Palliative Care for Newborns in India: Patterns of Care in a Neonatal Palliative Care Program at a Tertiary Government Children's Hospital.

Neonatal palliative care is a specialized area within children's palliative care, which focusses on the needs of infants with life-limiting or life-threatening conditions. Nearly one quarter of global neonatal deaths occur in India, where neonatal palliative care evidence is limited. This study describes the development and implementation of a neonatal palliative care program within a neonatal intensive care unit (NICU) at a government hospital, describing the implementing an 8-month pilot palliative care program for neonates, including the patterns of care, and barriers and enablers of success. The hospital-based palliative care team included trained pediatric palliative care physicians, a nurse, and a counselor. There was a steady increase in monthly referrals. There were 110 referrals in total, including 89 (81%) deaths and 18 (16%) babies were alive at the time of final follow-up, 10 months after the pilot program was completed. The program addressed physical symptoms, including providing morphine, as well as psychosocial and spiritual concerns of families. A model of hospital-based palliative care for neonates can be implemented within NICUs in tertiary government hospitals in India. Neonatal palliative care programs should include partnerships with charitable organizations to support implementation costs and provide palliative care training, mentorship, and capacity-building support.

Oral Methadone versus Morphine IR for Patients with Cervical Cancer and Neuropathic Pain: A Prospective Randomised Controlled Trial.

Objectives: In India, cervical cancer is the most common cancer among women and makes up for up to 29% of all registered cancer in females. Cancer-related pain is one of the major distressing symptoms for all cancer patients. Pain is characterised as somatic or neuropathic, and the total pain experience is often mixed. Conventional opioids are the backbone of analgesic treatment but are most often not sufficient in alleviating neuropathic pain, common in cervical cancer. Accumulating evidence of the advantage of methadone compared to conventional opioids, due to agonist action at both µ and q opioid receptors, N-methyl-D-aspartate (NMDA) antagonist activity and the ability to inhibit the reuptake of monoamines has been demonstrated. We hypothesised that, with these properties', methadone might be a good option for the treatment of neuropathic pain in patients with cervical cancer. Material and Methods: Patients with cervical cancer stages ll-lll were enrolled in this randomized controlled trial. A comparison was made between methadone versus immediate release morphine (IR morphine), with increasing doses until pain was controlled. Inclusion-period was from October 3rd to December 31st 2020, and the total patient-study period was 12 weeks. Pain intensity was assessed according to the Numeric Rating Scale (NRS) and Douleur Neuropathique (DN4). The primary objective was to determine whether methadone was clinically superior versus noninferior to morphine as an analgesic for the treatment of cancer related neuropathic pain in women with cervical cancer. Results: A total of 85 women were included; five withdrew and six died during the study period, leaving 74 patients completing the study. All participants showed a reduction in mean values of NRS and DN4 from the time of inclusion and to the end of the study period, for IR morphine and methadone 8.4-2.7 and 8.6-1.5, respectively (P < 0.001). The DN4 score mean reduction for Morphine and Methadone were 6.12-1.37 and 6.05-0, respectively (P < 0.001). Side effects were more common in the group of patients receiving IR morphine compared to the patients treated with methadone. Conclusion: We found that Methadone had a superior analgesic effect with good overall tolerability compared with morphine as a first-line strong opioid for the management of cancer-related neuropathic pain.

Use of DNA image cytometry in conducting oral cancer screening in rural India.

OBJECTIVES: Oral cancer screening can assist in the early detection of oral potentially malignant lesions (OPMLs) and prevention of oral cancers. It can be challenging for clinicians to differentiate OPMLs from benign conditions. Adjunct screening tools such as fluorescence visualisation (FV) and DNA image cytometry (DNA-ICM) have shown success in identifying OPMLs in high-risk clinics. For the first time we aimed to assess these technologies in Indian rural settings and evaluate if these tools helped clinicians identify high-risk lesions during screening. METHODS: Dental students and residents screened participants in five screening camps held in villages outside of Hyderabad, India, using extraoral, intraoral, and FV examinations. Lesion and normal tissue brushings were collected for DNA-ICM analysis and cytology. RESULTS: Of the 1116 participants screened, 184 lesions were observed in 152 participants. Based on white light examination (WLE), 45 lesions were recommended for biopsy. Thirty-five were completed on site; 25 (71%) were diagnosed with low-grade dysplasias (17 mild, 8 moderate) and the remaining 10 showed no signs of dysplasia. FV loss was noted in all but one dysplastic lesion and showed a sensitivity of 96% and specificity of 17%. Cytology combined with DNA-ICM had a sensitivity of 64% and specificity of 86% in detecting dysplasia. CONCLUSION: DNA-ICM combined with cytology identified the majority of dysplastic lesions and identified additional lesions, which were not considered high-risk during WLE and biopsy on site. Efforts to follow-up with these participants are ongoing. FV identified most high-risk lesions but added limited value over WLE.

