about cardiopulmonary-resuscitation (CPR) within a broader plan for emergency care and treatment. METHODS: ReSPECT was developed iteratively, with integral stakeholder engagement, informed by the Knowledge-to-Action cycle. Mixed methods included: synthesis of existing literature; a national online consultation exercise; cognitive interviews with users; a patient-public involvement (PPI) workshop and a usability pilot, to ensure acceptability by both patients and professionals. RESULTS: The majority (89%) of consultation respondents supported the concept of emergency care and treatment plans. Key features identified in the evaluation and incorporated into ReSPECT were: The importance of discussions between patient and clinician to inform realistic treatment preferences and clarity in the resulting recommendations recorded by the clinician on the form. The process is compliant with UK mental capacity laws. Documentation should be recognised across all health and care settings. There should be opportunity for timely review based on individual need. CONCLUSION: ReSPECT is designed to facilitate discussions about a person's preferences to inform emergency care and treatment plans (including CPR) for use across all health and care settings. It has been developed iteratively with a range of stakeholders. Further research will be needed to assess the influence of ReSPECT on patient-centred decisions, experience and health outcomes.

An exploratory randomized-controlled trial of the efficacy of the Src-kinase inhibitor saracatinib as a novel analgesic for cancer-induced bone pain.

Pain is a major symptom of bone metastases from advanced cancer and represents a clinical challenge to treat effectively. Basic neurobiology in preclinical animal models implicates enhanced sensory processing in the central nervous system, acting through N-methyl-D-aspartate (NMDA) glutamate receptors, as an important mechanism underpinning persistent pain. The non-receptor tyrosine kinase Src is thought to act as a hub for regulating NMDA receptor activity and the orally available Src inhibitor saracatinib has shown promise as a potential analgesic in recent animal studies. Here we tested the efficacy of saracatinib as a novel analgesic in an exploratory phase II randomized controlled trial on cancer patients with painful bone metastases. Twelve patients completed the study, with 6 receiving saracatinib 125 mg/day for 28 days and 6 receiving placebo. Pharmacokinetic measurements confirmed appropriate plasma levels of drug in the saracatinib-treated group and Src inhibition was achieved clinically by a significant reduction in the bone resorption biomarker serum cross-linked C-terminal telopeptide of type I collagen. Differences between the saracatinib and placebo groups self-reported pain scores, measured using the short form of the Brief Pain Inventory, were not clinically significant after 4 weeks of treatment. There was also no change in consumption of maintenance analgesia in the saracatinib-treated group and no improvement in Quality-of-Life scores. The data were insufficient to demonstrate saracatinib has efficacy as analgesic, although it may have a role as an anti-bone resorptive agent.

Cebranopadol, a Novel First-in-Class Analgesic Drug Candidate: First Experience With Cancer-Related Pain for up to 26 Weeks.

CONTEXT: Pain is one of the most prevalent symptoms associated with cancer. Strong opioids are commonly used in the analgesic management of the disease, but carry the risk of severe side effects. Cebranopadol is a first-in-class drug candidate, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. For cancer patients, frequently experiencing multimorbidities and often exposed to polypharmacy, cebranopadol is easy to handle given its once-daily dosing, the small tablet size that enables swallowing, and the option to flexibly titrate to an effective dose. OBJECTIVES: We assessed the safety and tolerability of prolonged treatment with oral cebranopadol for up to 26 weeks in patients suffering from chronic moderate-to-severe cancer-related pain. METHODS: This was a non-randomized, multi-site, open-label, single-arm clinical trial with patients who had completed a double-blind trial comparing morphine prolonged release with cebranopadol. In this extension trial, patients were treated with oral cebranopadol for up to 26 weeks. RESULTS: Cebranopadol was safe and well tolerated in patients with chronic moderate-to-severe pain related to cancer in the dose range tested (200-1000 µg once daily). The median and mean pain levels remained in the range of mild pain during the treatment period. CONCLUSION: Our data suggest that cebranopadol was safe and well tolerated when administered for up to 26 weeks in patients with chronic cancer-related pain who were previously treated with cebranopadol or morphine prolonged release.

Patient-Reported Outcome Results From the Open-Label, Randomized Phase III Myeloma X Trial Evaluating Salvage Autologous Stem-Cell Transplantation in Relapsed Multiple Myeloma.

