Relationship between reasons for intermittent missing patient-reported outcomes data and missing data mechanisms.

PURPOSE: Non-response (NR) to patient-reported outcome (PRO) questionnaires may cause bias if not handled appropriately. Collecting reasons for NR is recommended, but how reasons for NR are related to missing data mechanisms remains unexplored. We aimed to explore this relationship for intermittent NRs. METHODS: Patients with multiple myeloma completed validated PRO questionnaires at enrolment and 12 follow-up time-points. NR was defined as non-completion of a follow-up assessment within seven days, which triggered contact with the patient, recording the reason for missingness and an invitation to complete the questionnaire (denoted "salvage response"). Mean differences between salvage and previous on-time scores were estimated for groups defined by reasons for NR using linear regression with clustered standard errors. Statistically significant mean differences larger than minimal important difference thresholds were interpreted as "missing not at random" (MNAR) mechanism (i.e. assumed to be related to declining health), and the remainder interpreted as aligned with "missing completely at random" (MCAR) mechanism (i.e. assumed unrelated to changes in health). RESULTS: Most (7228/7534 (96%)) follow-up questionnaires were completed; 11% (802/7534) were salvage responses. Mean salvage scores were compared to previous on-time scores by reason: those due to hospital admission, mental or physical reasons were worse in 10/22 PRO domains; those due to technical difficulties/procedural errors were no different in 21/22 PRO domains; and those due to overlooked/forgotten or other/unspecified reasons were no different in any domains. CONCLUSION: Intermittent NRs due to hospital admission, mental or physical reasons were aligned with MNAR mechanism for nearly half of PRO domains, while intermittent NRs due to technical difficulties/procedural errors or other/unspecified reasons generally were aligned with MCAR mechanism.

Early, Patient-Centered, and Multidisciplinary Approach in Newly Diagnosed Multiple Myeloma: What Are We Talking About? A Case Description and Discussion.

Specialized palliative care (SPC) is a multidisciplinary need-based approach from the time a life-threatening disease is diagnosed. Patients with multiple myeloma (MM) will, at the time of diagnosis, often present with symptoms and needs that require a multidisciplinary approach. This case describes the course of a patient with newly diagnosed MM, involving all vertebrae and with no common analgesic treatment providing sufficient relief. High symptom burden and psychosocial and existential factors contribute to his total suffering. SPC, anesthesiological, and radio-oncological disciplines are integrated early, and the multidisciplinary approach includes support from social worker, psychologist, and physiotherapist. The needs and distress of the patients' wife are addressed. Barriers for further integration and the role of standardized care pathways are discussed, and the importance of systematic screening for symptoms and needs is highlighted. Integrating several disciplines may be a prerequisite for antineoplastic treatment being initiated for patients with newly diagnosed malignant disease.

Screening for Cardiac Amyloidosis 5 to 15 Years After Surgery for Bilateral Carpal Tunnel Syndrome.

BACKGROUND: Bilateral carpal tunnel syndrome (CTS) is a common extracardiac manifestation of amyloidosis and usually predates overt cardiac amyloidosis (CA) by several years. Screening studies on patients undergoing CTS surgery have shown a low yield of CA (2.0%), but high prevalence of amyloid in the carpal ligament. The proportion of patients with amyloid in the carpal ligament who later develop CA is unknown. OBJECTIVES: The authors sought to investigate the prevalence of undiagnosed CA 5 to 15 years after surgery for bilateral CTS. METHODS: Using national registries, the authors identified subjects aged 60 to 85 years with prior CTS surgery, where the first procedure on the second wrist was performed 5 to 15 years earlier. Invitations to participate in the study were sent by mail. Per international recommendations, the initial cardiac evaluation included echocardiography, 99mtechnetium-pyrophosphate scintigraphy, and assessment of monoclonal proteins in serum and urine. RESULTS: A total of 250 subjects (35.7% of those invited) participated in the study. The median age was 70.4 years, and 50% were female. CA was diagnosed in 12 patients (4.8%; 95% CI: 2.5%-8.2%), and all cases were wild-type transthyretin amyloidosis (ATTRwt). The prevalence of ATTRwt in men was 8.8% (95% CI: 4.5%-15.2%; n = 11), and 21.2% (95% CI: 11.1%-34.7%) in male subjects ≥70 years with a BMI <30 kg/m2. All but 2 patients diagnosed with ATTRwt were in the lowest disease severity score (Mayo score). CONCLUSIONS: Screening for CA in patients with prior surgery for bilateral CTS finds approximately 5% with early-stage transthyretin CA. The clinical yield was higher (>1 in 5) when focusing on nonobese men ≥70 years, showing potential for systematic screening.