Perceived stigma and its correlates among Asian patients with advanced cancer: A multi-country APPROACH study.

OBJECTIVES: Perceived cancer-related stigma can affect mental health and potentially treatment choices for patients with cancer. Nevertheless, perceived stigma is not very well understood in Asia. This study investigated across six developing Asian countries: (1) the prevalence of perceived stigma among advanced cancer patients, (2) its risk factors, and (3) its association with patient treatment preferences. METHODS: This cross-sectional study recruited patients receiving oncology care across major hospitals in Bangladesh, China, India, Philippines, Sri Lanka and Vietnam. Participants (N = 1358) were adults diagnosed with stage IV metastatic solid cancer who completed self-reported surveys. Multi-variable logistic regression and ordered logit models examined the associations with perceived stigma and variables of interest. RESULTS: Across the countries, 35%, 95% CI [32%, 38%] of patients reported experiencing at least one facet of cancer-related stigma often or always, while 60% [57%, 63%] reported it occurring occasionally. Top-endorsed facets of perceived stigma across the Asian countries suggest a distinct pattern. Having knowingly engaged in health-risk behaviours (OR = 2.03-2.24, 95% CI [1.14-1.19, 3.43-4.41]), unemployment (2.64 [1.67, 4.19]) and body image change (1.57 [1.00, 2.45]) were associated with higher odds of perceived stigma, while time mitigated perceived stigma (0.49-0.65 [0.30-0.45, 0.76-0.92]). Perceived stigma was associated with lower odds of preference for life-extending treatments, although the associations did not hold up in the adjusted model. CONCLUSIONS: Perceived stigma is unique among Asian advanced cancer patients. Stigma is important to assess and address, taking into consideration the various sociodemographic, clinical and psychological factors of cancer patients.

The Introduction and Experiences of Methadone for Treatment of Cancer Pain at a Low-resource Governmental Cancer Center in India.

OBJECTIVES: This study aimed to describe the clinical experience of the health-care professionals (HCPs) responsible for the introduction of methadone, for the treatment of complex cancer pain, at a low-resource hospital in India in a patient-group, burdened by illiteracy, and low socio-economic status. MATERIALS AND METHODS: Ten HCPs: Four medical doctors, four nurses, one pharmacist, and one hospital administrator were interviewed. The interviews are examined using a qualitative conventional content analysis. RESULTS: The interviews showed a confidence amongst the HCPs, responsible for the safe introduction of methadone in a stressful and low-resource surrounding, to patients with cancer pain and the different aspects of methadone, as initiation, titration, and maintenance of treatment. CONCLUSION: Introduction of methadone for cancer pain management is safe and feasible although low resources in a challenging hospital setting and care environment.

Patient-Reported Roles in Decision-Making Among Asian Patients With Advanced Cancer: A Multicountry Study.

Purpose. We investigated 1) perceived roles in decision-making among advanced cancer patients in 5 Asian countries 2) associations of patient characteristics with these roles, and 3) the association of perceived roles with quality of life and perceived quality of care. Methods. We surveyed 1585 patients with stage IV solid cancer. Multinomial logistic regressions were used to analyze associations of patient characteristics with decision-making roles. Multivariate regressions were used to analyze associations of decision-making roles with quality of life and care. Results. The most common perceived-role was no patient involvement. Most patients (73%) reported roles consistent with their preferences. Being male, nonminority, higher educated, aware of advanced cancer diagnosis, and knowledge of cancer diagnosis for ≥1 year were associated with higher levels of patient involvement in decision-making. Compared to no patient involvement, joint decision-making (together with physicians/family) was associated with higher social (ß = 2.49, P < 0.01) and spiritual (ß = 2.64, P < 0.01) well-being, and better quality of physician communication (ß = 9.73, P < 0.01) and care coordination (ß = 13.96, P < 0.01) while making decisions alone was associated with lower emotional (ß = -1.43, P < 0.01), social (ß = -2.39, P < 0.01), and spiritual (ß = -2.98, P < 0.01) well-being. Conclusions. Findings suggest that a substantial number of advanced cancer patients were not (and preferred not to be) involved in decision-making. Despite this finding, joint decision-making together with physicians/family was associated with better quality of life and care. Implications. Physicians should explain the benefits of shared decision making to patients and encourage participation in decision-making, while ensuring that patients feel supported and do not find decision-making overwhelming.

