Caring for depression in the dying is complex and challenging – survey of palliative physicians

Background Depression is prevalent in people with very poor prognoses (days to weeks). Clinical practices and perceptions of palliative physicians towards depression care have not been characterised in this setting. The objective of this study was to characterise current palliative clinicians’ reported practices and perceptions in depression screening, assessment and management in the very poor prognosis setting. Methods In this cross-sectional cohort study, 72 palliative physicians and 32 psychiatrists were recruited from Australian and New Zealand Society of Palliative Medicine and Royal Australian and New Zealand College of Psychiatrists between February and July 2020 using a 23-item anonymous online survey. Results Only palliative physicians results were reported due to poor psychiatry representation. Palliative physicians perceived depression care in this setting to be complex and challenging. 40.0% reported screening for depression. All experienced uncertainty when assessing depression aetiology. Approaches to somatic symptom assessment varied. Physicians were generally less likely to intervene for depression than in the better prognosis setting. Most reported barriers to care included the perceived lack of rapidly effective therapeutic options (77.3%), concerns of patient burden and intolerance (71.2%), and the complexity in diagnostic differentiation (53.0%). 66.7% desired better collaboration between palliative care and psychiatry. Conclusions Palliative physicians perceived depression care in patients with very poor prognoses to be complex and challenging. The lack of screening, variations in assessment approaches, and the reduced likelihood of intervening in comparison to the better prognosis setting necessitate better collaboration between palliative care and psychiatry in service delivery, training and research.

A post pandemic roadmap toward remote assessment for neuromuscular disorders: limitations and opportunities

Recent advances in technology and expanding therapeutic opportunities in neuromuscular disorders has resulted in greater interest in and development of remote assessments. Over the past year, the rapid and abrupt COVID-19 shutdowns and stay-at-home orders imposed challenges to routine clinical management and clinical trials. As in-person services were severely limited, clinicians turned to remote assessments through telehealth to allow for continued care. Typically, disease-specific clinical outcome assessments (COAs) for neuromuscular disorders (NMD) are developed over many years through rigorous and iterative processes to fully understand their psychometric properties. While efforts were underway towards developing remote assessments for NMD before the pandemic, few if any were fully developed or validated. These included assessments of strength, respiratory function and patient-reported outcomes, as well as wearable technology and other devices to quantify physical activity and function. Without many choices, clinicians modified COAs for a virtual environment recognizing it was not yet known how they compared to standard in-person administration. Despite being able to quickly adapt to the demands of the COVID-19 pandemic, these experiences with remote assessments uncovered limitations and opportunities. It became clear that existing COAs required modifications for use in a virtual environment limiting the interpretation of the information gathered. Still, the opportunity for real-world evaluation and reduced patient burden were clear benefits to remote assessment and may provide a more robust understanding and characterization of disease impact in NMD. Hence, we propose a roadmap navigating an informed post-pandemic path toward development and implementation of safe and successful use of remote assessments for patients with NMD.

An economic evaluation of reducing colorectal cancer surveillance intensity

Aim: Analyze the impact of national implementation of ‘low intensity’ post-treatment colorectal cancer surveillance compared with current practices. Materials & methods: Create a population-level Markov model to estimate impacts of expansion of low versus high intensity surveillance post-treatment on healthcare utilization, costs and caregiver time loss. Results: Shifting to low intensity colorectal cancer surveillance would reduce patient burden by 301,830 h per patient annually over 5 years. Cost reductions over 5 years were US$43.5 million for Medicare and US$4.2 million for Medicaid. Total societal cost savings equaled US$104.2 million. Conclusion: National implementation of low intensity post-treatment colorectal cancer surveillance has the potential to significantly reduce burden and costs on patients and their caregivers with no added risks to health.

Hikoboshi Study: Remaining Burden and Current Medical Care Status of Patients with Congenital Hemophilia a: A Study Using Two Japanese Medical Information Databases

