First Accuracy and User-Experience Evaluation of New Continuous Glucose Monitoring System for Hypoglycemia Due to Hyperinsulinism.

INTRODUCTION: Patients with congenital hyperinsulinism (HI) require constant glucose monitoring to detect and treat recurrent and severe hypoglycemia. Historically, this has been achieved with intermittent self-monitoring blood glucose (SMBG), but patients are increasingly using continuous glucose monitoring (CGM). Given the rapidity of CGM device development, and increasing calls for CGM use from HI families, it is vital that new devices are evaluated early. METHODS: We provided two months of supplies for the new Dexcom G7 CGM device to 10 patients with HI who had recently finished using the Dexcom G6. Self-monitoring blood glucose was performed concurrently with paired readings providing accuracy calculations. Patients and families completed questionnaires about device use at the end of the two-month study period. RESULTS: Compared to the G6, the G7 showed a significant reduction in mean absolute relative difference (25%-18%, P < .001) and in the over-read error (Bland Altman +1.96 SD; 3.54 mmol/L to 2.95 mmol/L). This resulted in an improvement in hypoglycemia detection from 42% to 62% (P < .001). Families reported an overall preference for the G7 but highlighted concerns about high sensor failure rates. DISCUSSION: The reduction in mean absolute relative difference and over-read error and the improvement in hypoglycemia detection implies that the G7 is a safer and more useful device in the management of hypoglycemia for patients with HI. Accuracy, while improved from previous devices, remains suboptimal with 40% of hypoglycemia episodes not detected.

Brain magnetic resonance imaging review suggests unrecognised hypoglycaemia in childhood.

Introduction: Neonatal and early-life hypoglycaemia, is a frequent finding but is often non-specific and asymptomatic, making detection and diagnosis challenging. Hypoglycaemia-induced cerebral injury can be identified by magnetic resonance imaging (MRI) changes in cerebral white matter, occipital lobes, and posterior parietotemporal regions. It is unknown if children may have hypoglycaemic brain injury secondary to unrecognised hypoglycaemia in early life. We have examined retrospective radiological findings of likely brain injury by neuroimaging to investigate the existence of previous missed hypoglycaemic events. Methods: Retrospective MRI data in children in a single tertiary centre, over a ten-year period was reviewed to identify potential cases of unrecognised early-life hypoglycaemia. A detailed search from an electronic radiology repository involved the term "hypoglycaemia'' from text-based reports. The initial report was used for those who required serial scanning. Images specific to relevant reports were further reviewed by a designated paediatric neuroradiologist to confirm likely hypoglycaemia induced brain injury. Medical records of those children were subsequently reviewed to assess if the hypoglycaemia had been diagnosed prior to imaging. Results: A total of 107 MR imaging reports were identified for review, and 52 (48.5%) showed typical features strongly suggestive of hypoglycaemic brain injury. Medical note review confirmed no documented clinical information of hypoglycaemia prior to imaging in 22 (42%) patients, raising the likelihood of missed hypoglycaemic events resulting in brain injury. Conclusions: We have identified the existence of unrecognised childhood hypoglycaemia through neuroimaging review. This study highlights the need for heightened awareness of early life hypoglycaemia to prevent adverse neurological outcomes later in childhood.

Standardised practices in the networked management of congenital hyperinsulinism: a UK national collaborative consensus.

Congenital hyperinsulinism (CHI) is a condition characterised by severe and recurrent hypoglycaemia in infants and young children caused by inappropriate insulin over-secretion. CHI is of heterogeneous aetiology with a significant genetic component and is often unresponsive to standard medical therapy options. The treatment of CHI can be multifaceted and complex, requiring multidisciplinary input. It is important to manage hypoglycaemia in CHI promptly as the risk of long-term neurodisability arising from neuroglycopaenia is high. The UK CHI consensus on the practice and management of CHI was developed to optimise and harmonise clinical management of patients in centres specialising in CHI as well as in non-specialist centres engaged in collaborative, networked models of care. Using current best practice and a consensus approach, it provides guidance and practical advice in the domains of diagnosis, clinical assessment and treatment to mitigate hypoglycaemia risk and improve long term outcomes for health and well-being.

High patient satisfaction and increased physical activity following a remote multidisciplinary team multiple myeloma clinic.

PURPOSE: Patients with multiple myeloma suffer from disease-related complications such as bone destruction, toxicities from repeated therapies and age-related co-morbidities. With improved treatment options, patients are living longer and have specific survivorship needs such as low exercise levels that need to be addressed. In this study, we designed, implemented and evaluated a multidisciplinary team (MDT) myeloma clinic that provided participants with tailored exercise and lifestyle advice. METHODS: The Promoting Individualised Self-Management and Survivorship (PrISMS) clinic was set up in two UK myeloma centres. This remote MDT clinic comprised of a doctor, a nurse specialist and a physiotherapist. Patients were required to complete blood tests and a questionnaire about their symptoms and concerns before each consultation. Patient-reported outcome measures were captured using validated questionnaires. Patient feedback was collected using a specially designed survey and structured telephone interviews. RESULTS: Sixty-one patients were enrolled in the pilot clinic with 210 consultations held during the study period. Nine patients had disease progression and were referred safely back to face-to-face clinics. There was a significant improvement in patients' exercise score (p = 0.02) after PrISMS clinic. Patient satisfaction was high, with 83% feeling more confident in self-managing myeloma after PrISMS clinic. CONCLUSION: PrISMS clinic is safe and feasible, with high patient compliant and acceptability. It empowers patients to self-manage their condition and encourages physical activity, which is associated with improved quality of life and fatigue level. Future randomised controlled trials will help to confirm its benefits on patient clinical outcomes and cost-effectiveness.