Strategies to improve patient-reported outcome completion rates in longitudinal studies.

PURPOSE: The quality of patient-reported outcome (PRO) data can be compromised by non-response (NR) to scheduled questionnaires, particularly if reasons for NR are related to health problems, which may lead to unintended bias. The aim was to investigate whether electronic reminders and real-time monitoring improve PRO completion rate. METHODS: The population-based study "Quality of life in Danish multiple myeloma patients" is a longitudinal, multicentre study with consecutive inclusion of treatment-demanding newly diagnosed or relapsed patients with multiple myeloma. Education of study nurses in the avoidance of NR, electronic reminders, 7-day response windows and real-time monitoring of NR were integrated in the study. Patients complete PRO assessments at study entry and at 12 follow-up time points using electronic or paper questionnaires. The effect of the electronic reminders and real-time monitoring were investigated by comparison of proportions of completed questionnaires before and after each intervention. RESULTS: The first 271 included patients were analysed; of those, 249 (85%) chose electronic questionnaires. Eighty-four percent of the 1441 scheduled PRO assessments were completed within the 7-day response window and 11% after real-time monitoring, achieving a final PRO completion rate of 95%. A significant higher proportion of uncompleted questionnaires were completed after the patients had received the electronic reminder and after real-time monitoring. CONCLUSIONS: Electronic reminders and real-time monitoring contributed to a very high completion rate in the study. To increase the quality of PRO data, we propose integrating these strategies in PRO studies, however highlighting that an increase in staff resources is required for implementation.

Chemerin is elevated in multiple myeloma patients and is expressed by stromal cells and pre-adipocytes.

Chemerin is a recently discovered adipokine shown to be involved in both inflammatory and metabolic processes. Here, we demonstrate that chemerin serum levels are elevated in patients with multiple myeloma and that it increases with disease progression. We found that chemerin is expressed by stromal cells and preadipocytes, whereas its receptor CCRL2 is expressed by primary myeloma cells, suggesting a paracrine signaling loop between bone marrow stromal cells/adipocytes and myeloma cells. This is the first study exploring chemerin and its receptors in multiple myeloma.

Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B.

BACKGROUND: Activins are members of the TGF-ß family of ligands that have multiple biological functions in embryonic stem cells as well as in differentiated tissue. Serum levels of activin A were found to be elevated in pathological conditions such as cachexia, osteoporosis and cancer. Signaling by activin A through canonical ALK4-ACVR2 receptor complexes activates the transcription factors SMAD2 and SMAD3. Activin A has a strong affinity to type 2 receptors, a feature that they share with some of the bone morphogenetic proteins (BMPs). Activin A is also elevated in myeloma patients with advanced disease and is involved in myeloma bone disease. RESULTS: In this study we investigated effects of activin A binding to receptors that are shared with BMPs using myeloma cell lines with well-characterized BMP-receptor expression and responses. Activin A antagonized BMP-6 and BMP-9, but not BMP-2 and BMP-4. Activin A was able to counteract BMPs that signal through the type 2 receptors ACVR2A and ACVR2B in combination with ALK2, but not BMPs that signal through BMPR2 in combination with ALK3 and ALK6. CONCLUSIONS: We propose that one important way that activin A regulates cell behavior is by antagonizing BMP-ACVR2A/ACVR2B/ALK2 signaling.