Introduction: FVIII prophylaxis for hemophilia A (HA) has reduced the bleeding frequency in patients and enabled the prevention of hemophilic arthropathy and severe bleeding. However, the treatment/disease burden remains a concern, as evidenced by requiring intravenous injections two/three times a week; regular hospital visits to receive a prescription for medication, as drug delivery is not a provision in Japan; and frequent hospital visits because of complications, like bleeding. Moreover, there is no national patient registry for hemophilia in Japan, and few studies have examined the state of medical care and patient burden due to symptoms and medical practices. Herein, data from medical information databases (DBs) were assessed to investigate the state of medical care and patient burden for HA patients in Japan. Methods: The DBs of health insurance subscribers provided by JMDC Inc. (JMDC-DB) and of electronic medical care records provided by Real World Data Co., Ltd. (RWD-DB) were reviewed. Two DBs were used because the differences between them, such as data source for HA patients, may lead to intergroup differences in the characteristics and traceability of each patient. The targets of analysis were HA patients (ICD-10 code: D66) prescribed FVIII concentrates, emicizumab, or bypassing agents. The definition of targets in this analysis was deemed appropriate in a separate validation study. The occurrence rates of intracranial hemorrhage, ischemic heart disease, hospitalizations, emergency visits, and outpatient visits were calculated to evaluate patient burden. Further, data on the number of hospitals visited and prescribed amounts of FVIII concentrates per month were tabulated and descriptive statistics, applied. Table 1 shows the outcome measures. Results: The number of patients included, based on the target period and inclusion criteria, was 459 from JMDC-DB (January 2005 to March 2020) and 229 from RWD-DB (January 1985 to March 2020). Both DBs had a large proportion of patients aged 0-9 years (23.09% in JMDC-DB and 47.16% in RWD-DB) and a small proportion of patients aged ≥60 years (2.61% in JMDC-DB and 5.68% in RWD-DB). The mean (standard deviation [SD]) and median values for the monthly prescribed amount of FVIII concentrate were 10526.36 IU (11260.42) and 8594.91 IU in JMDC-DB and 12569.11 IU (54846.02) and 1514.35 IU in RWD-DB, respectively. The yearly trends of monthly prescribed amounts of FVIII concentrate for patients in JMDC-DB were analyzed. The median values for every 3 years since 2007 were as follows: 1916.67 IU (2007), 3375.00 IU (2010), 7229.17 IU (2013), 8614.58 IU (2016), and 10000.00 IU (2019), indicating an increasing trend in recent years. The occurrence rates (95% confidence intervals [CIs]) of intracranial hemorrhage, ischemic heart disease, and hospitalizations were 2.61% (1.36-4.52), 0.00%, and 32.68% (28.40-37.18) in JMDC-DB and 4.42% (2.14-7.99), 0.44% (0.01-2.44), and 57.08% (50.35-63.62) in RWD-DB, respectively. The age-stratified occurrence rates (95% CIs) of intracranial hemorrhage in JMDC-DB and RWD-DB were 9.43% (4.62-16.67) for 0-9 years, 1.67% (0.04-8.94) for 40-49 years, and 4.00% (0.10-20.35) for 50-59 years and 3.70% (1.02-9.21) for 0-9 years, 13.04% (2.78-33.59) for 10-19 years, 9.09% (1.12-29.16) for 30-39 years, and 6.67% (0.17-31.95) for 40-49 years, respectively. The overall occurrence rates of intracranial hemorrhage were similar in the two DBs: 2.61% (JMDC-DB) vs. 4.42% (RWD-DB). Additional results of our analysis will be presented at the conference. Conclusions: The prescription of FVIII concentrates for Japanese patients with HA is increasing, probably because FVIII prophylaxis in the clinical setting has become more common. The widespread use of FVIII has many benefits for HA patients. However, there are still treatment burdens that should be considered, such as the need for several drug prescriptions and severe bleeding, such as intracranial hemorrhage. Figure 1 Figure 1. Disclosures Nagao: CHUGAI PHARMACEUTICAL CO., LTD.: Consultancy, Honoraria, Speakers Bureau; Takeda Pharmaceutical Company Limited.: Honoraria, Research Funding; Bayer Yakuhin, Ltd.: Honoraria, Research Funding; Sanofi K.K.: Honoraria; Fujimoto Pharmaceutical Corporation: Honoraria; KM Biologics Co., Ltd.: Honoraria; Pfizer Japan Inc.: Honoraria; Japan Blood Products Organization: Honoraria; Novo Nordisk Pharma Ltd.: Honoraria; CSL Behring K.K.: Honoraria. Ioka: Chugai Pharmaceutical, Co., Ltd.: Current Employment. Nakamura: Chugai Pharmaceutical Co., Ltd.: Current Employment. Murakami: Chugai Pharmaceutical Co., Ltd.: Current Employment. Makishima: Chugai Pharmaceutical, Co., Ltd.: Current Employment. Okada: Chugai Pharmaceutical Co., Ltd.: Current Employment. Sakai: Bayer Yakuhin, Ltd.: Consultancy, Speakers Bureau; Novo Nordisk Pharma Ltd.: Consultancy, Speakers Bureau; CSL Behring K.K.: Speakers Bureau; Takeda Pharmaceutical Company Limited.: Speakers Bureau; CHUGAI PHARMACEUTICAL CO., LTD.: Speakers Bureau; Sanofi K.K.: Speakers Bureau.