Impact of a Longitudinal Intervention to Improve Care Coordination between a Hospital and a Hospice: A Quality Improvement Project.

OBJECTIVES: When patients with advanced cancer transition from systemic cancer treatments at MNJ Institute of Oncology to palliative and end-of-life care at a separate stand-alone non-governmental organisation-run hospice facility, there is insufficient transfer of health information, including details of cancer diagnosis and staging, past treatments, imaging reports and goals for future care. Without this information, the hospice care team is not adequately prepared to receive and deliver high-quality palliative care for these patients. This project aims to improve the care coordination between the hospital and hospice. MATERIALS AND METHODS: The measures used are the self-reported confidence score on a scale of 0 to 10 related to knowledge about plan of care among staff who receives patients at hospice at baseline and during and after interventions. Interventions included recognizing the workplace culture and promoting ownership of the tasks, enhancing communication by creating user-friendly transfer forms and on-going assessment of the process. RESULTS: Improvement in the care coordination in terms of communication of patient goals of care, from hospital to hospice. CONCLUSION: QI project and the steps involved helped the team to work towards solutions objectively. Seemingly excellent ideas may not be the most impactful and data collection demonstrates this and helps identify the most successful interventions.

Exploring Health Professionals' Experiences With a Virtual Learning and Mentoring Program (Project ECHO) on Pediatric Palliative Care in South Asia.

Project ECHO (Extension of Community Healthcare Outcomes) is an innovative model of online education which has been proposed to enhance access to palliative care in resource-limited settings. There is limited literature describing how health care providers in low-and middle-income countries benefit from and learn from this type of training. This qualitative description study explores the learning experiences of participants in a Project ECHO program on pediatric palliative care in South Asia through focus group discussions. Discussions were transcribed, coded, independently verified, and arranged into overarching themes. We identified learning themes including the importance of creating a supportive learning community; the opportunity to share ideas and experiences; gaining knowledge and skills, and access to additional learning materials. Designing future programs to ensure a supportive and interactive learning community with attention cultural challenges may enhance learning from future Project ECHO programs.

Assessment of Caregiving Burden of Family Caregivers of Advanced Cancer Patients and Their Satisfaction with the Dedicated Inpatient Palliative Care Provided to Their Patients: A Cross-Sectional Study from a Tertiary Care Centre in South Asia.

BACKGROUND AND OBJECTIVES: Family Caregivers (FCs) of advanced cancer patients often suffer from caregiving burden due to stress arising from the responsibility of caregiving. During the course of their patients palliative therapy, FCs quality of life seems to be influenced by their satisfaction with the quality of patient care. In this study, caregiving burden of FCs and their satisfaction with dedicate Inpatient palliative care (IPC) services provided to their patients  were studied. MATERIAL AND METHODS: This cross-sectional study assessed 211 FCs of advanced cancer patients. Caregiving burden of FCs and their satisfaction with IPC were studied through Zarith Burden Interview (ZBI-12 version) and Family Carer Satisfaction with Palliative Care scale (FAMCARE-2)  questionnaires, respectively. Descriptive and correlation analyses were deployed for data analysis. RESULTS: The summative mean ZBI-12 score for FCs was 20.26±5.92, suggesting moderate to high caregiving burden among FCs. Significantly higher scores were observed among FCs who belonged to below poverty line (BPL) families(p=0.025), revealing higher caregiving burden among this lower income group. FCs who were male, unmarried, unemployed, and residing in rural experienced higher caregiving burden. However, it did not lead to a statistically significant difference. The summative mean FAMCARE-2 scale scores was 74.01±4.34, which suggested FCs high satisfaction with the palliative care services provided to their patients. FAMCARE-2 scale scores were lower for BPL families, but it was not statistically significant. CONCLUSION: FCs from lower-income groups experienced higher caregiving burden. It seems that IPC unit provided satisfactory services to advanced cancer patients, leading to enhancement of FCs satisfaction and consequently quality of life. 
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Comprehensive Conservative Care in End-Stage Kidney Disease.

