| 1. |
- Auchus, RJ, et al.
(author)
-
Treatment patterns and unmet needs in adults with classic congenital adrenal hyperplasia: A modified Delphi consensus study
- 2022
-
In: Frontiers in endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13, s. 1005963-
-
Journal article (peer-reviewed)abstract
- Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a rare autosomal recessive condition characterized by cortisol deficiency and excess androgen production. The current standard of care is glucocorticoid (GC) therapy, and sometimes mineralocorticoids, to replace endogenous cortisol deficiency; however, supraphysiologic GC doses are usually needed to reduce excess androgen production. Monitoring/titrating GC treatment remains a major challenge, and there is no agreement on assessment of treatment adequacy. This study surveyed expert opinions on current treatment practices and unmet needs in adults with classic CAH.MethodsA modified two-round Delphi process with adult endocrinologists was conducted via online questionnaire. Survey questions were organized into three categories: practice characteristics/CAH experience, GC management, and unmet needs/complications. Anonymized aggregate data from Round 1 were provided as feedback for Round 2. Responses from both rounds were analyzed using descriptive statistics. Consensus was defined a priori as: full consensus (100%, n=9/9); near consensus (78% to <100%, n=7/9 or 8/9); no consensus (<78%, n<7/9).ResultsThe same nine panelists participated in both survey rounds; five (56%) were based in North America and four (44%) in Europe. Most panelists (78%) used hydrocortisone in the majority of patients, but two (22%) preferred prednisone/prednisolone. Panelists agreed (89%) that adequate control is best evaluated using a balance of clinical presentation and androgen/precursor laboratory values; no consensus was reached on optimal timing of collecting samples for androgen testing or laboratory values indicating good control. Despite lack of consensus on many aspects of CAH management, panelists agreed on the importance of many disease- and GC-related complications, and that there is a large unmet need for new treatments. With currently available treatments, panelists reported that 46% of classic CAH patients did not have optimized androgen levels, regardless of GC dose.ConclusionsThe limited areas of consensus obtained in this study reflect the variability in treatment practices for adults with classic CAH, even among clinicians with expertise in treating this population. However, all panelists agreed on the need for new treatments for classic CAH and the importance of many disease- and GC-related complications, which are difficult to manage with currently available treatments.
|
|
| 2. |
|
|
| 3. |
- Jendle, Johan, 1963-, et al.
(author)
-
Cost-Effectiveness of the FreeStyle Libre(R) System Versus Blood Glucose Self-Monitoring in Individuals with Type 2 Diabetes on Insulin Treatment in Sweden
- 2021
-
In: Diabetes Therapy. - : Springer Science and Business Media LLC. - 1869-6953 .- 1869-6961. ; 12, s. 3137-3152
-
Journal article (peer-reviewed)abstract
- Introduction Frequent glucose monitoring is essential to obtain glucose control. This is done by periodic self-monitoring of blood glucose (SMBG) using finger-prick testing, or by using continuous glucose monitoring devices, wherein a sensor records interstitial glucose data automatically. This study assessed the cost-effectiveness of using the FreeStyle Libre Flash Continuous Glucose Monitoring System (FSL) compared to SMBG in individuals with type 2 diabetes (T2D) treated with insulin from a Swedish societal perspective. Methods Cost-effectiveness analysis was conducted using the IQVIA Core Diabetes model v9.5, with demographic and clinical inputs from a real-world study using Swedish National Diabetes Register data. Two cohorts of individuals with T2D were considered based on baseline HbA1C (HbA1c: 8-9% [64-75 mmol/mol]; HbA1c: 9-12% [75-108 mmol/mol]). HbA1c reductions with FSL were - 0.41% (- 4 mmol/mol; SD: 0.94%-10 mmol/mol) and - 1.30% (- 14 mmol/mol; SD: 1.40%-15 mmol/mol) for the two cohorts, respectively. Utilities, treatment costs and diabetes-related complication costs were obtained from published sources. Analyses were conducted over a lifetime horizon, applying annual discounting of 3% on costs and effects. Scenario analyses and probabilistic sensitivity analyses were performed. Results Individuals with T2D who had a baseline HbA1c of 8-9% (64-75 mmol/mol) and 9-12% (75-108 mmol/mol) and used FSL gained 0.50 and 0.57 quality-adjusted life-years (QALYs), respectively, at an incremental cost of SEK109,957 and SEK82,170 compared to SMBG, generating an incremental cost-utility ratio of SEK219,127 and SEK144,412 per QALY gained. Assuming a willingness-to-pay threshold of SEK300,000 per QALY gained, FSL use was considered cost-effective compared to SMBG for the majority of the individuals in both the lower and higher HbA1c cohorts. The key driver identified was the additional quality-of-life benefit that applied to FSL use. Conclusion The FreeStyle Libre Flash Continuous Glucose Monitoring System is a cost-effective glucose monitoring alternative to SMBG for individuals with T2D in Sweden who are treated with insulin but are not reaching their glycaemic goals.
|
|
| 4. |
- Perry, Sharn, et al.
(author)
-
Firing properties of Renshaw cells defined by Chrna2 are modulated by hyperpolarizing and small conductance ion currents I-h and I-SK
- 2015
-
In: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 41:7, s. 887-898
-
Journal article (peer-reviewed)abstract
- Renshaw cells in the spinal cord ventral horn regulate motoneuron output through recurrent inhibition. Renshaw cells can be identified in vitro using anatomical and cellular criteria; however, their functional role in locomotion remains poorly defined because of the difficulty of functionally isolating Renshaw cells from surrounding motor circuits. Here we aimed to investigate whether the cholinergic nicotinic receptor alpha2 (Chrna2) can be used to identify Renshaw cells (RCs2) in the mouse spinal cord. Immunohistochemistry and electrophysiological characterization of passive and active RCs2 properties confirmed that neurons genetically marked by the Chrna2-Cre mouse line together with a fluorescent reporter mouse line are Renshaw cells. Whole-cell patch-clamp recordings revealed that RCs2 constitute an electrophysiologically stereotyped population with a resting membrane potential of -50.5 +/- 0.4mV and an input resistance of 233.1 +/- 11M. We identified a ZD7288-sensitive hyperpolarization-activated cation current (I-h) in all RCs2, contributing to membrane repolarization but not to the resting membrane potential in neonatal mice. Additionally, we found RCs2 to express small calcium-activated potassium currents (I-SK) that, when blocked by apamin, resulted in a complete attenuation of the afterhyperpolarisation potential, increasing cellular firing frequency. We conclude that RCs2 can be genetically targeted through their selective Chrna2 expression and that they display currents known to modulate rebound excitation and firing frequency. The genetic identification of Renshaw cells and their electrophysiological profile is required for genetic and pharmacological manipulation as well as computational simulations with the aim to understand their functional role.
|
|
