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.

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.

[Status and perspectives on chronic myeloproliferative neoplasm treatment]. / Status og perspektiver for behandling af de kroniske myeloproliferative neoplasier.

Polycythaemia vera, essential thrombocytosis and primary myelofibrosis are closely related, clonal myeloproliferative neoplasms. Our knowledge of the underlying molecular mechanisms driving these diseases has increased dramatically during the latest ten years. Traditionally, treatment of these malignancies has focused on lowering their inherent thromboembolic risk but with the discovery of the JAK2-V617F mutation and most recently the calreticulin mutations new therapeutic options such as interferon-alpha, JAK2-inhibitors and statins are being contemplated. This article reviews these new treatment options.

Prevalence, clinical significance, and genetic basis of hypertrophic cardiomyopathy with restrictive phenotype.

OBJECTIVES: The purpose of this study was to determine the prevalence, clinical significance, and genetic basis of hypertrophic cardiomyopathy (HCM) with "restrictive phenotype" characterized by restrictive filling and minimal or no left ventricular hypertrophy. BACKGROUND: Hypertrophic cardiomyopathy is a heterogeneous myocardial disorder with a broad spectrum of clinical presentation and morphologic features. Recent reports indicated that some patients with restrictive cardiomyopathy, which is an uncommon condition defined by restrictive filling and reduced diastolic volumes with normal or near normal left ventricular wall thickness and contractile function, have features suggestive of HCM with mutations in cardiac troponin I, myocyte disarray at explant/autopsy, and relatives with HCM. Systematic evaluation of the restrictive phenotype in HCM patients has not been performed. METHODS: We evaluated 1,226 patients from 688 consecutive HCM families to identify individuals who fulfilled diagnostic criteria for "restrictive phenotype." RESULTS: Nineteen of 1,226 affected individuals (1.5%) from 16 families (2.3%) had the "restrictive phenotype." During follow up (53.7 +/- 49.2 months), 17 patients (89%) experienced dyspnea (New York Heart Association functional class > or =2). The 5-year survival rate from all-cause mortality, cardiac transplantation, or implantable cardioverter-defibrillator discharge was 56.4%. Mutation analysis for 5 sarcomere genes was feasible in 15 of 16 probands. Mutations were found in 8: 4 in beta-myosin heavy chain, and 4 in cardiac troponin I. CONCLUSIONS: The "restrictive phenotype" in isolation is an uncommon presentation of the clinical spectrum of HCM and is associated with severe limitation and poor prognosis. This phenotype may be associated with beta-myosin heavy chain and cardiac troponin I mutations.