PURPOSE: Salvage autologous stem-cell transplantation (sASCT) in patients with multiple myeloma (MM) relapsing after a prior autologous stem-cell transplantation leads to increased remission duration and overall survival. We report a comprehensive study on patient-reported outcomes, including quality of life (QoL) and pain in sASCT. METHODS: Patients were randomly assigned to either sASCT or nontransplantation consolidation (NTC). Pain and QoL were assessed as secondary outcomes using validated QoL instruments (European Organisation for Research and Treatment of Cancer QLQ-C30 and myeloma-specific module, QLQ-MY20; the Brief Pain Inventory [Short Form]; and the Leeds Assessment of Neuropathic Symptoms and Signs [Self-Assessment] scale). RESULTS: A total of 288 patients (> 96%) consented to the QoL substudy. The median follow-up was 52 months. The European Organisation for Research and Treatment of Cancer QLQ-C30 Global health status scores were higher (better) in the NTC group at 100 days after random assignment (P = .0496), but not at later time points. Pain interference was higher (worse) in the sASCT group than in the NTC group at 6 months after random assignment (P = .0267), with patients with sASCT reporting higher scores for Pain interference with daily living for up to 2 years after random assignment. Patients reporting lower concerns about adverse effects of treatment after sASCT had a time to progression advantage. CONCLUSION: Patients with sASCT with relapsed MM demonstrated a comparative reduction in QoL and greater impact of treatment adverse effects lasting for 6 months and up to 2 years for pain, after which patients who had received sASCT reported better outcomes. Patients who experienced lower adverse effects after sASCT had longer time to progression and overall survival, showing the need to improve symptom management peritransplantation. To our knowledge, this study provides the most comprehensive picture of QoL before and after sASCT in patients with relapsed MM.

Cancer-related chronic pain: Investigation of the novel analgesic drug candidate cebranopadol in a randomized, double-blind, noninferiority trial.

BACKGROUND: Cancer-related pain is a growing health problem given the increasing life expectancy of cancer patients. Opioids are commonly used to treat cancer-related pain, but carry the risk of severe side effects, limiting their use. Cebranopadol is a first-in-class drug candidate, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. This trial examined the analgesic efficacy of cebranopadol compared with morphine prolonged release (PR) in patients with moderate-to-severe cancer-related pain. METHODS: This double-blind, parallel-group, multiple-dose trial was designed as noninferiority trial for efficacy of cebranopadol versus morphine PR. Planned with 524 patients, finally 126 patients were treated for up to 7 weeks (low accrual). The primary efficacy endpoint was the average amount of daily rescue medication intake (morphine immediate release) over the last 2 weeks of treatment. RESULTS: For the primary endpoint, noninferiority of cebranopadol with and superiority over morphine PR were demonstrated (Full Analysis Set: ∆[95%CI] = -7.48 mg [-12.05, -2.92]; Per Protocol Set: ∆[95%CI] = -4.67 mg [-9.25, -0.10]). The vast majority of patients (≥75%, either treatment) had clinically relevant pain reduction, and noninferiority on this secondary endpoint was not shown. Mostly used doses were ≤800 µg cebranopadol or ≤120 mg morphine PR daily. A total of 83.1% of patients on cebranopadol and 82.0% on morphine PR experienced treatment-emergent adverse events. CONCLUSIONS: Cebranopadol was effective, safe and well tolerated in the dose range tested (200-1,000 µg) in patients suffering from chronic moderate-to-severe cancer-related pain and was superior to morphine PR on the primary endpoint. SIGNIFICANCE: Cebranopadol presents a new approach to treat cancer pain. The drug candidate was easy to titrate, safe and well tolerated, and as effective as morphine PR in patients suffering from chronic moderate-to-severe cancer-related pain.

Standards for the management of cancer-related pain across Europe-A position paper from the EFIC Task Force on Cancer Pain.

BACKGROUND AND OBJECTIVE: Pain is a common symptom in patients who survive cancer and in those who live with progressive advanced disease. Evidence from meta-analyses suggests that pain remains poorly controlled for a large proportion of patients; barriers to good management include poor assessment of pain, inadequate support for patient self-management and late or inadequate access to strong opioid analgesia in those with advanced disease. METHODS: The European Pain Federation (EFIC) established a Task Force in 2017 which convened a European group of experts, drawn from a diverse range of relevant clinical disciplines, to prepare a position paper on appropriate standards for the management of cancer-related pain. The expert panel reviewed the available literature and made recommendations using the GRADE system to combine quality of evidence with strength of recommendation. The panel took into account the desirable and undesirable effects of the management recommendation, including the cost and inconvenience of each when deciding the recommendation. RESULTS AND CONCLUSIONS: The 10 standards presented are aimed to improve cancer pain management and reduce variation in practice across Europe. The Task Force believes that adoption of these standards by all 37 countries will promote the quality of care of patients with cancer-related pain and reduce unnecessary suffering. SIGNIFICANCE: Pain affects up to 40% of cancer survivors and affects at least 66% of patients with advanced progressive disease, many of whom experience poor pain control. These 10 standards are aimed to improve cancer pain management, promote the quality of care of patients and reduce variation across Europe.