Halting targeted and collateral damage to red blood cells by the complement system

The complement system is an important defense mechanism against pathogens; however, in certain pathologies, the system also attacks human cells, such as red blood cells (RBCs). In paroxysmal nocturnal hemoglobinuria (PNH), RBCs lack certain complement regulators which sensitize them to complement-mediated lysis, while in autoimmune hemolytic anemia (AIHA), antibodies against RBCs may initiate complement-mediated hemolysis. In recent years, complement inhibition has improved treatment prospects for these patients, with eculizumab now the standard of care for PNH patients. Current complement inhibitors are however not sufficient for all patients, and they come with high costs, patient burden, and increased infection risk. This review gives an overview of the underlying pathophysiology of complement-mediated hemolysis in PNH and AIHA, the role of therapeutic complement inhibition nowadays, and the high number of complement inhibitors currently under investigation, as for almost every complement protein, an inhibitor is being developed. The focus lies with novel therapeutics that inhibit complement activity specifically in the pathway that causes pathology or those that reduce costs or patient burden through novel administration routes.

POS0739 DEVELOPMENT OF A CONCEPTUAL MODEL TO UNDERSTAND DISEASE BURDEN IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND LONG-TERM ORGAN DAMAGE

Background:Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease resulting in increased morbidity and mortality and reduced health-related quality of life (HRQoL). Patients with SLE are at risk of developing irreversible long-term organ damage (LTOD) caused by both disease activity and cumulative medication toxicities. Data regarding the overall disease burden and impact of LTOD in patients with SLE are limited.Objectives:The primary objective of this qualitative study was to develop a conceptual model to describe the burden experienced by patients with SLE and LTOD.Methods:This study (GSK Study 209754) was conducted in three phases. First, a targeted literature review was performed to aid the development of an initial draft conceptual model. Key opinion leaders (KOLs) with experience in SLE and LTOD were then interviewed to assess the clarity, language, comprehensibility, and potential use of the conceptual model, and to help shape the patient interview materials. Finally, one-on-one interviews were performed with patients with SLE and LTOD in any of the 12 organ areas (defined by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), to gather patient perspectives on the common symptoms, functional impacts, treatment experiences, and HRQoL factors associated with LTOD. Data from the interviews were coded and analysed using NVivo software to identify patterns in responses concerning the key concepts of the overall patient burden of LTOD, and used to identify concepts to include in the model.Results:The literature review produced the preliminary conceptual model of LTOD. Results of the KOL interviews (n=5 clinicians and n=1 patient advocate) indicated that the preliminary conceptual model broadly captured the patient experience of LTOD. KOLs emphasised the difference between SLE activity (flares) and LTOD; the conceptual model was subsequently updated in accordance with these recommendations. Interviews conducted with patients with confirmed single (n=9) and multiple LTOD (n=31) indicated that the burden of LTOD associated with SLE was more severe, debilitating, and life threatening than that caused by SLE flares. Almost all patients (39/40) reported aspects of their lives that were more severely affected since their LTOD diagnosis. All 40 patients reported LTOD-related physical impacts, which often affected patients’ ability to perform everyday tasks. The most frequent physical impacts reported were a loss of vitality (39/40), long-term complications (e.g. unstable blood pressure, extreme pain, poor mobility, inflammation, dialysis, infection; 36/40), and severe fatigue (29/40). Cognitive impairments that became more pronounced after their LTOD diagnosis were reported by 27/40 of patients. Typically characterised as “brain fog”, these impairments were described as slower cognitive processing, forgetfulness, confusion, and aphasia. Economic impacts associated with LTOD included patients’ inability to work (31/40), costs of care (33/40), and non-medical-related costs (17/30). Psychosocial impacts reported by patients with LTOD affected their emotional state (39/40), ability to socialise (40/40) and relationships (30/40). Additionally, 30/40 patients reported symptoms as more severe since their LTOD diagnosis, including pain (14/40), fatigue (9/40), and oedema (8/40). Patients’ treatment goals were largely aligned with their experienced impacts of LTOD, including managing the disease and symptoms (25/40), limiting further organ damage (15/40), and improving HRQoL (11/40).Conclusion:The findings from this research clearly indicate that the patient burden of LTOD far surpasses that of SLE without LTOD. These data were incorporated and refined into a conceptual model that fully represents the patient experience of LTOD. The model will help researchers, clinicians, and patients to better understand the impact of SLE-related LTOD progression.Funding:GSKAcknowledgements:Medical writing assistance was provided by Casmira Brazaitis, PhD, Fishawack Indicia Ltd., UK, part of Fishawack Health, and was funded by GSK.Disclosure of Interests:Lynne Broderick Consultant of: GSK, Wen-Hung Chen Shareholder of: GSK, Employee of: GSK, Roger Levy Shareholder of: GSK, Employee of: GSK, April Foster Consultant of: GSK, Cindy Umanzor Consultant of: GSK, Deven Chauhan Shareholder of: GSK, Employee of: GSK

