RESUMO
Background: Hypertension remains one of the most important modifiable risk factors for stroke and heart disease. Anti-hypertensive medications are effective, but are often not used to maximum benefit. Sub-optimal dosing by prescribers and challenges with medication-taking for patients remain barriers to effective blood pressure control. Objectives: We aimed to systematically develop a theory-based complex intervention to support General Practitioners (GPs) and people with hypertension to maximise medication use to control blood pressure. Methods: We used the three-phase Behaviour Change Wheel (BCW) as the overarching intervention development framework. Collective Intelligence methodology was used to operationalise the stakeholder input to Phases 2 and 3 of the BCW. This took the form of a Collective Intelligence workshop with 19 stakeholders from diverse backgrounds including lived experience, general practice, nursing, pharmacy and health psychology. Techniques such as barrier identification, idea-writing and scenario-based design were used to generate possible intervention options. Intervention options were then selected and refined using the Acceptability, Practicability, Effectiveness, Affordability, Side-effects and Equity (APEASE) criteria and guidance from the MIAMI Public and Patient Involvement Panel. Results: The finalised MIAMI intervention consists of both GP and patient supports. GP supports include a 30-minute online training, information booklet and consultation guide (drop-down menu) embedded within the patient electronic health system. Patient supports include a pre-consultation plan, website, and a structured GP consultation with results from an Ambulatory Blood Pressure Monitor and urine chemical adherence test. The intervention components have been mapped to the intervention functions of the BCW and Behaviour Change Technique Ontology. Conclusion: Collective Intelligence offered a novel method to operationalise stakeholder input to Phases 2 and 3 of the BCW. The MIAMI intervention is now at pilot evaluation stage.
RESUMO
Developmental and Epileptic Encephalopathies (DEEs), a class of devastating neurological disorders characterized by recurrent seizures and exacerbated by disruptions to excitatory/inhibitory balance in the brain, are commonly caused by mutations in ion channels. Disruption of, or variants in, FGF13 were implicated as causal for a set of DEEs, but the underlying mechanisms were clouded because FGF13 is expressed in both excitatory and inhibitory neurons, FGF13 undergoes extensive alternative splicing producing multiple isoforms with distinct functions, and the overall roles of FGF13 in neurons are incompletely cataloged. To overcome these challenges, we generated a set of novel cell type-specific conditional knockout mice. Interneuron-targeted deletion of Fgf13 led to perinatal mortality associated with extensive seizures and impaired the hippocampal inhibitory/excitatory balance while excitatory neuron-targeted deletion of Fgf13 caused no detectable seizures and no survival deficits. While best studied as a voltage-gated sodium channel (Nav) regulator, we observed no effect of Fgf13 ablation in interneurons on Navs but rather a marked reduction in K+ channel currents. Re-expressing different Fgf13 splice isoforms could partially rescue deficits in interneuron excitability and restore K+ channel current amplitude. These results enhance our understanding of the molecular mechanisms that drive the pathogenesis of Fgf13-related seizures and expand our understanding of FGF13 functions in different neuron subsets.