Rapid response to single agent daratumumab is associated with improved progression-free survival in relapsed/refractory AL amyloidosis.

Background: Daratumumab is a monoclonal antibody, which targets CD38; an antigen expressed on malignant plasma cells in AL amyloidosis thus providing a rationale for its use.Method: Patients treated with daratumumab monotherapy (2016-2019) for relapsed/refractory systemic AL amyloidosis were identified from the database at the UK National Amyloidosis Centre.Results: Of 50 evaluable patients, haematological responses at 3 months were: CR - 19 (38%), VGPR - 14 (28%), PR - 9 (18%) and no response - 8 (16%). Median time to response was 1 (1-6) month. Of assessable patients, cardiac, renal and hepatic responses were seen in 43.8%, 25.0% and 0% of patients whilst progression occurred in 25.0%, 12.5% and 37.5% respectively. Patients achieving a CR had longer median OS (not reached vs. 22.7 months [95% CI 17.0-28.4 months]) (p = .036). Furthermore, patients achieving a rapid response (at 1 month) had a longer median PFS (not reached vs. 9 months [95% CI 5.8-12.2 months]) (p = .013).Conclusion: Daratumumab monotherapy is effective in multiply-relapsed systemic AL amyloidosis and should be considered, if available, in patients who have not received prior daratumumab therapy. Responses are achieved rapidly and overall response rate was 84%. CR predicts overall survival whilst speed of response is predictive of a longer PFS.

Cytomegalovirus reactivation after bortezomib treatment for multiple myeloma and light chain amyloidosis.

OBJECTIVE: Cytomegalovirus (CMV) is an opportunistic herpesvirus, and reactivation of infection is possible in immunocompromised patients. Historically, the risk for haematology patients is restricted to those treated with an allogeneic transplant or T-cell depleting agents. Bortezomib is a highly efficacious proteasome inhibitor widely used to treat multiple myeloma and light chain (AL) amyloidosis patients. The objective of this small prospective study was to quantify the risk of CMV reactivation associated with bortezomib treatment. METHODS: Fifty-seven consecutive multiple myeloma or AL amyloidosis patients commencing bortezomib-based therapy were included. Viral copy numbers were established at baseline and then at fortnightly intervals during treatment. Pre-emptive anti-viral treatment was initiated in patients with a viral load >7500 copies/mL. RESULTS: Reactivation of CMV was detected in 39% (n = 12/31) of seropositive bortezomib treated patients compared with 0% of CMV seronegative patients. Detectable DNAemia developed during the first two cycles of treatment in 83% (n = 10/12) patients. Anti-viral treatment was initiated in 42% (n = 5/12), but no cases of active CMV disease were seen. CONCLUSION: This study suggests that there is a substantial risk of CMV reactivation in CMV-seropositive plasma cell dyscrasia patients treated with bortezomib.

Carfilzomib is an effective upfront treatment in AL amyloidosis patients with peripheral and autonomic neuropathy.

Bortezomib is standard treatment in AL amyloidosis (AL), but is contraindicated in patients with significant neuropathy. Carfilzomib, a second-generation proteosomal inhibitor, results in a lower incidence of neuropathy than bortezomib, but data in AL is scant. We report a cohort of five AL patients treated with upfront carfilzomib. All had cardiac, peripheral and autonomic neuropathy at presentation. All achieved at least a very good partial haematological response. There was no worsening in cardiac function, peripheral or autonomic neuropathy. Carfilzomib is an effective upfront treatment option in AL patients with peripheral and/or autonomic neuropathy (without severe cardiac or renal involvement).

A survey tool for measuring evidence-based decision making capacity in public health agencies.

BACKGROUND: While increasing attention is placed on using evidence-based decision making (EBDM) to improve public health, there is little research assessing the current EBDM capacity of the public health workforce. Public health agencies serve a wide range of populations with varying levels of resources. Our survey tool allows an individual agency to collect data that reflects its unique workforce. METHODS: Health department leaders and academic researchers collaboratively developed and conducted cross-sectional surveys in Kansas and Mississippi (USA) to assess EBDM capacity. Surveys were delivered to state- and local-level practitioners and community partners working in chronic disease control and prevention. The core component of the surveys was adopted from a previously tested instrument and measured gaps (importance versus availability) in competencies for EBDM in chronic disease. Other survey questions addressed expectations and incentives for using EBDM, self-efficacy in three EBDM skills, and estimates of EBDM within the agency. RESULTS: In both states, participants identified communication with policymakers, use of economic evaluation, and translation of research to practice as top competency gaps. Self-efficacy in developing evidence-based chronic disease control programs was lower than in finding or using data. Public health practitioners estimated that approximately two-thirds of programs in their agency were evidence-based. Mississippi participants indicated that health department leaders' expectations for the use of EBDM was approximately twice that of co-workers' expectations and that the use of EBDM could be increased with training and leadership prioritization. CONCLUSIONS: The assessment of EBDM capacity in Kansas and Mississippi built upon previous nationwide findings to identify top gaps in core competencies for EBDM in chronic disease and to estimate a percentage of programs in U.S. health departments that are evidence-based. The survey can serve as a valuable tool for other health departments and non-governmental organizations to assess EBDM capacity within their own workforce and to assist in the identification of approaches that will enhance the uptake of EBDM processes in public health programming and policymaking. Localized survey findings can provide direction for focusing workforce training programs and can indicate the types of incentives and policies that could affect the culture of EBDM in the workplace.