Objectives
The current coronavirus disease 2019 (COVID‐19) pandemic stresses an urgency to accelerate much‐needed health service reform. Rapid and courageous changes being made to address the ...immediate impact of the pandemic are demonstrating that the means and technology to enable new models of health care exist. For example, innovations such as electronic patient portals (ePortal) can facilitate (a) radical reform of outpatient care; (b) cost containment in the economically constrained aftermath of the pandemic; (c) environmental sustainability by reduction of unnecessary journeys/transport. Herein, the development of Providing Individualised Services and Care in Epilepsy (PiSCES), an ePortal to the Irish National Epilepsy Electronic Patient Record, is demonstrated. This project, which pre‐dates the COVID‐19 crisis, aims to facilitate better patient‐ and family‐centered epilepsy care.
Methods
A combination of ethnographic research, document analysis, and joint application design sessions was used to elicit PiSCES requirements. From these, a specification of desired modules of functionality was established and guided the software development.
Results
PiSCES functional features include “My Epilepsy Care Summary,” “My Epilepsy Care Goals,” “My Epilepsy Clinic Letters,” “Help Us Measure Your Progress,” “Prepare For Your Clinic Visit,” “Information for Your Healthcare Provider.” The system provides people with epilepsy access to, and engages them as co‐authors of, their own medical record. It can promote improved patient‐clinician partnerships and facilitate patient self‐management.
Significance
In the aftermath of COVID‐19, it is highly unlikely that the healthcare sector will return to a “business as usual” way of delivering services. The pandemic is expected to accelerate adoption of innovations like PiSCES. It is therefore a catalyst for change that will deliver care that is more responsive to individual patient needs and preferences.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
Recent clinical trials have shown that cenobamate substantially improves seizure control in focal‐onset drug‐resistant epilepsy (DRE). However, little is known about cenobamate's ...performance in highly active (≥20 seizures/month) and ultra‐refractory focal epilepsy (≥6 failed epilepsy treatments, including antiseizure medications ASMs, epilepsy surgery, and vagus nerve stimulation). Here, we studied cenobamate's efficacy and tolerability in a “real‐world” severe DRE cohort.
Methods
We conducted a single‐center retrospective analysis of consecutive adults treated with cenobamate between October 2020 and September 2022. All patients received cenobamate through an Early Access Program. Cenobamate retention, seizure outcomes, treatment‐emergent adverse events, and adjustments to concomitant ASMs were analyzed.
Results
Fifty‐seven patients received cenobamate for at least 3 months (median duration, 11 months). The median cenobamate dose was 250 mg/day (range 75–350 mg). Baseline demographics were consistent with highly active (median seizure frequency, 60/month) and ultra‐refractory epilepsy (median previously failed ASMs, nine). Most (87.8%) had prior epilepsy surgery and/or vagus nerve stimulation. Six patients stopped cenobamate due to lack of efficacy and/or adverse events. One patient died from factors unrelated to cenobamate. Among patients who continued cenobamate, three achieved seizure freedom (5.3% of cohort), 24 had a 75%–99% reduction in seizures (42.1% of cohort), and 16 had a 50%–74% reduction (28.1% of cohort). Cenobamate led to abolition of focal to bilateral tonic–clonic seizures in 55.6% (20/36) of patients. Among treatment responders, 67.4% (29/43) were treated with cenobamate doses of ≥250 mg/day. Three‐fourths of patients reported at least one side‐effect, most commonly fatigue and somnolence. Adverse events most commonly emerged at cenobamate doses of ≥250 mg/day. Side‐effects were partially manageable by reducing the overall ASM burden, most often clobazam, eslicarbazepine, and perampanel.
Significance
Patients with highly active and ultra‐refractory focal epilepsy experienced meaningful seizure outcomes on cenobamate. Emergence of adverse events at doses above 250 mg/day may limit the potential for further improvements in seizure control at higher cenobamate doses.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•Co-production is about provider-beneficiary partnerships to optimize healthcare.•PiSCES, the Irish epilepsy patient portal, aims to foster greater coproduction.•What epilepsy care beneficiaries and ...providers value about PiSCES was examined.•Participants found access their healthcare record via PiSCES empowering.•PiSCES is seen as a potential passport of care between different clinical settings.
Coproduced epilepsy care sees people with epilepsy (PwE), their care-proxies, and healthcare providers (HCPs), working together as partners to build strong relationships, improve communication, trust, and share decision-making. Coproduction underpins good quality patient- and family-centered care (PFCC) that is responsive to individual patient needs, preferences, and values. By facilitating information sharing and exchange between partners, electronic patient portals (ePortal) can enable coproduction. This paper explores what HCPs, PwE, and their care-proxies value from their user experience of PiSCES, the Irish epilepsy ePortal.
A purposeful sample of actors involved in the receipt and delivery of epilepsy care and services were recruited via adult epilepsy centers at St James’s and Beaumont Hospitals in Dublin. Interactive codesign sessions, surveys, and focus groups were used to elicit perspectives from PwE, care-proxies, and HCPs to understand their perception of how PiSCES could enhance or inhibit the epilepsy care process.
Results illustrate that participants welcome the role PiSCES can play in: empowering PwE/care-proxies, strengthening confidence in the healthcare system; aiding memory; advancing health literacy, motivating PwE to understand their condition better; acting as a passport of care between different clinical settings; and creating a foundation for stronger coproduction partnerships. PiSCES was generally embraced; however, some HCPs expressed plausible concerns about how clinical implementation might impact their work practices.
“Nothing about me without me” is a core value of the PiSCES initiative, recognizing that people need to be included in the planning of their own treatment and care. Our data show that PwE, their care-proxies, and HCPs value PiSCES potential, particularly in bolstering healthcare partnerships that foster inclusion, confidence, and trust.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract We show that hard encounters in the central regions of globular clusters (GCs) embedded in dark matter (DM) haloes necessarily lead to the formation of gravitationally bound stellar ...envelopes that extend far beyond the nominal tidal radius of the system. Using statistical arguments and numerical techniques, we derive the equilibrium distribution function of stars ejected from the centre of a non-divergent spherical potential. Independently of the velocity distribution with which stars are ejected, GC envelopes have density profiles that approach asymptotically ρ ∼ r−4 at large distances and become isothermal towards the centre. Adding a DM halo component leaves two clear-cut observational signatures: (i) a flattening, or slightly increase of the projected velocity dispersion profile at large distances, and (ii) an outer surface density profile that is systematically shallower than in models with no DM.
Retinal dopamine is released by a specialized subset of amacrine cells in response to light and has a potent influence on how the retina responds to, and encodes, visual information. Here, we address ...the critical question of which retinal photoreceptor is responsible for coordinating the release of this neuromodulator. Although all three photoreceptor classes—rods, cones, and melanopsin-containing retinal ganglion cells (mRGCs)—have been shown to provide electrophysiological inputs to dopaminergic amacrine cells (DACs), we show here that the release of dopamine is defined only by rod photoreceptors. Remarkably, this rod signal coordinates both a suppressive signal at low intensities and drives dopamine release at very bright light intensities. These data further reveal that dopamine release does not necessarily correlate with electrophysiological activity of DACs and add to a growing body of evidence that rods define aspects of retinal function at very bright light levels.
•Rod activation alone mediates light-dependent retinal dopamine release•Rod-driven light-induced dopamine release is confined to photopic light levels•Rods suppress dopamine release under scotopic and mesopic light conditions•Spiking activity of dopaminergic amacrines is not correlated with dopamine release
Pérez-Fernández et al. find that light-induced dopamine release in the mouse retina is defined by rod photoreceptor activation. Stimulation under dim to mesopic light intensities causes dopamine release to be suppressed, and bright photopic light intensities cause extensive dopamine release.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Breen and Meyer discuss their study on the impact of disasters on college students. College students in the US occupy a unique social space between adolescence and adulthood. Traditional-age college ...students are learning how to live independently from their parents, although many still depend on their family members for financial and emotional support. In addition, college students often move away from home to new geographic locations, potentially exposing them to different hazard contexts. Their position within the social structure may generate unique risks for college students during disasters.
GDF15 is a distant TGF-β family member that induces anorexia and weight loss. Due to its function, GDF15 has attracted attention as a potential therapeutic for the treatment of obesity and its ...associated metabolic diseases. However, the pharmacokinetic and physicochemical properties of GDF15 present several challenges for its development as a therapeutic, including a short half-life, high aggregation propensity, and protease susceptibility in serum. Here, we report the design, characterization and optimization of GDF15 in an Fc-fusion protein format with improved therapeutic properties. Using a structure-based engineering approach, we combined knob-into-hole Fc technology and N-linked glycosylation site mutagenesis for half-life extension, improved solubility and protease resistance. In addition, we identified a set of mutations at the receptor binding site of GDF15 that show increased GFRAL binding affinity and led to significant half-life extension. We also identified a single point mutation that increases p-ERK signaling activity and results in improved weight loss efficacy in vivo. Taken together, our findings allowed us to develop GDF15 in a new therapeutic format that demonstrates better efficacy and potential for improved manufacturability.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as an important tool for the diagnosis and staging of lung cancer but its role in the diagnosis of tuberculous ...intrathoracic lymphadenopathy has not been established. The aim of this study was to describe the diagnostic utility of EBUS-TBNA in patients with intrathoracic lymphadenopathy due to tuberculosis (TB).
156 consecutive patients with isolated intrathoracic TB lymphadenitis were studied across four centres over a 2-year period. Only patients with a confirmed diagnosis or unequivocal clinical and radiological response to antituberculous treatment during follow-up for a minimum of 6 months were included. All patients underwent routine clinical assessment and a CT scan prior to EBUS-TBNA. Demographic data, HIV status, pathological findings and microbiological results were recorded.
EBUS-TBNA was diagnostic of TB in 146 patients (94%; 95% CI 88% to 97%). Pathological findings were consistent with TB in 134 patients (86%). Microbiological investigations yielded a positive culture of TB in 74 patients (47%) with a median time to positive culture of 16 days (range 3-84) and identified eight drug-resistant cases (5%). Ten patients (6%) did not have a specific diagnosis following EBUS; four underwent mediastinoscopy which confirmed the diagnosis of TB while six responded to empirical antituberculous therapy. There was one complication requiring an inpatient admission.
EBUS-TBNA is a safe and effective first-line investigation in patients with tuberculous intrathoracic lymphadenopathy.
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