In patients with end-stage kidney disease (ESKD), when there maybe situations where dialysis does not offer benefits in terms of survival or health-related quality of life, dialysis should not be viewed as the default therapy. Such patients can be offered comprehensive conservative care as an alternative to dialysis. Conservative (nondialytic) management of ESKD includes careful attention to fluid balance, treatment of anemia, correction of acidosis and hyperkalemia, blood pressure, and calcium/phosphorus metabolism management and dietary modification. Individualized symptom management and supportive care are crucial to maximize the quality of life. We propose that model of comprehensive conservative care in ESKD should manage both diseases as well as provide supportive care. Facilitating implementation of comprehensive conservative care requires coordination between nephrology and palliative care at patient, professional, administrative, and social levels to maximize benefit with the motto to improve the overall quality of life.

The Use of Methadone in Pediatric Cancer Pain - A Retrospective Study from a Governmental Cancer Center in India.

BACKGROUND: The management of cancer-related pain relies on access to opioids. When regular opioids are not tolerated, or are insufficient, methadone is an affordable and effective analgesic. AIM: The aim of the project was to describe the pattern of use and clinical experience of methadone in pediatric cancer pain at a governmental cancer hospital in Hyderabad, one of the four Indian cancer centers with permission to prescribe methadone. METHODS: This was a retrospective study of medical records of all children, under the age of 18, who had been prescribed methadone from September 9, 2017, to November 19, 2019. Data on analgesic effect, prior and concomitant analgesic treatment, opioid side effects, and the handling of methadone were analyzed. RESULTS: A total of 11 children were identified and studied. Methadone was introduced mainly when pain was uncontrolled by regular opioids. Initial daily doses ranged from 1 to 15 mg. The duration of treatment ranged from 7 to 307, with a median of 50 days in the nine patients where treatment exceeded one single dosage. Good analgesic effect was reported in 5/9 children, unchanged from previous analgesic treatment in three patients and without any effect in one child. No severe side effects were reported. CONCLUSION: Low-dose methadone in the treatment of pediatric cancer pain at a low-resource cancer center was safe and well tolerated by the patients, with long treatment durations. It was safely managed, administered with single to double daily dosages, hence easy for patients and family to handle, and an affordable treatment option.

The Use of Methadone in Adult Patients with Cancer Pain at a Governmental Cancer Center in India.

BACKGROUND: Management of cancer-related pain relies on the access to opioids. When regular opioids as morphine are not tolerated or are insufficient, adjuvant opioids as methadone are an affordable and effective analgesic. AIM: The aim of the project was to describe the pattern of use and clinical experiences of methadone in patients with cancer-related pain at a low-resource hospital in Hyderabad, one of few Indian cancer centers with permission to prescribe methadone. METHODS: Medical records of all patients who had been prescribed methadone, September 9, 2017 and November 19, 2019 were studied retrospectively. Data on analgesic treatment and opioid side effects were analyzed. RESULTS: A total of 93 adult cancer patients were included in the study. A majority of patients (79%) were prescribed opioid analgesic, mainly morphine, before methadone introduction. The initial daily dose of methadone ranged between 5 and 22.5 years and in the vast majority of the patients 5 mg, divided in two daily administrations. A good analgesic effect, with decreased pain, was reported in 60% of the patients. No severe side effects were reported. CONCLUSIONS: In this study, methadone as a primary opioid was used with a good analgesic effect for cancer pain in a low-resource setting. Indication for methadone was mainly uncontrolled pain with a regular opioid treatment. No severe adverse effects were reported. Further research and prospective studies are needed on methadone treatment in low-resource settings to establish the robust guidelines to support prescribing physicians.

High anxiety and depression scores and mental health service use among South Asian advanced cancer patients: A multi-country study.

