Mast Cell Diseases in Practice and Research:Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond

Background: Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes. Objective: This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patients’ quality of life by addressing unmet needs. Methods: In collaboration with mast cell disease specialists, 13 patient advocacy groups from 12 countries and regions developed lists of top patient needs. A core team of leaders from patient advocacy groups collected and analyzed the data and proposed possible actions to address patient needs. Results: Findings identified similarities and differences among participating countries in unmet needs between patients with mastocytosis and those with mast cell activation syndromes. Issues emphasized struggles relating to the nature and rarity of mast cell diseases, their impact on quality of life, the diagnostic process, access to appropriate care, more effective treatment, and the need for research. Conclusions: Solutions vary across countries because situations differ, in particular regarding the existence of and access to centers of excellence and reference centers. Multifaceted mast cell activation syndrome barriers necessitate innovative approaches to improve access to appropriate care. The outcomes of this project should greatly support scientists and clinicians in their efforts to improve diagnosis, management, and treatment of patients with mastocytosis and mast cell activation disorders

Differentiating Peer and Friend Social Information-Processing Effects on Stress and Glycemic Control Among Youth With Type 1 Diabetes

Objective: Many adolescents with Type 1 diabetes (T1D) find adherence difficult in social situations because they fear negative evaluations by others. These negative reaction attributions are associated with anticipated adherence difficulties, stress, and glycemic control. It is unclear whether peer versus friend attributions are distinct constructs, or whether there is a differential impact on glycemic control moderated by youth characteristics. Method: Youth with T1D (n = 142; 58% female; 84% Caucasian, mean = 13.79 years, standard deviation = 2.10) completed the Peer Attribution and Diabetes Stress Questionnaires. HbA1cs were obtained from medical records. Results: Negative peer versus friend attributions appear distinct and were differentially related to anticipated adherence difficulties, stress, and glycemic control, with peer attributions having the strongest effect. Grade, age, and sex were not moderators for these relationships. Conclusion: Peer-related attributions may be a particularly salient target for interventions to improve adherence and distress among youth with T1D

Assessing measurement invariance of the diabetes stress questionnaire in youth with type 1 diabetes

Objective To evaluate the factor structure and measurement invariance of the Diabetes Stress Questionnaire (DSQ), a measure of diabetes-specific stress, across sex, age (\u3c9th grade vs. ≥9th grade), and glycemic control (optimal vs. suboptimal). Methods Data from 318 adolescent participants were pooled from four archival data sets and the ongoing Predicting Resiliency in Youth with Type 1 Diabetes study in which the DSQ was completed. Confirmatory factor and measurement invariance analyses were conducted to confirm the proposed factor structure and measurement invariance across sex, age, and glycemic control. Results The DSQ factor structure was found to have an acceptable fit, which was invariant across sex, age, and glycemic control. Conclusions When using the DSQ, differences in diabetes-related stress with respect to sex, age, or glycemic control can be considered meaningful. This study supports the DSQ as an evidence-based and well-established assessment of perceived diabetes stress in youth with type 1 diabetes

Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment.

BACKGROUND: Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and to test whether affected patients were genetically predisposed to multiple sclerosis [MS]. METHODS: We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure. We compared genetic risk scores [GRS], calculated using carriage of 43 susceptibility loci for MS, in 48 cases with 1219 patients exposed to anti-TNF who did not develop demyelination. RESULTS: Overall, 39 [74%] cases were female. The median age [range] of patients at time of demyelination was 41.5 years [20.7-63.2]. The median duration of anti-TNF treatment was 21.3 months [0.5-99.4] and 19 [36%] patients were receiving concomitant immunomodulators. Most patients had central demyelination affecting the brain, spinal cord, or both. Complete recovery was reported in 12 [23%] patients after a median time of 6.8 months [0.1-28.7]. After 33.0 months of follow-up, partial recovery was observed in 29 [55%] patients, relapsing and remitting episodes in nine [17%], progressive symptoms in three [6%]: two [4%] patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 × 10-4, standard deviation [SD] 0.0039) and controls [mean -1.1 × 10-3, SD 0.0042] [p = 0.23]. CONCLUSIONS: Patients who experienced demyelination events following anti-TNF exposure were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not experience demyelination events. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci