SUMMARYPurpose: Current treatments for epilepsy may control seizures, but have no known effects on the underlying disease. We sought to determine whether early treatment in a model of genetic epilepsy would reduce the severity of the epilepsy phenotype in adulthood. Methods: We used Wistar albino Glaxo rats of Rijswijk (WAG/Rij) rats, an established model of human absence epilepsy. Oral ethosuximide was given from age p21 to 5 months, covering the usual period in which seizures develop in this model (age ∼3 months). Two experiments were performed: (1) cortical expression of ion channels Nav1.1, Nav1.6, and HCN1 (previously shown to be dysregulated in WAG/Rij) measured by immunocytochemistry in adult treated rats; and (2) electroencephalogram (EEG) recordings to measure seizure severity at serial time points after stopping the treatment.Results: Early treatment with ethosuximide blocked changes in the expression of ion channels Nav1.1, Nav1.6, and HCN1 normally associated with epilepsy in this model. In addition, the treatment led to a persistent suppression of seizures, even after therapy was discontinued. Thus, animals treated with ethosuximide from age p21 to 5 months still had a marked suppression of seizures at age 8 months. Discussion: These findings suggest that early treatment during development may provide a new strategy for preventing epilepsy in susceptible individuals. If confirmed with other drugs and epilepsy paradigms, the availability of a model in which epileptogenesis can be controlled has important implications both for future basic studies, and human therapeutic trials.

BackgroundNepal’s Female Community Health Volunteer (FCHV) program has been described as an exemplary public-sector community health worker program. However, despite its merits, the program still struggles to provide high-quality, accessible services nation-wide. Both in Nepal and globally, best practices for community health worker program implementation are not yet known: there is a dearth of empiric research, and the research that has been done has shown inconsistent results.MethodsHere we evaluate a pilot program designed to strengthen the Nepali government’s FCHV network. The program was structured with five core components: 1) improve local FCHV leadership; 2) facilitate structured weekly FCHV meetings and 3) weekly FCHV trainings at the village level; 4) implement a monitoring and evaluation system for FCHV patient encounters; and 5) provide financial compensation for FCHV work. Following twenty-four months of program implementation, a retrospective programmatic evaluation was conducted, including qualitative analysis of focus group discussions and semi-structured interviews.ResultsQualitative data analysis demonstrated that the program was well-received by program participants and community members, and suggests that the five core components of this program were valuable additions to the pre-existing FCHV network. Analysis also revealed key challenges to program implementation including geographic limitations, literacy limitations, and limitations of professional respect from healthcare workers to FCHVs. Descriptive statistics are presented for programmatic process metrics and costs throughout the first twenty four months of implementation.ConclusionsThe five components of this pilot program were well-received as a mechanism for strengthening Nepal’s FCHV program. To our knowledge, this is the first study to present such data, specifically informing programmatic design and management of the FCHV program. Despite limitations in its scope, this study offers tangible steps forward for further research and community health worker program improvement, both within Nepal and globally.

The beneficial effects of chronic and early pharmacological treatment with ethosuximide on epileptogenesis were studied in a genetic absence epilepsy model comorbid for depression. It was also investigated whether there is a critical treatment period and treatment length. Cortical excitability in the form of electrical evoked potentials, but also to cortico-thalamo-cortical network activity (spike–wave discharges, SWD and afterdischarges), white matter changes representing extra corticothalamic functions and depressive-like behavior were investigated. WAG/Rij rats received either ethosuximide for 2 months (post natal months 2–3 or 4–5), or ethosuximide for 4 months (2–5) in their drinking water, while control rats drank plain water. EEG measurements were made during treatment, and 6 days and 2 months post treatment. Behavioral test were also done 6 days post treatment. DTI was performed ex vivo post treatment. SWD were suppressed during treatment, and 6 days and 2 months post treatment in the 4 month treated group, as well as the duration of AD elicited by cortical electrical stimulation 6 days post treatment. Increased fractional anisotropy in corpus callosum and internal capsula on DTI was found, an increased P8 evoked potential amplitude and a decreased immobility in the forced swim test. Shorter treatments with ETX had no large effects on any parameter. Chronic ETX has widespread effects not only within but also outside the circuitry in which SWD are initiated and generated, including preventing epileptogenesis and reducing depressive-like symptoms. The treatment of patients before symptom onset might prevent many of the adverse consequences of chronic epilepsy.

Health systems strengthening (HSS) is a priority for global health funders, policy-makers and practitioners. Although many HSS efforts have focused on policy levers such as financing approaches, payment schemes or regulatory reforms, less attention has been directed to targeting the organisations that deliver health services such as hospitals, health centres and clinics. Evidence suggests that the impact of organisation-level interventions varies by context; however, we lack a general framework for integrating organisational context into performance improvement strategies for health service delivery organisations. Drawing on open systems theories from organisational behaviour and management as well as a review of 181 empirical studies of health service delivery organisations in low- and middle-income countries, we propose a taxonomy of seven strategy areas for improving organisational performance as well as a multistage conceptual framework for selecting among them. We propose that the choice of strategy for improving health service delivery organisational performance should be informed by: (i) the root cause of the organisation's performance gap; (ii) the environmental conditions facing the organisation; and (iii) the implementation capability of the organisation. We also highlight conditions under which different strategy areas may be expected to be optimally effective. The approaches presented in this paper offer a way for health system decision-makers and researchers to systematically assess and incorporate organisational context in the process of developing strategies to improve the performance of health service delivery organisations and, ultimately, of health systems.

Summary C3H/HeJ mice have been reported to have relatively early onset of spike-wave discharges (SWD), and a defective AMPA receptor subunit Gria4 as the genetic cause. We investigated the time course of SWD development through serial EEG recordings in C3H/HeJ mice to better characterize this model. We found that at immature postnatal ages of 5–15 days, rare SWD-like events were observed at an average rate of 3 per hour, and with relatively broad spikes, irregular rhythm, slow frequency (5–6 Hz), and short duration (mean 1.75 s). This was followed by a transitional period of increasing SWD incidence, which then stabilized in mature animals at age 26–62 days, with SWD at an average rate of 45 per hour, narrower spike morphology, regular rhythm, higher frequency (7–8 Hz), and longer duration (mean 3.40 s). This sequence of maturational changes in SWD development suggests that effects of early intervention could be tested in C3H/HeJ mice over the course of a few weeks, rather than a few months as in rats, greatly facilitating future research on anti-epileptogenesis.