CONTEXT: Addressing symptoms of anxiety and depression is important in cancer palliative care. However, little information exists on the prevalence of anxiety and depression and mental health service use among advanced cancer patients in South Asia. OBJECTIVES: To examine among South Asian advanced cancer patients, the 1) prevalence of high anxiety and depression scores, 2) factors associated with high anxiety and depression scores, and 3) mental health service use. METHODS: This cross-sectional, multi-site study recruited patients receiving oncology care across six major public hospitals in India, Bangladesh and Sri Lanka. Participants were adults, diagnosed with stage IV metastatic solid cancer and aware they had cancer. Participants' high anxiety and depression scores (using clinically-relevant Hospital Anxiety and Depression Scale threshold of >10), sociodemographic characteristics, patient-perceived cancer stigma and mental health service use were assessed. RESULTS: In the overall sample (N = 1140), 54% met threshold for high anxiety and/or depression scores: 32% reported high anxiety scores and 47% reported high depression scores. Symptom burden (OR's [95% CI's] = 1.09-1.13 [1.05-1.09, 1.12-1.17]) and perceived stigma (1.11-1.16 [1.06-1.11, 1.16-1.22]) were statistically significantly associated with high anxiety and depression scores. Of the patients with high anxiety and/or depression scores (n = 617), 97% had not received mental health services, and 38% of them indicated they were open to a referral. CONCLUSION: High, clinically-relevant anxiety and depression scores are common among South Asian advanced cancer patients. Efforts should be made to alleviate psychological morbidity, including providing greater access to supportive/palliative medicine teams or mental health services.

Using Virtual Learning to Build Pediatric Palliative Care Capacity in South Asia: Experiences of Implementing a Teleteaching and Mentorship Program (Project ECHO).

Palliative care is an important component of pediatric cancer treatment that provides holistic support for children and their families. In low- and middle-income countries, where 98% of the children needing palliative care reside, access to palliative care services is often very limited. Training opportunities for healthcare professionals are essential to improve access to palliative care in these settings. Virtual learning, which brings training and mentorship directly to learners, can improve access to educational opportunities for staff in resource-limited settings. In this report, we describe a novel and evolving model of building pediatric palliative care (PPC) capacity in South Asia. We describe the design, implementation, challenges, and subsequent modifications of our program, as well as the impact of the program for participants and for PPC service delivery in South Asia. Our teleteaching and mentoring program (Project ECHO) [Extension for Community Healthcare Outcomes] consisted of biweekly videoconference sessions with didactic teaching and case-based discussions. The program focused on engaging participants in meaningful learning by focusing on opportunities for participant interaction through teachings and case discussions. Participants identified the program as particularly beneficial for improving their knowledge and confidence in managing seriously ill children. Project ECHO is a novel model of building PPC capacity that is suitable for resource-limited settings. Key modifications to the Project ECHO model include a course-specific leadership team, developing learning plans to address the specific learning needs of participants, focusing on ensuring learner participation during sessions, and using social media and electronic resources to create opportunities for further learning outside of ECHO sessions. These adaptations may improve the efficacy of Project ECHO and others using virtual learning programs in resource-limited settings.

The Palliative Care-Promoting Access and Improvement of the Cancer Experience (PC-PAICE) Project in India: A Multisite International Quality Improvement Collaborative.

Mentors at seven U.S. and Australian academic institutions initially partnered with seven leading Indian academic palliative care and cancer centers in 2017 to undertake a program combining remote and in-person mentorship, didactic instruction, and project-based learning in quality improvement (QI). From its inception in 2017 to 2020, the Palliative Care-Promoting Accesst and Improvement of the Cancer Experience Program conducted three cohorts for capacity building of 22 Indian palliative care and cancer programs. Indian leadership established a Mumbai QI training hub in 2019 with philanthropic support. In 2020, the project which is now named Enable Quality, Improve Patient care - India (EQuIP-India) focuses on both palliative care and cancer teams. EQuIP-India now leads ongoing Indian national collaboratives and training in QI and is integrated into India's National Cancer Grid. Palliative Care-Promoting Accesst and Improvement of the Cancer Experience demonstrates a feasible model of international collaboration and capacity building in palliative care and cancer QI. It is one of the several networked and blended learning approaches with potential for rapid scaling of evidence-based practices.

Palliative Care in Coronavirus Disease 2019 Pandemic: Position Statement of the Indian Association of Palliative Care.