MO524CALCIMIMETIC ADHERENCE AND PREFERENCE IN THE MANAGEMENT OF SECONDARY HYPERPARATHYROIDISM IN EUROPE: A PILOT STUDY

Background and Aims Oral cinacalcet (CIN) and IV-administered etelcalcetide (ETEL) are calcimimetics available for the management of secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients. This pilot study assessed patient adherence to calcimimetic therapy and calcimimetic preference of nephrologists and nurses based on adapted questionnaires. Method A cross-sectional survey was conducted with HD patients currently using a calcimimetic, and nephrologists and dialysis nurses who prescribed/administered calcimimetic in 7 European countries (Belgium, France, Germany, Italy, Spain, Sweden and the United Kingdom). Patient questionnaires were adapted from the Medication Adherence Report Scale (MARS), the Beliefs about Medicines Questionnaire (BMQ-specific Necessity and Concern), and Treatment Intrusiveness Scale (TIS) to understand patterns of adherence and perceptions of medications; questions about gastrointestinal (GI) symptoms were included. Questionnaires for nephrologists and nurses were adapted from the Treatment Rating Scale (TRS), Health Professional Preference Scale (HPPS), and Prescribing Comparator Scale (PCS) to understand calcimimetic preference. Questionnaires were translated and administered in the local language. Results Sixty HD patients (33 CIN and 27 ETEL), 16 nephrologists and 18 dialysis nurses participated in the survey. ETEL patients were younger than CIN patients (mean age: 57 vs. 59 yrs). ETEL patients also had a lower pill burden (mean no. of pills: 6 vs. 11) and had numerically fewer hospitalizations in the last 6 months (mean no. of days: 1.5 vs 3.9) than CIN patients. Self-reported adherence to CIN was high (mean MARS: 4.7±0.7). ETEL and CIN patients did not perceive medications (excluding dialysis, diet and dietary restrictions) as interfering with their life (mean TIS: 1.5±0.5 vs. 1.6±1.6) and neither calcimimetic group had a specific belief in medicines in terms of necessity (mean BMQ CIN: 2.4±0.6 and ETEL: 2.3±0.4) or concerns about potential side-effects (mean BMQ CIN: 3.1±0.6 and ETEL: 3.5±0.7). ETEL patients were less likely than CIN patients to experience GI symptoms in the prior month: nausea (11% vs. 49%), vomiting (11% vs. 24%), and diarrhea (15% vs. 33%). Overall, the adapted patient questionnaires showed good internal consistency for MARS (Cronbach’s α=0.99) and BMQ-Necessity and BMQ-Concerns scales (CIN: α=0.74 and ETEL: α=0.81) but lower consistency for TIS (α=0.3 for both CIN and ETEL). Nephrologists and nurses had been practicing for a mean of 17 yrs. Nephrologists and nurses viewed ETEL to have more efficacy, lower risk of side effects, lower risk of non-adherence, lower burden for patients compared to CIN according to the TRS. According to HPPS, the top 3 treatment attributes for ETEL preference vs. CIN among nephrologists were encouraging patient adherence (93%; n=14/15), minimizing patient burden (87%; n=13/15) and having fewer side effects (80%; 12/15). Similar for nurses, encouraging patient adherence (88%; n=15/17) and minimizing patient burden (94%; n=16/17) were top attributes for ETEL preference as well as improving patient quality of life (82%; 14/17). Based on PCS, the majority of nephrologists agreed that compared to CIN, ETEL will ensure high adherence (100%), achieve better PTH control (93%; 14/15), reduce treatment burden for patients (87%; 13/15), improve patient’s quality of life (80%; 12/15), and improve effectiveness without increasing side-effects (80%; 12/15); they also agreed that ETEL created more work for nursing staff (80%; 12/15). Two thirds of nephrologists (n=10/15) agreed that ETEL would be more efficacious than CIN. Conclusion In this pilot study, CIN patients self-reported high adherence and both calcimimetic groups did not perceive medications to be concerning or intrusive. Nephrologists and nurses showed preference for ETEL than CIN. The questionnaires were validated and will be administered in a large study.