The global pandemic involving severe acute respiratory syndrome-coronavirus-2 has brought new challenges to clinical practice and care in the provision of palliative care. This position statement of the Indian Association of Palliative Care (IAPC) represents the collective opinion of the experts chosen by the society and reports on the current situation based on recent scientific evidence. It purports to guide all health-care professionals caring for coronavirus disease 2019 (COVID-19) patients and recommends palliative care principles into government decisions and policies. The statement provides recommendations for palliative care for both adults and children with severe COVID-19 illness, cancer, and chronic end-stage organ impairment in the hospital, hospice, and home setting. Holistic care incorporating physical, psychological, social, and spiritual support for patients and their families together with recommendations on the rational use of personal protective equipment has been discussed in brief. Detailed information can be accessed freely from the website of the IAPC http://www.palliativecare.in/. We hope that this position statement will serve as a guiding light in these uncertain times.

Socio-economic inequalities in suffering at the end of life among advanced cancer patients: results from the APPROACH study in five Asian countries.

BACKGROUND: A systematic understanding of socio-economic inequalities in end-of-life (EOL) suffering among advanced cancer patients is required to inform efforts to reduce these inequalities as part of Universal Health Coverage goals. AIMS: To assess inequalities in multiple domains of EOL suffering among advanced cancer patients - physical, functional, psychological, social, and spiritual -, using two socio-economic status (SES) indicators, education and perceived economic status of the household. METHODS: We used cross-sectional data from surveys of stage IV cancer patients (n = 1378) from seven hospitals across five countries (China, Sri Lanka, India, Vietnam and Myanmar). We conducted separate multivariable linear regression models for each EOL suffering domain. We also tested interactions between the two SES indicators and between each SES indicator and patient age. RESULTS: Patients living in low economic status households /with fewer years of education reported greater suffering in several domains. We also found significant interaction effects between economic status of the household and years of education for all EOL suffering outcomes. Age significantly moderated the association between economic status of the household and social suffering and between years of education and psychological, social, and spiritual suffering (p < 0.05 for all). CONCLUSION: Results highlight that SES inequalities in EOL suffering vary depending on the suffering domain, the SES indicator assessed, and by patient age. Greater palliative care resources for patients with low SES may help reduce these inequalities.

Correction to: Health-related quality of life and its socio-economic and cultural predictors among advanced cancer patients: evidence from the APPROACH cross-sectional survey in Hyderabad-India.

Following publication of the original article [1], the corresponding author reported an error on the name of the fourth author.

Low-dose Oral Ketamine as a Procedural Analgesia in Pediatric Cancer Patients Undergoing Bone Marrow Aspirations at a Resource-limited Cancer Hospital in India.

AIM: Many pediatric cancer patients undergo repeated bone marrow aspirations (BMAs) for diagnostic and treatment evaluation purposes. Full anesthesia is the standard of care during this procedure in high-income countries. At hospitals with low resources in low/middle-income countries many children undergo these painful procedures without sufficient pain relief. This study aimed to evaluate the usefulness of low-dose oral ketamine as a procedural analgesic in a low-resource pediatric cancer care department. MATERIALS AND METHODS: Pediatric patients, 4-15 years of age, who underwent BMAs between September 31 and November 30, 2018, were invited to participate. The study was designed as a placebo-controlled, single-blinded trial with three trial groups. Group K received 1.0 mg/kg of ketamine and Group KM received 1.0 mg/kg ketamine with an addition of 0.2 mg/kg midazolam, mixed in juice 30 min before procedures. Group P received placebo consisting of plain juice. All three groups also received the hospital's current standard treatment for procedural pain in BMAs. Patients and caregivers assessed the procedural pain, as did the performing doctors. For the patients, Faces Pain Scale - Revised was used and the Numeric Rating Scale-11 for caregivers and doctors. RESULTS: A total of 87 patients were included in the study distributed with 29 in Group K, 29 in Group KM, and 29 in Group P. Seven patients were excluded, one patient denied participation and the remaining did not meet the inclusion criteria. There was no significant difference between the pain reported by the groups. A total of 69% patients in Group KM and 35% in Group K had somnolence reported as a side effect compared to 14% in Group P. CONCLUSION: We found no significant effects on the procedural pain in any of the treatment groups compared to placebo. There were only mild side effects. The doses of ketamine might be insufficient for this painful and stressful procedure.